Motif 918 (n=2,338)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A0A0A6YYL1 | ST20-MTHFS | S73 | ochoa | 5-formyltetrahydrofolate cyclo-ligase (EC 6.3.3.2) | None |
| A0A0B4J203 | None | S304 | ochoa | receptor protein-tyrosine kinase (EC 2.7.10.1) | None |
| A0A0B4J269 | None | S519 | ochoa | Melanocyte-stimulating hormone receptor (Melanocortin receptor 1) | Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Mediates melanogenesis, the production of eumelanin (black/brown) and phaeomelanin (red/yellow), via regulation of cAMP signaling in melanocytes. {ECO:0000256|ARBA:ARBA00023428}. |
| A1L390 | PLEKHG3 | S962 | ochoa | Pleckstrin homology domain-containing family G member 3 (PH domain-containing family G member 3) | Plays a role in controlling cell polarity and cell motility by selectively binding newly polymerized actin and activating RAC1 and CDC42 to enhance local actin polymerization. {ECO:0000269|PubMed:27555588}. |
| A1XBS5 | CIBAR1 | S243 | ochoa | CBY1-interacting BAR domain-containing protein 1 | Plays a critical role in regulating mitochondrial ultrastructure and function by maintaining the integrity of mitochondrial morphology, particularly the organization of cristae (PubMed:30404948). Preferentially binds to negatively charged phospholipids like cardiolipin and phosphatidylinositol 4,5-bisphosphate enhancing its interaction with mitochondrial membranes (PubMed:30404948). Induces membrane curvature and tubulation, which are critical for maintaining mitochondrial ultrastructure and the organization of cristae (PubMed:30404948). Plays a crucial role in ciliogenesis (PubMed:27528616, PubMed:30395363). May play a role in limb development through its role in ciliogenesis (PubMed:30395363). Plays a key role in the correct positioning of the annulus, a septin-based ring structure in the sperm flagellum, serving both as a physical barrier and a membrane diffusion barrier that separates the midpiece (MP) from the principal piece (PP) (By similarity). This positioning is essential for proper sperm motility and function (By similarity). Interacts with CBY3 to form a complex which localizes to the curved membrane region of the flagellar pocket (By similarity). By doing so, may provide stability and rigidity to the periannular membrane to prevent membrane deformation (By similarity). This function is crucial for halting annulus migration at the proximal end of the fibrous sheath-containing PP (By similarity). {ECO:0000250|UniProtKB:Q8BP22, ECO:0000269|PubMed:27528616, ECO:0000269|PubMed:30395363, ECO:0000269|PubMed:30404948}. |
| A4D1E1 | ZNF804B | S877 | ochoa | Zinc finger protein 804B | None |
| A4D1P6 | WDR91 | S256 | ochoa | WD repeat-containing protein 91 | Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May play a role in meiosis (By similarity). {ECO:0000250|UniProtKB:Q7TMQ7, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989}. |
| A6H8Y1 | BDP1 | S1317 | ochoa | Transcription factor TFIIIB component B'' homolog (Transcription factor IIIB 150) (TFIIIB150) (Transcription factor-like nuclear regulator) | General activator of RNA polymerase III transcription. Requires for transcription from all three types of polymerase III promoters. Requires for transcription of genes with internal promoter elements and with promoter elements upstream of the initiation site. {ECO:0000269|PubMed:11040218}. |
| A6NKT7 | RGPD3 | S128 | ochoa | RanBP2-like and GRIP domain-containing protein 3 | None |
| A6QL64 | ANKRD36 | S478 | ochoa | Ankyrin repeat domain-containing protein 36A | None |
| A7KAX9 | ARHGAP32 | S592 | ochoa | Rho GTPase-activating protein 32 (Brain-specific Rho GTPase-activating protein) (GAB-associated Cdc42/Rac GTPase-activating protein) (GC-GAP) (GTPase regulator interacting with TrkA) (Rho-type GTPase-activating protein 32) (Rho/Cdc42/Rac GTPase-activating protein RICS) (RhoGAP involved in the beta-catenin-N-cadherin and NMDA receptor signaling) (p200RhoGAP) (p250GAP) | GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:12446789, ECO:0000269|PubMed:12454018, ECO:0000269|PubMed:12531901, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:12819203, ECO:0000269|PubMed:12857875, ECO:0000269|PubMed:17663722}. |
| A7KAX9 | ARHGAP32 | S1234 | ochoa | Rho GTPase-activating protein 32 (Brain-specific Rho GTPase-activating protein) (GAB-associated Cdc42/Rac GTPase-activating protein) (GC-GAP) (GTPase regulator interacting with TrkA) (Rho-type GTPase-activating protein 32) (Rho/Cdc42/Rac GTPase-activating protein RICS) (RhoGAP involved in the beta-catenin-N-cadherin and NMDA receptor signaling) (p200RhoGAP) (p250GAP) | GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity (By similarity). {ECO:0000250, ECO:0000269|PubMed:12446789, ECO:0000269|PubMed:12454018, ECO:0000269|PubMed:12531901, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:12819203, ECO:0000269|PubMed:12857875, ECO:0000269|PubMed:17663722}. |
| B8ZZF3 | None | S369 | ochoa | Mediator of RNA polymerase II transcription subunit 26 (Cofactor required for Sp1 transcriptional activation subunit 7) (Mediator complex subunit 26) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. {ECO:0000256|ARBA:ARBA00057523}. |
| D6RIA3 | C4orf54 | S1187 | ochoa | Uncharacterized protein C4orf54 (Familial obliterative portal venopathy) | None |
| H7C1W4 | None | S242 | ochoa | Uncharacterized protein | None |
| J3QQQ9 | None | S32 | ochoa | KOW domain-containing protein | None |
| O00139 | KIF2A | S586 | ochoa | Kinesin-like protein KIF2A (Kinesin-2) (hK2) | Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity. {ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:30785839}. |
| O00257 | CBX4 | S182 | ochoa | E3 SUMO-protein ligase CBX4 (EC 2.3.2.-) (Chromobox protein homolog 4) (Polycomb 2 homolog) (Pc2) (hPc2) | E3 SUMO-protein ligase that catalyzes sumoylation of target proteins by promoting the transfer of SUMO from the E2 enzyme to the substrate (PubMed:12679040, PubMed:22825850). Involved in the sumoylation of HNRNPK, a p53/TP53 transcriptional coactivator, hence indirectly regulates p53/TP53 transcriptional activation resulting in p21/CDKN1A expression. Monosumoylates ZNF131 (PubMed:22825850). {ECO:0000269|PubMed:12679040, ECO:0000269|PubMed:22825850}.; FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:12167701, PubMed:19636380, PubMed:21282530). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:12167701, PubMed:19636380, PubMed:21282530). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) (By similarity). Plays a role in the lineage differentiation of the germ layers in embryonic development (By similarity). {ECO:0000250|UniProtKB:O55187, ECO:0000269|PubMed:12167701, ECO:0000269|PubMed:19636380, ECO:0000269|PubMed:21282530}. |
| O00294 | TULP1 | S219 | ochoa | Tubby-related protein 1 (Tubby-like protein 1) | Required for normal development of photoreceptor synapses. Required for normal photoreceptor function and for long-term survival of photoreceptor cells. Interacts with cytoskeleton proteins and may play a role in protein transport in photoreceptor cells (By similarity). Binds lipids, especially phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 3,4,5-bisphosphate, phosphatidylserine and phosphatidic acid (in vitro). Contribute to stimulation of phagocytosis of apoptotic retinal pigment epithelium (RPE) cells and macrophages. {ECO:0000250, ECO:0000269|PubMed:16303976, ECO:0000269|PubMed:19837063}. |
| O00764 | PDXK | S285 | ochoa | Pyridoxal kinase (EC 2.7.1.35) (Pyridoxine kinase) | Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (Probable) (PubMed:10987144, PubMed:17766369, PubMed:19351586, PubMed:31187503, PubMed:9099727). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions. {ECO:0000269|PubMed:10987144, ECO:0000269|PubMed:17766369, ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:31187503, ECO:0000269|PubMed:9099727, ECO:0000305}. |
| O14513 | NCKAP5 | S600 | ochoa | Nck-associated protein 5 (NAP-5) (Peripheral clock protein) | None |
| O14715 | RGPD8 | S128 | ochoa | RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) | None |
| O14974 | PPP1R12A | S432 | ochoa | Protein phosphatase 1 regulatory subunit 12A (Myosin phosphatase-targeting subunit 1) (Myosin phosphatase target subunit 1) (Protein phosphatase myosin-binding subunit) | Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity. {ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:20354225}. |
| O14976 | GAK | S326 | ochoa | Cyclin-G-associated kinase (EC 2.7.11.1) (DnaJ homolog subfamily C member 26) | Associates with cyclin G and CDK5. Seems to act as an auxilin homolog that is involved in the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells. Expression oscillates slightly during the cell cycle, peaking at G1 (PubMed:10625686). May play a role in clathrin-mediated endocytosis and intracellular trafficking, and in the dynamics of clathrin assembly/disassembly (PubMed:18489706). {ECO:0000269|PubMed:10625686, ECO:0000269|PubMed:18489706}. |
| O14981 | BTAF1 | S95 | ochoa | TATA-binding protein-associated factor 172 (EC 3.6.4.-) (ATP-dependent helicase BTAF1) (B-TFIID transcription factor-associated 170 kDa subunit) (TAF(II)170) (TBP-associated factor 172) (TAF-172) | Regulates transcription in association with TATA binding protein (TBP). Removes TBP from the TATA box in an ATP-dependent manner. |
| O15085 | ARHGEF11 | S1413 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15245 | SLC22A1 | S331 | ochoa | Solute carrier family 22 member 1 (Organic cation transporter 1) (hOCT1) | Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930). {ECO:0000250|UniProtKB:O08966, ECO:0000250|UniProtKB:Q63089, ECO:0000269|PubMed:11388889, ECO:0000269|PubMed:11408531, ECO:0000269|PubMed:11907186, ECO:0000269|PubMed:12439218, ECO:0000269|PubMed:12719534, ECO:0000269|PubMed:15389554, ECO:0000269|PubMed:15817714, ECO:0000269|PubMed:16263091, ECO:0000269|PubMed:16272756, ECO:0000269|PubMed:16581093, ECO:0000269|PubMed:17460754, ECO:0000269|PubMed:19536068, ECO:0000269|PubMed:21128598, ECO:0000269|PubMed:23680637, ECO:0000269|PubMed:24961373, ECO:0000269|PubMed:34040533, ECO:0000269|PubMed:35469921, ECO:0000269|PubMed:9187257, ECO:0000269|PubMed:9260930, ECO:0000269|PubMed:9655880, ECO:0000305|PubMed:35307651}.; FUNCTION: [Isoform 1]: Mediates the uptake of 1-methyl-4-phenylpyridinium (MPP(+)). {ECO:0000269|PubMed:11388889}.; FUNCTION: [Isoform 2]: Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)). {ECO:0000269|PubMed:11388889}.; FUNCTION: [Isoform 3]: Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)). {ECO:0000269|PubMed:11388889}.; FUNCTION: [Isoform 4]: Not able to uptake 1-methyl-4-phenylpyridinium (MPP(+)). {ECO:0000269|PubMed:11388889}. |
| O15350 | TP73 | S145 | ochoa | 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}. |
| O15357 | INPPL1 | S241 | 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}. |
| O43149 | ZZEF1 | S240 | ochoa | Zinc finger ZZ-type and EF-hand domain-containing protein 1 | Histone H3 reader which may act as a transcriptional coactivator for KLF6 and KLF9 transcription factors. {ECO:0000269|PubMed:33227311}. |
| O43167 | ZBTB24 | S134 | ochoa | Zinc finger and BTB domain-containing protein 24 (Zinc finger protein 450) | May be involved in BMP2-induced transcription. {ECO:0000250}. |
| O43172 | PRPF4 | S240 | ochoa | U4/U6 small nuclear ribonucleoprotein Prp4 (PRP4 homolog) (hPrp4) (U4/U6 snRNP 60 kDa protein) (WD splicing factor Prp4) | Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). {ECO:0000269|PubMed:25383878, ECO:0000269|PubMed:28781166}. |
| O43379 | WDR62 | S501 | 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}. |
| O43639 | NCK2 | S176 | ochoa | Cytoplasmic protein NCK2 (Growth factor receptor-bound protein 4) (NCK adaptor protein 2) (Nck-2) (SH2/SH3 adaptor protein NCK-beta) | Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16835242}. |
| O60303 | KATNIP | S660 | ochoa | Katanin-interacting protein | May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex. {ECO:0000269|PubMed:26714646}. |
| O60336 | MAPKBP1 | S488 | ochoa | Mitogen-activated protein kinase-binding protein 1 (JNK-binding protein 1) (JNKBP-1) | Negative regulator of NOD2 function. It down-regulates NOD2-induced processes such as activation of NF-kappa-B signaling, IL8 secretion and antibacterial response (PubMed:22700971). Involved in JNK signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q6NS57, ECO:0000269|PubMed:22700971}. |
| O60566 | BUB1B | S884 | 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}. |
| O60658 | PDE8A | S20 | 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}. |
| O75132 | ZBED4 | S255 | ochoa | Zinc finger BED domain-containing protein 4 | Transcriptional regulator that binds to poly-guanine tracts in gene promoters and activates transcription (By similarity). Able to bind single- and double-stranded DNA and RNA (By similarity). {ECO:0000250|UniProtKB:Q80WQ9}. |
| O75182 | SIN3B | S1003 | ochoa | Paired amphipathic helix protein Sin3b (Histone deacetylase complex subunit Sin3b) (Transcriptional corepressor Sin3b) | Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression. As part of the SIN3B complex represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription (PubMed:21041482). {ECO:0000250|UniProtKB:Q62141, ECO:0000269|PubMed:21041482, ECO:0000269|PubMed:37137925}. |
| O75362 | ZNF217 | S570 | ochoa | Zinc finger protein 217 | Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:16203743, ECO:0000269|PubMed:16940172, ECO:0000269|PubMed:17259635, ECO:0000269|PubMed:18625718}. |
| O75364 | PITX3 | S52 | ochoa | Pituitary homeobox 3 (Homeobox protein PITX3) (Paired-like homeodomain transcription factor 3) | Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. In addition to its importance during development, it also has roles in the long-term survival and maintenance of the mdDA neurons. Activates NR4A2/NURR1-mediated transcription of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons. Acts by decreasing the interaction of NR4A2/NURR1 with the corepressor NCOR2/SMRT which acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state. Essential for the normal lens development and differentiation. Plays a critical role in the maintenance of mitotic activity of lens epithelial cells, fiber cell differentiation and in the control of the temporal and spatial activation of fiber cell-specific crystallins. Positively regulates FOXE3 expression and negatively regulates PROX1 in the anterior lens epithelium, preventing activation of CDKN1B/P27Kip1 and CDKN1C/P57Kip2 and thus maintains lens epithelial cells in cell cycle (By similarity). {ECO:0000250}. |
| O75376 | NCOR1 | S1263 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75385 | ULK1 | S225 | ochoa | Serine/threonine-protein kinase ULK1 (EC 2.7.11.1) (Autophagy-related protein 1 homolog) (ATG1) (hATG1) (Unc-51-like kinase 1) | Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708). {ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:20921139, ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:37306101}. |
| O75396 | SEC22B | S48 | 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}. |
| O75417 | POLQ | S1587 | ochoa | DNA polymerase theta (DNA polymerase eta) [Includes: Helicase POLQ (EC 3.6.4.12); DNA polymerase POLQ (EC 2.7.7.7) (RNA-directed DNA polymerase POLQ) (EC 2.7.7.49)] | Low-fidelity DNA polymerase with a helicase activity that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery required to repair double-strand breaks in DNA during mitosis (PubMed:14576298, PubMed:18503084, PubMed:24648516, PubMed:25642963, PubMed:25643323, PubMed:25775267, PubMed:26636256, PubMed:27311885, PubMed:27591252, PubMed:30655289, PubMed:31562312, PubMed:32873648, PubMed:34140467, PubMed:34179826, PubMed:36455556, PubMed:37440612, PubMed:37674080). MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation (PubMed:25642963, PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252, PubMed:31562312, PubMed:32873648). MMEJ is required during mitosis to repair persistent double-strand breaks that originate in S-phase (PubMed:37440612, PubMed:37674080). Although error-prone, MMEJ protects against chromosomal instability and tumorigenesis (By similarity). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs (PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252). It then extends each strand from the base-paired region using the opposing overhang as a template (PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252). Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ (PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252). The polymerase lacks proofreading activity and is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). When the ends of a break do not contain terminal microhomology must identify embedded complementary sequences through a scanning step (PubMed:32234782). Also acts as a DNA helicase, promoting dissociation of the replication protein A complex (RPA/RP-A), composed of RPA1, RPA2 and RPA3, from resected double-strand breaks to allow their annealing and subsequent joining by MMEJ (PubMed:36455556). Removal of RPA/RP-A complex proteins prevents RAD51 accumulation at resected ends, thereby inhibiting homology-recombination repair (HR) pathway (PubMed:25642963, PubMed:28695890). Also shows RNA-directed DNA polymerase activity to mediate DNA repair in vitro; however this activity needs additional evidence in vivo (PubMed:34117057). May also have lyase activity (PubMed:19188258). Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs (By similarity). POLQ-mediated end joining activity is involved in random integration of exogenous DNA hampers (PubMed:28695890). {ECO:0000250|UniProtKB:Q8CGS6, ECO:0000269|PubMed:14576298, ECO:0000269|PubMed:18503084, ECO:0000269|PubMed:19188258, ECO:0000269|PubMed:21050863, ECO:0000269|PubMed:22135286, ECO:0000269|PubMed:24648516, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:25643323, ECO:0000269|PubMed:25775267, ECO:0000269|PubMed:26636256, ECO:0000269|PubMed:27311885, ECO:0000269|PubMed:27591252, ECO:0000269|PubMed:28695890, ECO:0000269|PubMed:30655289, ECO:0000269|PubMed:31562312, ECO:0000269|PubMed:32234782, ECO:0000269|PubMed:32873648, ECO:0000269|PubMed:34117057, ECO:0000269|PubMed:34140467, ECO:0000269|PubMed:34179826, ECO:0000269|PubMed:36455556, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080}. |
| O75427 | LRCH4 | S589 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 4 (Leucine-rich repeat neuronal protein 4) (Leucine-rich neuronal protein) | Accessory protein that regulates signaling by multiple TLRs, acting as a broad-spanning regulator of the innate immune response. In macrophages, binds LPS and promotes proper docking of LPS in lipid raft membrane. May be required for lipid raft maintenance. {ECO:0000250|UniProtKB:Q921G6}. |
| O75815 | BCAR3 | S182 | ochoa | Breast cancer anti-estrogen resistance protein 3 (Novel SH2-containing protein 2) (SH2 domain-containing protein 3B) | Acts as an adapter protein downstream of several growth factor receptors to promote cell proliferation, migration, and redistribution of actin fibers (PubMed:24216110). Specifically involved in INS/insulin signaling pathway by mediating MAPK1/ERK2-MAPK3/ERK1 activation and DNA synthesis (PubMed:24216110). Promotes insulin-mediated membrane ruffling (By similarity). In response to vasoconstrictor peptide EDN1, involved in the activation of RAP1 downstream of PTK2B via interaction with phosphorylated BCAR1 (PubMed:19086031). Inhibits cell migration and invasion via regulation of TGFB-mediated matrix digestion, actin filament rearrangement, and inhibition of invadopodia activity (By similarity). May inhibit TGFB-SMAD signaling, via facilitating BCAR1 and SMAD2 and/or SMAD3 interaction (By similarity). Regulates EGF-induced DNA synthesis (PubMed:18722344). Required for the maintenance of ocular lens morphology and structural integrity, potentially via regulation of focal adhesion complex signaling (By similarity). Acts upstream of PTPRA to regulate the localization of BCAR1 and PTPRA to focal adhesions, via regulation of SRC-mediated phosphorylation of PTPRA (By similarity). Positively regulates integrin-induced tyrosine phosphorylation of BCAR1 (By similarity). Acts as a guanine nucleotide exchange factor (GEF) for small GTPases RALA, RAP1A and RRAS (By similarity). However, in a contrasting study, lacks GEF activity towards RAP1 (PubMed:22081014). {ECO:0000250|UniProtKB:D3ZAZ5, ECO:0000250|UniProtKB:Q9QZK2, ECO:0000269|PubMed:18722344, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:22081014, ECO:0000269|PubMed:24216110}. |
| O75821 | EIF3G | S42 | ochoa|psp | Eukaryotic translation initiation factor 3 subunit G (eIF3g) (Eukaryotic translation initiation factor 3 RNA-binding subunit) (eIF-3 RNA-binding subunit) (Eukaryotic translation initiation factor 3 subunit 4) (eIF-3-delta) (eIF3 p42) (eIF3 p44) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). This subunit can bind 18S rRNA. {ECO:0000255|HAMAP-Rule:MF_03006, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| O75828 | CBR3 | S56 | ochoa | Carbonyl reductase [NADPH] 3 (EC 1.1.1.184) (NADPH-dependent carbonyl reductase 3) (Quinone reductase CBR3) (EC 1.6.5.10) (Short chain dehydrogenase/reductase family 21C member 2) | Catalyzes the NADPH-dependent reduction of carbonyl compounds to their corresponding alcohols (PubMed:18493841). Has low NADPH-dependent oxidoreductase activity. Acts on several orthoquinones, acts as well on non-quinone compounds, such as isatin or on the anticancer drug oracin (PubMed:15537833, PubMed:18493841, PubMed:19841672). Best substrates for CBR3 is 1,2- naphthoquinone, hence could play a role in protection against cytotoxicity of exogenous quinones (PubMed:19841672). Exerts activity toward ortho-quinones but not paraquinones. No endogenous substrate for CBR3 except isatin has been identified (PubMed:19841672). {ECO:0000269|PubMed:15537833, ECO:0000269|PubMed:18493841, ECO:0000269|PubMed:19841672}. |
| O76094 | SRP72 | S443 | ochoa | Signal recognition particle subunit SRP72 (SRP72) (Signal recognition particle 72 kDa protein) | Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (PubMed:34020957). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER (PubMed:34020957). The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER (PubMed:34020957). Binds the signal recognition particle RNA (7SL RNA) in presence of SRP68 (PubMed:21073748, PubMed:27899666). Can bind 7SL RNA with low affinity (PubMed:21073748, PubMed:27899666). The SRP complex possibly participates in the elongation arrest function (By similarity). {ECO:0000250|UniProtKB:P38688, ECO:0000269|PubMed:21073748, ECO:0000269|PubMed:27899666, ECO:0000269|PubMed:34020957}. |
| O94811 | TPPP | S160 | ochoa|psp | Tubulin polymerization-promoting protein (TPPP) (EC 3.6.5.-) (25 kDa brain-specific protein) (TPPP/p25) (p24) (p25-alpha) | Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath (PubMed:31522887). Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath (PubMed:31522887, PubMed:33831707). Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes (PubMed:31522887). Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear (PubMed:21316364, PubMed:21995432). In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network (PubMed:17105200, PubMed:17693641, PubMed:18028908, PubMed:26289831). Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407). Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility (PubMed:23093407). Plays a role in cell proliferation by regulating the G1/S-phase transition (PubMed:23355470). Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2 (PubMed:22328514). {ECO:0000269|PubMed:17105200, ECO:0000269|PubMed:17693641, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:20308065, ECO:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:26289831, ECO:0000269|PubMed:31522887}. |
| O94818 | NOL4 | S309 | ochoa | Nucleolar protein 4 (Nucleolar-localized protein) | None |
| O94850 | DDN | S508 | ochoa | Dendrin | Promotes apoptosis of kidney glomerular podocytes. Podocytes are highly specialized cells essential to the ultrafiltration of blood, resulting in the extraction of urine and the retention of protein (By similarity). {ECO:0000250}. |
| O94885 | SASH1 | S101 | ochoa | SAM and SH3 domain-containing protein 1 (Proline-glutamate repeat-containing protein) | Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}. |
| O94916 | NFAT5 | S145 | ochoa | Nuclear factor of activated T-cells 5 (NF-AT5) (T-cell transcription factor NFAT5) (Tonicity-responsive enhancer-binding protein) (TonE-binding protein) (TonEBP) | Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394). Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:34049076). {ECO:0000269|PubMed:10051678, ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:22266867, ECO:0000269|PubMed:34049076}. |
| O94916 | NFAT5 | S649 | ochoa | Nuclear factor of activated T-cells 5 (NF-AT5) (T-cell transcription factor NFAT5) (Tonicity-responsive enhancer-binding protein) (TonE-binding protein) (TonEBP) | Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394). Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:34049076). {ECO:0000269|PubMed:10051678, ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:22266867, ECO:0000269|PubMed:34049076}. |
| O95071 | UBR5 | S2424 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95155 | UBE4B | S238 | ochoa | Ubiquitin conjugation factor E4 B (EC 2.3.2.27) (Homozygously deleted in neuroblastoma 1) (RING-type E3 ubiquitin transferase E4 B) (Ubiquitin fusion degradation protein 2) | Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). {ECO:0000250|UniProtKB:P54860, ECO:0000250|UniProtKB:Q9ES00, ECO:0000269|PubMed:17369820}. |
| O95201 | ZNF205 | S94 | ochoa | Transcriptional repressor RHIT (Repressor of heat-inducible transcription) (RhitH) (Zinc finger protein 205) (Zinc finger protein 210) | Transcriptional repressor involved in regulating MPV17L expression (PubMed:22306510). By regulating MPV17L expression, contributes to the regulation of genes involved in H(2)O(2) metabolism and the mitochondrial apoptotic cascade (PubMed:22306510). {ECO:0000269|PubMed:22306510}. |
| O95382 | MAP3K6 | S1129 | ochoa | Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2) | Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways. {ECO:0000269|PubMed:17210579, ECO:0000269|PubMed:9875215}. |
| O95402 | MED26 | S361 | ochoa | Mediator of RNA polymerase II transcription subunit 26 (Activator-recruited cofactor 70 kDa component) (ARC70) (Cofactor required for Sp1 transcriptional activation subunit 7) (CRSP complex subunit 7) (Mediator complex subunit 26) (Transcriptional coactivator CRSP70) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. |
| O95466 | FMNL1 | S950 | ochoa | Formin-like protein 1 (CLL-associated antigen KW-13) (Leukocyte formin) | May play a role in the control of cell motility and survival of macrophages (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| O95478 | NSA2 | S205 | ochoa | Ribosome biogenesis protein NSA2 homolog (Hairy cell leukemia protein 1) (TGF-beta-inducible nuclear protein 1) | Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles (By similarity). {ECO:0000250}. |
| O95714 | HERC2 | S368 | ochoa | E3 ubiquitin-protein ligase HERC2 (EC 2.3.2.26) (HECT domain and RCC1-like domain-containing protein 2) (HECT-type E3 ubiquitin transferase HERC2) | E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation (IR) and facilitates the assembly of UBE2N and RNF8 promoting DNA damage-induced formation of 'Lys-63'-linked ubiquitin chains. Acts as a mediator of binding specificity between UBE2N and RNF8. Involved in the maintenance of RNF168 levels. E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of XPA which influences the circadian oscillation of DNA excision repair activity. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). Also modulates iron metabolism by regulating the basal turnover of FBXL5 (PubMed:24778179). {ECO:0000269|PubMed:20023648, ECO:0000269|PubMed:20304803, ECO:0000269|PubMed:22508508, ECO:0000269|PubMed:24778179, ECO:0000269|PubMed:26692333}. |
| O95825 | CRYZL1 | S143 | ochoa | Quinone oxidoreductase-like protein 1 (EC 1.-.-.-) (Ferry endosomal RAB5 effector complex subunit 4) (Fy-4) (Protein 4P11) (Quinone oxidoreductase homolog 1) (QOH-1) (Zeta-crystallin homolog) | 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). {ECO:0000269|PubMed:37267905, ECO:0000269|PubMed:37267906}. |
| P00558 | PGK1 | S203 | ochoa|psp | Phosphoglycerate kinase 1 (EC 2.7.11.1) (EC 2.7.2.3) (Cell migration-inducing gene 10 protein) (Primer recognition protein 2) (PRP 2) | Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:18463139, ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:30323285, ECO:0000269|PubMed:36849569, ECO:0000269|PubMed:7391028}. |
| P04150 | NR3C1 | S267 | ochoa|psp | Glucocorticoid receptor (GR) (Nuclear receptor subfamily 3 group C member 1) | Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:28139699, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9590696}.; FUNCTION: [Isoform Alpha]: Has transcriptional activation and repression activity (PubMed:11435610, PubMed:15769988, PubMed:15866175, PubMed:17635946, PubMed:19141540, PubMed:19248771, PubMed:20484466, PubMed:21664385, PubMed:23820903). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15769988, ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:17635946, ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:21664385, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903, ECO:0000269|PubMed:25847991}.; FUNCTION: [Isoform Beta]: Acts as a dominant negative inhibitor of isoform Alpha (PubMed:20484466, PubMed:7769088, PubMed:8621628). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:26711253, ECO:0000269|PubMed:7769088, ECO:0000269|PubMed:8621628}.; FUNCTION: [Isoform Alpha-2]: Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466).; FUNCTION: [Isoform GR-P]: Increases activity of isoform Alpha. {ECO:0000269|PubMed:11358809}.; FUNCTION: [Isoform Alpha-B]: More effective than isoform Alpha in transcriptional activation, but not repression activity. {ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform 10]: Has transcriptional activation activity. {ECO:0000269|PubMed:20484466}.; FUNCTION: [Isoform Alpha-C1]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-C2]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-C3]: Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903). {ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}.; FUNCTION: [Isoform Alpha-D1]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-D2]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-D3]: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). {ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}. |
| P04350 | TUBB4A | S172 | 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. |
| P06748 | NPM1 | S70 | ochoa|psp | Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) | Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}. |
| P07437 | TUBB | S172 | 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. |
| P0DJD0 | RGPD1 | S119 | ochoa | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P0DJD1 | RGPD2 | S127 | ochoa | RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) | None |
| P10746 | UROS | S245 | 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}. |
| P12883 | MYH7 | S210 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P13196 | ALAS1 | S85 | ochoa | 5-aminolevulinate synthase, non-specific, mitochondrial (ALAS-H) (EC 2.3.1.37) (5-aminolevulinic acid synthase 1) (Delta-ALA synthase 1) (Delta-aminolevulinate synthase 1) | Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products. {ECO:0000269|PubMed:16234850, ECO:0000269|PubMed:17975826}. |
| P13639 | EEF2 | S279 | ochoa | 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}. |
| P16152 | CBR1 | S56 | ochoa | Carbonyl reductase [NADPH] 1 (EC 1.1.1.184) (15-hydroxyprostaglandin dehydrogenase [NADP(+)]) (EC 1.1.1.196, EC 1.1.1.197) (20-beta-hydroxysteroid dehydrogenase) (Alcohol dehydrogenase [NAD(P)+] CBR1) (EC 1.1.1.71) (NADPH-dependent carbonyl reductase 1) (Prostaglandin 9-ketoreductase) (PG-9-KR) (Prostaglandin-E(2) 9-reductase) (EC 1.1.1.189) (Short chain dehydrogenase/reductase family 21C member 1) | NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol (PubMed:15799708, PubMed:17344335, PubMed:17912391, PubMed:18449627, PubMed:18826943, PubMed:1921984, PubMed:7005231). Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione (PubMed:17344335, PubMed:18826943). In addition, participates in the glucocorticoid metabolism by catalyzing the NADPH-dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue (PubMed:28878267). {ECO:0000250|UniProtKB:Q28960, ECO:0000269|PubMed:15799708, ECO:0000269|PubMed:17344335, ECO:0000269|PubMed:17912391, ECO:0000269|PubMed:18449627, ECO:0000269|PubMed:18826943, ECO:0000269|PubMed:1921984, ECO:0000269|PubMed:28878267, ECO:0000269|PubMed:7005231}. |
| P18206 | VCL | S566 | 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}. |
| P22314 | UBA1 | S24 | 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}. |
| P23443 | RPS6KB1 | S394 | ochoa|psp | Ribosomal protein S6 kinase beta-1 (S6K-beta-1) (S6K1) (EC 2.7.11.1) (70 kDa ribosomal protein S6 kinase 1) (P70S6K1) (p70-S6K 1) (Ribosomal protein S6 kinase I) (Serine/threonine-protein kinase 14A) (p70 ribosomal S6 kinase alpha) (p70 S6 kinase alpha) (p70 S6K-alpha) (p70 S6KA) | Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating MAPKAP1/SIN1, MTOR and RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (PubMed:15899889, PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (By similarity). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (PubMed:17936702). The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function (PubMed:17936702). Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (PubMed:17052453). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239). {ECO:0000250|UniProtKB:P67999, ECO:0000250|UniProtKB:Q8BSK8, ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500, ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:15899889, ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:28178239}. |
| P24534 | EEF1B2 | S43 | 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}. |
| P26045 | PTPN3 | S434 | ochoa | Tyrosine-protein phosphatase non-receptor type 3 (EC 3.1.3.48) (Protein-tyrosine phosphatase H1) (PTP-H1) | May act at junctions between the membrane and the cytoskeleton. Possesses tyrosine phosphatase activity. |
| P27105 | STOM | S244 | ochoa | Stomatin (Erythrocyte band 7 integral membrane protein) (Erythrocyte membrane protein band 7.2) (Protein 7.2b) | Regulates ion channel activity and transmembrane ion transport. Regulates ASIC2 and ASIC3 channel activity. |
| P27361 | MAPK3 | S263 | ochoa | Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}. |
| P27694 | RPA1 | S38 | ochoa | Replication protein A 70 kDa DNA-binding subunit (RP-A p70) (Replication factor A protein 1) (RF-A protein 1) (Single-stranded DNA-binding protein) [Cleaved into: Replication protein A 70 kDa DNA-binding subunit, N-terminally processed] | As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism (PubMed:17596542, PubMed:27723717, PubMed:27723720). Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage (PubMed:9430682). In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response (PubMed:24332808). It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin in response to DNA damage (PubMed:17765923). Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair (PubMed:7697716). Also plays a role in base excision repair (BER) probably through interaction with UNG (PubMed:9765279). Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. Plays a role in telomere maintenance (PubMed:17959650, PubMed:34767620). As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange (PubMed:19996105). RPA stimulates 5'-3' helicase activity of the BRIP1/FANCJ (PubMed:17596542). {ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:17596542, ECO:0000269|PubMed:17765923, ECO:0000269|PubMed:17959650, ECO:0000269|PubMed:19116208, ECO:0000269|PubMed:19996105, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:34767620, ECO:0000269|PubMed:7697716, ECO:0000269|PubMed:7700386, ECO:0000269|PubMed:9430682, ECO:0000269|PubMed:9765279}. |
| P27816 | MAP4 | S358 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P27816 | MAP4 | S384 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P28482 | MAPK1 | S246 | ochoa|psp | Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}. |
| P28562 | DUSP1 | S323 | psp | Dual specificity protein phosphatase 1 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity protein phosphatase hVH1) (Mitogen-activated protein kinase phosphatase 1) (MAP kinase phosphatase 1) (MKP-1) (Protein-tyrosine phosphatase CL100) | Dual specificity phosphatase that dephosphorylates MAP kinase MAPK1/ERK2 on both 'Thr-183' and 'Tyr-185', regulating its activity during the meiotic cell cycle. {ECO:0000250|UniProtKB:P28563}. |
| P28749 | RBL1 | S762 | ochoa | Retinoblastoma-like protein 1 (107 kDa retinoblastoma-associated protein) (p107) (pRb1) | Key regulator of entry into cell division (PubMed:17671431). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (By similarity). Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression (By similarity). Controls histone H4 'Lys-20' trimethylation (By similarity). Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters (By similarity). Potent inhibitor of E2F-mediated trans-activation (PubMed:8319904). May act as a tumor suppressor (PubMed:8319904). {ECO:0000250|UniProtKB:Q64701, ECO:0000269|PubMed:17671431, ECO:0000269|PubMed:8319904}. |
| P30038 | ALDH4A1 | S410 | ochoa | Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial (P5C dehydrogenase) (EC 1.2.1.88) (Aldehyde dehydrogenase family 4 member A1) (L-glutamate gamma-semialdehyde dehydrogenase) | Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes. {ECO:0000269|PubMed:22516612}. |
| P30101 | PDIA3 | S456 | ochoa | 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}. |
| P30566 | ADSL | S434 | ochoa | Adenylosuccinate lyase (ADSL) (ASL) (EC 4.3.2.2) (Adenylosuccinase) (ASase) | Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate. {ECO:0000269|PubMed:10888601}. |
| P31150 | GDI1 | S222 | ochoa | Rab GDP dissociation inhibitor alpha (Rab GDI alpha) (Guanosine diphosphate dissociation inhibitor 1) (GDI-1) (Oligophrenin-2) (Protein XAP-4) | Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Promotes the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Promotes the dissociation of RAB1A, RAB3A, RAB5A and RAB10 from membranes. {ECO:0000269|PubMed:23815289}. |
| P32519 | ELF1 | S432 | ochoa | ETS-related transcription factor Elf-1 (E74-like factor 1) | Transcription factor that activates the LYN and BLK promoters. Appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression. Binds specifically to two purine-rich motifs in the HIV-2 enhancer. {ECO:0000269|PubMed:8756667}. |
| P35222 | CTNNB1 | S246 | 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}. |
| P37275 | ZEB1 | S583 | ochoa | Zinc finger E-box-binding homeobox 1 (NIL-2-A zinc finger protein) (Negative regulator of IL2) (Transcription factor 8) (TCF-8) | Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (By similarity). {ECO:0000250|UniProtKB:Q64318, ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. |
| P41252 | IARS1 | S1047 | ochoa | Isoleucine--tRNA ligase, cytoplasmic (EC 6.1.1.5) (Isoleucyl-tRNA synthetase) (IRS) (IleRS) | 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:0000269|PubMed:8052601}. |
| P42566 | EPS15 | S140 | ochoa | Epidermal growth factor receptor substrate 15 (Protein Eps15) (Protein AF-1p) | Involved in cell growth regulation. May be involved in the regulation of mitogenic signals and control of cell proliferation. Involved in the internalization of ligand-inducible receptors of the receptor tyrosine kinase (RTK) type, in particular EGFR. Plays a role in the assembly of clathrin-coated pits (CCPs). Acts as a clathrin adapter required for post-Golgi trafficking. Seems to be involved in CCPs maturation including invagination or budding. 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:16903783, ECO:0000269|PubMed:18362181, ECO:0000269|PubMed:19458185, ECO:0000269|PubMed:22648170}. |
| P46087 | NOP2 | S67 | ochoa | 28S rRNA (cytosine(4447)-C(5))-methyltransferase (EC 2.1.1.-) (Nucleolar protein 1) (Nucleolar protein 2 homolog) (Proliferating-cell nucleolar antigen p120) (Proliferation-associated nucleolar protein p120) | S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA (PubMed:26196125). Required for efficient rRNA processing and 60S ribosomal subunit biogenesis (PubMed:24120868, PubMed:36161484). Regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs and facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes (PubMed:36161484). May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation (PubMed:24120868). {ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:26196125, ECO:0000269|PubMed:36161484}. |
| P48553 | TRAPPC10 | S683 | ochoa | Trafficking protein particle complex subunit 10 (Epilepsy holoprosencephaly candidate 1 protein) (EHOC-1) (Protein GT334) (Trafficking protein particle complex subunit TMEM1) (Transport protein particle subunit TMEM1) (TRAPP subunit TMEM1) | Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether. {ECO:0000269|PubMed:11805826, ECO:0000269|PubMed:31467083, ECO:0000269|PubMed:35298461}. |
| P49327 | FASN | S1254 | 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}. |
| P49643 | PRIM2 | S170 | ochoa | DNA primase large subunit (DNA primase 58 kDa subunit) (p58) | Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:17893144, PubMed:25550159, PubMed:26975377, PubMed:9705292). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:17893144). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:17893144, PubMed:25550159). Binds RNA:DNA duplex and coordinates the catalytic activities of PRIM1 and POLA2 during primase-to-polymerase switch. {ECO:0000250|UniProtKB:P09884, ECO:0000250|UniProtKB:P33610, ECO:0000269|PubMed:17893144, ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377, ECO:0000269|PubMed:9705292}. |
| P49792 | RANBP2 | S128 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49792 | RANBP2 | S948 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49795 | RGS19 | S151 | psp | 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. |
| P49914 | MTHFS | S97 | ochoa | 5-formyltetrahydrofolate cyclo-ligase (EC 6.3.3.2) (5,10-methenyl-tetrahydrofolate synthetase) (MTHFS) (Methenyl-THF synthetase) | Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate. {ECO:0000269|PubMed:8522195}. |
| P50395 | GDI2 | S222 | 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}. |
| P51531 | SMARCA2 | S1377 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SAMRCA2) (EC 3.6.4.-) (BRG1-associated factor 190B) (BAF190B) (Probable global transcription activator SNF2L2) (Protein brahma homolog) (hBRM) (SNF2-alpha) | ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:15075294, PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6DIC0, ECO:0000269|PubMed:15075294, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P51587 | BRCA2 | S1946 | ochoa | Breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein) | Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}. |
| P51610 | HCFC1 | S1222 | ochoa | Host cell factor 1 (HCF) (HCF-1) (C1 factor) (CFF) (VCAF) (VP16 accessory protein) [Cleaved into: HCF N-terminal chain 1; HCF N-terminal chain 2; HCF N-terminal chain 3; HCF N-terminal chain 4; HCF N-terminal chain 5; HCF N-terminal chain 6; HCF C-terminal chain 1; HCF C-terminal chain 2; HCF C-terminal chain 3; HCF C-terminal chain 4; HCF C-terminal chain 5; HCF C-terminal chain 6] | Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity). {ECO:0000250|UniProtKB:D3ZN95, ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26416877}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:17578910}. |
| P51790 | CLCN3 | S745 | ochoa | H(+)/Cl(-) exchange transporter 3 (Chloride channel protein 3) (ClC-3) (Chloride transporter ClC-3) | [Isoform 1]: Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (PubMed:29845874). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (PubMed:29845874). {ECO:0000250|UniProtKB:P51791, ECO:0000303|PubMed:29845874}.; FUNCTION: [Isoform 2]: Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons. {ECO:0000269|PubMed:11967229}. |
| P51825 | AFF1 | S307 | ochoa | AF4/FMR2 family member 1 (ALL1-fused gene from chromosome 4 protein) (Protein AF-4) (Protein FEL) (Proto-oncogene AF4) | None |
| P52333 | JAK3 | S493 | ochoa | 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}. |
| P52948 | NUP98 | S1192 | ochoa | 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}. |
| P54136 | RARS1 | S38 | ochoa | Arginine--tRNA ligase, cytoplasmic (EC 6.1.1.19) (Arginyl-tRNA synthetase) (ArgRS) | Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis (PubMed:25288775). Modulates the secretion of AIMP1 and may be involved in generation of the inflammatory cytokine EMAP2 from AIMP1 (PubMed:17443684). {ECO:0000269|PubMed:17443684, ECO:0000269|PubMed:25288775}. |
| P55265 | ADAR | S614 | ochoa | Double-stranded RNA-specific adenosine deaminase (DRADA) (EC 3.5.4.37) (136 kDa double-stranded RNA-binding protein) (p136) (Interferon-inducible protein 4) (IFI-4) (K88DSRBP) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}. |
| P61254 | RPL26 | S32 | ochoa | Large ribosomal subunit protein uL24 (60S ribosomal protein L26) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:26100019, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:26100019, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:26100019}. |
| P68371 | TUBB4B | S172 | 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. |
| P78352 | DLG4 | S295 | psp | Disks large homolog 4 (Postsynaptic density protein 95) (PSD-95) (Synapse-associated protein 90) (SAP-90) (SAP90) | Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723). {ECO:0000250|UniProtKB:Q62108, ECO:0000269|PubMed:26334723}. |
| P80192 | MAP3K9 | S693 | ochoa | Mitogen-activated protein kinase kinase kinase 9 (EC 2.7.11.25) (Mixed lineage kinase 1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Also plays a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. {ECO:0000269|PubMed:11416147, ECO:0000269|PubMed:15610029}. |
| P81877 | SSBP2 | S321 | ochoa | Single-stranded DNA-binding protein 2 (Sequence-specific single-stranded-DNA-binding protein 2) | None |
| Q00537 | CDK17 | S122 | 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}. |
| Q00653 | NFKB2 | S812 | ochoa | Nuclear factor NF-kappa-B p100 subunit (DNA-binding factor KBF2) (H2TF1) (Lymphocyte translocation chromosome 10 protein) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2) (Oncogene Lyt-10) (Lyt10) [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The 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. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. {ECO:0000269|PubMed:7925301}. |
| Q01094 | E2F1 | S403 | psp | Transcription factor E2F1 (E2F-1) (PBR3) (Retinoblastoma-associated protein 1) (RBAP-1) (Retinoblastoma-binding protein 3) (RBBP-3) (pRB-binding protein E2F-1) | Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication (PubMed:10675335, PubMed:12717439, PubMed:17050006, PubMed:17704056, PubMed:18625225, PubMed:28992046). The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase (PubMed:10675335, PubMed:12717439, PubMed:17704056). E2F1 binds preferentially RB1 in a cell-cycle dependent manner (PubMed:10675335, PubMed:12717439, PubMed:17704056). It can mediate both cell proliferation and TP53/p53-dependent apoptosis (PubMed:8170954). Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812). Directly activates transcription of PEG10 (PubMed:17050006, PubMed:18625225, PubMed:28992046). Positively regulates transcription of RRP1B (PubMed:20040599). {ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:18625225, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20176812, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:8170954}. |
| Q01484 | ANK2 | S3840 | ochoa | Ankyrin-2 (ANK-2) (Ankyrin-B) (Brain ankyrin) (Non-erythroid ankyrin) | Plays an essential role in the localization and membrane stabilization of ion transporters and ion channels in several cell types, including cardiomyocytes, as well as in striated muscle cells. In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions. In cardiomyocytes, required for coordinate assembly of Na/Ca exchanger, SLC8A1/NCX1, Na/K ATPases ATP1A1 and ATP1A2 and inositol 1,4,5-trisphosphate (InsP3) receptors at sarcoplasmic reticulum/sarcolemma sites. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate (PubMed:12571597). In the inner segment of rod photoreceptors, required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) (By similarity). Plays a role in endocytosis and intracellular protein transport. Associates with phosphatidylinositol 3-phosphate (PI3P)-positive organelles and binds dynactin to promote long-range motility of cells. Recruits RABGAP1L to (PI3P)-positive early endosomes, where RABGAP1L inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity). {ECO:0000250|UniProtKB:Q8C8R3, ECO:0000269|PubMed:12571597}. |
| Q02078 | MEF2A | S355 | psp | Myocyte-specific enhancer factor 2A (Serum response factor-like protein 1) | Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Also involved in the activation of numerous 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. In cerebellar granule neurons, phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. Associates with chromatin to the ZNF16 promoter. {ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:16484498, ECO:0000269|PubMed:16563226, ECO:0000269|PubMed:21468593, ECO:0000269|PubMed:9858528}. |
| Q02952 | AKAP12 | S483 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q05D32 | CTDSPL2 | S134 | ochoa|psp | CTD small phosphatase-like protein 2 (CTDSP-like 2) (EC 3.1.3.-) | Probable phosphatase. {ECO:0000250}. |
| Q06203 | PPAT | S399 | ochoa | Amidophosphoribosyltransferase (ATase) (EC 2.4.2.14) (Glutamine phosphoribosylpyrophosphate amidotransferase) (GPAT) | Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine. {ECO:0000250|UniProtKB:P35433}. |
| Q06413 | MEF2C | S240 | ochoa | Myocyte-specific enhancer factor 2C (Myocyte enhancer factor 2C) | Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoforms that lack the repressor domain are more active than isoform 1. {ECO:0000250|UniProtKB:Q8CFN5, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15340086, ECO:0000269|PubMed:15831463, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:9069290, ECO:0000269|PubMed:9384584}. |
| Q08357 | SLC20A2 | S268 | ochoa | Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. |
| Q12802 | AKAP13 | S1282 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12931 | TRAP1 | S568 | ochoa|psp | Heat shock protein 75 kDa, mitochondrial (HSP 75) (Heat shock protein family C member 5) (TNFR-associated protein 1) (Tumor necrosis factor type 1 receptor-associated protein) (TRAP-1) | Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. {ECO:0000269|PubMed:23525905, ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:23747254}. |
| Q12955 | ANK3 | S2672 | ochoa | Ankyrin-3 (ANK-3) (Ankyrin-G) | Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity). {ECO:0000250|UniProtKB:G5E8K5, ECO:0000250|UniProtKB:O70511, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:7836469}.; FUNCTION: [Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin. {ECO:0000305|PubMed:17974005}. |
| Q12980 | NPRL3 | S189 | ochoa | GATOR1 complex protein NPRL3 (-14 gene protein) (Alpha-globin regulatory element-containing gene protein) (Nitrogen permease regulator 3-like protein) (Protein CGTHBA) | As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, PubMed:35338845). In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling (PubMed:23723238, PubMed:29590090, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is negatively regulated by GATOR2, the other GATOR subcomplex, in this amino acid-sensing branch of the TORC1 pathway (PubMed:23723238). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:29590090, ECO:0000269|PubMed:35338845}. |
| Q12986 | NFX1 | S50 | ochoa | Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) | Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}. |
| Q12986 | NFX1 | S95 | ochoa | Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) | Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}. |
| Q13085 | ACACA | S756 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13127 | REST | S861 | psp | RE1-silencing transcription factor (Neural-restrictive silencer factor) (X2 box repressor) | Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:11741002, PubMed:11779185, PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247). Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes (PubMed:10449787, PubMed:10734093). Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (PubMed:19061646). Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3 (By similarity). Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes (PubMed:11779185). Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes (By similarity). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:21258371). Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits (By similarity). Acts as a regulator of osteoblast differentiation (By similarity). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct binding to an RE1/NRSE site on their promoter regions (PubMed:27531581). May also function in stress resistance in the brain during aging; possibly by regulating expression of genes involved in cell death and in the stress response (PubMed:24670762). Repressor of gene expression in the hippocampus after ischemia by directly binding to RE1/NRSE sites and recruiting SIN3A and RCOR1 to promoters of target genes, thereby promoting changes in chromatin modifications and ischemia-induced cell death (By similarity). After ischemia, might play a role in repression of miR-132 expression in hippocampal neurons, thereby leading to neuronal cell death (By similarity). Negatively regulates the expression of SRRM3 in breast cancer cell lines (PubMed:26053433). {ECO:0000250|UniProtKB:O54963, ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:10449787, ECO:0000269|PubMed:10734093, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185, ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:24670762, ECO:0000269|PubMed:26053433, ECO:0000269|PubMed:26551668, ECO:0000269|PubMed:27531581, ECO:0000269|PubMed:7697725, ECO:0000269|PubMed:7871435, ECO:0000269|PubMed:8568247}.; FUNCTION: [Isoform 3]: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1 (By similarity). Exhibits weaker repressor activity compared to isoform 1 (PubMed:11779185). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (PubMed:11741002). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing (By similarity). {ECO:0000250|UniProtKB:Q8VIG1, ECO:0000269|PubMed:11741002, ECO:0000269|PubMed:11779185}. |
| Q13131 | PRKAA1 | S356 | ochoa | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| Q13237 | PRKG2 | S97 | ochoa | cGMP-dependent protein kinase 2 (cGK 2) (cGK2) (EC 2.7.11.12) (cGMP-dependent protein kinase II) (cGKII) | Crucial regulator of intestinal secretion and bone growth. Phosphorylates and activates CFTR on the plasma membrane. Plays a key role in intestinal secretion by regulating cGMP-dependent translocation of CFTR in jejunum (PubMed:33106379). Acts downstream of NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863 (By similarity). Acts as a regulator of gene expression and activator of the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear stress, mediates ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast anabolic response to mechanical stimulation (By similarity). {ECO:0000250|UniProtKB:Q61410, ECO:0000250|UniProtKB:Q64595, ECO:0000269|PubMed:33106379}. |
| Q13309 | SKP2 | S64 | ochoa|psp | S-phase kinase-associated protein 2 (Cyclin-A/CDK2-associated protein p45) (F-box protein Skp2) (F-box/LRR-repeat protein 1) (p45skp2) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (PubMed:9736735, PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16262255, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:22770219, PubMed:32267835). Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity). Degradation of CDKN1B/p27kip also requires CKS1 (By similarity). Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, NBN, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22464731, PubMed:32267835). Degradation of TAL1 also requires STUB1 (PubMed:17962192). Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:9736735, PubMed:16262255). Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219). Following phosphorylation in response to DNA damage, mediates 'Lys-63'-linked ubiquitination of NBN, promoting ATM recruitment to DNA damage sites and DNA repair via homologous recombination (PubMed:22464731). {ECO:0000250|UniProtKB:Q9Z0Z3, ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16103164, ECO:0000269|PubMed:16262255, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:22464731, ECO:0000269|PubMed:22770219, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:9736735}.; FUNCTION: Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus. {ECO:0000269|PubMed:27194766}. |
| Q13439 | GOLGA4 | S78 | ochoa | Golgin subfamily A member 4 (256 kDa golgin) (Golgin-245) (Protein 72.1) (Trans-Golgi p230) | Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking (PubMed:29084197). {ECO:0000269|PubMed:15265687, ECO:0000269|PubMed:29084197}. |
| Q13469 | NFATC2 | S814 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 2 (NF-ATc2) (NFATc2) (NFAT pre-existing subunit) (NF-ATp) (T-cell transcription factor NFAT1) | Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF (PubMed:15790681). Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway (PubMed:21871017). Is involved in the negative regulation of chondrogenesis (PubMed:35789258). Recruited by AKAP5 to ORAI1 pore-forming subunit of CRAC channels in Ca(2+) signaling microdomains where store-operated Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT-dependent transcriptional responses. {ECO:0000250|UniProtKB:Q60591, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:21871017, ECO:0000269|PubMed:35789258}. |
| Q13495 | MAMLD1 | S190 | ochoa | Mastermind-like domain-containing protein 1 (F18) (Protein CG1) | Transactivates the HES3 promoter independently of NOTCH proteins. HES3 is a non-canonical NOTCH target gene which lacks binding sites for RBPJ. {ECO:0000269|PubMed:18162467}. |
| Q13509 | TUBB3 | S172 | ochoa | Tubulin beta-3 chain (Tubulin beta-4 chain) (Tubulin beta-III) | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:34996871, PubMed:38305685, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:34996871, PubMed:38305685, PubMed:38609661). Below the cap, alpha-beta tubulin heterodimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). TUBB3 plays a critical role in proper axon guidance and maintenance (PubMed:20074521). Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977). Plays a role in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977). {ECO:0000269|PubMed:20074521, ECO:0000269|PubMed:28483977, ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| Q13535 | ATR | S428 | ochoa|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}. |
| Q13561 | DCTN2 | S320 | ochoa | Dynactin subunit 2 (50 kDa dynein-associated polypeptide) (Dynactin complex 50 kDa subunit) (DCTN-50) (p50 dynamitin) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (By similarity). {ECO:0000250|UniProtKB:A0A5G2QD80, ECO:0000250|UniProtKB:Q99KJ8}. |
| Q13615 | MTMR3 | S883 | ochoa | Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3 (EC 3.1.3.95) (FYVE domain-containing dual specificity protein phosphatase 1) (FYVE-DSP1) (Myotubularin-related protein 3) (Phosphatidylinositol-3,5-bisphosphate 3-phosphatase) (Phosphatidylinositol-3-phosphate phosphatase) (Zinc finger FYVE domain-containing protein 10) | Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate (PubMed:10733931, PubMed:11302699, PubMed:11676921, PubMed:12646134). Decreases the levels of phosphatidylinositol 3-phosphate, a phospholipid found in cell membranes where it acts as key regulator of both cell signaling and intracellular membrane traffic (PubMed:11302699, PubMed:11676921, PubMed:12646134). Could also have a molecular sequestering/adapter activity and regulate biological processes independently of its phosphatase activity. It includes the regulation of midbody abscission during mitotic cytokinesis (PubMed:25659891). {ECO:0000269|PubMed:10733931, ECO:0000269|PubMed:11302699, ECO:0000269|PubMed:11676921, ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:25659891}. |
| Q13615 | MTMR3 | S913 | ochoa | Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3 (EC 3.1.3.95) (FYVE domain-containing dual specificity protein phosphatase 1) (FYVE-DSP1) (Myotubularin-related protein 3) (Phosphatidylinositol-3,5-bisphosphate 3-phosphatase) (Phosphatidylinositol-3-phosphate phosphatase) (Zinc finger FYVE domain-containing protein 10) | Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate (PubMed:10733931, PubMed:11302699, PubMed:11676921, PubMed:12646134). Decreases the levels of phosphatidylinositol 3-phosphate, a phospholipid found in cell membranes where it acts as key regulator of both cell signaling and intracellular membrane traffic (PubMed:11302699, PubMed:11676921, PubMed:12646134). Could also have a molecular sequestering/adapter activity and regulate biological processes independently of its phosphatase activity. It includes the regulation of midbody abscission during mitotic cytokinesis (PubMed:25659891). {ECO:0000269|PubMed:10733931, ECO:0000269|PubMed:11302699, ECO:0000269|PubMed:11676921, ECO:0000269|PubMed:12646134, ECO:0000269|PubMed:25659891}. |
| Q13637 | RAB32 | S134 | ochoa | Ras-related protein Rab-32 (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:11784320, PubMed:21808068). 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:11784320). Also acts as an A-kinase anchoring protein by binding to the type II regulatory subunit of protein kinase A and anchoring it to the mitochondrion. Also involved in synchronization of mitochondrial fission (PubMed:12186851). Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis (PubMed:21255211). Plays an important role in the control of melanin production and melanosome biogenesis (PubMed:23084991). In concert with RAB38, regulates the proper trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes (By similarity). Stimulates phosphorylation of RAB10 'Thr-73' by LRRK2 (PubMed:38127736). {ECO:0000250|UniProtKB:Q9CZE3, ECO:0000269|PubMed:11784320, ECO:0000269|PubMed:12186851, ECO:0000269|PubMed:21255211, ECO:0000269|PubMed:21808068, ECO:0000269|PubMed:23084991, ECO:0000269|PubMed:38127736}. |
| Q13885 | TUBB2A | S172 | 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. |
| Q14139 | UBE4A | S551 | ochoa | Ubiquitin conjugation factor E4 A (EC 2.3.2.27) (RING-type E3 ubiquitin transferase E4 A) | Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates. {ECO:0000250|UniProtKB:E9Q735, ECO:0000250|UniProtKB:P54860}. |
| Q14161 | GIT2 | S724 | ochoa | ARF GTPase-activating protein GIT2 (ARF GAP GIT2) (Cool-interacting tyrosine-phosphorylated protein 2) (CAT-2) (CAT2) (G protein-coupled receptor kinase-interactor 2) (GRK-interacting protein 2) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. {ECO:0000269|PubMed:10896954}. |
| Q14202 | ZMYM3 | S464 | ochoa | Zinc finger MYM-type protein 3 (Zinc finger protein 261) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q14669 | TRIP12 | S1036 | ochoa | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12) | E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair (PubMed:19028681, PubMed:22884692). Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins (PubMed:19028681). Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress (PubMed:20208519). In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation (PubMed:20208519). Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A (PubMed:20208519). Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation (PubMed:18627766). Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins (PubMed:20829358). Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex (PubMed:30982744). {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:30982744}. |
| Q14671 | PUM1 | S229 | ochoa | Pumilio homolog 1 (HsPUM) (Pumilio-1) | Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:18328718, PubMed:21397187, PubMed:21572425, PubMed:21653694). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000250|UniProtKB:Q80U78, ECO:0000269|PubMed:18328718, ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:20818387, ECO:0000269|PubMed:20860814, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:21572425, ECO:0000269|PubMed:21653694, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25768905, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:29474920}. |
| Q15031 | LARS2 | S711 | ochoa | Leucine--tRNA ligase, mitochondrial (EC 6.1.1.4) (Leucyl-tRNA synthetase) (LeuRS) | Catalyzes the attachment of leucine to its cognate tRNA. {ECO:0000269|PubMed:26537577}. |
| Q15046 | KARS1 | S207 | psp | Lysine--tRNA ligase (EC 2.7.7.-) (EC 6.1.1.6) (Lysyl-tRNA synthetase) (LysRS) | 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:18029264, PubMed:18272479, PubMed:9278442). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:14975237, PubMed:19524539, PubMed:23159739, PubMed:5338216). {ECO:0000269|PubMed:14975237, ECO:0000269|PubMed:15851690, ECO:0000269|PubMed:18029264, ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:28887846, ECO:0000269|PubMed:5338216, ECO:0000269|PubMed:9278442}.; FUNCTION: (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. {ECO:0000269|PubMed:15220430}. |
| Q15047 | SETDB1 | S505 | ochoa | Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1) | Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation (PubMed:12869583, PubMed:27237050, PubMed:39096901). Required for HUSH-mediated heterochromatin formation and gene silencing. Forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation (PubMed:14536086, PubMed:27732843). Its activity is dependent on MBD1 and is heritably maintained through DNA replication by being recruited by CAF-1 (PubMed:14536086). SETDB1 is targeted to histone H3 by TRIM28/TIF1B, a factor recruited by KRAB zinc-finger proteins. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). In ESCs, in collaboration with TRIM28, is also required for H3K9me3 and silencing of endogenous and introduced retroviruses in a DNA-methylation independent-pathway (By similarity). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000250|UniProtKB:O88974, ECO:0000269|PubMed:12869583, ECO:0000269|PubMed:14536086, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:27237050, ECO:0000269|PubMed:27732843, ECO:0000269|PubMed:39096901}. |
| Q15149 | PLEC | S1194 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15562 | TEAD2 | S260 | ochoa | Transcriptional enhancer factor TEF-4 (TEA domain family member 2) (TEAD-2) | Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, 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. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds to the SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3'). May be involved in the gene regulation of neural development. Binds to the M-CAT motif. {ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:19324877}. |
| Q15596 | NCOA2 | S402 | ochoa | Nuclear receptor coactivator 2 (NCoA-2) (Class E basic helix-loop-helix protein 75) (bHLHe75) (Transcriptional intermediary factor 2) (hTIF2) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:22504882, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:26553876, ECO:0000269|PubMed:8670870, ECO:0000269|PubMed:9430642}. |
| Q15596 | NCOA2 | S655 | ochoa | Nuclear receptor coactivator 2 (NCoA-2) (Class E basic helix-loop-helix protein 75) (bHLHe75) (Transcriptional intermediary factor 2) (hTIF2) | Transcriptional coactivator for steroid receptors and nuclear receptors (PubMed:23508108, PubMed:8670870, PubMed:9430642, PubMed:22504882, PubMed:26553876). Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1) (PubMed:23508108, PubMed:8670870, PubMed:9430642). Required with NCOA1 to control energy balance between white and brown adipose tissues (PubMed:23508108, PubMed:8670870, PubMed:9430642). Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression (PubMed:23508108, PubMed:8670870, PubMed:9430642). Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3 (PubMed:23508108). Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q61026, ECO:0000269|PubMed:22504882, ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:26553876, ECO:0000269|PubMed:8670870, ECO:0000269|PubMed:9430642}. |
| Q16836 | HADH | S290 | ochoa | Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (HCDH) (EC 1.1.1.35) (Medium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase) (Short-chain 3-hydroxyacyl-CoA dehydrogenase) | Mitochondrial fatty acid beta-oxidation enzyme that catalyzes the third step of the beta-oxidation cycle for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) (PubMed:10231530, PubMed:11489939, PubMed:16725361). Plays a role in the control of insulin secretion by inhibiting the activation of glutamate dehydrogenase 1 (GLUD1), an enzyme that has an important role in regulating amino acid-induced insulin secretion (By similarity). Plays a role in the maintenance of normal spermatogenesis through the reduction of fatty acid accumulation in the testes (By similarity). {ECO:0000250|UniProtKB:Q61425, ECO:0000269|PubMed:10231530, ECO:0000269|PubMed:11489939, ECO:0000269|PubMed:16725361}. |
| Q17R98 | ZNF827 | S102 | ochoa | Zinc finger protein 827 | As part of a ribonucleoprotein complex composed at least of HNRNPK, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). Could also recruit the nucleosome remodeling and histone deacetylase/NuRD complex to telomeric regions of chromosomes to regulate chromatin remodeling as part of telomere maintenance (PubMed:25150861). {ECO:0000269|PubMed:25150861, ECO:0000269|PubMed:33174841}. |
| Q29RF7 | PDS5A | S1097 | ochoa | Sister chromatid cohesion protein PDS5 homolog A (Cell proliferation-inducing gene 54 protein) (Sister chromatid cohesion protein 112) (SCC-112) | Probable regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15855230, ECO:0000269|PubMed:19907496}. |
| Q2LD37 | BLTP1 | S2287 | ochoa | Bridge-like lipid transfer protein family member 1 (Fragile site-associated protein) | Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum (Probable). Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics (PubMed:30906834). Acts as a regulator of phagocytosis (PubMed:31540829). {ECO:0000269|PubMed:30906834, ECO:0000269|PubMed:31540829, ECO:0000305|PubMed:35015055, ECO:0000305|PubMed:35491307}. |
| Q2M1K9 | ZNF423 | S1054 | ochoa | Zinc finger protein 423 (Olf1/EBF-associated zinc finger protein) (hOAZ) (Smad- and Olf-interacting zinc finger protein) | Transcription factor that can both act as an activator or a repressor depending on the context. Plays a central role in BMP signaling and olfactory neurogenesis. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved in terminal olfactory receptor neurons differentiation; this interaction preventing EBF1 to bind DNA and activate olfactory-specific genes. Involved in olfactory neurogenesis by participating in a developmental switch that regulates the transition from differentiation to maturation in olfactory receptor neurons. Controls proliferation and differentiation of neural precursors in cerebellar vermis formation. {ECO:0000269|PubMed:10660046}. |
| Q2M2I8 | AAK1 | S327 | ochoa | AP2-associated protein kinase 1 (EC 2.7.11.1) (Adaptor-associated kinase 1) | Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:17494869, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124). {ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:11877461, ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:21464124, ECO:0000269|PubMed:25653444}.; FUNCTION: (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue. {ECO:0000269|PubMed:25653444, ECO:0000305|PubMed:31136173}. |
| Q2M2Z5 | KIZ | S276 | ochoa | Centrosomal protein kizuna (Polo-like kinase 1 substrate 1) | Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole. {ECO:0000269|PubMed:16980960}. |
| Q2M3G4 | SHROOM1 | S49 | ochoa | Protein Shroom1 (Apical protein 2) | May be involved in the assembly of microtubule arrays during cell elongation. {ECO:0000250}. |
| Q2PPJ7 | RALGAPA2 | S821 | ochoa | Ral GTPase-activating protein subunit alpha-2 (250 kDa substrate of Akt) (AS250) (p220) | Catalytic subunit of the heterodimeric RalGAP2 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q2PPJ7 | RALGAPA2 | S981 | ochoa | Ral GTPase-activating protein subunit alpha-2 (250 kDa substrate of Akt) (AS250) (p220) | Catalytic subunit of the heterodimeric RalGAP2 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q3L8U1 | CHD9 | S2079 | ochoa | Chromodomain-helicase-DNA-binding protein 9 (CHD-9) (EC 3.6.4.-) (ATP-dependent helicase CHD9) (Chromatin-related mesenchymal modulator) (CReMM) (Chromatin-remodeling factor CHROM1) (Kismet homolog 2) (PPAR-alpha-interacting complex protein 320 kDa) (Peroxisomal proliferator-activated receptor A-interacting complex 320 kDa protein) | Probable ATP-dependent chromatin-remodeling factor. Acts as a transcriptional coactivator for PPARA and possibly other nuclear receptors. Has DNA-dependent ATPase activity and binds to A/T-rich DNA. Associates with A/T-rich regulatory regions in promoters of genes that participate in the differentiation of progenitors during osteogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:16095617, ECO:0000269|PubMed:16554032}. |
| Q3LXA3 | TKFC | S511 | ochoa | Triokinase/FMN cyclase (Bifunctional ATP-dependent dihydroxyacetone kinase/FAD-AMP lyase (cyclizing)) [Includes: ATP-dependent dihydroxyacetone kinase (DHA kinase) (EC 2.7.1.28) (EC 2.7.1.29) (Glycerone kinase) (Triokinase) (Triose kinase); FAD-AMP lyase (cyclizing) (EC 4.6.1.15) (FAD-AMP lyase (cyclic FMN forming)) (FMN cyclase)] | Catalyzes both the phosphorylation of dihydroxyacetone and of glyceraldehyde, and the splitting of ribonucleoside diphosphate-X compounds among which FAD is the best substrate. Represses IFIH1-mediated cellular antiviral response (PubMed:17600090). {ECO:0000250|UniProtKB:F1RKQ4, ECO:0000250|UniProtKB:Q4KLZ6, ECO:0000269|PubMed:16289032, ECO:0000269|PubMed:17600090, ECO:0000269|PubMed:32004446, ECO:0000269|PubMed:4688871}. |
| Q3T8J9 | GON4L | S206 | ochoa | GON-4-like protein (GON-4 homolog) | Has transcriptional repressor activity, probably as part of a complex with YY1, SIN3A and HDAC1. Required for B cell lymphopoiesis. {ECO:0000250|UniProtKB:Q9DB00}. |
| Q4AC94 | C2CD3 | S339 | ochoa | C2 domain-containing protein 3 | Component of the centrioles that acts as a positive regulator of centriole elongation (PubMed:24997988). Promotes assembly of centriolar distal appendage, a structure at the distal end of the mother centriole that acts as an anchor of the cilium, and is required for recruitment of centriolar distal appendages proteins CEP83, SCLT1, CEP89, FBF1 and CEP164. Not required for centriolar satellite integrity or RAB8 activation. Required for primary cilium formation (PubMed:23769972). Required for sonic hedgehog/SHH signaling and for proteolytic processing of GLI3. {ECO:0000269|PubMed:23769972, ECO:0000269|PubMed:24997988}. |
| Q4KWH8 | PLCH1 | S1255 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-1) (Phospholipase C-eta-1) (PLC-eta-1) (Phospholipase C-like protein 3) (PLC-L3) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes. {ECO:0000269|PubMed:15702972}. |
| Q52LR7 | EPC2 | S754 | ochoa | Enhancer of polycomb homolog 2 (EPC-like) | May play a role in transcription or DNA repair. {ECO:0000250}. |
| Q53EL6 | PDCD4 | S94 | ochoa | Programmed cell death protein 4 (Neoplastic transformation inhibitor protein) (Nuclear antigen H731-like) (Protein 197/15a) | Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA (By similarity). {ECO:0000250, ECO:0000269|PubMed:16357133, ECO:0000269|PubMed:16449643, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:18296639, ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291}. |
| Q53GI3 | ZNF394 | S258 | ochoa | Zinc finger protein 394 (Zinc finger protein with KRAB and SCAN domains 14) | May be involved in transcriptional regulation. |
| Q53GL7 | PARP10 | S431 | ochoa | Protein mono-ADP-ribosyltransferase PARP10 (EC 2.4.2.-) (ADP-ribosyltransferase diphtheria toxin-like 10) (ARTD10) (Poly [ADP-ribose] polymerase 10) (PARP-10) | ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate and aspartate residues on target proteins (PubMed:18851833, PubMed:23332125, PubMed:23474714, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:18851833). Catalyzes mono-ADP-ribosylation of GSK3B, leading to negatively regulate GSK3B kinase activity (PubMed:23332125). Involved in translesion DNA synthesis in response to DNA damage via its interaction with PCNA (PubMed:24695737). {ECO:0000269|PubMed:18851833, ECO:0000269|PubMed:23332125, ECO:0000269|PubMed:23474714, ECO:0000269|PubMed:24695737, ECO:0000269|PubMed:25043379}. |
| Q56NI9 | ESCO2 | S75 | ochoa | N-acetyltransferase ESCO2 (EC 2.3.1.-) (Establishment factor-like protein 2) (EFO2) (EFO2p) (hEFO2) (Establishment of cohesion 1 homolog 2) (ECO1 homolog 2) | Acetyltransferase required for the establishment of sister chromatid cohesion (PubMed:15821733, PubMed:15958495). Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during the S phase. Acetylates the cohesin component SMC3 (PubMed:21111234). {ECO:0000269|PubMed:15821733, ECO:0000269|PubMed:15958495, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234}. |
| Q5BKX6 | SLC45A4 | S389 | ochoa | Solute carrier family 45 member 4 | Proton-associated sucrose transporter. May be able to transport also glucose and fructose. {ECO:0000250|UniProtKB:Q0P5V9}. |
| Q5JPF3 | ANKRD36C | S512 | ochoa | Ankyrin repeat domain-containing protein 36C (Protein immuno-reactive with anti-PTH polyclonal antibodies) | None |
| Q5JSH3 | WDR44 | S27 | ochoa | WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) | Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| Q5SVQ8 | ZBTB41 | S57 | ochoa | Zinc finger and BTB domain-containing protein 41 | May be involved in transcriptional regulation. |
| Q5SW79 | CEP170 | S313 | 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}. |
| Q5SW79 | CEP170 | S1251 | 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}. |
| Q5T0F9 | CC2D1B | S751 | ochoa | Coiled-coil and C2 domain-containing protein 1B (Five prime repressor element under dual repression-binding protein 2) (FRE under dual repression-binding protein 2) (Freud-2) | Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. {ECO:0000269|PubMed:19423080}. |
| Q5T4S7 | UBR4 | S178 | ochoa | E3 ubiquitin-protein ligase UBR4 (EC 2.3.2.27) (600 kDa retinoblastoma protein-associated factor) (p600) (N-recognin-4) (Retinoblastoma-associated factor of 600 kDa) (RBAF600) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm (PubMed:25582440, PubMed:29033132, PubMed:34893540, PubMed:37891180, PubMed:38030679, PubMed:38182926, PubMed:38297121). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (PubMed:34893540, PubMed:37891180, PubMed:38030679). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:38030679). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:37891180). Together with UBR5, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR4 probably synthesizes mixed chains containing multiple linkages, while UBR5 is likely branching multiple 'Lys-48'-linked chains of substrates initially modified (PubMed:29033132). Together with KCMF1, part of a protein quality control pathway that catalyzes ubiquitination and degradation of proteins that have been oxidized in response to reactive oxygen species (ROS): recognizes proteins with an Arg-CysO3(H) degron at the N-terminus, and mediates assembly of heterotypic 'Lys-63'-/'Lys-27'-linked branched ubiquitin chains on oxidized proteins, leading to their degradation by autophagy (PubMed:34893540). Catalytic component of the SIFI complex, a multiprotein complex required to inhibit the mitochondrial stress response after a specific stress event has been resolved: ubiquitinates and degrades (1) components of the HRI-mediated signaling of the integrated stress response, such as DELE1 and EIF2AK1/HRI, as well as (2) unimported mitochondrial precursors (PubMed:38297121). Within the SIFI complex, UBR4 initiates ubiquitin chain that are further elongated or branched by KCMF1 (PubMed:38297121). Mediates ubiquitination of ACLY, leading to its subsequent degradation (PubMed:23932781). Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization (PubMed:16214886). {ECO:0000269|PubMed:16214886, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:25582440, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:37891180, ECO:0000269|PubMed:38030679, ECO:0000269|PubMed:38182926, ECO:0000269|PubMed:38297121}. |
| Q5T5Y3 | CAMSAP1 | S375 | ochoa | Calmodulin-regulated spectrin-associated protein 1 | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}. |
| Q5T5Y3 | CAMSAP1 | S416 | ochoa | Calmodulin-regulated spectrin-associated protein 1 | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}. |
| Q5T5Y3 | CAMSAP1 | S563 | 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}. |
| Q5TCX8 | MAP3K21 | S618 | 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}. |
| Q5THK1 | PRR14L | S1029 | ochoa | Protein PRR14L (Proline rich 14-like protein) | None |
| Q5VST9 | OBSCN | S6881 | ochoa | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q5VUB5 | FAM171A1 | S525 | ochoa | Protein FAM171A1 (Astroprincin) (APCN) | Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation. {ECO:0000269|PubMed:30312582}. |
| Q5VV67 | PPRC1 | S1076 | ochoa | Peroxisome proliferator-activated receptor gamma coactivator-related protein 1 (PGC-1-related coactivator) (PRC) | Acts as a coactivator during transcriptional activation of nuclear genes related to mitochondrial biogenesis and cell growth. Involved in the transcription coactivation of CREB and NRF1 target genes. {ECO:0000269|PubMed:11340167, ECO:0000269|PubMed:16908542}. |
| Q5VWG9 | TAF3 | S755 | ochoa | Transcription initiation factor TFIID subunit 3 (140 kDa TATA box-binding protein-associated factor) (TBP-associated factor 3) (Transcription initiation factor TFIID 140 kDa subunit) (TAF(II)140) (TAF140) (TAFII-140) (TAFII140) | The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C (PubMed:33795473). TAF3 forms the TFIID-A module together with TAF5 and TBP (PubMed:33795473). Required in complex with TBPL2 for the differentiation of myoblasts into myocytes (PubMed:11438666). The TAF3-TBPL2 complex replaces TFIID at specific promoters at an early stage in the differentiation process (PubMed:11438666). {ECO:0000269|PubMed:11438666, ECO:0000269|PubMed:33795473}. |
| Q5VWN6 | TASOR2 | S384 | ochoa | Protein TASOR 2 | None |
| Q5VWN6 | TASOR2 | S1539 | ochoa | Protein TASOR 2 | None |
| Q5VZL5 | ZMYM4 | S306 | ochoa | Zinc finger MYM-type protein 4 (Zinc finger protein 262) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q5VZL5 | ZMYM4 | S1241 | ochoa | Zinc finger MYM-type protein 4 (Zinc finger protein 262) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q63HN8 | RNF213 | S2904 | ochoa | E3 ubiquitin-protein ligase RNF213 (EC 2.3.2.27) (EC 3.6.4.-) (ALK lymphoma oligomerization partner on chromosome 17) (E3 ubiquitin-lipopolysaccharide ligase RNF213) (EC 2.3.2.-) (Mysterin) (RING finger protein 213) | Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (PubMed:21799892, PubMed:26126547, PubMed:26278786, PubMed:26766444, PubMed:30705059, PubMed:32139119, PubMed:34012115). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (PubMed:34012115). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (PubMed:34012115). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (PubMed:30705059). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (PubMed:30846318). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (PubMed:32139119, PubMed:33842849). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression (PubMed:26766444). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:34012115). {ECO:0000269|PubMed:21799892, ECO:0000269|PubMed:26126547, ECO:0000269|PubMed:26278786, ECO:0000269|PubMed:26766444, ECO:0000269|PubMed:30705059, ECO:0000269|PubMed:30846318, ECO:0000269|PubMed:32139119, ECO:0000269|PubMed:33842849, ECO:0000269|PubMed:34012115}. |
| Q641Q2 | WASHC2A | S1169 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q66K14 | TBC1D9B | S741 | ochoa | TBC1 domain family member 9B | May act as a GTPase-activating protein for Rab family protein(s). |
| Q676U5 | ATG16L1 | S331 | ochoa | Autophagy-related protein 16-1 (APG16-like 1) | Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP) (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576, PubMed:29317426, PubMed:30778222, PubMed:33909989). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non-canonical signaling (PubMed:29317426, PubMed:30778222). During canonical autophagy, interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to produce a membrane-bound activated form of ATG8 (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576). Thereby, controls the elongation of the nascent autophagosomal membrane (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576). As part of the ATG8 conjugation system with ATG5 and ATG12, required for recruitment of LRRK2 to stressed lysosomes and induction of LRRK2 kinase activity in response to lysosomal stress (By similarity). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, probably by catalyzing conjugation of phosphatidylserine (PS) to ATG8 (PubMed:33909989). Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus (By similarity). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (PubMed:22749352, PubMed:25645662). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response (PubMed:24238340). Instead, promotes an autophagy-dependent antibacterial pathway together with NOD1 or NOD2 (PubMed:20637199). Plays a role in regulating morphology and function of Paneth cell (PubMed:18849966). {ECO:0000250|UniProtKB:Q8C0J2, ECO:0000269|PubMed:18849966, ECO:0000269|PubMed:20637199, ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:23392225, ECO:0000269|PubMed:24238340, ECO:0000269|PubMed:24553140, ECO:0000269|PubMed:24954904, ECO:0000269|PubMed:25645662, ECO:0000269|PubMed:27273576, ECO:0000269|PubMed:29317426, ECO:0000269|PubMed:30778222, ECO:0000269|PubMed:33909989}. |
| Q69YH5 | CDCA2 | S437 | ochoa | Cell division cycle-associated protein 2 (Recruits PP1 onto mitotic chromatin at anaphase protein) (Repo-Man) | Regulator of chromosome structure during mitosis required for condensin-depleted chromosomes to retain their compact architecture through anaphase. Acts by mediating the recruitment of phopsphatase PP1-gamma subunit (PPP1CC) to chromatin at anaphase and into the following interphase. At anaphase onset, its association with chromatin targets a pool of PPP1CC to dephosphorylate substrates. {ECO:0000269|PubMed:16492807, ECO:0000269|PubMed:16998479}. |
| Q6AI39 | BICRAL | S980 | ochoa | BRD4-interacting chromatin-remodeling complex-associated protein-like (Glioma tumor suppressor candidate region gene 1 protein-like) | Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. {ECO:0000269|PubMed:29374058}. |
| Q6DN90 | IQSEC1 | S211 | ochoa | IQ motif and SEC7 domain-containing protein 1 (ADP-ribosylation factors guanine nucleotide-exchange protein 100) (ADP-ribosylation factors guanine nucleotide-exchange protein 2) (Brefeldin-resistant Arf-GEF 2 protein) (BRAG2) | Guanine nucleotide exchange factor for ARF1 and ARF6 (PubMed:11226253, PubMed:24058294). Guanine nucleotide exchange factor activity is enhanced by lipid binding (PubMed:24058294). Accelerates GTP binding by ARFs of all three classes. Guanine nucleotide exchange protein for ARF6, mediating internalization of beta-1 integrin (PubMed:16461286). Involved in neuronal development (Probable). In neurons, plays a role in the control of vesicle formation by endocytoc cargo. Upon long term depression, interacts with GRIA2 and mediates the activation of ARF6 to internalize synaptic AMPAR receptors (By similarity). {ECO:0000250|UniProtKB:A0A0G2JUG7, ECO:0000269|PubMed:11226253, ECO:0000269|PubMed:16461286, ECO:0000269|PubMed:24058294, ECO:0000305|PubMed:31607425}. |
| Q6IAA8 | LAMTOR1 | S27 | 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}. |
| Q6IQ23 | PLEKHA7 | S485 | ochoa | Pleckstrin homology domain-containing family A member 7 (PH domain-containing family A member 7) | Required for zonula adherens biogenesis and maintenance (PubMed:19041755). Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site (PubMed:19041755). Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33 (PubMed:30463011). {ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:30463011}. |
| Q6MZP7 | LIN54 | S150 | ochoa | Protein lin-54 homolog (CXC domain-containing protein 1) | Component of the DREAM complex, a multiprotein complex that can both act as a transcription activator or repressor depending on the context (PubMed:17531812, PubMed:17671431). In G0 phase, the complex binds to more than 800 promoters and is required for repression of E2F target genes (PubMed:17531812, PubMed:17671431). In S phase, the complex selectively binds to the promoters of G2/M genes whose products are required for mitosis and participates in their cell cycle dependent activation (PubMed:17531812, PubMed:17671431). In the complex, acts as a DNA-binding protein that binds the promoter of CDK1 in a sequence-specific manner (PubMed:19725879). Specifically recognizes the consensus motif 5'-TTYRAA-3' in target DNA (PubMed:27465258). {ECO:0000269|PubMed:17531812, ECO:0000269|PubMed:17671431, ECO:0000269|PubMed:19725879, ECO:0000269|PubMed:27465258}. |
| Q6MZP7 | LIN54 | S635 | ochoa | Protein lin-54 homolog (CXC domain-containing protein 1) | Component of the DREAM complex, a multiprotein complex that can both act as a transcription activator or repressor depending on the context (PubMed:17531812, PubMed:17671431). In G0 phase, the complex binds to more than 800 promoters and is required for repression of E2F target genes (PubMed:17531812, PubMed:17671431). In S phase, the complex selectively binds to the promoters of G2/M genes whose products are required for mitosis and participates in their cell cycle dependent activation (PubMed:17531812, PubMed:17671431). In the complex, acts as a DNA-binding protein that binds the promoter of CDK1 in a sequence-specific manner (PubMed:19725879). Specifically recognizes the consensus motif 5'-TTYRAA-3' in target DNA (PubMed:27465258). {ECO:0000269|PubMed:17531812, ECO:0000269|PubMed:17671431, ECO:0000269|PubMed:19725879, ECO:0000269|PubMed:27465258}. |
| Q6MZQ0 | PRR5L | S29 | ochoa | Proline-rich protein 5-like (Protein observed with Rictor-2) (Protor-2) | Associates with the mTORC2 complex that regulates cellular processes including survival and organization of the cytoskeleton (PubMed:17461779). Regulates the activity of the mTORC2 complex in a substrate-specific manner preventing for instance the specific phosphorylation of PKCs and thereby controlling cell migration (PubMed:22609986). Plays a role in the stimulation of ZFP36-mediated mRNA decay of several ZFP36-associated mRNAs, such as TNF-alpha and GM-CSF, in response to stress (PubMed:21964062). Required for ZFP36 localization to cytoplasmic stress granule (SG) and P-body (PB) in response to stress (PubMed:21964062). {ECO:0000269|PubMed:17461779, ECO:0000269|PubMed:21964062, ECO:0000269|PubMed:22609986}. |
| Q6NXG1 | ESRP1 | S543 | ochoa | Epithelial splicing regulatory protein 1 (RNA-binding motif protein 35A) (RNA-binding protein 35A) | mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Also regulates the splicing of CD44, CTNND1, ENAH, 3 transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of FGFR2 (PubMed:19285943). Regulates splicing and expression of genes involved in inner ear development, auditory hair cell differentiation, and cell fate specification in the cochlear epithelium (By similarity). {ECO:0000250|UniProtKB:Q3US41, ECO:0000269|PubMed:19285943}. |
| Q6NZI2 | CAVIN1 | S366 | 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}. |
| Q6NZY4 | ZCCHC8 | S557 | ochoa | Zinc finger CCHC domain-containing protein 8 (TRAMP-like complex RNA-binding factor ZCCHC8) | Scaffolding subunit of the trimeric nuclear exosome targeting (NEXT) complex that is involved in the surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. May be involved in pre-mRNA splicing (Probable). It is required for 3'-end maturation of telomerase RNA component (TERC), TERC 3'-end targeting to the nuclear RNA exosome, and for telomerase function (PubMed:31488579). {ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:31488579, ECO:0000305|PubMed:16263084}. |
| Q6P0N0 | MIS18BP1 | S541 | ochoa | Mis18-binding protein 1 (Kinetochore-associated protein KNL-2 homolog) (HsKNL-2) (P243) | Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038, ECO:0000269|PubMed:17339379}. |
| Q6PGQ7 | BORA | S137 | ochoa|psp | Protein aurora borealis (HsBora) | Required for the activation of AURKA at the onset of mitosis. {ECO:0000269|PubMed:16890155}. |
| Q6PIF6 | MYO7B | S1582 | ochoa | Unconventional myosin-VIIb | Myosins are actin-based motor molecules with ATPase activity. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length (PubMed:24725409, PubMed:26812018, PubMed:32209652). May link the complex to the actin core bundle of microvilli. {ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812018, ECO:0000269|PubMed:32209652, ECO:0000305|PubMed:24725409, ECO:0000305|PubMed:26812018}. |
| Q6PJ61 | FBXO46 | S313 | ochoa | F-box only protein 46 (F-box only protein 34-like) | Substrate-recognition component of the SCF(FBXO46) protein ligase complex, which mediates the ubiquitination and degradation of target proteins (PubMed:30171069). In absence of stress, the SCF(FBXO46) complex catalyzes ubiquitination and degradation of MTOR-phosphorylated FBXO31 (PubMed:30171069). {ECO:0000269|PubMed:30171069}. |
| Q6T310 | RASL11A | S217 | ochoa | Ras-like protein family member 11A (EC 3.6.5.2) | Regulator of rDNA transcription. Acts in cooperation UBF/UBTF and positively regulates RNA polymerase I transcription (By similarity). {ECO:0000250}. |
| Q6UB99 | ANKRD11 | S276 | ochoa | Ankyrin repeat domain-containing protein 11 (Ankyrin repeat-containing cofactor 1) | Chromatin regulator which modulates histone acetylation and gene expression in neural precursor cells (By similarity). May recruit histone deacetylases (HDACs) to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation (PubMed:15184363). Has a role in proliferation and development of cortical neural precursors (PubMed:25556659). May also regulate bone homeostasis (By similarity). {ECO:0000250|UniProtKB:E9Q4F7, ECO:0000269|PubMed:15184363, ECO:0000269|PubMed:25556659}. |
| Q6UN15 | FIP1L1 | S304 | ochoa | Pre-mRNA 3'-end-processing factor FIP1 (hFip1) (FIP1-like 1 protein) (Factor interacting with PAP) (Rearranged in hypereosinophilia) | Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex. {ECO:0000269|PubMed:14749727}. |
| Q6WBX8 | RAD9B | S282 | ochoa | Cell cycle checkpoint control protein RAD9B (DNA repair exonuclease rad9 homolog B) (hRAD9B) | None |
| Q6XZF7 | DNMBP | S689 | 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}. |
| Q6ZN55 | ZNF574 | S113 | ochoa | Zinc finger protein 574 | May be involved in transcriptional regulation. |
| Q6ZU35 | CRACD | S579 | ochoa | Capping protein-inhibiting regulator of actin dynamics (Cancer-related regulator of actin dynamics) | Involved in epithelial cell integrity by acting on the maintenance of the actin cytoskeleton. Positively regulates the actin polymerization, by inhibiting the interaction of actin-capping proteins with actin. {ECO:0000269|PubMed:30361697}. |
| Q6ZU65 | UBN2 | S1123 | ochoa | Ubinuclein-2 | None |
| Q6ZW49 | PAXIP1 | S332 | ochoa | PAX-interacting protein 1 (PAX transactivation activation domain-interacting protein) | Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires RNF8 and UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with TP53BP1 phosphorylated by ATM at 'Ser-25'. Together with TP53BP1 regulates ATM association. Proposed to recruit PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probably independent of MLL-containing histone methyltransferase (HMT) complexes. However, this function has been questioned (By similarity). Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and RAD51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as PAX2. Associates with gene promoters that are known to be regulated by KMT2D/MLL2. During immunoglobulin class switching in activated B-cells is involved in trimethylation of histone H3 at 'Lys-4' and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus; this function appears to involve the recruitment of MLL-containing HMT complexes. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex (By similarity). {ECO:0000250|UniProtKB:Q6NZQ4, ECO:0000269|PubMed:14576432, ECO:0000269|PubMed:15456759, ECO:0000269|PubMed:17690115, ECO:0000269|PubMed:17925232, ECO:0000269|PubMed:18353733, ECO:0000269|PubMed:20088963, ECO:0000269|PubMed:23727112}. |
| Q711Q0 | CEFIP | S517 | ochoa | Cardiac-enriched FHL2-interacting protein | Plays an important role in cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway. {ECO:0000250|UniProtKB:M0RD54}. |
| Q765P7 | MTSS2 | S441 | ochoa | Protein MTSS 2 (Actin-bundling with BAIAP2 homology protein 1) (ABBA-1) (MTSS1-like protein) | Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}. |
| Q765P7 | MTSS2 | S634 | ochoa | Protein MTSS 2 (Actin-bundling with BAIAP2 homology protein 1) (ABBA-1) (MTSS1-like protein) | Involved in plasma membrane dynamics. Potentiated PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts, acting via RAC1 activation (PubMed:14752106). May function in actin bundling (PubMed:14752106). {ECO:0000269|PubMed:14752106}. |
| Q76FK4 | NOL8 | S1099 | ochoa | Nucleolar protein 8 (Nucleolar protein Nop132) | Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells. {ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:15132771, ECO:0000269|PubMed:16963496}. |
| Q7L3B6 | CDC37L1 | S32 | ochoa | Hsp90 co-chaperone Cdc37-like 1 (Hsp90-associating relative of Cdc37) | Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90. {ECO:0000250}. |
| Q7L9B9 | EEPD1 | S220 | ochoa | Endonuclease/exonuclease/phosphatase family domain-containing protein 1 | None |
| Q7Z2Z1 | TICRR | S923 | ochoa | Treslin (TopBP1-interacting checkpoint and replication regulator) (TopBP1-interacting, replication-stimulating protein) | Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}. |
| Q7Z2Z1 | TICRR | S1013 | ochoa | Treslin (TopBP1-interacting checkpoint and replication regulator) (TopBP1-interacting, replication-stimulating protein) | Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}. |
| Q7Z333 | SETX | S1686 | ochoa | Probable helicase senataxin (EC 3.6.4.-) (Amyotrophic lateral sclerosis 4 protein) (SEN1 homolog) (Senataxin) | Probable RNA/DNA helicase involved in diverse aspects of RNA metabolism and genomic integrity. Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription (PubMed:19515850, PubMed:21700224). Contributes to the mRNA splicing efficiency and splice site selection (PubMed:19515850). Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination (PubMed:19515850, PubMed:21700224, PubMed:26700805). Required for the 3' transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation (By similarity). Involved in DNA double-strand breaks damage response generated by oxidative stress (PubMed:17562789). In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage (PubMed:24105744). Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI) (By similarity). May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription (PubMed:21112256). Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis (PubMed:21576111). {ECO:0000250|UniProtKB:A2AKX3, ECO:0000269|PubMed:17562789, ECO:0000269|PubMed:19515850, ECO:0000269|PubMed:21112256, ECO:0000269|PubMed:21576111, ECO:0000269|PubMed:21700224, ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:26700805}. |
| Q7Z3B3 | KANSL1 | S1082 | ochoa | KAT8 regulatory NSL complex subunit 1 (MLL1/MLL complex subunit KANSL1) (MSL1 homolog 1) (hMSL1v1) (NSL complex protein NSL1) (Non-specific lethal 1 homolog) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:22547026, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). In addition to its role in transcription, KANSL1 also plays an essential role in spindle assembly during mitosis (PubMed:26243146). Associates with microtubule ends and contributes to microtubule stability (PubMed:26243146). {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}. |
| Q7Z3J3 | RGPD4 | S128 | ochoa | RanBP2-like and GRIP domain-containing protein 4 | None |
| Q7Z3T8 | ZFYVE16 | S815 | ochoa | Zinc finger FYVE domain-containing protein 16 (Endofin) (Endosome-associated FYVE domain protein) | May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes. {ECO:0000269|PubMed:11546807, ECO:0000269|PubMed:14613930}. |
| Q7Z401 | DENND4A | S1117 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z417 | NUFIP2 | S629 | 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}. |
| Q7Z4H7 | HAUS6 | S914 | ochoa | HAUS augmin-like complex subunit 6 | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q7Z6I6 | ARHGAP30 | S349 | ochoa | Rho GTPase-activating protein 30 (Rho-type GTPase-activating protein 30) | GTPase-activating protein (GAP) for RAC1 and RHOA, but not for CDC42. {ECO:0000269|PubMed:21565175}. |
| Q86UR5 | RIMS1 | S1613 | ochoa | Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) | Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}. |
| Q86UW9 | DTX2 | S360 | ochoa | Probable E3 ubiquitin-protein ligase DTX2 (EC 2.3.2.27) (Protein deltex-2) (Deltex2) (hDTX2) (RING finger protein 58) (RING-type E3 ubiquitin transferase DTX2) | Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Probably acts both as a positive and negative regulator of Notch, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Functions as a ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. |
| Q86UZ6 | ZBTB46 | S294 | ochoa | Zinc finger and BTB domain-containing protein 46 (BTB-ZF protein expressed in effector lymphocytes) (BZEL) (BTB/POZ domain-containing protein 4) (Zinc finger protein 340) | Functions as a transcriptional repressor for PRDM1. {ECO:0000250}. |
| Q86VP1 | TAX1BP1 | S124 | ochoa | Tax1-binding protein 1 (TRAF6-binding protein) | Ubiquitin-binding adapter that participates in inflammatory, antiviral and innate immune processes as well as selective autophagy regulation (PubMed:29940186, PubMed:30459273, PubMed:30909570). Plays a key role in the negative regulation of NF-kappa-B and IRF3 signalings by acting as an adapter for the ubiquitin-editing enzyme A20/TNFAIP3 to bind and inactivate its substrates (PubMed:17703191). Disrupts the interactions between the E3 ubiquitin ligase TRAF3 and TBK1/IKBKE to attenuate 'Lys63'-linked polyubiquitination of TBK1 and thereby IFN-beta production (PubMed:21885437). Also recruits A20/TNFAIP3 to ubiquitinated signaling proteins TRAF6 and RIPK1, leading to their deubiquitination and disruption of IL-1 and TNF-induced NF-kappa-B signaling pathways (PubMed:17703191). Inhibits virus-induced apoptosis by inducing the 'Lys-48'-linked polyubiquitination and degradation of MAVS via recruitment of the E3 ligase ITCH, thereby attenuating MAVS-mediated apoptosis signaling (PubMed:27736772). As a macroautophagy/autophagy receptor, facilitates the xenophagic clearance of pathogenic bacteria such as Salmonella typhimurium and Mycobacterium tuberculosis (PubMed:26451915). Upon NBR1 recruitment to the SQSTM1-ubiquitin condensates, acts as the major recruiter of RB1CC1 to these ubiquitin condensates to promote their autophagic degradation (PubMed:33226137, PubMed:34471133). Mediates the autophagic degradation of other substrates including TICAM1 (PubMed:28898289). {ECO:0000269|PubMed:10435631, ECO:0000269|PubMed:10920205, ECO:0000269|PubMed:17703191, ECO:0000269|PubMed:21885437, ECO:0000269|PubMed:26451915, ECO:0000269|PubMed:27736772, ECO:0000269|PubMed:28898289, ECO:0000269|PubMed:29940186, ECO:0000269|PubMed:30459273, ECO:0000269|PubMed:30909570, ECO:0000269|PubMed:33226137, ECO:0000269|PubMed:34471133}. |
| Q86W92 | PPFIBP1 | S40 | ochoa | Liprin-beta-1 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 1) (PTPRF-interacting protein-binding protein 1) (hSGT2) | May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}. |
| Q86WH2 | RASSF3 | S137 | ochoa | Ras association domain-containing protein 3 | None |
| Q86YA3 | ZGRF1 | S877 | ochoa | 5'-3' DNA helicase ZGRF1 (EC 5.6.2.3) (GRF-type zinc finger domain-containing protein 1) | 5'-3' DNA helicase which is recruited to sites of DNA damage and promotes repair of replication-blocking DNA lesions through stimulation of homologous recombination (HR) (PubMed:32640219, PubMed:34552057). Promotes HR by directly stimulating RAD51-mediated strand exchange activity (PubMed:32640219). Not required to load RAD51 at sites of DNA damage but promotes recombinational repair after RAD51 recruitment (PubMed:32640219). Also promotes HR by positively regulating EXO1-mediated DNA end resection of double-strand breaks (PubMed:34552057). Required for recruitment of replication protein RPA2 to DNA damage sites (PubMed:34552057). Promotes the initiation of the G2/M checkpoint but not its maintenance (PubMed:34552057). Catalyzes Holliday junction branch migration and dissociation of D-loops and DNA flaps (PubMed:32640219). {ECO:0000269|PubMed:32640219, ECO:0000269|PubMed:34552057}. |
| Q86YN6 | PPARGC1B | S638 | ochoa | Peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC-1-beta) (PPAR-gamma coactivator 1-beta) (PPARGC-1-beta) (PGC-1-related estrogen receptor alpha coactivator) | Plays a role of stimulator of transcription factors and nuclear receptors activities. Activates transcriptional activity of estrogen receptor alpha, nuclear respiratory factor 1 (NRF1) and glucocorticoid receptor in the presence of glucocorticoids. May play a role in constitutive non-adrenergic-mediated mitochondrial biogenesis as suggested by increased basal oxygen consumption and mitochondrial number when overexpressed. May be involved in fat oxidation and non-oxidative glucose metabolism and in the regulation of energy expenditure. Induces the expression of PERM1 in the skeletal muscle in an ESRRA-dependent manner. {ECO:0000269|PubMed:11854298, ECO:0000269|PubMed:12678921, ECO:0000269|PubMed:15546003, ECO:0000269|PubMed:23836911}. |
| Q86YS6 | RAB43 | S193 | ochoa | Ras-related protein Rab-43 (Ras-related protein Rab-41) | 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. The low intrinsic GTPase activity of RAB43 is activated by USP6NL. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for the structural integrity of the Golgi complex. Plays a role in the maturation of phagosomes that engulf pathogens, such as S.aureus and M.tuberculosis. {ECO:0000269|PubMed:17562788, ECO:0000269|PubMed:17684057, ECO:0000269|PubMed:18664496, ECO:0000269|PubMed:21255211}. |
| Q8IVL0 | NAV3 | S654 | ochoa | Neuron navigator 3 (Pore membrane and/or filament-interacting-like protein 1) (Steerin-3) (Unc-53 homolog 3) (unc53H3) | Plays a role in cell migration (PubMed:21471154). May be involved in neuron regeneration. May regulate IL2 production by T-cells. {ECO:0000269|PubMed:16166283, ECO:0000269|PubMed:21471154}. |
| Q8IW40 | DNAAF19 | S91 | ochoa | Dynein axonemal assembly factor 19 (Coiled-coil domain-containing protein 103) | Dynein-attachment factor required for cilia motility. {ECO:0000269|PubMed:22581229}. |
| Q8IWU2 | LMTK2 | S1124 | ochoa | Serine/threonine-protein kinase LMTK2 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase 2) (Brain-enriched kinase) (hBREK) (CDK5/p35-regulated kinase) (CPRK) (Kinase/phosphatase/inhibitor 2) (Lemur tyrosine kinase 2) (Serine/threonine-protein kinase KPI-2) | Phosphorylates PPP1C, phosphorylase b and CFTR. |
| Q8IWX8 | CHERP | S186 | ochoa | Calcium homeostasis endoplasmic reticulum protein (ERPROT 213-21) (SR-related CTD-associated factor 6) | Involved in calcium homeostasis, growth and proliferation. {ECO:0000269|PubMed:10794731, ECO:0000269|PubMed:12656674}. |
| Q8IX90 | SKA3 | S152 | ochoa | Spindle and kinetochore-associated protein 3 | Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation (PubMed:19289083, PubMed:19360002, PubMed:23085020). The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies (PubMed:19289083, PubMed:19360002). The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner (PubMed:19289083). In the complex, it mediates the microtubule-stimulated oligomerization (PubMed:19289083). Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules (PubMed:23085020). {ECO:0000269|PubMed:19289083, ECO:0000269|PubMed:19360002, ECO:0000269|PubMed:23085020}. |
| Q8IXM6 | NRM | S185 | ochoa | Nurim (Nuclear envelope membrane protein) (Nuclear rim protein) | None |
| Q8IY92 | SLX4 | S1185 | ochoa | Structure-specific endonuclease subunit SLX4 (BTB/POZ domain-containing protein 12) | Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks. {ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19596236}. |
| Q8IYW5 | RNF168 | S481 | ochoa | E3 ubiquitin-protein ligase RNF168 (hRNF168) (EC 2.3.2.27) (RING finger protein 168) (RING-type E3 ubiquitin transferase RNF168) | E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively). {ECO:0000255|HAMAP-Rule:MF_03066, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22713238, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538}. |
| Q8IYX8 | CEP57L1 | S49 | ochoa | Centrosomal protein CEP57L1 (Centrosomal protein 57kDa-like protein 1) (Centrosomal protein of 57 kDa-related protein) (Cep57R) (Cep57-related protein) | Centrosomal protein which may be required for microtubule attachment to centrosomes. {ECO:0000250}. |
| Q8N1G1 | REXO1 | S794 | ochoa | RNA exonuclease 1 homolog (EC 3.1.-.-) (Elongin-A-binding protein 1) (EloA-BP1) (Transcription elongation factor B polypeptide 3-binding protein 1) | Seems to have no detectable effect on transcription elongation in vitro. {ECO:0000269|PubMed:12943681}. |
| Q8N1G1 | REXO1 | S914 | ochoa | RNA exonuclease 1 homolog (EC 3.1.-.-) (Elongin-A-binding protein 1) (EloA-BP1) (Transcription elongation factor B polypeptide 3-binding protein 1) | Seems to have no detectable effect on transcription elongation in vitro. {ECO:0000269|PubMed:12943681}. |
| Q8N2G8 | GHDC | S467 | ochoa | GH3 domain-containing protein | None |
| Q8N883 | ZNF614 | S92 | ochoa | Zinc finger protein 614 | May be involved in transcriptional regulation. |
| Q8N884 | CGAS | S305 | ochoa|psp | Cyclic GMP-AMP synthase (cGAMP synthase) (cGAS) (h-cGAS) (EC 2.7.7.86) (2'3'-cGAMP synthase) (Mab-21 domain-containing protein 1) | Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:21478870, PubMed:23258413, PubMed:23707061, PubMed:23707065, PubMed:23722159, PubMed:24077100, PubMed:24116191, PubMed:24462292, PubMed:25131990, PubMed:26300263, PubMed:29976794, PubMed:30799039, PubMed:31142647, PubMed:32814054, PubMed:33273464, PubMed:33542149, PubMed:37217469, PubMed:37802025). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:28214358, PubMed:28363908). Acts as a key DNA sensor: directly binds double-stranded DNA (dsDNA), inducing the formation of liquid-like droplets in which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates STING1, thereby triggering type-I interferon production (PubMed:28314590, PubMed:28363908, PubMed:29976794, PubMed:32817552, PubMed:33230297, PubMed:33606975, PubMed:35322803, PubMed:35438208, PubMed:35460603, PubMed:35503863). Preferentially recognizes and binds curved long dsDNAs of a minimal length of 40 bp (PubMed:30007416). Acts as a key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:28363908). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908, PubMed:35613581). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-2, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945, PubMed:24269171, PubMed:30270045, PubMed:32852081). In contrast, HIV-1 is poorly sensed by CGAS, due to its capsid that cloaks viral DNA from CGAS detection (PubMed:24269171, PubMed:30270045, PubMed:32852081). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (PubMed:26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed:26048138). 2',3'-cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote STING1 activation and convey immune response to connecting cells (PubMed:24077100). 2',3'-cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but STING1-dependent manner (PubMed:26229115). Also senses the presence of neutrophil extracellular traps (NETs) that are translocated to the cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP (PubMed:33688080). In addition to foreign DNA, can also be activated by endogenous nuclear or mitochondrial DNA (PubMed:28738408, PubMed:28759889, PubMed:31299200, PubMed:33031745, PubMed:33230297). When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, SARS-CoV-2 infection causing severe COVID-19 disease, DNA damage, mitotic arrest or senescence), or is present in form of cytosolic micronuclei, CGAS is activated leading to a state of sterile inflammation (PubMed:28738408, PubMed:28759889, PubMed:31299200, PubMed:33031745, PubMed:33230297, PubMed:35045565). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via STING1 and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability (PubMed:28738408, PubMed:28759889). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to 2',3'-cGAMP synthesis and subsequent activation of STING1 and type-I interferon production (PubMed:28738408, PubMed:28759889). Activated in response to prolonged mitotic arrest, promoting mitotic cell death (PubMed:31299200). In a healthy cell, CGAS is however kept inactive even in cellular events that directly expose it to self-DNA, such as mitosis, when cGAS associates with chromatin directly after nuclear envelope breakdown or remains in the form of postmitotic persistent nuclear cGAS pools bound to chromatin (PubMed:31299200, PubMed:33542149). Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity (PubMed:31299200, PubMed:32911482, PubMed:32912999, PubMed:33051594, PubMed:33542149). Also acts as a suppressor of DNA repair in response to DNA damage: inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214, PubMed:31544964). In addition to DNA, also sense translation stress: in response to translation stress, translocates to the cytosol and associates with collided ribosomes, promoting its activation and triggering type-I interferon production (PubMed:34111399). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less 2',3'-cGAMP, allowing a more fine-tuned response to pathogens (PubMed:30007416). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:21478870, ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:23929945, ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:24116191, ECO:0000269|PubMed:24269171, ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:26046437, ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:26229115, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:28214358, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28363908, ECO:0000269|PubMed:28738408, ECO:0000269|PubMed:28759889, ECO:0000269|PubMed:29976794, ECO:0000269|PubMed:30007416, ECO:0000269|PubMed:30270045, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:31142647, ECO:0000269|PubMed:31299200, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:32814054, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:32852081, ECO:0000269|PubMed:32911482, ECO:0000269|PubMed:32912999, ECO:0000269|PubMed:33031745, ECO:0000269|PubMed:33051594, ECO:0000269|PubMed:33230297, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33542149, ECO:0000269|PubMed:33606975, ECO:0000269|PubMed:33688080, ECO:0000269|PubMed:34111399, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35322803, ECO:0000269|PubMed:35438208, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:35503863, ECO:0000269|PubMed:35613581, ECO:0000269|PubMed:37217469, ECO:0000269|PubMed:37802025}. |
| Q8N9B5 | JMY | S889 | ochoa | Junction-mediating and -regulatory protein | Acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions (PubMed:30420355). In nucleus, acts as a cofactor that increases p53/TP53 response via its interaction with p300/EP300. Increases p53/TP53-dependent transcription and apoptosis, suggesting an important role in p53/TP53 stress response such as DNA damage. In cytoplasm, acts as a nucleation-promoting factor for both branched and unbranched actin filaments (PubMed:30420355). Activates the Arp2/3 complex to induce branched actin filament networks. Also catalyzes actin polymerization in the absence of Arp2/3, creating unbranched filaments (PubMed:30420355). Contributes to cell motility by controlling actin dynamics. May promote the rapid formation of a branched actin network by first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments. Upon nutrient stress, directly recruited by MAP1LC3B to the phagophore membrane surfaces to promote actin assembly during autophagy (PubMed:30420355). The p53/TP53-cofactor and actin activator activities are regulated via its subcellular location (By similarity). {ECO:0000250|UniProtKB:Q9QXM1, ECO:0000269|PubMed:30420355}. |
| Q8NBT0 | POC1A | S70 | ochoa | POC1 centriolar protein homolog A (Pix2) (Proteome of centriole protein 1A) (WD repeat-containing protein 51A) | Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control. Acts in concert with POC1B to ensure centriole integrity and proper mitotic spindle formation. {ECO:0000269|PubMed:19109428, ECO:0000269|PubMed:23015594}. |
| Q8NCD3 | HJURP | S140 | ochoa | Holliday junction recognition protein (14-3-3-associated AKT substrate) (Fetal liver-expressing gene 1 protein) (Up-regulated in lung cancer 9) | Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres. Acts as a specific chaperone for CENPA and is required for the incorporation of newly synthesized CENPA molecules into nucleosomes at replicated centromeres. Prevents CENPA-H4 tetramerization and prevents premature DNA binding by the CENPA-H4 tetramer. Directly binds Holliday junctions. {ECO:0000269|PubMed:19410544, ECO:0000269|PubMed:19410545}. |
| Q8ND24 | RNF214 | S154 | ochoa | RING finger protein 214 | None |
| Q8NDB2 | BANK1 | S663 | ochoa | B-cell scaffold protein with ankyrin repeats | Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores. Promotes Lyn-mediated phosphorylation of IP3 receptors 1 and 2. {ECO:0000269|PubMed:11782428}. |
| Q8NEM0 | MCPH1 | S277 | ochoa | Microcephalin | Implicated in chromosome condensation and DNA damage induced cellular responses. May play a role in neurogenesis and regulation of the size of the cerebral cortex. {ECO:0000269|PubMed:12046007, ECO:0000269|PubMed:15199523, ECO:0000269|PubMed:15220350}. |
| Q8NFC6 | BOD1L1 | S2905 | 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}. |
| Q8NFJ5 | GPRC5A | S59 | ochoa | Retinoic acid-induced protein 3 (G-protein coupled receptor family C group 5 member A) (Phorbol ester induced gene 1) (PEIG-1) (Retinoic acid-induced gene 1 protein) (RAIG-1) | Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218). {ECO:0000250|UniProtKB:Q8BHL4, ECO:0000269|PubMed:18000218}. |
| Q8NFU7 | TET1 | S871 | ochoa | Methylcytosine dioxygenase TET1 (EC 1.14.11.80) (CXXC-type zinc finger protein 6) (Leukemia-associated protein with a CXXC domain) (Ten-eleven translocation 1 gene protein) | Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) (PubMed:19372391, PubMed:21496894, PubMed:21778364, PubMed:35798741). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression (PubMed:33833093). Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair (PubMed:31278917). Involved in the balance between pluripotency and lineage commitment of cells and plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Together with QSER1, plays an essential role in the protection and maintenance of transcriptional and developmental programs to inhibit the binding of DNMT3A/3B and therefore de novo methylation (PubMed:33833093). May play a role in pancreatic beta-cell specification during development. In this context, may function as an upstream epigenetic regulator of PAX4 presumably through direct recruitment by FOXA2 to a PAX4 enhancer to preserve its unmethylated status, thereby potentiating PAX4 expression to adopt beta-cell fate during endocrine lineage commitment (PubMed:35798741). Under DNA hypomethylation conditions, such as in female meiotic germ cells, may induce epigenetic reprogramming of pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions. PCH forms chromocenters in the interphase nucleus and chromocenters cluster at the prophase of meiosis. In this context, may also be essential for chromocenter clustering in a catalytic activity-independent manner, possibly through the recruitment polycomb repressive complex 1 (PRC1) to the chromocenters (By similarity). During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation (By similarity). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:12124344, ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:19372393, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:29276034, ECO:0000269|PubMed:31278917, ECO:0000269|PubMed:33833093, ECO:0000269|PubMed:35798741}.; FUNCTION: [Isoform 1]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:28531272). Binds to promoters, particularly to those with high CG content (By similarity). In hippocampal neurons, isoform 1 regulates the expression of a unique subset of genes compared to isoform 2, although some overlap exists between both isoforms, hence differentially regulates excitatory synaptic transmission (By similarity). In hippocampal neuron cell cultures, isoform 1 controls both miniature excitatory postsynaptic current amplitude and frequency (By similarity). Isoform 1 may regulate genes involved in hippocampal-dependent memory, leading to positive regulation of memory, contrary to isoform 2 that may decrease memory (By similarity). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:28531272}.; FUNCTION: [Isoform 2]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:28531272). As isoform 1, binds to promoters, particularly to those with high CG content, however displays reduced global chromatin affinity compared with isoform 1, leading to decreased global DNA demethylation compared with isoform 1 (By similarity). Contrary to isoform 1, isoform 2 localizes during S phase to sites of ongoing DNA replication in heterochromatin, causing a significant de novo 5hmC formation, globally, and more so in heterochromatin, including LINE 1 interspersed DNA repeats leading to their activation (By similarity). In hippocampal neurons, isoform 2 regulates the expression of a unique subset of genes compared to isoform 1, although some overlap between both isoforms, hence differentially regulates excitatory synaptic transmission (By similarity). In hippocampal neuron cell cultures, isoform 2 controls miniature excitatory postsynaptic current frequency, but not amplitude (By similarity). Isoform 2 may regulate genes involved in hippocampal-dependent memory, leading to negative regulation of memory, contrary to isoform 1 that may improve memory (By similarity). In immature and partially differentiated gonadotrope cells, directly represses luteinizing hormone gene LHB expression and does not catalyze 5hmC at the gene promoter (By similarity). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:28531272}. |
| Q8NHV4 | NEDD1 | S215 | psp | Protein NEDD1 (Neural precursor cell expressed developmentally down-regulated protein 1) (NEDD-1) | Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19509060}. |
| Q8TEK3 | DOT1L | S775 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-79 specific (EC 2.1.1.360) (DOT1-like protein) (Histone H3-K79 methyltransferase) (H3-K79-HMTase) (Lysine N-methyltransferase 4) | Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones (PubMed:12123582). Binds to DNA (PubMed:12628190). {ECO:0000269|PubMed:12123582, ECO:0000269|PubMed:12628190}. |
| Q8TER5 | ARHGEF40 | S419 | ochoa | Rho guanine nucleotide exchange factor 40 (Protein SOLO) | May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}. |
| Q8TEW0 | PARD3 | S695 | 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}. |
| Q8WU58 | FAM222B | S296 | ochoa | Protein FAM222B | None |
| Q8WUA4 | GTF3C2 | S25 | 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. |
| Q8WUF5 | PPP1R13L | S280 | ochoa | RelA-associated inhibitor (Inhibitor of ASPP protein) (Protein iASPP) (NFkB-interacting protein 1) (PPP1R13B-like protein) | Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (PubMed:12524540). Is involved in NF-kappa-B dependent negative regulation of inflammatory response (PubMed:28069640). {ECO:0000269|PubMed:10336463, ECO:0000269|PubMed:12134007, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:15489900, ECO:0000269|PubMed:28069640}. |
| Q8WUY3 | PRUNE2 | S2416 | ochoa | Protein prune homolog 2 (BNIP2 motif-containing molecule at the C-terminal region 1) | May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. {ECO:0000269|PubMed:16288218}. |
| Q8WVM7 | STAG1 | S756 | ochoa | Cohesin subunit SA-1 (SCC3 homolog 1) (Stromal antigen 1) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. |
| Q8WWI1 | LMO7 | S960 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WY36 | BBX | S844 | ochoa | HMG box transcription factor BBX (Bobby sox homolog) (HMG box-containing protein 2) | Transcription factor that is necessary for cell cycle progression from G1 to S phase. {ECO:0000269|PubMed:11680820}. |
| Q8WYB5 | KAT6B | S647 | ochoa | Histone acetyltransferase KAT6B (EC 2.3.1.48) (Histone acetyltransferase MOZ2) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4) (MYST-4) (Monocytic leukemia zinc finger protein-related factor) | Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. {ECO:0000269|PubMed:10497217, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:16387653}. |
| Q92576 | PHF3 | S1642 | ochoa | PHD finger protein 3 | None |
| Q92585 | MAML1 | S45 | ochoa | Mastermind-like protein 1 (Mam-1) | Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}. |
| Q92598 | HSPH1 | S554 | ochoa | Heat shock protein 105 kDa (Antigen NY-CO-25) (Heat shock 110 kDa protein) (Heat shock protein family H member 1) | Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity). {ECO:0000250|UniProtKB:Q60446, ECO:0000250|UniProtKB:Q61699, ECO:0000269|PubMed:24318877}. |
| Q92753 | RORB | S175 | ochoa | Nuclear receptor ROR-beta (Nuclear receptor RZR-beta) (Nuclear receptor subfamily 1 group F member 2) (Retinoid-related orphan receptor-beta) | Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity). {ECO:0000250|UniProtKB:P45446}.; FUNCTION: Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity). {ECO:0000250|UniProtKB:Q8R1B8}. |
| Q92766 | RREB1 | S1225 | ochoa | Ras-responsive element-binding protein 1 (RREB-1) (Finger protein in nuclear bodies) (Raf-responsive zinc finger protein LZ321) (Zinc finger motif enhancer-binding protein 1) (Zep-1) | Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters (PubMed:10390538, PubMed:15067362, PubMed:17550981, PubMed:8816445, PubMed:9305772). Represses the angiotensinogen gene (PubMed:15067362). Negatively regulates the transcriptional activity of AR (PubMed:17550981). Potentiates the transcriptional activity of NEUROD1 (PubMed:12482979). Promotes brown adipocyte differentiation (By similarity). May be involved in Ras/Raf-mediated cell differentiation by enhancing calcitonin expression (PubMed:8816445). {ECO:0000250|UniProtKB:Q3UH06, ECO:0000269|PubMed:10390538, ECO:0000269|PubMed:12482979, ECO:0000269|PubMed:15067362, ECO:0000269|PubMed:17550981, ECO:0000269|PubMed:8816445, ECO:0000269|PubMed:9305772}. |
| Q92945 | KHSRP | S181 | ochoa | Far upstream element-binding protein 2 (FUSE-binding protein 2) (KH type-splicing regulatory protein) (KSRP) (p75) | Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs. {ECO:0000250, ECO:0000269|PubMed:11003644, ECO:0000269|PubMed:8940189, ECO:0000269|PubMed:9136930}. |
| Q93045 | STMN2 | S73 | psp | Stathmin-2 (Superior cervical ganglion-10 protein) (Protein SCG10) | Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone (By similarity). {ECO:0000250}. |
| Q93075 | TATDN2 | S299 | ochoa | 3'-5' RNA nuclease TATDN2 (EC 3.1.13.-) (TatD DNase domain containing 2) | Mg(2+)-dependent 3'RNA exonuclease and endonuclease that resolves R-loops via specific degradation of R-loop RNA stucture (PubMed:37953292). Shows no activity against D-loop and minimal activity against the RNA strand of an RNA-DNA hybrid duplex oligomer. Has no 3' or 5' exonuclease activity, no uracil glycosylase activity, and no 5' flap endonuclease activity on DNA substrates (PubMed:37953292). May have a role in maintaining genomic stability through its role in R-loop resolution (PubMed:37953292). {ECO:0000269|PubMed:37953292}. |
| Q96AY2 | EME1 | S117 | ochoa | Structure-specific endonuclease subunit EME1 (Crossover junction endonuclease EME1) (Essential meiotic structure-specific endonuclease 1) (MMS4 homolog) (hMMS4) | Non-catalytic subunit of the structure-specific, heterodimeric DNA endonuclease MUS81-EME1 which is involved in the maintenance of genome stability. In the complex, EME1 is required for DNA cleavage, participating in DNA recognition and bending (PubMed:12686547, PubMed:12721304, PubMed:14617801, PubMed:17289582, PubMed:24733841, PubMed:24813886, PubMed:35290797, PubMed:39015284). MUS81-EME1 cleaves 3'-flaps and nicked Holliday junctions, and exhibit limited endonuclease activity with 5' flaps and nicked double-stranded DNAs (PubMed:24733841, PubMed:35290797). Active during prometaphase, MUS81-EME1 resolves mitotic recombination intermediates, including Holliday junctions, which form during homologous recombination (PubMed:14617801, PubMed:24813886). {ECO:0000269|PubMed:12686547, ECO:0000269|PubMed:12721304, ECO:0000269|PubMed:14617801, ECO:0000269|PubMed:17289582, ECO:0000269|PubMed:24733841, ECO:0000269|PubMed:24813886, ECO:0000269|PubMed:35290797, ECO:0000269|PubMed:39015284}. |
| Q96BU1 | S100PBP | S187 | ochoa | S100P-binding protein (S100P-binding protein Riken) | None |
| Q96DM3 | RMC1 | S329 | ochoa | Regulator of MON1-CCZ1 complex (Colon cancer-associated protein Mic1) (Mic-1) (WD repeat-containing protein 98) | Component of the CCZ1-MON1 RAB7A guanine exchange factor (GEF). Acts as a positive regulator of CCZ1-MON1A/B function necessary for endosomal/autophagic flux and efficient RAB7A localization (PubMed:29038162). {ECO:0000269|PubMed:29038162}. |
| Q96DZ5 | CLIP3 | S402 | ochoa | CAP-Gly domain-containing linker protein 3 (Cytoplasmic linker protein 170-related 59 kDa protein) (CLIP-170-related 59 kDa protein) (CLIPR-59) | Functions as a cytoplasmic linker protein. Involved in TGN-endosome dynamics. May modulate the cellular compartmentalization of AKT kinase family and promote its cell membrane localization, thereby playing a role in glucose transport in adipocytes. {ECO:0000269|PubMed:19139280}. |
| Q96EB6 | SIRT1 | S27 | ochoa|psp | NAD-dependent protein deacetylase sirtuin-1 (hSIRT1) (EC 2.3.1.286) (NAD-dependent protein deacylase sirtuin-1) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 1) (SIR2-like protein 1) (hSIR2) [Cleaved into: SirtT1 75 kDa fragment (75SirT1)] | NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy (PubMed:11672523, PubMed:12006491, PubMed:14976264, PubMed:14980222, PubMed:15126506, PubMed:15152190, PubMed:15205477, PubMed:15469825, PubMed:15692560, PubMed:16079181, PubMed:16166628, PubMed:16892051, PubMed:16998810, PubMed:17283066, PubMed:17290224, PubMed:17334224, PubMed:17505061, PubMed:17612497, PubMed:17620057, PubMed:17936707, PubMed:18203716, PubMed:18296641, PubMed:18662546, PubMed:18687677, PubMed:19188449, PubMed:19220062, PubMed:19364925, PubMed:19690166, PubMed:19934257, PubMed:20097625, PubMed:20100829, PubMed:20203304, PubMed:20375098, PubMed:20620956, PubMed:20670893, PubMed:20817729, PubMed:20955178, PubMed:21149730, PubMed:21245319, PubMed:21471201, PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047, PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893, PubMed:21947282, PubMed:22274616, PubMed:22918831, PubMed:24415752, PubMed:24824780, PubMed:29681526, PubMed:29765047, PubMed:30409912). Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression (PubMed:15469825). Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively (PubMed:14976264, PubMed:14980222, PubMed:15152190). Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction (PubMed:15205477). Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT) (By similarity). 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 (PubMed:18485871). 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 (PubMed:18485871, PubMed:21504832). Deacetylates 'Lys-266' of SUV39H1, leading to its activation (PubMed:21504832). Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1 (PubMed:19188449). Deacetylates H2A and 'Lys-26' of H1-4 (PubMed:15469825). Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression (PubMed:20375098). Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting (By similarity). Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1 (PubMed:15469825, PubMed:18004385). Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2 (PubMed:18004385, PubMed:21504832). This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response (PubMed:18004385, PubMed:21504832). Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence (PubMed:11672523, PubMed:12006491, PubMed:22542455). Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I (By similarity). Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability (PubMed:19364925, PubMed:21807113). Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation (PubMed:14976264, PubMed:14980222, PubMed:21841822). Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis (PubMed:15126506). Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing (PubMed:21947282). Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha (PubMed:15152190). Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1 (PubMed:17283066, PubMed:17620057, PubMed:20100829, PubMed:20620956). Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver (PubMed:15692560). Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation (PubMed:16892051). Involved in HES1- and HEY2-mediated transcriptional repression (PubMed:12535671). In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62' (PubMed:21698133). Deacetylates MEF2D (PubMed:16166628). Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3 (PubMed:17505061). Represses HNF1A-mediated transcription (By similarity). Required for the repression of ESRRG by CREBZF (PubMed:19690166). Deacetylates NR1H3 and NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteasomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed (PubMed:17936707). Involved in lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol synthesis (PubMed:20817729, PubMed:29765047). Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2 (By similarity). Deacetylates p300/EP300 and PRMT1 (By similarity). Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation (PubMed:21701047). Involved in liver and muscle metabolism. Through deacetylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletal muscle under low-glucose conditions and is involved in glucose homeostasis (PubMed:23142079). Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression (PubMed:17290224, PubMed:20817729). Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2 (PubMed:15205477, PubMed:16998810, PubMed:17334224, PubMed:17612497, PubMed:20670893, PubMed:21149730). Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN (PubMed:15205477, PubMed:17334224, PubMed:20097625). Promotes DNA double-strand breaks by mediating deacetylation of SIRT6 (PubMed:32538779). Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage (PubMed:18203716). Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1 (PubMed:19934257). Catalyzes deacetylation of ERCC4/XPF, thereby impairing interaction with ERCC1 and nucleotide excision repair (NER) (PubMed:32034146). Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8 (PubMed:18296641). Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation (PubMed:21775285). Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear (PubMed:18687677, PubMed:20203304). In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transactivation and contributes to its stability (PubMed:21890893). Deacetylates MECOM/EVI1 (PubMed:21555002). Deacetylates PML at 'Lys-487' and this deacetylation promotes PML control of PER2 nuclear localization (PubMed:22274616). During the neurogenic transition, represses selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling (PubMed:18662546). Deacetylates BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator (By similarity). Deacetylates PER2, facilitating its ubiquitination and degradation by the proteasome (By similarity). Protects cardiomyocytes against palmitate-induced apoptosis (By similarity). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity (PubMed:20955178). Deacetylates PCK1 and directs its activity toward phosphoenolpyruvate production promoting gluconeogenesis (PubMed:30193097). Involved in the CCAR2-mediated regulation of PCK1 and NR1D1 (PubMed:24415752). Deacetylates CTNB1 at 'Lys-49' (PubMed:24824780). In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (By similarity). Deacetylates SOX9; promoting SOX9 nuclear localization and transactivation activity (By similarity). Involved in the regulation of centrosome duplication: deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on the centrosome and subsequent procentriole assembly (PubMed:31722219). Deacetylates NDC80/HEC1 (PubMed:30409912). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by mediating protein delactylation, depropionylation and decrotonylation (PubMed:28497810, PubMed:38512451). Mediates depropionylation of Osterix (SP7) (By similarity). Catalyzes decrotonylation of histones; it however does not represent a major histone decrotonylase (PubMed:28497810). Mediates protein delactylation of TEAD1 and YAP1 (PubMed:38512451). {ECO:0000250|UniProtKB:Q923E4, ECO:0000269|PubMed:11672523, ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:12535671, ECO:0000269|PubMed:14976264, ECO:0000269|PubMed:14980222, ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:15152190, ECO:0000269|PubMed:15205477, ECO:0000269|PubMed:15469825, ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:16892051, ECO:0000269|PubMed:16998810, ECO:0000269|PubMed:17283066, ECO:0000269|PubMed:17290224, ECO:0000269|PubMed:17334224, ECO:0000269|PubMed:17505061, ECO:0000269|PubMed:17612497, ECO:0000269|PubMed:17620057, ECO:0000269|PubMed:17936707, ECO:0000269|PubMed:18203716, ECO:0000269|PubMed:18296641, ECO:0000269|PubMed:18485871, ECO:0000269|PubMed:18662546, ECO:0000269|PubMed:18687677, ECO:0000269|PubMed:19188449, ECO:0000269|PubMed:19220062, ECO:0000269|PubMed:19364925, ECO:0000269|PubMed:19690166, ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20097625, ECO:0000269|PubMed:20100829, ECO:0000269|PubMed:20203304, ECO:0000269|PubMed:20375098, ECO:0000269|PubMed:20620956, ECO:0000269|PubMed:20670893, ECO:0000269|PubMed:20817729, ECO:0000269|PubMed:20955178, ECO:0000269|PubMed:21149730, ECO:0000269|PubMed:21245319, ECO:0000269|PubMed:21471201, ECO:0000269|PubMed:21504832, ECO:0000269|PubMed:21555002, ECO:0000269|PubMed:21698133, ECO:0000269|PubMed:21701047, ECO:0000269|PubMed:21775285, ECO:0000269|PubMed:21807113, ECO:0000269|PubMed:21841822, ECO:0000269|PubMed:21890893, ECO:0000269|PubMed:21947282, ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:22542455, ECO:0000269|PubMed:22918831, ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29681526, ECO:0000269|PubMed:29765047, ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:31722219, ECO:0000269|PubMed:32034146, ECO:0000269|PubMed:32538779, ECO:0000269|PubMed:38512451}.; FUNCTION: [Isoform 2]: Deacetylates 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. {ECO:0000269|PubMed:20975832}.; FUNCTION: [SirtT1 75 kDa fragment]: Catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly. {ECO:0000269|PubMed:21987377}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection. {ECO:0000269|PubMed:18329615}. |
| Q96II8 | LRCH3 | S707 | ochoa | DISP complex protein LRCH3 (Leucine-rich repeat and calponin homology domain-containing protein 3) | As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. {ECO:0000269|PubMed:29467281}. |
| Q96JA1 | LRIG1 | S1069 | ochoa | Leucine-rich repeats and immunoglobulin-like domains protein 1 (LIG-1) | Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation. {ECO:0000269|PubMed:15282549}. |
| Q96JY6 | PDLIM2 | S72 | ochoa | PDZ and LIM domain protein 2 (PDZ-LIM protein mystique) | Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity. {ECO:0000269|PubMed:15659642}. |
| Q96KB5 | PBK | S32 | ochoa|psp | 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}. |
| Q96KC8 | DNAJC1 | S381 | ochoa | DnaJ homolog subfamily C member 1 (DnaJ protein homolog MTJ1) | May modulate protein synthesis. {ECO:0000250}. |
| Q96L91 | EP400 | S2476 | ochoa | E1A-binding protein p400 (EC 3.6.4.-) (CAG repeat protein 32) (Domino homolog) (hDomino) (Trinucleotide repeat-containing gene 12 protein) (p400 kDa SWI2/SNF2-related protein) | Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. May be required for transcriptional activation of E2F1 and MYC target genes during cellular proliferation. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. May regulate ZNF42 transcription activity. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome. {ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:24463511}. |
| Q96MU7 | YTHDC1 | S424 | ochoa | YTH domain-containing protein 1 (Splicing factor YT521) (YT521-B) | Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:25242552, PubMed:26318451, PubMed:26876937, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:25242552, PubMed:26318451). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Also recognizes and binds m6A-containing single-stranded DNA (PubMed:32663306). Involved in germline development: required for spermatogonial development in males and oocyte growth and maturation in females, probably via its role in alternative splicing (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:32663306}. |
| Q96P47 | AGAP3 | S443 | ochoa | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 3 (AGAP-3) (CRAM-associated GTPase) (CRAG) (Centaurin-gamma-3) (Cnt-g3) (MR1-interacting protein) (MRIP-1) | GTPase-activating protein for the ADP ribosylation factor family (Potential). GTPase which may be involved in the degradation of expanded polyglutamine proteins through the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:16461359, ECO:0000305}. |
| Q96PK6 | RBM14 | S627 | ochoa | RNA-binding protein 14 (Paraspeckle protein 2) (PSP2) (RNA-binding motif protein 14) (RRM-containing coactivator activator/modulator) (Synaptotagmin-interacting protein) (SYT-interacting protein) | Isoform 1 may function as a nuclear receptor coactivator, enhancing transcription through other coactivators such as NCOA6 and CITED1. Isoform 2, functions as a transcriptional repressor, modulating transcriptional activities of coactivators including isoform 1, NCOA6 and CITED1 (PubMed:11443112). Regulates centriole biogenesis by suppressing the formation of aberrant centriolar protein complexes in the cytoplasm and thus preserving mitotic spindle integrity. Prevents the formation of the STIL-CPAP complex (which can induce the formation of aberrant centriolar protein complexes) by interfering with the interaction of STIL with CPAP (PubMed:25385835). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also involved in the regulation of pre-mRNA alternative splicing (PubMed:37548402). {ECO:0000269|PubMed:11443112, ECO:0000269|PubMed:25385835, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:37548402}. |
| Q96Q11 | TRNT1 | S289 | ochoa | CCA tRNA nucleotidyltransferase 1, mitochondrial (EC 2.7.7.72) (Mitochondrial tRNA nucleotidyl transferase, CCA-adding) (mt CCA-adding enzyme) (mt tRNA CCA-diphosphorylase) (mt tRNA CCA-pyrophosphorylase) (mt tRNA adenylyltransferase) | Nucleotidyltransferase that catalyzes the addition and repair of the essential 3'-terminal CCA sequence in tRNAs, which is necessary for the attachment of amino acids to the 3' terminus of tRNA molecules, using CTP and ATP as substrates (PubMed:11504732, PubMed:25193871, PubMed:25640237, PubMed:25652405, PubMed:29454993, PubMed:30959222, PubMed:31011209, PubMed:34023389). tRNA 3'-terminal CCA addition is required both for tRNA processing and repair (PubMed:22076379, PubMed:25640237). Promotes tRNA repair and recycling downstream of the ribosome-associated quality control (RQC) pathway by mediating addition of the tRNA 3'-terminal CCA following cleavage by ANKZF1 and repair by ELAC1 (PubMed:31011209). Also involved in tRNA surveillance by mediating tandem CCA addition to generate a CCACCA at the 3' terminus of unstable tRNAs and tRNA-like transcripts (PubMed:22076379, PubMed:25640237). While stable tRNAs receive only 3'-terminal CCA, unstable tRNAs beginning with GG are marked with CCACCA and rapidly degraded (PubMed:22076379, PubMed:25640237). The structural flexibility of RNA controls the choice between CCA versus CCACCA addition: following the first CCA addition cycle, nucleotide-binding to the active site triggers a clockwise screw motion, producing torque on the RNA (PubMed:25640237). This ejects stable RNAs, whereas unstable RNAs are refolded while bound to the enzyme and subjected to a second CCA catalytic cycle (PubMed:25640237). {ECO:0000269|PubMed:11504732, ECO:0000269|PubMed:22076379, ECO:0000269|PubMed:25193871, ECO:0000269|PubMed:25640237, ECO:0000269|PubMed:25652405, ECO:0000269|PubMed:29454993, ECO:0000269|PubMed:30959222, ECO:0000269|PubMed:31011209, ECO:0000269|PubMed:34023389}.; FUNCTION: [Isoform 2]: Adds 2 C residues (CC-) to the 3' terminus of tRNA molecules instead of a complete CCA end as isoform 1 does (in vitro). {ECO:0000269|PubMed:17204286}. |
| Q96QB1 | DLC1 | S946 | ochoa|psp | Rho GTPase-activating protein 7 (Deleted in liver cancer 1 protein) (DLC-1) (HP protein) (Rho-type GTPase-activating protein 7) (START domain-containing protein 12) (StARD12) (StAR-related lipid transfer protein 12) | Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality. Required for growth factor-induced epithelial cell migration; in resting cells, interacts with TNS3 while PTEN interacts with the p85 regulatory subunit of the PI3K kinase complex but growth factor stimulation induces phosphorylation of TNS3 and PTEN, causing them to change their binding preference so that PTEN interacts with DLC1 and TNS3 interacts with p85 (PubMed:26166433). The PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA while the TNS3-p85 complex translocates to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433). {ECO:0000269|PubMed:18786931, ECO:0000269|PubMed:19170769, ECO:0000269|PubMed:19710422, ECO:0000269|PubMed:26166433}. |
| Q96QZ7 | MAGI1 | S730 | ochoa | Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 (Atrophin-1-interacting protein 3) (AIP-3) (BAI1-associated protein 1) (BAP-1) (Membrane-associated guanylate kinase inverted 1) (MAGI-1) (Trinucleotide repeat-containing gene 19 protein) (WW domain-containing protein 3) (WWP3) | Plays a role in coupling actin fibers to cell junctions in endothelial cells, via its interaction with AMOTL2 and CDH5 (By similarity). May regulate acid-induced ASIC3 currents by modulating its expression at the cell surface (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q6RHR9}. |
| Q96RG2 | PASK | S524 | 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}. |
| Q96SK2 | TMEM209 | S98 | ochoa | Transmembrane protein 209 | Nuclear envelope protein which in association with NUP205, may be involved in nuclear transport of various nuclear proteins in addition to MYC. {ECO:0000269|PubMed:22719065}. |
| Q96ST3 | SIN3A | S860 | ochoa | Paired amphipathic helix protein Sin3a (Histone deacetylase complex subunit Sin3a) (Transcriptional corepressor Sin3a) | Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (By similarity). Required for cortical neuron differentiation and callosal axon elongation (By similarity). {ECO:0000250|UniProtKB:Q60520, ECO:0000269|PubMed:12150998}. |
| Q96T23 | RSF1 | S397 | ochoa | Remodeling and spacing factor 1 (Rsf-1) (HBV pX-associated protein 8) (Hepatitis B virus X-associated protein) (p325 subunit of RSF chromatin-remodeling complex) | Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF-alpha induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984). {ECO:0000269|PubMed:11788598, ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:28801535}. |
| Q96T58 | SPEN | S1392 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96T58 | SPEN | S2159 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96T88 | UHRF1 | S709 | ochoa | E3 ubiquitin-protein ligase UHRF1 (EC 2.3.2.27) (Inverted CCAAT box-binding protein of 90 kDa) (Nuclear protein 95) (Nuclear zinc finger protein Np95) (HuNp95) (hNp95) (RING finger protein 106) (RING-type E3 ubiquitin transferase UHRF1) (Transcription factor ICBP90) (Ubiquitin-like PHD and RING finger domain-containing protein 1) (hUHRF1) (Ubiquitin-like-containing PHD and RING finger domains protein 1) | Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF2 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation. Acts as a critical player of proper spindle architecture by catalyzing the 'Lys-63'-linked ubiquitination of KIF11, thereby controlling KIF11 localization on the spindle (PubMed:37728657). {ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:22945642, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:37728657}. |
| Q99567 | NUP88 | S50 | ochoa | Nuclear pore complex protein Nup88 (88 kDa nucleoporin) (Nucleoporin Nup88) | Component of nuclear pore complex. {ECO:0000269|PubMed:30543681}. |
| Q99590 | SCAF11 | S629 | ochoa | Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) | Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}. |
| Q99611 | SEPHS2 | S109 | ochoa | Selenide, water dikinase 2 (EC 2.7.9.3) (Selenium donor protein 2) (Selenophosphate synthase 2) | Synthesizes selenophosphate from selenide and ATP. {ECO:0000250|UniProtKB:P49903}. |
| Q99618 | CDCA3 | S209 | ochoa | Cell division cycle-associated protein 3 (Gene-rich cluster protein C8) (Trigger of mitotic entry protein 1) (TOME-1) | F-box-like protein which is required for entry into mitosis. Acts by participating in E3 ligase complexes that mediate the ubiquitination and degradation of WEE1 kinase at G2/M phase (By similarity). {ECO:0000250}. |
| Q99666 | RGPD5 | S128 | ochoa | RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) | None |
| Q99798 | ACO2 | S559 | ochoa | Aconitate hydratase, mitochondrial (Aconitase) (EC 4.2.1.3) (Citrate hydro-lyase) | Catalyzes the isomerization of citrate to isocitrate via cis-aconitate. {ECO:0000250|UniProtKB:P16276}. |
| Q99814 | EPAS1 | S696 | 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}. |
| Q9BQ52 | ELAC2 | S618 | ochoa | Zinc phosphodiesterase ELAC protein 2 (EC 3.1.26.11) (ElaC homolog protein 2) (Heredity prostate cancer protein 2) (Ribonuclease Z 2) (RNase Z 2) (tRNA 3 endonuclease 2) (tRNase Z 2) | Zinc phosphodiesterase, which displays mitochondrial tRNA 3'-processing endonuclease activity. Involved in tRNA maturation, by removing a 3'-trailer from precursor tRNA (PubMed:21593607). Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly (PubMed:24703694). {ECO:0000269|PubMed:21593607, ECO:0000269|PubMed:24703694}. |
| Q9BQA1 | WDR77 | S306 | psp | Methylosome protein WDR77 (Androgen receptor cofactor p44) (Methylosome protein 50) (MEP-50) (WD repeat-containing protein 77) (p44/Mep50) | Non-catalytic component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones (PubMed:11756452). This modification targets Sm proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein core particles. Might play a role in transcription regulation. The methylosome complex also 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 (PubMed:23071334). {ECO:0000269|PubMed:11756452, ECO:0000269|PubMed:23071334}. |
| Q9BQC3 | DPH2 | S446 | ochoa | 2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 (Diphthamide biosynthesis protein 2) (Diphtheria toxin resistance protein 2) (S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 2) | Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (PubMed:32576952). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit (By similarity). {ECO:0000250|UniProtKB:P32461, ECO:0000269|PubMed:32576952}. |
| Q9BSE2 | TMEM79 | S41 | ochoa | Transmembrane protein 79 (Mattrin) | Contributes to the epidermal integrity and skin barrier function. Plays a role in the lamellar granule (LG) secretory system and in the stratum corneum (SC) epithelial cell formation (By similarity). {ECO:0000250}. |
| Q9BTX1 | NDC1 | S471 | ochoa | Nucleoporin NDC1 (hNDC1) (Transmembrane protein 48) | Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane. {ECO:0000269|PubMed:16600873, ECO:0000269|PubMed:16702233}. |
| Q9BUF5 | TUBB6 | S172 | ochoa | Tubulin beta-6 chain (Tubulin beta class V) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}. |
| Q9BVA1 | TUBB2B | S172 | 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}. |
| Q9BWT7 | CARD10 | S815 | ochoa | Caspase recruitment domain-containing protein 10 (CARD-containing MAGUK protein 3) (Carma 3) | Scaffold protein that plays an important role in mediating the activation of NF-kappa-B via BCL10 or EGFR. {ECO:0000269|PubMed:27991920}. |
| Q9BXA9 | SALL3 | S1268 | ochoa | Sal-like protein 3 (Zinc finger protein 796) (Zinc finger protein SALL3) (hSALL3) | Probable transcription factor. |
| Q9BXK5 | BCL2L13 | S38 | ochoa | Bcl-2-like protein 13 (Bcl2-L-13) (Bcl-rambo) (Protein Mil1) | May promote the activation of caspase-3 and apoptosis. |
| Q9BXW6 | OSBPL1A | S465 | ochoa | Oxysterol-binding protein-related protein 1 (ORP-1) (OSBP-related protein 1) | Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (By similarity). Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A (PubMed:16176980). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000250, ECO:0000269|PubMed:16176980, ECO:0000269|PubMed:17428193}. |
| Q9BY89 | KIAA1671 | S981 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BZC7 | ABCA2 | S2381 | ochoa | ATP-binding cassette sub-family A member 2 (EC 7.6.2.-) (ATP-binding cassette transporter 2) (ATP-binding cassette 2) | Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis (Probable) (PubMed:15238223, PubMed:21810484, PubMed:24201375). May alter the transbilayer distribution of ceramide in the intraluminal membrane lipid bilayer, favoring its retention in the outer leaflet that results in increased acid ceramidase activity in the late endosome/lysosome, facilitating ceramide deacylation to sphingosine leading to the sequestration of free cholesterol in lysosomes (PubMed:24201375). In addition regulates amyloid-beta production either by activating a signaling pathway that regulates amyloid precursor protein transcription through the modulation of sphingolipid metabolism or through its role in gamma-secretase processing of APP (PubMed:22086926, PubMed:26510981). May play a role in myelin formation (By similarity). {ECO:0000250|UniProtKB:P41234, ECO:0000269|PubMed:15238223, ECO:0000269|PubMed:21810484, ECO:0000269|PubMed:22086926, ECO:0000269|PubMed:24201375, ECO:0000269|PubMed:26510981, ECO:0000305|PubMed:15999530}. |
| Q9C0D5 | TANC1 | S132 | 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}. |
| Q9C0J9 | BHLHE41 | S122 | ochoa | Class E basic helix-loop-helix protein 41 (bHLHe41) (Class B basic helix-loop-helix protein 3) (bHLHb3) (Differentially expressed in chondrocytes protein 2) (hDEC2) (Enhancer-of-split and hairy-related protein 1) (SHARP-1) | Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:11278948, PubMed:14672706, PubMed:15193144, PubMed:15560782, PubMed:18411297, PubMed:19786558, PubMed:25083013). Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes (PubMed:25083013). Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity). {ECO:0000250|UniProtKB:Q99PV5, ECO:0000269|PubMed:11278948, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:15193144, ECO:0000269|PubMed:15560782, ECO:0000269|PubMed:18411297, ECO:0000269|PubMed:19786558, ECO:0000269|PubMed:25083013}. |
| Q9GZL7 | WDR12 | S306 | ochoa | Ribosome biogenesis protein WDR12 (WD repeat-containing protein 12) | 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_03029, ECO:0000269|PubMed:16043514, ECO:0000269|PubMed:17353269}. |
| Q9GZU2 | PEG3 | S547 | ochoa | Paternally-expressed gene 3 protein (Zinc finger and SCAN domain-containing protein 24) | Induces apoptosis in cooperation with SIAH1A. Acts as a mediator between p53/TP53 and BAX in a neuronal death pathway that is activated by DNA damage. Acts synergistically with TRAF2 and inhibits TNF induced apoptosis through activation of NF-kappa-B (By similarity). Possesses a tumor suppressing activity in glioma cells. {ECO:0000250, ECO:0000269|PubMed:11260267}. |
| Q9H0A8 | COMMD4 | S115 | ochoa | COMM domain-containing protein 4 | Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex (PubMed:37172566, PubMed:38459129). May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). Down-regulates activation of NF-kappa-B (PubMed:23637203). {ECO:0000269|PubMed:15799966, ECO:0000269|PubMed:37172566, ECO:0000269|PubMed:38459129, ECO:0000305|PubMed:21778237}. |
| Q9H0K1 | SIK2 | S379 | ochoa | Serine/threonine-protein kinase SIK2 (EC 2.7.11.1) (Qin-induced kinase) (Salt-inducible kinase 2) (SIK-2) (Serine/threonine-protein kinase SNF1-like kinase 2) | Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:23322770, PubMed:26983400). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity (PubMed:21084751, PubMed:26983400). In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (PubMed:21084751, PubMed:26983400). Also plays a role in thymic T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751, ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}. |
| Q9H257 | CARD9 | S277 | ochoa | Caspase recruitment domain-containing protein 9 (hCARD9) | Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors (PubMed:26961233, PubMed:33558980). CARD9-mediated signals are essential for antifungal immunity against a subset of fungi from the phylum Ascomycota (PubMed:24231284, PubMed:25057046, PubMed:25702837, PubMed:26521038, PubMed:26679537, PubMed:26961233, PubMed:27777981, PubMed:29080677, PubMed:33558980). Transduces signals in myeloid cells downstream of C-type lectin receptors CLEC7A (dectin-1), CLEC6A (dectin-2) and CLEC4E (Mincle), which detect pathogen-associated molecular pattern metabolites (PAMPs), such as fungal carbohydrates, and trigger CARD9 activation (By similarity). Upon activation, CARD9 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to activation of NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways which stimulate expression of genes encoding pro-inflammatory cytokines and chemokines (PubMed:11053425, PubMed:26488816, PubMed:26961233, PubMed:31296852, PubMed:33558980). CARD9 signaling in antigen-presenting cells links innate sensing of fungi to the activation of adaptive immunity and provides a cytokine milieu that induces the development and subsequent of interleukin 17-producing T helper (Th17) cells (PubMed:24231284). Also involved in activation of myeloid cells via classical ITAM-associated receptors and TLR: required for TLR-mediated activation of MAPK, while it is not required for TLR-induced activation of NF-kappa-B (By similarity). CARD9 can also be engaged independently of BCL10: forms a complex with RASGRF1 downstream of C-type lectin receptors, which recruits and activates HRAS, leading to ERK activation and the production of cytokines (By similarity). Acts as an important regulator of the intestinal commensal fungi (mycobiota) component of the gut microbiota (PubMed:33548172). Plays an essential role in antifungal immunity against dissemination of gut fungi: acts by promoting induction of antifungal IgG antibodies response in CX3CR1(+) macrophages to confer protection against disseminated C.albicans or C.auris infection (PubMed:33548172). Also mediates immunity against other pathogens, such as certain bacteria, viruses and parasites; CARD9 signaling is however redundant with other innate immune responses (By similarity). In response to L.monocytogenes infection, required for the production of inflammatory cytokines activated by intracellular peptidoglycan: acts by connecting NOD2 recognition of peptidoglycan to downstream activation of MAP kinases (MAPK) without activating NF-kappa-B (By similarity). {ECO:0000250|UniProtKB:A2AIV8, ECO:0000269|PubMed:11053425, ECO:0000269|PubMed:24231284, ECO:0000269|PubMed:25057046, ECO:0000269|PubMed:25702837, ECO:0000269|PubMed:26488816, ECO:0000269|PubMed:26521038, ECO:0000269|PubMed:26679537, ECO:0000269|PubMed:26961233, ECO:0000269|PubMed:27777981, ECO:0000269|PubMed:29080677, ECO:0000269|PubMed:31296852, ECO:0000269|PubMed:33548172, ECO:0000269|PubMed:33558980}. |
| Q9H2F5 | EPC1 | S427 | ochoa | Enhancer of polycomb homolog 1 | Component of the NuA4 histone acetyltransferase (HAT) complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:14966270). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR) (PubMed:27153538). The NuA4 complex is also required for spermatid development by promoting acetylation of histones: histone acetylation is required for histone replacement during the transition from round to elongating spermatids (By similarity). In the NuA4 complex, EPC1 is required to recruit MBTD1 into the complex (PubMed:32209463). {ECO:0000250|UniProtKB:Q8C9X6, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:32209463}. |
| Q9H2G9 | BLZF1 | S59 | ochoa | Golgin-45 (Basic leucine zipper nuclear factor 1) (JEM-1) (p45 basic leucine-zipper nuclear factor) | Required for normal Golgi structure and for protein transport from the endoplasmic reticulum (ER) through the Golgi apparatus to the cell surface. {ECO:0000269|PubMed:11739401}. |
| Q9H2Y7 | ZNF106 | S661 | 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}. |
| Q9H329 | EPB41L4B | S254 | ochoa | Band 4.1-like protein 4B (Erythrocyte membrane protein band 4.1-like 4B) (FERM-containing protein CG1) (Protein EHM2) | Up-regulates the activity of the Rho guanine nucleotide exchange factor ARHGEF18 (By similarity). Involved in the regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950). Promotes cellular adhesion, migration and motility in vitro and may play a role in wound healing (PubMed:23664528). May have a role in mediating cytoskeletal changes associated with steroid-induced cell differentiation (PubMed:14521927). {ECO:0000250|UniProtKB:Q9JMC8, ECO:0000269|PubMed:14521927, ECO:0000269|PubMed:22006950, ECO:0000269|PubMed:23664528}. |
| Q9H3D4 | TP63 | S395 | ochoa|psp | Tumor protein 63 (p63) (Chronic ulcerative stomatitis protein) (CUSP) (Keratinocyte transcription factor KET) (Transformation-related protein 63) (TP63) (Tumor protein p73-like) (p73L) (p40) (p51) | Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter. {ECO:0000269|PubMed:11641404, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12446779, ECO:0000269|PubMed:12446784, ECO:0000269|PubMed:20123734, ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:9774969}. |
| Q9H410 | DSN1 | S331 | ochoa|psp | Kinetochore-associated protein DSN1 homolog | Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. {ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:16585270}. |
| Q9H4A3 | WNK1 | S1978 | ochoa | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9H4A5 | GOLPH3L | S112 | ochoa | Golgi phosphoprotein 3-like (GPP34-related protein) | Phosphatidylinositol-4-phosphate-binding protein that may antagonize the action of GOLPH3 which is required for the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane. {ECO:0000269|PubMed:23345592}. |
| Q9H6T0 | ESRP2 | S573 | ochoa | Epithelial splicing regulatory protein 2 (RNA-binding motif protein 35B) (RNA-binding protein 35B) | mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Also regulates the splicing of CD44, CTNND1, ENAH, 3 transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of FGFR2. {ECO:0000269|PubMed:19285943}. |
| Q9H7P9 | PLEKHG2 | S911 | ochoa | Pleckstrin homology domain-containing family G member 2 (PH domain-containing family G member 2) | May be a transforming oncogene with exchange activity for CDC42 (By similarity). May be a guanine-nucleotide exchange factor (GEF) for RAC1 and CDC42. Activated by the binding to subunits beta and gamma of the heterotrimeric guanine nucleotide-binding protein (G protein) (PubMed:18045877). Involved in the regulation of actin polymerization (PubMed:26573021). {ECO:0000250|UniProtKB:Q6KAU7, ECO:0000269|PubMed:18045877, ECO:0000269|PubMed:26573021}. |
| Q9H8K7 | PAAT | S201 | ochoa | ATPase PAAT (EC 3.6.1.-) (Protein associated with ABC transporters) (PAAT) | ATPase that regulates mitochondrial ABC transporters ABCB7, ABCB8/MITOSUR and ABCB10 (PubMed:25063848). Regulates mitochondrial ferric concentration and heme biosynthesis and plays a role in the maintenance of mitochondrial homeostasis and cell survival (PubMed:25063848). {ECO:0000269|PubMed:25063848}. |
| Q9HBI1 | PARVB | S51 | ochoa | Beta-parvin (Affixin) | Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration. {ECO:0000269|PubMed:11402068, ECO:0000269|PubMed:15005707, ECO:0000269|PubMed:15159419, ECO:0000269|PubMed:15284246, ECO:0000269|PubMed:18325335}. |
| Q9HC77 | CPAP | S859 | ochoa | Centrosomal P4.1-associated protein (Centromere protein J) (CENP-J) (Centrosome assembly and centriole elongation protein) (LAG-3-associated protein) (LYST-interacting protein 1) | Plays an important role in cell division and centrosome function by participating in centriole duplication (PubMed:17681131, PubMed:20531387). Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as a microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles (PubMed:15047868, PubMed:27219064, PubMed:27306797). Required for centriole elongation and for STIL-mediated centriole amplification (PubMed:22020124). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (PubMed:27306797). {ECO:0000269|PubMed:15047868, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:20531387, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27185865, ECO:0000269|PubMed:27219064, ECO:0000305|PubMed:27306797}. |
| Q9HCC9 | ZFYVE28 | S384 | ochoa | Lateral signaling target protein 2 homolog (hLst2) (Zinc finger FYVE domain-containing protein 28) | Negative regulator of epidermal growth factor receptor (EGFR) signaling. Acts by promoting EGFR degradation in endosomes when not monoubiquitinated. {ECO:0000269|PubMed:19460345}. |
| Q9HCD6 | TANC2 | S1744 | ochoa | Protein TANC2 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2) | Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines. {ECO:0000269|PubMed:30021165}. |
| Q9HCE3 | ZNF532 | S418 | ochoa | Zinc finger protein 532 | May be involved in transcriptional regulation. |
| Q9HCL0 | PCDH18 | S891 | ochoa | Protocadherin-18 | Potential calcium-dependent cell-adhesion protein. |
| Q9NP71 | MLXIPL | S631 | ochoa | Carbohydrate-responsive element-binding protein (ChREBP) (Class D basic helix-loop-helix protein 14) (bHLHd14) (MLX interactor) (MLX-interacting protein-like) (WS basic-helix-loop-helix leucine zipper protein) (WS-bHLH) (Williams-Beuren syndrome chromosomal region 14 protein) | Binds DNA as a heterodimer with MLX/TCFL4 and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation (By similarity). Regulates transcription 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 gluconeogenesis, respectively (By similarity). {ECO:0000250|UniProtKB:Q2VPU4, ECO:0000250|UniProtKB:Q9HAP2}. |
| Q9NQ66 | PLCB1 | S308 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (EC 3.1.4.11) (PLC-154) (Phosphoinositide phospholipase C-beta-1) (Phospholipase C-I) (PLC-I) (Phospholipase C-beta-1) (PLC-beta-1) | Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors (PubMed:9188725). Regulates the function of the endothelial barrier. {ECO:0000250|UniProtKB:Q9Z1B3, ECO:0000269|PubMed:9188725}. |
| Q9NR45 | NANS | S275 | ochoa | N-acetylneuraminate-9-phosphate synthase (EC 2.5.1.57) (3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase) (EC 2.5.1.132) (N-acetylneuraminic acid phosphate synthase) (NANS) (Sialic acid phosphate synthase) (Sialic acid synthase) | Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) (PubMed:10749855). Also catalyzes the condensation of PEP and D-mannose 6-phosphate (Man-6-P) to produce 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate (KDN-9-P) (PubMed:10749855). Neu5Ac-9-P and KDN-9-P are the phosphorylated forms of sialic acids N-acetylneuraminic acid (Neu5Ac) and deaminoneuraminic acid (KDN), respectively (PubMed:10749855). Required for brain and skeletal development (PubMed:27213289). {ECO:0000269|PubMed:10749855, ECO:0000269|PubMed:27213289}. |
| Q9NR80 | ARHGEF4 | S109 | ochoa | Rho guanine nucleotide exchange factor 4 (APC-stimulated guanine nucleotide exchange factor 1) (Asef) (Asef1) | Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression. {ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:12598901, ECO:0000269|PubMed:17145773, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19893577}. |
| Q9NRI5 | DISC1 | S58 | psp | Disrupted in schizophrenia 1 protein | Involved in the regulation of multiple aspects of embryonic and adult neurogenesis (PubMed:19303846, PubMed:19502360). Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus (By similarity). Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance (PubMed:19303846). Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation (By similarity). Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A (By similarity). Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development (PubMed:19502360). Inhibits ATF4 transcription factor activity in neurons by disrupting ATF4 dimerization and DNA-binding (By similarity). Plays a role, together with PCNT, in the microtubule network formation (PubMed:18955030). {ECO:0000250|UniProtKB:Q811T9, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:19303846, ECO:0000269|PubMed:19502360}. |
| Q9NRM7 | LATS2 | S342 | ochoa | Serine/threonine-protein kinase LATS2 (EC 2.7.11.1) (Kinase phosphorylated during mitosis protein) (Large tumor suppressor homolog 2) (Serine/threonine-protein kinase kpm) (Warts-like kinase) | Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:18158288, PubMed:26437443, PubMed:26598551, PubMed:34404733). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:26437443, PubMed:26598551, PubMed:34404733). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:26598551, PubMed:34404733). Also phosphorylates YAP1 in response to cell contact inhibition-driven WWP1 ubiquitination of AMOTL2, which results in LATS2 activation (PubMed:34404733). Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability (PubMed:10871863). Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity (PubMed:12853976). Negative regulator of the androgen receptor (PubMed:15131260). Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities (PubMed:21952048). This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ (PubMed:21952048). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10871863, ECO:0000269|PubMed:12853976, ECO:0000269|PubMed:15131260, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:39173637}. |
| Q9NSI6 | BRWD1 | S649 | ochoa | Bromodomain and WD repeat-containing protein 1 (WD repeat-containing protein 9) | May be a transcriptional activator. May be involved in chromatin remodeling (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000250, ECO:0000269|PubMed:21834987}. |
| Q9NTI5 | PDS5B | S1087 | ochoa | Sister chromatid cohesion protein PDS5 homolog B (Androgen-induced proliferation inhibitor) (Androgen-induced prostate proliferative shutoff-associated protein AS3) | Regulator of sister chromatid cohesion in mitosis which may stabilize cohesin complex association with chromatin. May couple sister chromatid cohesion during mitosis to DNA replication. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Plays a role in androgen-induced proliferative arrest in prostate cells. {ECO:0000269|PubMed:10963680, ECO:0000269|PubMed:15855230, ECO:0000269|PubMed:19696148}. |
| Q9NU22 | MDN1 | S2492 | ochoa | Midasin (Dynein-related AAA-ATPase MDN1) (MIDAS-containing protein) | Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits (PubMed:27814492). Functions at successive maturation steps to remove ribosomal factors at critical transition points, first driving the exit of early pre-60S particles from the nucleolus and then driving late pre-60S particles from the nucleus (By similarity). At an early stage in 60S maturation, mediates the dissociation of the PeBoW complex (PES1-BOP1-WDR12) from early pre-60S particles, rendering them competent for export from the nucleolus to the nucleoplasm (By similarity). Subsequently recruited to the nucleoplasmic particles through interaction with SUMO-conjugated PELP1 complex (PubMed:27814492). This binding is only possible if the 5S RNP at the central protuberance has undergone the rotation to complete its maturation (By similarity). {ECO:0000250|UniProtKB:Q12019, ECO:0000269|PubMed:27814492}. |
| Q9NVD7 | PARVA | S62 | ochoa | Alpha-parvin (Actopaxin) (CH-ILKBP) (Calponin-like integrin-linked kinase-binding protein) (Matrix-remodeling-associated protein 2) | Plays a role in sarcomere organization and in smooth muscle cell contraction. Required for normal development of the embryonic cardiovascular system, and for normal septation of the heart outflow tract. Plays a role in sprouting angiogenesis and is required for normal adhesion of vascular smooth muscle cells to endothelial cells during blood vessel development (By similarity). Plays a role in the reorganization of the actin cytoskeleton, formation of lamellipodia and ciliogenesis. Plays a role in the establishment of cell polarity, cell adhesion, cell spreading, and directed cell migration. Within the IPP (ILK-PINCH-PARVIN) complex, binds to F-actin, promoting F-actin bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration (PubMed:30367047). {ECO:0000250, ECO:0000269|PubMed:11134073, ECO:0000269|PubMed:11331308, ECO:0000269|PubMed:15284246, ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:30367047}. |
| Q9NVH2 | INTS7 | S338 | ochoa | Integrator complex subunit 7 (Int7) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:33243860, PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:33243860, PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144). May be not involved in the recruitment of cytoplasmic dynein to the nuclear envelope by different components of the INT complex (PubMed:23904267). Plays a role in DNA damage response (DDR) signaling during the S phase (PubMed:21659603). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:33243860, ECO:0000269|PubMed:38570683}. |
| Q9NW68 | BSDC1 | S166 | ochoa | BSD domain-containing protein 1 | None |
| Q9NWZ3 | IRAK4 | S152 | ochoa|psp | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q9NX95 | SYBU | S496 | ochoa | Syntabulin (Golgi-localized syntaphilin-related protein) (Syntaxin-1-binding protein) | Part of a kinesin motor-adapter complex that is critical for the anterograde axonal transport of active zone components and contributes to activity-dependent presynaptic assembly during neuronal development. {ECO:0000250, ECO:0000269|PubMed:15459722}. |
| Q9NXH9 | TRMT1 | S517 | ochoa | tRNA (guanine(26)-N(2))-dimethyltransferase (EC 2.1.1.216) (tRNA 2,2-dimethylguanosine-26 methyltransferase) (tRNA methyltransferase 1) (hTRM1) (tRNA(guanine-26,N(2)-N(2)) methyltransferase) (tRNA(m(2,2)G26)dimethyltransferase) | Dimethylates a single guanine residue at position 26 of most nuclear- and mitochondrial-encoded tRNAs using S-adenosyl-L-methionine as donor of the methyl groups (PubMed:10982862, PubMed:28784718, PubMed:37204604, PubMed:39786990). tRNA guanine(26)-dimethylation is required for redox homeostasis and ensure proper cellular proliferation and oxidative stress survival (PubMed:28784718). {ECO:0000269|PubMed:10982862, ECO:0000269|PubMed:28784718, ECO:0000269|PubMed:37204604, ECO:0000269|PubMed:39786990}. |
| Q9NY74 | ETAA1 | S111 | ochoa | Ewing's tumor-associated antigen 1 (Ewing's tumor-associated antigen 16) | Replication stress response protein that accumulates at DNA damage sites and promotes replication fork progression and integrity (PubMed:27601467, PubMed:27723717, PubMed:27723720). Recruited to stalled replication forks via interaction with the RPA complex and directly stimulates ATR kinase activity independently of TOPBP1 (PubMed:27723717, PubMed:27723720, PubMed:30139873). Probably only regulates a subset of ATR targets (PubMed:27723717, PubMed:27723720). {ECO:0000269|PubMed:27601467, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873}. |
| Q9NYB0 | TERF2IP | S36 | ochoa | Telomeric repeat-binding factor 2-interacting protein 1 (TERF2-interacting telomeric protein 1) (TRF2-interacting telomeric protein 1) (Dopamine receptor-interacting protein 5) (Repressor/activator protein 1 homolog) (RAP1 homolog) (hRap1) | Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes. {ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:19763083}. |
| Q9NYB0 | TERF2IP | S203 | ochoa|psp | Telomeric repeat-binding factor 2-interacting protein 1 (TERF2-interacting telomeric protein 1) (TRF2-interacting telomeric protein 1) (Dopamine receptor-interacting protein 5) (Repressor/activator protein 1 homolog) (RAP1 homolog) (hRap1) | Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes. {ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:19763083}. |
| Q9NZM1 | MYOF | S1915 | 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}. |
| Q9NZN8 | CNOT2 | S126 | ochoa | CCR4-NOT transcription complex subunit 2 (CCR4-associated factor 2) | Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754, ECO:0000269|PubMed:22367759}. |
| Q9P1Y5 | CAMSAP3 | S1031 | ochoa | Calmodulin-regulated spectrin-associated protein 3 (Protein Nezha) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19041755, PubMed:23169647). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153). Required for the biogenesis and the maintenance of zonula adherens by anchoring the minus-end of microtubules to zonula adherens and by recruiting the kinesin KIFC3 to those junctional sites (PubMed:19041755). Required for orienting the apical-to-basal polarity of microtubules in epithelial cells: acts by tethering non-centrosomal microtubules to the apical cortex, leading to their longitudinal orientation (PubMed:26715742, PubMed:27802168). Plays a key role in early embryos, which lack centrosomes: accumulates at the microtubule bridges that connect pairs of cells and enables the formation of a non-centrosomal microtubule-organizing center that directs intracellular transport in the early embryo (By similarity). Couples non-centrosomal microtubules with actin: interaction with MACF1 at the minus ends of non-centrosomal microtubules, tethers the microtubules to actin filaments, regulating focal adhesion size and cell migration (PubMed:27693509). Plays a key role in the generation of non-centrosomal microtubules by accumulating in the pericentrosomal region and cooperating with KATNA1 to release non-centrosomal microtubules from the centrosome (PubMed:28386021). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:28089391). Through interaction with AKAP9, involved in translocation of Golgi vesicles in epithelial cells, where microtubules are mainly non-centrosomal (PubMed:28089391). Plays an important role in motile cilia function by facilitatating proper orientation of basal bodies and formation of central microtubule pairs in motile cilia (By similarity). {ECO:0000250|UniProtKB:Q80VC9, ECO:0000269|PubMed:19041755, ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:26715742, ECO:0000269|PubMed:27693509, ECO:0000269|PubMed:27802168, ECO:0000269|PubMed:28089391, ECO:0000269|PubMed:28386021}. |
| Q9P243 | ZFAT | S21 | ochoa | Zinc finger protein ZFAT (Zinc finger gene in AITD susceptibility region) (Zinc finger protein 406) | May be involved in transcriptional regulation. Overexpression causes down-regulation of a number of genes involved in the immune response. Some genes are also up-regulated (By similarity). {ECO:0000250}. |
| Q9P2D0 | IBTK | S1116 | 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}. |
| Q9UBS8 | RNF14 | S451 | ochoa | E3 ubiquitin-protein ligase RNF14 (EC 2.3.2.31) (Androgen receptor-associated protein 54) (HFB30) (RING finger protein 14) | E3 ubiquitin-protein ligase that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Recruited to stalled ribosomes by the ribosome collision sensor GCN1 and mediates 'Lys-6'-linked ubiquitination of target proteins, leading to their degradation (PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Mediates ubiquitination of EEF1A1/eEF1A and ETF1/eRF1 translation factors on stalled ribosomes, leading to their degradation (PubMed:36638793, PubMed:37651229). Also catalyzes ubiquitination of ribosomal proteins RPL0, RPL1, RPL12, RPS13 and RPS17 (PubMed:36638793). Specifically required to resolve RNA-protein cross-links caused by reactive aldehydes, which trigger translation stress by stalling ribosomes: acts by catalying 'Lys-6'-linked ubiquitination of RNA-protein cross-links, leading to their removal by the ATP-dependent unfoldase VCP and subsequent degradation by the proteasome (PubMed:37951215, PubMed:37951216). Independently of its function in the response to stalled ribosomes, acts as a regulator of transcription in Wnt signaling via its interaction with TCF transcription factors (TCF7/TCF1, TCF7L1/TCF3 and TCF7L2/TCF4) (PubMed:23449499). May also play a role as a coactivator for androgen- and, to a lesser extent, progesterone-dependent transcription (PubMed:19345326). {ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:23449499, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229, ECO:0000269|PubMed:37951215, ECO:0000269|PubMed:37951216}. |
| Q9UBU7 | DBF4 | S130 | ochoa | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UBU7 | DBF4 | S613 | ochoa | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UGP5 | POLL | S230 | psp | DNA polymerase lambda (Pol Lambda) (EC 2.7.7.7) (EC 4.2.99.-) (DNA polymerase beta-2) (Pol beta2) (DNA polymerase kappa) | DNA polymerase that functions in several pathways of DNA repair (PubMed:11457865, PubMed:19806195, PubMed:20693240, PubMed:30250067). Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA (PubMed:11457865, PubMed:19806195). Also contributes to DNA double-strand break repair by non-homologous end joining and homologous recombination (PubMed:19806195, PubMed:20693240, PubMed:30250067). Has both template-dependent and template-independent (terminal transferase) DNA polymerase activities (PubMed:10887191, PubMed:10982892, PubMed:12809503, PubMed:14627824, PubMed:15537631, PubMed:19806195). Also has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity (PubMed:11457865, PubMed:19806195). {ECO:0000269|PubMed:10887191, ECO:0000269|PubMed:10982892, ECO:0000269|PubMed:11457865, ECO:0000269|PubMed:12809503, ECO:0000269|PubMed:14627824, ECO:0000269|PubMed:15537631, ECO:0000269|PubMed:19806195, ECO:0000269|PubMed:20693240, ECO:0000269|PubMed:30250067}. |
| Q9UGU0 | TCF20 | S1053 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UGU0 | TCF20 | S1418 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UID6 | ZNF639 | S88 | ochoa | Zinc finger protein 639 (Zinc finger protein ANC_2H01) (Zinc finger protein ZASC1) | Binds DNA and may function as a transcriptional repressor. {ECO:0000269|PubMed:16182284}. |
| Q9UJU6 | DBNL | S24 | 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}. |
| Q9UK61 | TASOR | S979 | ochoa | Protein TASOR (CTCL tumor antigen se89-1) (Retinoblastoma-associated protein RAP140) (Transgene activation suppressor protein) | Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression (PubMed:26022416, PubMed:28581500). The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2 (PubMed:26022416, PubMed:28581500). Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Plays a crucial role in early embryonic development (By similarity). Involved in the organization of spindle poles and spindle apparatus assembly during zygotic division (By similarity). Plays an important role in maintaining epiblast fitness or potency (By similarity). {ECO:0000250|UniProtKB:Q69ZR9, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:30487602}. |
| Q9UK97 | FBXO9 | S33 | ochoa | F-box only protein 9 (Cross-immune reaction antigen 1) (Renal carcinoma antigen NY-REN-57) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins and plays a role in several biological processes such as cell cycle, cell proliferation, or maintenance of chromosome stability (PubMed:23263282, PubMed:34480022). Ubiquitinates mTORC1-bound TTI1 and TELO2 when they are phosphorylated by CK2 following growth factor deprivation, leading to their degradation. In contrast, does not mediate ubiquitination of TTI1 and TELO2 when they are part of the mTORC2 complex. As a consequence, mTORC1 is inactivated to restrain cell growth and protein translation, while mTORC2 is the activated due to the relief of feedback inhibition by mTORC1 (PubMed:23263282). Plays a role in maintaining epithelial cell survival by regulating the turn-over of chromatin modulator PRMT4 through ubiquitination and degradation by the proteasomal pathway (PubMed:34480022). Regulates also PPARgamma stability by facilitating PPARgamma/PPARG ubiquitination and thereby plays a role in adipocyte differentiation (By similarity). {ECO:0000250|UniProtKB:Q8BK06, ECO:0000269|PubMed:23263282, ECO:0000269|PubMed:34480022}. |
| Q9UKZ1 | CNOT11 | S340 | ochoa | CCR4-NOT transcription complex subunit 11 | Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Is required for the association of CNOT10 with the CCR4-NOT complex. Seems not to be required for complex deadenylase function. |
| Q9ULD6 | INTU | S674 | ochoa | Protein inturned (Inturned planar cell polarity effector homolog) (PDZ domain-containing protein 6) | Plays a key role in ciliogenesis and embryonic development. Regulator of cilia formation by controlling the organization of the apical actin cytoskeleton and the positioning of the basal bodies at the apical cell surface, which in turn is essential for the normal orientation of elongating ciliary microtubules. Plays a key role in definition of cell polarity via its role in ciliogenesis but not via conversion extension. Has an indirect effect on hedgehog signaling (By similarity). Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (PubMed:27158779). Required for recruitment of CPLANE2 to the mother centriole (By similarity). Binds phosphatidylinositol 3-phosphate with highest affinity, followed by phosphatidylinositol 4-phosphate and phosphatidylinositol 5-phosphate (By similarity). {ECO:0000250|UniProtKB:Q059U7, ECO:0000250|UniProtKB:Q2I0E5, ECO:0000305|PubMed:27158779}. |
| Q9ULM2 | ZNF490 | S118 | ochoa | Zinc finger protein 490 | May be involved in transcriptional regulation. |
| Q9ULM3 | YEATS2 | S1043 | ochoa | YEATS domain-containing protein 2 | Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:18838386, PubMed:19103755, PubMed:27103431). YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}. |
| Q9ULV3 | CIZ1 | S350 | ochoa | Cip1-interacting zinc finger protein (CDKN1A-interacting zinc finger protein 1) (Nuclear protein NP94) (Zinc finger protein 356) | May regulate the subcellular localization of CIP/WAF1. |
| Q9ULV4 | CORO1C | S299 | ochoa | Coronin-1C (Coronin-3) (hCRNN4) | Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1 (PubMed:25074804, PubMed:25925950). Increases the presence of activated RAC1 at the leading edge of migrating cells (PubMed:25074804, PubMed:25925950). Required for normal organization of the cytoskeleton, including the actin cytoskeleton, microtubules and the vimentin intermediate filaments (By similarity). Plays a role in endoplasmic reticulum-associated endosome fission: localizes to endosome membrane tubules and promotes recruitment of TMCC1, leading to recruitment of the endoplasmic reticulum to endosome tubules for fission (PubMed:30220460). Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane (PubMed:30220460). Required for normal cell proliferation, cell migration, and normal formation of lamellipodia (By similarity). Required for normal distribution of mitochondria within cells (By similarity). {ECO:0000250|UniProtKB:Q9WUM4, ECO:0000269|PubMed:25074804, ECO:0000269|PubMed:25925950, ECO:0000269|PubMed:30220460, ECO:0000269|PubMed:34106209}.; FUNCTION: [Isoform 3]: Involved in myogenic differentiation. {ECO:0000269|PubMed:19651142}. |
| Q9UN79 | SOX13 | S335 | ochoa | Transcription factor SOX-13 (Islet cell antigen 12) (SRY (Sex determining region Y)-box 13) (Type 1 diabetes autoantigen ICA12) | Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3' (PubMed:10871192). Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube (By similarity). Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells (By similarity). Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells (By similarity). Promotes brown adipocyte differentiation (By similarity). Inhibitor of WNT signaling (PubMed:20028982). {ECO:0000250|UniProtKB:Q04891, ECO:0000269|PubMed:10871192, ECO:0000269|PubMed:20028982}. |
| Q9UNX3 | RPL26L1 | S32 | ochoa | Ribosomal protein uL24-like (60S ribosomal protein L26-like 1) (Large ribosomal subunit protein uL24-like 1) | None |
| Q9UP95 | SLC12A4 | S47 | ochoa | Solute carrier family 12 member 4 (Electroneutral potassium-chloride cotransporter 1) (Erythroid K-Cl cotransporter 1) (hKCC1) | Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:35759661). May contribute to cell volume homeostasis in single cells (PubMed:10913127, PubMed:34031912). May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). {ECO:0000250|UniProtKB:Q9JIS8, ECO:0000269|PubMed:10913127, ECO:0000269|PubMed:34031912, ECO:0000269|PubMed:35759661}.; FUNCTION: [Isoform 4]: No transporter activity. {ECO:0000269|PubMed:11551954}. |
| Q9UPW5 | AGTPBP1 | S1142 | ochoa | Cytosolic carboxypeptidase 1 (EC 3.4.17.-) (EC 3.4.17.24) (ATP/GTP-binding protein 1) (Nervous system nuclear protein induced by axotomy protein 1 homolog) (Protein deglutamylase CCP1) | Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:22170066, PubMed:24022482, PubMed:30420557). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:22170066, PubMed:24022482, PubMed:30420557). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:24022482). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK (PubMed:22170066). Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216). {ECO:0000269|PubMed:22170066, ECO:0000269|PubMed:24022482, ECO:0000269|PubMed:29593216, ECO:0000269|PubMed:30420557}. |
| Q9UPW5 | AGTPBP1 | S1168 | ochoa | Cytosolic carboxypeptidase 1 (EC 3.4.17.-) (EC 3.4.17.24) (ATP/GTP-binding protein 1) (Nervous system nuclear protein induced by axotomy protein 1 homolog) (Protein deglutamylase CCP1) | Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins (PubMed:22170066, PubMed:24022482, PubMed:30420557). Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin (PubMed:22170066, PubMed:24022482, PubMed:30420557). Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate (PubMed:24022482). Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins such as MYLK (PubMed:22170066). Involved in KLF4 deglutamylation which promotes KLF4 proteasome-mediated degradation, thereby negatively regulating cell pluripotency maintenance and embryogenesis (PubMed:29593216). {ECO:0000269|PubMed:22170066, ECO:0000269|PubMed:24022482, ECO:0000269|PubMed:29593216, ECO:0000269|PubMed:30420557}. |
| Q9UPY3 | DICER1 | S1852 | ochoa|psp | Endoribonuclease Dicer (EC 3.1.26.3) (Helicase with RNase motif) (Helicase MOI) | Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes. {ECO:0000269|PubMed:15242644, ECO:0000269|PubMed:15973356, ECO:0000269|PubMed:16142218, ECO:0000269|PubMed:16271387, ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16357216, ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:17452327, ECO:0000269|PubMed:18178619}. |
| Q9UQ35 | SRRM2 | S1311 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQR0 | SCML2 | S267 | ochoa|psp | Sex comb on midleg-like protein 2 | Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development (By similarity). {ECO:0000250}. |
| Q9UQR1 | ZNF148 | S306 | ochoa | Zinc finger protein 148 (Transcription factor ZBP-89) (Zinc finger DNA-binding protein 89) | Involved in transcriptional regulation. Represses the transcription of a number of genes including gastrin, stromelysin and enolase. Binds to the G-rich box in the enhancer region of these genes. |
| Q9Y210 | TRPC6 | S282 | psp | Short transient receptor potential channel 6 (TrpC6) (Transient receptor protein 6) (TRP-6) | Forms a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369, PubMed:26892346, PubMed:9930701). Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion. {ECO:0000269|PubMed:19936226, ECO:0000269|PubMed:23291369, ECO:0000269|PubMed:26892346, ECO:0000269|PubMed:9930701}. |
| Q9Y253 | POLH | S512 | ochoa|psp | DNA polymerase eta (EC 2.7.7.7) (RAD30 homolog A) (Xeroderma pigmentosum variant type protein) | DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS) (PubMed:10385124, PubMed:11743006, PubMed:16357261, PubMed:24449906, PubMed:24553286, PubMed:38212351). Due to low processivity on both damaged and normal DNA, cooperates with the heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer is further extended by the tetrameric POLZ complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine (PubMed:24449906). Particularly important for the repair of UV-induced pyrimidine dimers (PubMed:10385124, PubMed:11743006). Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes (PubMed:11376341, PubMed:14734526). Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have any lyase activity, preventing the release of the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity during base excision repair, thereby avoiding high incidence of mutagenesis (PubMed:14630940). Targets POLI to replication foci (PubMed:12606586). {ECO:0000269|PubMed:10385124, ECO:0000269|PubMed:11376341, ECO:0000269|PubMed:11743006, ECO:0000269|PubMed:12606586, ECO:0000269|PubMed:14630940, ECO:0000269|PubMed:14734526, ECO:0000269|PubMed:16357261, ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:24553286, ECO:0000269|PubMed:38212351}. |
| Q9Y2J2 | EPB41L3 | S962 | ochoa | Band 4.1-like protein 3 (4.1B) (Differentially expressed in adenocarcinoma of the lung protein 1) (DAL-1) (Erythrocyte membrane protein band 4.1-like 3) [Cleaved into: Band 4.1-like protein 3, N-terminally processed] | Tumor suppressor that inhibits cell proliferation and promotes apoptosis. Modulates the activity of protein arginine N-methyltransferases, including PRMT3 and PRMT5. {ECO:0000269|PubMed:15334060, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16420693, ECO:0000269|PubMed:9892180}. |
| Q9Y2K1 | ZBTB1 | S520 | ochoa | Zinc finger and BTB domain-containing protein 1 | Acts as a transcriptional repressor (PubMed:20797634). Represses cAMP-responsive element (CRE)-mediated transcriptional activation (PubMed:21706167). In addition, has a role in translesion DNA synthesis. Requires for UV-inducible RAD18 loading, PCNA monoubiquitination, POLH recruitment to replication factories and efficient translesion DNA synthesis (PubMed:24657165). Plays a key role in the transcriptional regulation of T lymphocyte development (By similarity). {ECO:0000250|UniProtKB:Q91VL9, ECO:0000269|PubMed:20797634, ECO:0000269|PubMed:21706167, ECO:0000269|PubMed:24657165}. |
| Q9Y2L1 | DIS3 | S730 | ochoa | Exosome complex exonuclease RRP44 (EC 3.1.13.-) (EC 3.1.26.-) (Protein DIS3 homolog) (Ribosomal RNA-processing protein 44) | Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. DIS3 has both 3'-5' exonuclease and endonuclease activities. {ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:20531386}. |
| Q9Y2T1 | AXIN2 | S244 | ochoa | Axin-2 (Axin-like protein) (Axil) (Axis inhibition protein 2) (Conductin) | Inhibitor of the Wnt signaling pathway. Down-regulates beta-catenin. Probably facilitate the phosphorylation of beta-catenin and APC by GSK3B. {ECO:0000250|UniProtKB:O15169}. |
| Q9Y2W1 | THRAP3 | S408 | ochoa | Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) | Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| Q9Y2X3 | NOP58 | S109 | ochoa | Nucleolar protein 58 (Nucleolar protein 5) | Required for the biogenesis of box C/D snoRNAs such as U3, U8 and U14 snoRNAs (PubMed:15574333, PubMed:17636026, PubMed:19620283, PubMed:34516797). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:39570315). {ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:19620283, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| Q9Y320 | TMX2 | S211 | ochoa | Thioredoxin-related transmembrane protein 2 (Cell proliferation-inducing gene 26 protein) (Thioredoxin domain-containing protein 14) | Endoplasmic reticulum and mitochondria-associated protein that probably functions as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. Indirectly regulates neuronal proliferation, migration, and organization in the developing brain. {ECO:0000269|PubMed:31735293}. |
| Q9Y3E2 | BOLA1 | S45 | ochoa | BolA-like protein 1 (hBolA) | Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins (By similarity). Probably acts together with the monothiol glutaredoxin GLRX5 (PubMed:27532772). May protect cells against oxidative stress (PubMed:22746225). {ECO:0000250|UniProtKB:Q3E793, ECO:0000269|PubMed:22746225, ECO:0000305|PubMed:27532772}. |
| Q9Y3R0 | GRIP1 | S996 | ochoa | Glutamate receptor-interacting protein 1 (GRIP-1) | May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P97879, ECO:0000269|PubMed:10197531}. |
| Q9Y4B4 | RAD54L2 | Y1426 | ochoa | Helicase ARIP4 (EC 3.6.4.12) (Androgen receptor-interacting protein 4) (RAD54-like protein 2) | DNA helicase that modulates androgen receptor (AR)-dependent transactivation in a promoter-dependent manner. Not able to remodel mononucleosomes in vitro (By similarity). {ECO:0000250}. |
| Q9Y4G8 | RAPGEF2 | S1223 | 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}. |
| Q9Y4H2 | IRS2 | S828 | 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}. |
| Q9Y4P3 | TBL2 | S340 | ochoa | Transducin beta-like protein 2 (WS beta-transducin repeats protein) (WS-betaTRP) (Williams-Beuren syndrome chromosomal region 13 protein) | None |
| Q9Y561 | LRP12 | S720 | ochoa | Low-density lipoprotein receptor-related protein 12 (LDLR-related protein 12) (LRP-12) (Suppressor of tumorigenicity 7 protein) | Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. May act as a tumor suppressor. {ECO:0000269|PubMed:12809483}. |
| Q9Y5Y5 | PEX16 | S138 | ochoa | Peroxisomal membrane protein PEX16 (Peroxin-16) (Peroxisomal biogenesis factor 16) | Required for peroxisome membrane biogenesis. May play a role in early stages of peroxisome assembly. Can recruit other peroxisomal proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from the endoplasmic reticulum (ER). May function as receptor for PEX3. {ECO:0000269|PubMed:10704444, ECO:0000269|PubMed:12223482, ECO:0000269|PubMed:16717127}. |
| Q9Y6X9 | MORC2 | S856 | psp | ATPase MORC2 (EC 3.6.1.-) (MORC family CW-type zinc finger protein 2) (Zinc finger CW-type coiled-coil domain protein 1) | Essential for epigenetic silencing by the HUSH (human silencing hub) complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing (PubMed:28581500, PubMed:29440755, PubMed:32693025). Represses germ cell-related genes and L1 retrotransposons in collaboration with SETDB1 and the HUSH complex, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). During DNA damage response, regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, is phosphorylated by PAK1, both colocalize to chromatin and induce H2AX expression. ATPase activity is required and dependent of phosphorylation by PAK1 and presence of DNA (PubMed:23260667). Recruits histone deacetylases, such as HDAC4, to promoter regions, causing local histone H3 deacetylation and transcriptional repression of genes such as CA9 (PubMed:20110259, PubMed:20225202). Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation (PubMed:24286864). {ECO:0000269|PubMed:20110259, ECO:0000269|PubMed:20225202, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:24286864, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:29440755, ECO:0000269|PubMed:32693025}. |
| O15146 | MUSK | S691 | 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}. |
| P13667 | PDIA4 | Y137 | Sugiyama | Protein disulfide-isomerase A4 (EC 5.3.4.1) (Endoplasmic reticulum resident protein 70) (ER protein 70) (ERp70) (Endoplasmic reticulum resident protein 72) (ER protein 72) (ERp-72) (ERp72) | None |
| O15067 | PFAS | S1062 | Sugiyama | Phosphoribosylformylglycinamidine synthase (FGAM synthase) (FGAMS) (EC 6.3.5.3) (Formylglycinamide ribonucleotide amidotransferase) (FGAR amidotransferase) (FGAR-AT) (Formylglycinamide ribotide amidotransferase) (Phosphoribosylformylglycineamide amidotransferase) | Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate. {ECO:0000305|PubMed:10548741}. |
| Q14697 | GANAB | S58 | Sugiyama | Neutral alpha-glucosidase AB (EC 3.2.1.207) (Alpha-glucosidase 2) (Glucosidase II subunit alpha) | Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:27259053). {ECO:0000269|PubMed:10929008, ECO:0000269|PubMed:27259053}. |
| Q15154 | PCM1 | S861 | Sugiyama | Pericentriolar material 1 protein (PCM-1) (hPCM-1) | Required for centrosome assembly and function (PubMed:12403812, PubMed:15659651, PubMed:16943179). Essential for the correct localization of several centrosomal proteins including CEP250, CETN3, PCNT and NEK2 (PubMed:12403812, PubMed:15659651). Required to anchor microtubules to the centrosome (PubMed:12403812, PubMed:15659651). Also involved in cilium biogenesis by recruiting the BBSome, a ciliary protein complex involved in cilium biogenesis, to the centriolar satellites (PubMed:20551181, PubMed:24121310, PubMed:27979967). Recruits the tubulin polyglutamylase complex (TPGC) to centriolar satellites (PubMed:34782749). {ECO:0000269|PubMed:12403812, ECO:0000269|PubMed:15659651, ECO:0000269|PubMed:16943179, ECO:0000269|PubMed:20551181, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:34782749}. |
| Q9BZK7 | TBL1XR1 | S451 | Sugiyama | F-box-like/WD repeat-containing protein TBL1XR1 (Nuclear receptor corepressor/HDAC3 complex subunit TBLR1) (TBL1-related protein 1) (Transducin beta-like 1X-related protein 1) | F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation. {ECO:0000269|PubMed:14980219}. |
| Q9UBS0 | RPS6KB2 | S370 | SIGNOR|EPSD | Ribosomal protein S6 kinase beta-2 (S6K-beta-2) (S6K2) (EC 2.7.11.1) (70 kDa ribosomal protein S6 kinase 2) (P70S6K2) (p70-S6K 2) (S6 kinase-related kinase) (SRK) (Serine/threonine-protein kinase 14B) (p70 ribosomal S6 kinase beta) (S6K-beta) (p70 S6 kinase beta) (p70 S6K-beta) (p70 S6KB) (p70-beta) | Phosphorylates specifically ribosomal protein S6 (PubMed:29750193). Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7 (PubMed:29750193). {ECO:0000269|PubMed:29750193}. |
| O95456 | PSMG1 | S186 | Sugiyama | Proteasome assembly chaperone 1 (PAC-1) (Chromosome 21 leucine-rich protein) (C21-LRP) (Down syndrome critical region protein 2) (Proteasome chaperone homolog 1) (Pba1) | Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG2. The PSMG1-PSMG2 heterodimer binds to the PSMA5 and PSMA7 proteasome subunits, promotes assembly of the proteasome alpha subunits into the heteroheptameric alpha ring and prevents alpha ring dimerization. {ECO:0000269|PubMed:16251969, ECO:0000269|PubMed:17707236}. |
| Q96JJ7 | TMX3 | Y99 | Sugiyama | Protein disulfide-isomerase TMX3 (EC 5.3.4.1) (Thioredoxin domain-containing protein 10) (Thioredoxin-related transmembrane protein 3) | Probable disulfide isomerase, which participates in the folding of proteins containing disulfide bonds. May act as a dithiol oxidase (PubMed:15623505). Acts as a regulator of endoplasmic reticulum-mitochondria contact sites via its ability to regulate redox signals (PubMed:31304984). {ECO:0000269|PubMed:15623505, ECO:0000269|PubMed:31304984}. |
| P41279 | MAP3K8 | S358 | Sugiyama | Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2) | Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19808894}. |
| P55786 | NPEPPS | S684 | Sugiyama | Puromycin-sensitive aminopeptidase (PSA) (EC 3.4.11.14) (Cytosol alanyl aminopeptidase) (AAP-S) | Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain. {ECO:0000269|PubMed:10978616, ECO:0000269|PubMed:11062501, ECO:0000269|PubMed:17154549, ECO:0000269|PubMed:17318184, ECO:0000269|PubMed:19917696}. |
| P07942 | LAMB1 | S1237 | Sugiyama | Laminin subunit beta-1 (Laminin B1 chain) (Laminin-1 subunit beta) (Laminin-10 subunit beta) (Laminin-12 subunit beta) (Laminin-2 subunit beta) (Laminin-6 subunit beta) (Laminin-8 subunit beta) | 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. Involved in the organization of the laminar architecture of cerebral cortex. It is probably required for the integrity of the basement membrane/glia limitans that serves as an anchor point for the endfeet of radial glial cells and as a physical barrier to migrating neurons. Radial glial cells play a central role in cerebral cortical development, where they act both as the proliferative unit of the cerebral cortex and a scaffold for neurons migrating toward the pial surface. {ECO:0000269|PubMed:23472759}. |
| Q6XUX3 | DSTYK | S337 | 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}. |
| P62714 | PPP2CB | S75 | 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 | S75 | 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}. |
| Q96J92 | WNK4 | S168 | Sugiyama | Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4) | Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:16832045). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16832045, PubMed:22989884). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (By similarity). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (By similarity). Also inhibits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (By similarity). May also phosphorylate NEDD4L (PubMed:20525693). {ECO:0000250|UniProtKB:Q80UE6, ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:22989884}. |
| A0A0B4J203 | None | S244 | ochoa | receptor protein-tyrosine kinase (EC 2.7.10.1) | None |
| A1L170 | C1orf226 | S207 | ochoa | Uncharacterized protein C1orf226 | None |
| B0I1T2 | MYO1G | S851 | ochoa | Unconventional myosin-Ig [Cleaved into: Minor histocompatibility antigen HA-2 (mHag HA-2)] | Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration. Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication. Also required in B-cells, where it regulates different membrane/cytoskeleton-dependent processes. Involved in Fc-gamma receptor (Fc-gamma-R) phagocytosis. {ECO:0000250|UniProtKB:Q5SUA5}.; FUNCTION: [Minor histocompatibility antigen HA-2]: Constitutes the minor histocompatibility antigen HA-2. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and their expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. HA-2 is restricted to MHC class I HLA-A*0201. {ECO:0000269|PubMed:11544309, ECO:0000305}. |
| B2RTY4 | MYO9A | S1240 | ochoa | Unconventional myosin-IXa (Unconventional myosin-9a) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Regulates Rho by stimulating it's GTPase activity in neurons. Required for the regulation of neurite branching and motor neuron axon guidance (By similarity). {ECO:0000250|UniProtKB:Q8C170, ECO:0000250|UniProtKB:Q9Z1N3}. |
| B2RTY4 | MYO9A | S1438 | ochoa | Unconventional myosin-IXa (Unconventional myosin-9a) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Regulates Rho by stimulating it's GTPase activity in neurons. Required for the regulation of neurite branching and motor neuron axon guidance (By similarity). {ECO:0000250|UniProtKB:Q8C170, ECO:0000250|UniProtKB:Q9Z1N3}. |
| H0YHG0 | None | S444 | ochoa | DnaJ homolog subfamily C member 14 (Nuclear protein Hcc-1) (SAP domain-containing ribonucleoprotein) | Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export. {ECO:0000256|ARBA:ARBA00054093}.; FUNCTION: Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface. {ECO:0000256|ARBA:ARBA00055510}. |
| H0YJW9 | None | S64 | ochoa | Uncharacterized protein | None |
| O00257 | CBX4 | S90 | ochoa | E3 SUMO-protein ligase CBX4 (EC 2.3.2.-) (Chromobox protein homolog 4) (Polycomb 2 homolog) (Pc2) (hPc2) | E3 SUMO-protein ligase that catalyzes sumoylation of target proteins by promoting the transfer of SUMO from the E2 enzyme to the substrate (PubMed:12679040, PubMed:22825850). Involved in the sumoylation of HNRNPK, a p53/TP53 transcriptional coactivator, hence indirectly regulates p53/TP53 transcriptional activation resulting in p21/CDKN1A expression. Monosumoylates ZNF131 (PubMed:22825850). {ECO:0000269|PubMed:12679040, ECO:0000269|PubMed:22825850}.; FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:12167701, PubMed:19636380, PubMed:21282530). PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:12167701, PubMed:19636380, PubMed:21282530). Binds to histone H3 trimethylated at 'Lys-9' (H3K9me3) (By similarity). Plays a role in the lineage differentiation of the germ layers in embryonic development (By similarity). {ECO:0000250|UniProtKB:O55187, ECO:0000269|PubMed:12167701, ECO:0000269|PubMed:19636380, ECO:0000269|PubMed:21282530}. |
| O00429 | DNM1L | S44 | psp | Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1) | Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:19411255, PubMed:19638400, PubMed:23283981, PubMed:23530241, PubMed:23921378, PubMed:26992161, PubMed:27145208, PubMed:27145933, PubMed:27301544, PubMed:27328748, PubMed:29478834, PubMed:32439975, PubMed:32484300, PubMed:9570752, PubMed:9786947). Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism (PubMed:23530241, PubMed:23584531, PubMed:33850055). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:23921378, PubMed:29899447). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:29899447). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity). Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:26992161, PubMed:27145208, PubMed:27301544, PubMed:27328748). Facilitates developmentally regulated apoptosis during neural tube formation (By similarity). Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues (By similarity). Required for formation of endocytic vesicles (PubMed:20688057, PubMed:23792689, PubMed:9570752). Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (PubMed:17015472, PubMed:23792689). Required for programmed necrosis execution (PubMed:22265414). Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834). {ECO:0000250|UniProtKB:Q8K1M6, ECO:0000269|PubMed:11514614, ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:17015472, ECO:0000269|PubMed:17301055, ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:17553808, ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19342591, ECO:0000269|PubMed:19411255, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:20688057, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531, ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:29899447, ECO:0000269|PubMed:32439975, ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9786947}.; FUNCTION: [Isoform 1]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}.; FUNCTION: [Isoform 4]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}. |
| O14646 | CHD1 | S1511 | ochoa | Chromodomain-helicase-DNA-binding protein 1 (CHD-1) (EC 3.6.4.-) (ATP-dependent helicase CHD1) | ATP-dependent chromatin-remodeling factor which functions as substrate recognition component of the transcription regulatory histone acetylation (HAT) complex SAGA. Regulates polymerase II transcription. Also required for efficient transcription by RNA polymerase I, and more specifically the polymerase I transcription termination step. Regulates negatively DNA replication. Not only involved in transcription-related chromatin-remodeling, but also required to maintain a specific chromatin configuration across the genome. Is also associated with histone deacetylase (HDAC) activity (By similarity). Required for the bridging of SNF2, the FACT complex, the PAF complex as well as the U2 snRNP complex to H3K4me3. Functions to modulate the efficiency of pre-mRNA splicing in part through physical bridging of spliceosomal components to H3K4me3 (PubMed:18042460, PubMed:28866611). Required for maintaining open chromatin and pluripotency in embryonic stem cells (By similarity). {ECO:0000250|UniProtKB:P40201, ECO:0000269|PubMed:18042460, ECO:0000269|PubMed:28866611}. |
| O15350 | TP73 | S48 | 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}. |
| O15397 | IPO8 | S439 | ochoa | Importin-8 (Imp8) (Ran-binding protein 8) (RanBP8) | Involved in nuclear protein import, either by acting as autonomous nuclear transport receptor or as an adapter-like protein in association with the importin-beta subunit KPNB1. Acting autonomously, may serve as receptor for nuclear localization signals (NLS) and promote translocation of import substrates through the nuclear pore complex (NPC) by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:9214382). In vitro mediates the nuclear import of the signal recognition particle protein SRP19 (PubMed:11682607). May also be involved in cytoplasm-to-nucleus shuttling of a broad spectrum of other cargos, including Argonaute-microRNAs complexes, the JUN protein, RELA/NF-kappa-B p65 subunit, the translation initiation factor EIF4E and a set of receptor-activated mothers against decapentaplegic homolog (SMAD) transcription factors that play a critical role downstream of the large family of transforming growth factor beta and bone morphogenetic protein (BMP) cytokines (Probable). {ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:9214382, ECO:0000305|PubMed:34010604}. |
| O15438 | ABCC3 | S281 | ochoa | ATP-binding cassette sub-family C member 3 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (Canalicular multispecific organic anion transporter 2) (Multi-specific organic anion transporter D) (MOAT-D) (Multidrug resistance-associated protein 3) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes (PubMed:10359813, PubMed:11581266, PubMed:15083066). Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) (PubMed:11581266, PubMed:15083066). Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells (PubMed:10359813, PubMed:11581266). {ECO:0000250|UniProtKB:O88563, ECO:0000269|PubMed:10359813, ECO:0000269|PubMed:11581266, ECO:0000269|PubMed:15083066, ECO:0000305|PubMed:35307651}. |
| O43149 | ZZEF1 | S1971 | ochoa | Zinc finger ZZ-type and EF-hand domain-containing protein 1 | Histone H3 reader which may act as a transcriptional coactivator for KLF6 and KLF9 transcription factors. {ECO:0000269|PubMed:33227311}. |
| O43166 | SIPA1L1 | S1603 | ochoa | Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (High-risk human papilloma viruses E6 oncoproteins targeted protein 1) (E6-targeted protein 1) | Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}. |
| O43353 | RIPK2 | S345 | ochoa | Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. |
| O43488 | AKR7A2 | S121 | ochoa | Aflatoxin B1 aldehyde reductase member 2 (EC 1.1.1.n11) (AFB1 aldehyde reductase 1) (AFB1-AR 1) (Aldoketoreductase 7) (Succinic semialdehyde reductase) (SSA reductase) | Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen. {ECO:0000269|PubMed:17591773, ECO:0000269|PubMed:9576847}. |
| O43524 | FOXO3 | S626 | psp | Forkhead box protein O3 (AF6q21 protein) (Forkhead in rhabdomyosarcoma-like 1) | Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882, PubMed:30513302). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (PubMed:30513302). {ECO:0000250|UniProtKB:Q9WVH4, ECO:0000269|PubMed:10102273, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:30513302}. |
| O60315 | ZEB2 | S741 | ochoa | Zinc finger E-box-binding homeobox 2 (Smad-interacting protein 1) (SMADIP1) (Zinc finger homeobox protein 1b) | Transcriptional inhibitor that binds to DNA sequence 5'-CACCT-3' in different promoters (PubMed:16061479, PubMed:20516212). Represses transcription of E-cadherin (PubMed:16061479). Represses expression of MEOX2 (PubMed:20516212). {ECO:0000269|PubMed:16061479, ECO:0000269|PubMed:20516212}. |
| O60664 | PLIN3 | S187 | 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}. |
| O75665 | OFD1 | S63 | 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}. |
| O75781 | PALM | S64 | ochoa | Paralemmin-1 (Paralemmin) | Involved in plasma membrane dynamics and cell process formation. Isoform 1 and isoform 2 are necessary for axonal and dendritic filopodia induction, for dendritic spine maturation and synapse formation in a palmitoylation-dependent manner. {ECO:0000269|PubMed:14978216}. |
| O94806 | PRKD3 | S44 | ochoa | Serine/threonine-protein kinase D3 (EC 2.7.11.13) (Protein kinase C nu type) (Protein kinase EPK2) (nPKC-nu) | Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress (By similarity). {ECO:0000250}. |
| O95155 | UBE4B | S1256 | ochoa | Ubiquitin conjugation factor E4 B (EC 2.3.2.27) (Homozygously deleted in neuroblastoma 1) (RING-type E3 ubiquitin transferase E4 B) (Ubiquitin fusion degradation protein 2) | Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). {ECO:0000250|UniProtKB:P54860, ECO:0000250|UniProtKB:Q9ES00, ECO:0000269|PubMed:17369820}. |
| P00558 | PGK1 | S175 | ochoa | Phosphoglycerate kinase 1 (EC 2.7.11.1) (EC 2.7.2.3) (Cell migration-inducing gene 10 protein) (Primer recognition protein 2) (PRP 2) | Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). Both L- and D- forms of purine and pyrimidine nucleotides can be used as substrates, but the activity is much lower on pyrimidines (PubMed:18463139). In addition to its role as a glycolytic enzyme, it seems that PGK1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). Acts as a protein kinase when localized to the mitochondrion where it phosphorylates pyruvate dehydrogenase kinase PDK1 to inhibit pyruvate dehydrogenase complex activity and suppress the formation of acetyl-coenzyme A from pyruvate, and consequently inhibit oxidative phosphorylation and promote glycolysis (PubMed:26942675, PubMed:36849569). May play a role in sperm motility (PubMed:26677959). {ECO:0000269|PubMed:18463139, ECO:0000269|PubMed:2324090, ECO:0000269|PubMed:26677959, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:30323285, ECO:0000269|PubMed:36849569, ECO:0000269|PubMed:7391028}. |
| P04004 | VTN | S406 | ochoa | Vitronectin (VN) (S-protein) (Serum-spreading factor) (V75) [Cleaved into: Vitronectin V65 subunit; Vitronectin V10 subunit; Somatomedin-B] | Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway.; FUNCTION: Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity. |
| P04150 | NR3C1 | S164 | ochoa | Glucocorticoid receptor (GR) (Nuclear receptor subfamily 3 group C member 1) | Receptor for glucocorticoids (GC) (PubMed:27120390, PubMed:37478846). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors (PubMed:28139699). Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:28139699, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9590696}.; FUNCTION: [Isoform Alpha]: Has transcriptional activation and repression activity (PubMed:11435610, PubMed:15769988, PubMed:15866175, PubMed:17635946, PubMed:19141540, PubMed:19248771, PubMed:20484466, PubMed:21664385, PubMed:23820903). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15769988, ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:17635946, ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:21664385, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903, ECO:0000269|PubMed:25847991}.; FUNCTION: [Isoform Beta]: Acts as a dominant negative inhibitor of isoform Alpha (PubMed:20484466, PubMed:7769088, PubMed:8621628). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253). {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:26711253, ECO:0000269|PubMed:7769088, ECO:0000269|PubMed:8621628}.; FUNCTION: [Isoform Alpha-2]: Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466).; FUNCTION: [Isoform GR-P]: Increases activity of isoform Alpha. {ECO:0000269|PubMed:11358809}.; FUNCTION: [Isoform Alpha-B]: More effective than isoform Alpha in transcriptional activation, but not repression activity. {ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform 10]: Has transcriptional activation activity. {ECO:0000269|PubMed:20484466}.; FUNCTION: [Isoform Alpha-C1]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-C2]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-C3]: Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903). {ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}.; FUNCTION: [Isoform Alpha-D1]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-D2]: Has transcriptional activation activity. {ECO:0000269|PubMed:15866175}.; FUNCTION: [Isoform Alpha-D3]: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). {ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}. |
| P06239 | LCK | S42 | ochoa|psp | 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 | S588 | 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}. |
| P06576 | ATP5F1B | S316 | ochoa | ATP synthase F(1) complex subunit beta, mitochondrial (EC 7.1.2.2) (ATP synthase F1 subunit beta) | Catalytic subunit beta, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable) (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the subunit alpha (ATP5F1A), forms the catalytic core in the F(1) domain (PubMed:37244256). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:25168243, ECO:0000305|PubMed:36239646, ECO:0000305|PubMed:37244256}. |
| P08195 | SLC3A2 | S531 | psp | Amino acid transporter heavy chain SLC3A2 (4F2 cell-surface antigen heavy chain) (4F2hc) (4F2 heavy chain antigen) (Lymphocyte activation antigen 4F2 large subunit) (Solute carrier family 3 member 2) (CD antigen CD98) | Acts as a chaperone that facilitates biogenesis and trafficking of functional transporters heterodimers to the plasma membrane. Forms heterodimer with SLC7 family transporters (SLC7A5, SLC7A6, SLC7A7, SLC7A8, SLC7A10 and SLC7A11), a group of amino-acid antiporters (PubMed:10574970, PubMed:10903140, PubMed:11557028, PubMed:30867591, PubMed:33298890, PubMed:33758168, PubMed:34880232, PubMed:9751058, PubMed:9829974, PubMed:9878049). Heterodimers function as amino acids exchangers, the specificity of the substrate depending on the SLC7A subunit. Heterodimers SLC3A2/SLC7A6 or SLC3A2/SLC7A7 mediate the uptake of dibasic amino acids (PubMed:10903140, PubMed:9829974). Heterodimer SLC3A2/SLC7A11 functions as an antiporter by mediating the exchange of extracellular anionic L-cystine and intracellular L-glutamate across the cellular plasma membrane (PubMed:34880232). SLC3A2/SLC7A10 translocates small neutral L- and D-amino acids across the plasma membrane (By similarity). SLC3A2/SLC75 or SLC3A2/SLC7A8 translocates neutral amino acids with broad specificity, thyroid hormones and L-DOPA (PubMed:10574970, PubMed:11389679, PubMed:11557028, PubMed:11564694, PubMed:11742812, PubMed:12117417, PubMed:12225859, PubMed:12716892, PubMed:15980244, PubMed:30867591, PubMed:33298890, PubMed:33758168). SLC3A2 is essential for plasma membrane localization, stability, and the transport activity of SLC7A5 and SLC7A8 (PubMed:10391915, PubMed:10574970, PubMed:11311135, PubMed:15769744, PubMed:33066406). When associated with LAPTM4B, the heterodimer SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Modulates integrin-related signaling and is essential for integrin-dependent cell spreading, migration and tumor progression (PubMed:11121428, PubMed:15625115). {ECO:0000250|UniProtKB:P63115, ECO:0000269|PubMed:10391915, ECO:0000269|PubMed:10574970, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11121428, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:11389679, ECO:0000269|PubMed:11557028, ECO:0000269|PubMed:11564694, ECO:0000269|PubMed:11742812, ECO:0000269|PubMed:12117417, ECO:0000269|PubMed:12225859, ECO:0000269|PubMed:12716892, ECO:0000269|PubMed:15625115, ECO:0000269|PubMed:15769744, ECO:0000269|PubMed:15980244, ECO:0000269|PubMed:25998567, ECO:0000269|PubMed:30867591, ECO:0000269|PubMed:33066406, ECO:0000269|PubMed:33298890, ECO:0000269|PubMed:33758168, ECO:0000269|PubMed:34880232, ECO:0000269|PubMed:9751058, ECO:0000269|PubMed:9829974, ECO:0000269|PubMed:9878049}.; FUNCTION: (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis. {ECO:0000269|PubMed:30341327}.; FUNCTION: (Microbial infection) Acts as a receptor for malaria parasite Plasmodium vivax (Thai isolate) in immature red blood cells. {ECO:0000269|PubMed:34294905}. |
| P09874 | PARP1 | S274 | 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 | S65 | ochoa|psp | 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 | S65 | 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}. |
| P10124 | SRGN | S64 | ochoa | Serglycin (Hematopoietic proteoglycan core protein) (Platelet proteoglycan core protein) (P.PG) (Secretory granule proteoglycan core protein) | Plays a role in formation of mast cell secretory granules and mediates storage of various compounds in secretory vesicles. Required for storage of some proteases in both connective tissue and mucosal mast cells and for storage of granzyme B in T-lymphocytes. Plays a role in localizing neutrophil elastase in azurophil granules of neutrophils. Mediates processing of MMP2. Plays a role in cytotoxic cell granule-mediated apoptosis by forming a complex with granzyme B which is delivered to cells by perforin to induce apoptosis. Regulates the secretion of TNF-alpha and may also regulate protease secretion. Inhibits bone mineralization. {ECO:0000269|PubMed:11911826, ECO:0000269|PubMed:16420477, ECO:0000269|PubMed:16870619}. |
| P10275 | AR | S220 | psp | Androgen receptor (Dihydrotestosterone receptor) (Nuclear receptor subfamily 3 group C member 4) | Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. {ECO:0000269|PubMed:14664718, ECO:0000269|PubMed:15563469, ECO:0000269|PubMed:17591767, ECO:0000269|PubMed:17911242, ECO:0000269|PubMed:18084323, ECO:0000269|PubMed:19022849, ECO:0000269|PubMed:19345326, ECO:0000269|PubMed:20812024, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:25091737}.; FUNCTION: [Isoform 3]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}.; FUNCTION: [Isoform 4]: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones. {ECO:0000269|PubMed:19244107}. |
| P10768 | ESD | S210 | ochoa | S-formylglutathione hydrolase (FGH) (EC 3.1.2.12) (Esterase D) (Methylumbelliferyl-acetate deacetylase) (EC 3.1.1.56) | Serine hydrolase involved in the detoxification of formaldehyde. {ECO:0000269|PubMed:3770744, ECO:0000269|PubMed:4768551}. |
| P11413 | G6PD | S184 | ochoa | Glucose-6-phosphate 1-dehydrogenase (G6PD) (EC 1.1.1.49) | Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:35122041, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:743300}. |
| P13569 | CFTR | S422 | ochoa|psp | Cystic fibrosis transmembrane conductance regulator (CFTR) (ATP-binding cassette sub-family C member 7) (Channel conductance-controlling ATPase) (EC 5.6.1.6) (cAMP-dependent chloride channel) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:12727866, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:29393851, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}. |
| P13861 | PRKAR2A | S383 | ochoa | cAMP-dependent protein kinase type II-alpha regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P14923 | JUP | S94 | ochoa | Junction plakoglobin (Catenin gamma) (Desmoplakin III) (Desmoplakin-3) | Common junctional plaque protein. The membrane-associated plaques are architectural elements in an important strategic position to influence the arrangement and function of both the cytoskeleton and the cells within the tissue. The presence of plakoglobin in both the desmosomes and in the intermediate junctions suggests that it plays a central role in the structure and function of submembranous plaques. Acts as a substrate for VE-PTP and is required by it to stimulate VE-cadherin function in endothelial cells. Can replace beta-catenin in E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton (By similarity). {ECO:0000250}. |
| P17661 | DES | Y83 | ochoa | Desmin | Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Required for nuclear membrane integrity, via anchoring at the cell tip and nuclear envelope, resulting in maintenance of microtubule-derived intracellular mechanical forces (By similarity). Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity). {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190, ECO:0000303|PubMed:25358400}. |
| P19634 | SLC9A1 | S648 | ochoa|psp | Sodium/hydrogen exchanger 1 (APNH) (Na(+)/H(+) antiporter, amiloride-sensitive) (Na(+)/H(+) exchanger 1) (NHE-1) (Solute carrier family 9 member 1) | Electroneutral Na(+) /H(+) antiporter that extrudes Na(+) in exchange for external protons driven by the inward sodium ion chemical gradient, protecting cells from acidification that occurs from metabolism (PubMed:11350981, PubMed:11532004, PubMed:14680478, PubMed:15035633, PubMed:15677483, PubMed:17073455, PubMed:17493937, PubMed:22020933, PubMed:27650500, PubMed:32130622, PubMed:7110335, PubMed:7603840). Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry (By similarity). Plays a key role in maintening intracellular pH neutral and cell volume, and thus is important for cell growth, proliferation, migration and survival (PubMed:12947095, PubMed:15096511, PubMed:22020933, PubMed:8901634). In addition, can transport lithium Li(+) and also functions as a Na(+)/Li(+) antiporter (PubMed:7603840). SLC9A1 also functions in membrane anchoring and organization of scaffolding complexes that coordinate signaling inputs (PubMed:15096511). {ECO:0000250|UniProtKB:P26431, ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:11532004, ECO:0000269|PubMed:12947095, ECO:0000269|PubMed:14680478, ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:15096511, ECO:0000269|PubMed:15677483, ECO:0000269|PubMed:17073455, ECO:0000269|PubMed:17493937, ECO:0000269|PubMed:22020933, ECO:0000269|PubMed:27650500, ECO:0000269|PubMed:32130622, ECO:0000269|PubMed:7110335, ECO:0000269|PubMed:7603840, ECO:0000269|PubMed:8901634}. |
| P23396 | RPS3 | S104 | ochoa | 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}. |
| P27448 | MARK3 | S606 | psp | MAP/microtubule affinity-regulating kinase 3 (EC 2.7.11.1) (C-TAK1) (cTAK1) (Cdc25C-associated protein kinase 1) (ELKL motif kinase 2) (EMK-2) (Protein kinase STK10) (Ser/Thr protein kinase PAR-1) (Par-1a) (Serine/threonine-protein kinase p78) | Serine/threonine-protein kinase (PubMed:16822840, PubMed:16980613, PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216' (PubMed:12941695). Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol (PubMed:16822840). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). Phosphorylates PKP2 and KSR1 (PubMed:12941695). {ECO:0000269|PubMed:12941695, ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}. |
| P28290 | ITPRID2 | S99 | ochoa | Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) | None |
| P28370 | SMARCA1 | S119 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 1 (SMARCA1) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin A1) (EC 3.6.4.-) (Global transcription activator SNF2L1) (Nucleosome-remodeling factor subunit SNF2L) (SNF2L) (SNF2 related chromatin remodeling ATPase 1) | [Isoform 1]: ATPase that possesses intrinsic ATP-dependent chromatin-remodeling activity (PubMed:14609955, PubMed:15310751, PubMed:15640247, PubMed:28801535). ATPase activity is substrate-dependent, and is increased when nucleosomes are the substrate, but is also catalytically active when DNA alone is the substrate (PubMed:14609955, PubMed:15310751, PubMed:15640247). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:14609955, PubMed:15310751, PubMed:15640247, PubMed:28801535). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:28801535). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (PubMed:28801535). The BAZ1A-, BAZ1B-, BAZ2A- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Within the NURF-1 and CERF-1 ISWI chromatin remodeling complexes, nucleosomes are the preferred substrate for its ATPase activity (PubMed:14609955, PubMed:15640247). Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development (PubMed:14609955). May promote neurite outgrowth (PubMed:14609955). May be involved in the development of luteal cells (PubMed:16740656). Facilitates nucleosome assembly during DNA replication, ensuring replication fork progression and genomic stability by preventing replication stress and nascent DNA gaps (PubMed:39413208). {ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:15310751, ECO:0000269|PubMed:15640247, ECO:0000269|PubMed:16740656, ECO:0000269|PubMed:28801535, ECO:0000269|PubMed:39413208}.; FUNCTION: [Isoform 2]: Catalytically inactive when either DNA or nucleosomes are the substrate and does not possess chromatin-remodeling activity (PubMed:15310751, PubMed:28801535). Acts as a negative regulator of chromatin remodelers by generating inactive complexes (PubMed:15310751). {ECO:0000269|PubMed:15310751, ECO:0000269|PubMed:28801535}. |
| P28715 | ERCC5 | S1069 | ochoa | DNA excision repair protein ERCC-5 (EC 3.1.-.-) (DNA repair protein complementing XP-G cells) (XPG) (Xeroderma pigmentosum group G-complementing protein) | Single-stranded structure-specific DNA endonuclease involved in DNA excision repair (PubMed:32522879, PubMed:32821917, PubMed:7651464, PubMed:8078765, PubMed:8090225, PubMed:8206890). Makes the 3'incision in DNA nucleotide excision repair (NER) (PubMed:32522879, PubMed:32821917, PubMed:8078765, PubMed:8090225). Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble (PubMed:32522879). Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA (PubMed:9927729). Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:16246722). Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II (PubMed:16246722). Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). Required for DNA replication fork maintenance and preservation of genomic stability (PubMed:26833090, PubMed:32522879). Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site (PubMed:26833090). In TFIIH stimulates the 5'-3' helicase activity of XPD/ERCC2 and the DNA translocase activity of XPB/ERCC3 (PubMed:31253769). During HRR, binds to the replication fork with high specificity and stabilizes it (PubMed:32522879). Also, acts upstream of HRR, to promote the release of BRCA1 from DNA (PubMed:26833090). {ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:31253769, ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:32821917, ECO:0000269|PubMed:7651464, ECO:0000269|PubMed:8078765, ECO:0000269|PubMed:8090225, ECO:0000269|PubMed:8206890, ECO:0000269|PubMed:9927729}. |
| P31949 | S100A11 | S41 | ochoa | Protein S100-A11 (Calgizzarin) (Metastatic lymph node gene 70 protein) (MLN 70) (Protein S100-C) (S100 calcium-binding protein A11) [Cleaved into: Protein S100-A11, N-terminally processed] | Facilitates the differentiation and the cornification of keratinocytes. {ECO:0000269|PubMed:18618420}. |
| P32780 | GTF2H1 | S357 | ochoa | General transcription factor IIH subunit 1 (Basic transcription factor 2 62 kDa subunit) (BTF2 p62) (General transcription factor IIH polypeptide 1) (TFIIH basal transcription factor complex p62 subunit) | Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:9852112}. |
| P32926 | DSG3 | S970 | ochoa | Desmoglein-3 (130 kDa pemphigus vulgaris antigen) (PVA) (Cadherin family member 6) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:31835537). Required for adherens and desmosome junction assembly in response to mechanical force in keratinocytes (PubMed:31835537). Required for desmosome-mediated cell-cell adhesion of cells surrounding the telogen hair club and the basal layer of the outer root sheath epithelium, consequently is essential for the anchoring of telogen hairs in the hair follicle (PubMed:9701552). Required for the maintenance of the epithelial barrier via promoting desmosome-mediated intercellular attachment of suprabasal epithelium to basal cells (By similarity). May play a role in the protein stability of the desmosome plaque components DSP, JUP, PKP1, PKP2 and PKP3 (PubMed:22294297). Required for YAP1 localization at the plasma membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, PKP1 and YWHAG (PubMed:31835537). May also be involved in the positive regulation of YAP1 target gene transcription and as a result cell proliferation (PubMed:31835537). Positively regulates cellular contractility and cell junction formation via organization of cortical F-actin bundles and anchoring of actin to tight junctions, in conjunction with RAC1 (PubMed:22796473). The cytoplasmic pool of DSG3 is required for the localization of CDH1 and CTNNB1 at developing adherens junctions, potentially via modulation of SRC activity (PubMed:22294297). Inhibits keratinocyte migration via suppression of p38MAPK signaling, may therefore play a role in moderating wound healing (PubMed:26763450). {ECO:0000250|UniProtKB:O35902, ECO:0000269|PubMed:22294297, ECO:0000269|PubMed:22796473, ECO:0000269|PubMed:26763450, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9701552}. |
| P37173 | TGFBR2 | S486 | ochoa | TGF-beta receptor type-2 (TGFR-2) (EC 2.7.11.30) (TGF-beta type II receptor) (Transforming growth factor-beta receptor type II) (TGF-beta receptor type II) (TbetaR-II) | Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, 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 thus regulates 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. 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 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. {ECO:0000269|PubMed:7774578}.; FUNCTION: [Isoform 1]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 2]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 3]: Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1. {ECO:0000269|PubMed:34568316}. |
| P41279 | MAP3K8 | S400 | psp | Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2) | Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19808894}. |
| P42166 | TMPO | S354 | ochoa | Lamina-associated polypeptide 2, isoform alpha (Thymopoietin isoform alpha) (TP alpha) (Thymopoietin-related peptide isoform alpha) (TPRP isoform alpha) [Cleaved into: Thymopoietin (TP) (Splenin); Thymopentin (TP5)] | May be involved in the structural organization of the nucleus and in the post-mitotic nuclear assembly. Plays an important role, together with LMNA, in the nuclear anchorage of RB1.; FUNCTION: TP and TP5 may play a role in T-cell development and function. TP5 is an immunomodulating pentapeptide. |
| P42345 | MTOR | S567 | ochoa | Serine/threonine-protein kinase mTOR (EC 2.7.11.1) (FK506-binding protein 12-rapamycin complex-associated protein 1) (FKBP12-rapamycin complex-associated protein) (Mammalian target of rapamycin) (mTOR) (Mechanistic target of rapamycin) (Rapamycin and FKBP12 target 1) (Rapamycin target protein 1) (Tyrosine-protein kinase mTOR) (EC 2.7.10.2) | Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742). MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:30171069, PubMed:29236692, PubMed:37751742). Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B, and the inhibitor of translation initiation PDCD4 (PubMed:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692). Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex (PubMed:23429703, PubMed:23429704). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197). The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670). The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity). As part of the mTORC2 complex, MTOR transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15467718, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:15268862, PubMed:15467718, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:21376236, PubMed:24670654, PubMed:29424687, PubMed:29567957). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). May also regulate insulin signaling by acting as a tyrosine protein kinase that catalyzes phosphorylation of IGF1R and INSR; additional evidence are however required to confirm this result in vivo (PubMed:26584640). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098, ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21376236, ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23426360, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:24403073, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:26584640, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:29424687, ECO:0000269|PubMed:29567957, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:31601708, ECO:0000269|PubMed:31695197, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:34289345, ECO:0000269|PubMed:34519269, ECO:0000269|PubMed:35926713, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:36691768, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37751742}. |
| P42684 | ABL2 | S96 | ochoa | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P43686 | PSMC4 | S21 | ochoa | 26S proteasome regulatory subunit 6B (26S proteasome AAA-ATPase subunit RPT3) (MB67-interacting protein) (MIP224) (Proteasome 26S subunit ATPase 4) (Tat-binding protein 7) (TBP-7) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC4 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798, ECO:0000269|PubMed:8060531}. |
| P48681 | NES | S325 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P49908 | SELENOP | S266 | ochoa | Selenoprotein P (SeP) | Might be responsible for some of the extracellular antioxidant defense properties of selenium or might be involved in the transport of selenium. May supply selenium to tissues such as brain and testis. |
| P49959 | MRE11 | S268 | ochoa | Double-strand break repair protein MRE11 (EC 3.1.-.-) (Meiotic recombination 11 homolog 1) (MRE11 homolog 1) (Meiotic recombination 11 homolog A) (MRE11 homolog A) | Core component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:11741547, PubMed:14657032, PubMed:22078559, PubMed:23080121, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:28867292, PubMed:29670289, PubMed:30464262, PubMed:30612738, PubMed:31353207, PubMed:37696958, PubMed:38128537, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:24316220, PubMed:28867292, PubMed:31353207, PubMed:38128537). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:24316220, PubMed:27889449, PubMed:28867292, PubMed:36050397, PubMed:38128537). Within the MRN complex, MRE11 possesses both single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity (PubMed:11741547, PubMed:22078559, PubMed:24316220, PubMed:26240375, PubMed:27889449, PubMed:29670289, PubMed:31353207, PubMed:36563124, PubMed:9590181, PubMed:9651580, PubMed:9705271). After DSBs, MRE11 is loaded onto DSBs sites and cleaves DNA by cooperating with RBBP8/CtIP to initiate end resection (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 first endonucleolytically cleaves the 5' strand at DNA DSB ends to prevent non-homologous end joining (NHEJ) and licence HR (PubMed:24316220). It then generates a single-stranded DNA gap via 3' to 5' exonucleolytic degradation to create entry sites for EXO1- and DNA2-mediated 5' to 3' long-range resection, which is required for single-strand invasion and recombination (PubMed:24316220, PubMed:28867292). RBBP8/CtIP specifically promotes the endonuclease activity of MRE11 to clear protein-DNA adducts and generate clean double-strand break ends (PubMed:27814491, PubMed:27889449, PubMed:30787182). MRE11 endonuclease activity is also enhanced by AGER/RAGE (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:14657032, PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). The MRN complex is involved in the activation of the cGAS-STING pathway induced by DNA damage during tumorigenesis: the MRN complex acts by displacing CGAS from nucleosome sequestration, thereby activating it (By similarity). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q61216, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:14657032, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:22078559, ECO:0000269|PubMed:23080121, ECO:0000269|PubMed:24316220, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:29670289, ECO:0000269|PubMed:30464262, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30787182, ECO:0000269|PubMed:31353207, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:36050397, ECO:0000269|PubMed:36563124, ECO:0000269|PubMed:37696958, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}.; FUNCTION: MRE11 contains two DNA-binding domains (DBDs), enabling it to bind both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). {ECO:0000305}. |
| P51531 | SMARCA2 | S587 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SAMRCA2) (EC 3.6.4.-) (BRG1-associated factor 190B) (BAF190B) (Probable global transcription activator SNF2L2) (Protein brahma homolog) (hBRM) (SNF2-alpha) | ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically (PubMed:15075294, PubMed:22952240, PubMed:26601204). Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6DIC0, ECO:0000269|PubMed:15075294, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| P51787 | KCNQ1 | S95 | psp | Potassium voltage-gated channel subfamily KQT member 1 (IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1) (KQT-like 1) (Voltage-gated potassium channel subunit Kv7.1) | Pore-forming subunit of the voltage-gated potassium (Kv) channel involved in the regulation of cardiomyocyte excitability and important in normal development and functions of myocardium, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, PubMed:11101505, PubMed:19687231, PubMed:8900283, PubMed:9108097, PubMed:9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, PubMed:11101505, PubMed:25441029, PubMed:8900283, PubMed:9108097, PubMed:9312006). Also promotes a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation, participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, PubMed:11101505, PubMed:8900283, PubMed:9108097, PubMed:9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity). {ECO:0000250|UniProtKB:P97414, ECO:0000250|UniProtKB:Q9Z0N7, ECO:0000269|PubMed:10646604, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11101505, ECO:0000269|PubMed:12324418, ECO:0000269|PubMed:19687231, ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:24855057, ECO:0000269|PubMed:25037568, ECO:0000269|PubMed:8900283, ECO:0000269|PubMed:9108097, ECO:0000269|PubMed:9312006}.; FUNCTION: [Isoform 2]: Non-functional alone but modulatory when coexpressed with the full-length isoform 1. {ECO:0000269|PubMed:9305853}. |
| P51798 | CLCN7 | S632 | 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}. |
| P53350 | PLK1 | S375 | ochoa | Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13) | Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250|UniProtKB:P70032, ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080, ECO:0000269|PubMed:8991084}. |
| P54198 | HIRA | S614 | ochoa | Protein HIRA (TUP1-like enhancer of split protein 1) | Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. {ECO:0000269|PubMed:12370293, ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:15621527}. |
| P54284 | CACNB3 | S138 | ochoa | Voltage-dependent L-type calcium channel subunit beta-3 (CAB3) (Calcium channel voltage-dependent subunit beta 3) | Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:8119293). Increases CACNA1B peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity). Increases CACNA1C peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity). {ECO:0000250|UniProtKB:P54287, ECO:0000250|UniProtKB:Q9MZL3, ECO:0000269|PubMed:8119293}. |
| P55265 | ADAR | S814 | ochoa | Double-stranded RNA-specific adenosine deaminase (DRADA) (EC 3.5.4.37) (136 kDa double-stranded RNA-binding protein) (p136) (Interferon-inducible protein 4) (IFI-4) (K88DSRBP) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}. |
| P61160 | ACTR2 | S307 | ochoa | Actin-related protein 2 (Actin-like protein 2) | ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9000076). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9000076). Seems to contact the pointed end of the daughter actin filament (PubMed:9000076). In podocytes, required for the formation of lamellipodia downstream of AVIL and PLCE1 regulation (PubMed:29058690). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:17220302, PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:17220302, ECO:0000269|PubMed:29058690, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9000076}. |
| P61978 | HNRNPK | S188 | 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}. |
| P78345 | RPP38 | S240 | ochoa | Ribonuclease P protein subunit p38 (RNaseP protein p38) | Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:10444065, PubMed:30454648, PubMed:9037013, PubMed:9630247). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465). {ECO:0000269|PubMed:10444065, ECO:0000269|PubMed:28115465, ECO:0000269|PubMed:30454648, ECO:0000269|PubMed:9037013, ECO:0000269|PubMed:9630247}. |
| P82979 | SARNP | S131 | ochoa | SAP domain-containing ribonucleoprotein (Cytokine-induced protein of 29 kDa) (Nuclear protein Hcc-1) (Proliferation-associated cytokine-inducible protein CIP29) | Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15338056, PubMed:17196963, PubMed:20844015). The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15338056, PubMed:17196963, PubMed:20844015). Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export (PubMed:37578863). {ECO:0000269|PubMed:15338056, ECO:0000269|PubMed:17196963, ECO:0000269|PubMed:20844015, ECO:0000269|PubMed:37578863}. |
| P98161 | PKD1 | S916 | psp | Polycystin-1 (PC1) (Autosomal dominant polycystic kidney disease 1 protein) | Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Both PKD1 and PKD2 are required for channel activity (PubMed:27214281). Involved in renal tubulogenesis (PubMed:12482949). Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). Acts as a regulator of cilium length, together with PKD2 (By similarity). The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling (By similarity). The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity). May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions. Likely to be involved with polycystin-1-interacting protein 1 in the detection, sequestration and exocytosis of senescent mitochondria (PubMed:37681898). {ECO:0000250|UniProtKB:O08852, ECO:0000269|PubMed:12482949, ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:37681898}. |
| Q00610 | CLTC | S1167 | 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}. |
| Q00653 | NFKB2 | S739 | ochoa | Nuclear factor NF-kappa-B p100 subunit (DNA-binding factor KBF2) (H2TF1) (Lymphocyte translocation chromosome 10 protein) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2) (Oncogene Lyt-10) (Lyt10) [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The 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. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. {ECO:0000269|PubMed:7925301}. |
| Q00872 | MYBPC1 | S427 | ochoa | Myosin-binding protein C, slow-type (Slow MyBP-C) (C-protein, skeletal muscle slow isoform) | Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. Slow skeletal protein that binds to both myosin and actin (PubMed:31025394, PubMed:31264822). In vitro, binds to native thin filaments and modifies the activity of actin-activated myosin ATPase. May modulate muscle contraction or may play a more structural role. {ECO:0000269|PubMed:31025394, ECO:0000269|PubMed:31264822}. |
| Q02241 | KIF23 | S303 | ochoa | Kinesin-like protein KIF23 (Kinesin-like protein 5) (Mitotic kinesin-like protein 1) | Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Essential for cytokinesis in Rho-mediated signaling. Required for the localization of ECT2 to the central spindle. Plus-end-directed motor enzyme that moves antiparallel microtubules in vitro. {ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:22522702, ECO:0000269|PubMed:23570799}. |
| Q02388 | COL7A1 | S828 | ochoa | Collagen alpha-1(VII) chain (Long-chain collagen) (LC collagen) | Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen. |
| Q02952 | AKAP12 | S75 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q03001 | DST | S2491 | ochoa | Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) | Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. |
| Q03111 | MLLT1 | S480 | ochoa | Protein ENL (YEATS domain-containing protein 1) | Chromatin reader component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA (PubMed:20159561, PubMed:20471948). Specifically recognizes and binds acetylated and crotonylated histones, with a preference for histones that are crotonylated (PubMed:27105114). Has a slightly higher affinity for binding histone H3 crotonylated at 'Lys-27' (H3K27cr) than 'Lys-20' (H3K9cr20) (PubMed:27105114). {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:27105114}.; FUNCTION: Acts as a key chromatin reader in acute myeloid leukemia by recognizing and binding to acetylated histones via its YEATS domain, thereby regulating oncogenic gene transcription. {ECO:0000269|PubMed:28241139, ECO:0000269|PubMed:28241141}. |
| Q04637 | EIF4G1 | S598 | ochoa | Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}. |
| Q06323 | PSME1 | S38 | ochoa | Proteasome activator complex subunit 1 (11S regulator complex subunit alpha) (REG-alpha) (Activator of multicatalytic protease subunit 1) (Interferon gamma up-regulated I-5111 protein) (IGUP I-5111) (Proteasome activator 28 subunit alpha) (PA28a) (PA28alpha) | Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome. |
| Q07912 | TNK2 | S529 | ochoa | Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Tyrosine kinase non-receptor protein 2) | Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). {ECO:0000269|PubMed:10652228, ECO:0000269|PubMed:11278436, ECO:0000269|PubMed:16247015, ECO:0000269|PubMed:16257963, ECO:0000269|PubMed:16472662, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:18262180, ECO:0000269|PubMed:18435854, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:20110370, ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20383201}. |
| Q08AD1 | CAMSAP2 | S464 | ochoa | Calmodulin-regulated spectrin-associated protein 2 (Calmodulin-regulated spectrin-associated protein 1-like protein 1) | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:23169647, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and autonomously decorates and stabilizes microtubule lattice formed by microtubule minus-end polymerization (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In addition, it also reduces the velocity of microtubule polymerization (PubMed:24486153, PubMed:24706919). Through the microtubule cytoskeleton, also regulates the organization of cellular organelles including the Golgi and the early endosomes (PubMed:27666745). Essential for the tethering, but not for nucleation of non-centrosomal microtubules at the Golgi: together with Golgi-associated proteins AKAP9 and PDE4DIP, required to tether non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745). Also acts as a regulator of neuronal polarity and development: localizes to non-centrosomal microtubule minus-ends in neurons and stabilizes non-centrosomal microtubules, which is required for neuronal polarity, axon specification and dendritic branch formation (PubMed:24908486). Through the microtubule cytoskeleton, regulates the autophagosome transport (PubMed:28726242). {ECO:0000269|PubMed:23169647, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919, ECO:0000269|PubMed:24908486, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28726242}. |
| Q09666 | AHNAK | S67 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12834 | CDC20 | S170 | psp | Cell division cycle protein 20 homolog (p55CDC) | Substrate-specific adapter of the anaphase promoting complex/cyclosome (APC/C) complex that confers substrate specificity by binding to substrates and targeting them to the APC/C complex for ubiquitination and degradation (PubMed:9734353, PubMed:27030811, PubMed:29343641). Recognizes and binds the destruction box (D box) on protein substrates (PubMed:29343641). Involved in the metaphase/anaphase transition of cell cycle (PubMed:32666501). Is regulated by MAD2L1: in metaphase the MAD2L1-CDC20-APC/C ternary complex is inactive and in anaphase the CDC20-APC/C binary complex is active in degrading substrates (PubMed:9811605, PubMed:9637688). The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons (By similarity). CDC20-APC/C-induced degradation of NEUROD2 induces presynaptic differentiation (By similarity). The CDC20-APC/C complex promotes proper dilation formation and radial migration by degrading CCDC41 (By similarity). {ECO:0000250|UniProtKB:Q9JJ66, ECO:0000269|PubMed:27030811, ECO:0000269|PubMed:29343641, ECO:0000269|PubMed:32666501, ECO:0000269|PubMed:9637688, ECO:0000269|PubMed:9734353, ECO:0000269|PubMed:9811605}. |
| Q12888 | TP53BP1 | S831 | ochoa|psp | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12923 | PTPN13 | S214 | ochoa | Tyrosine-protein phosphatase non-receptor type 13 (EC 3.1.3.48) (Fas-associated protein-tyrosine phosphatase 1) (FAP-1) (PTP-BAS) (Protein-tyrosine phosphatase 1E) (PTP-E1) (hPTPE1) (Protein-tyrosine phosphatase PTPL1) | Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}. |
| Q13023 | AKAP6 | S1983 | ochoa | A-kinase anchor protein 6 (AKAP-6) (A-kinase anchor protein 100 kDa) (AKAP 100) (Protein kinase A-anchoring protein 6) (PRKA6) (mAKAP) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum. May act as an adapter for assembling multiprotein complexes. |
| Q13136 | PPFIA1 | S839 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13185 | CBX3 | S133 | ochoa | Chromobox protein homolog 3 (HECH) (Heterochromatin protein 1 homolog gamma) (HP1 gamma) (Modifier 2 protein) | Seems to be involved in transcriptional silencing in heterochromatin-like complexes. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. May contribute to the association of the heterochromatin with the inner nuclear membrane through its interaction with lamin B receptor (LBR). Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins. Contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation, mediates the recruitment of the methyltransferases SUV39H1 and/or SUV39H2 by the PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1. Mediates the recruitment of NIPBL to sites of DNA damage at double-strand breaks (DSBs) (PubMed:28167679). {ECO:0000250|UniProtKB:P23198, ECO:0000269|PubMed:28167679}. |
| Q13393 | PLD1 | S611 | psp | Phospholipase D1 (PLD 1) (hPLD1) (EC 3.1.4.4) (Choline phosphatase 1) (Phosphatidylcholine-hydrolyzing phospholipase D1) | Function as phospholipase selective for phosphatidylcholine (PubMed:25936805, PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). {ECO:0000250|UniProtKB:Q9Z280, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:8530346, ECO:0000269|PubMed:9582313}. |
| Q13416 | ORC2 | S284 | ochoa | Origin recognition complex subunit 2 | 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, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3. {ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22935713}. |
| Q13535 | ATR | S1333 | 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}. |
| Q14149 | MORC3 | S771 | 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}. |
| Q14155 | ARHGEF7 | S25 | ochoa | 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}. |
| Q14156 | EFR3A | S56 | ochoa | Protein EFR3 homolog A (Protein EFR3-like) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:25608530, PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, EFR3A probably acts as the membrane-anchoring component (PubMed:23229899). Also involved in responsiveness to G-protein-coupled receptors; it is however unclear whether this role is direct or indirect (PubMed:25380825). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:25380825, ECO:0000269|PubMed:25608530, ECO:0000305}. |
| Q14687 | GSE1 | S970 | ochoa | Genetic suppressor element 1 | None |
| Q15003 | NCAPH | S256 | ochoa | Condensin complex subunit 2 (Barren homolog protein 1) (Chromosome-associated protein H) (hCAP-H) (Non-SMC condensin I complex subunit H) (XCAP-H homolog) | Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases (PubMed:11136719). Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}. |
| Q15149 | PLEC | S201 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q16563 | SYPL1 | S20 | ochoa | Synaptophysin-like protein 1 (Pantophysin) | None |
| Q16706 | MAN2A1 | S939 | ochoa | Alpha-mannosidase 2 (EC 3.2.1.114) (Golgi alpha-mannosidase II) (AMan II) (Man II) (Mannosidase alpha class 2A member 1) (Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase) | Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway. {ECO:0000250|UniProtKB:P28494}. |
| Q5H9R7 | PPP6R3 | S300 | ochoa | Serine/threonine-protein phosphatase 6 regulatory subunit 3 (SAPS domain family member 3) (Sporulation-induced transcript 4-associated protein SAPL) | Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit. May have an important role in maintaining immune self-tolerance. {ECO:0000269|PubMed:11401438, ECO:0000269|PubMed:16769727}. |
| Q5T7N3 | KANK4 | S163 | ochoa | KN motif and ankyrin repeat domain-containing protein 4 (Ankyrin repeat domain-containing protein 38) | May be involved in the control of cytoskeleton formation by regulating actin polymerization. {ECO:0000269|PubMed:17996375}. |
| Q5UIP0 | RIF1 | S2352 | 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}. |
| Q5VST9 | OBSCN | S7450 | ochoa | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q641Q2 | WASHC2A | S763 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q6PL18 | ATAD2 | S1233 | ochoa | ATPase family AAA domain-containing protein 2 (EC 3.6.1.-) (AAA nuclear coregulator cancer-associated protein) (ANCCA) | May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells. {ECO:0000269|PubMed:17998543}. |
| Q6UN15 | FIP1L1 | S244 | ochoa | Pre-mRNA 3'-end-processing factor FIP1 (hFip1) (FIP1-like 1 protein) (Factor interacting with PAP) (Rearranged in hypereosinophilia) | Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. FIP1L1 contributes to poly(A) site recognition and stimulates poly(A) addition. Binds to U-rich RNA sequence elements surrounding the poly(A) site. May act to tether poly(A) polymerase to the CPSF complex. {ECO:0000269|PubMed:14749727}. |
| Q6WKZ4 | RAB11FIP1 | S280 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6WKZ4 | RAB11FIP1 | S384 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6XZF7 | DNMBP | S440 | 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}. |
| Q6ZRV2 | FAM83H | S1025 | ochoa | Protein FAM83H | May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration (PubMed:23902688). {ECO:0000269|PubMed:18252228, ECO:0000269|PubMed:23902688}. |
| Q7L590 | MCM10 | S26 | ochoa | Protein MCM10 homolog (HsMCM10) | Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. Additionally, plays a role in preventing DNA damage during replication. Key effector of the RBBP6 and ZBTB38-mediated regulation of DNA-replication and common fragile sites stability; acts as a direct target of transcriptional repression by ZBTB38 (PubMed:24726359). {ECO:0000269|PubMed:11095689, ECO:0000269|PubMed:15136575, ECO:0000269|PubMed:17699597, ECO:0000269|PubMed:19608746, ECO:0000269|PubMed:24726359, ECO:0000269|PubMed:32865517}. |
| Q7RTP6 | MICAL3 | S506 | 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}. |
| Q7Z2W4 | ZC3HAV1 | S312 | 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}. |
| Q7Z2Z1 | TICRR | S841 | ochoa | Treslin (TopBP1-interacting checkpoint and replication regulator) (TopBP1-interacting, replication-stimulating protein) | Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}. |
| Q7Z3B3 | KANSL1 | S268 | ochoa | KAT8 regulatory NSL complex subunit 1 (MLL1/MLL complex subunit KANSL1) (MSL1 homolog 1) (hMSL1v1) (NSL complex protein NSL1) (Non-specific lethal 1 homolog) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:22547026, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). In addition to its role in transcription, KANSL1 also plays an essential role in spindle assembly during mitosis (PubMed:26243146). Associates with microtubule ends and contributes to microtubule stability (PubMed:26243146). {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}. |
| Q7Z401 | DENND4A | S1015 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z478 | DHX29 | S75 | ochoa | ATP-dependent RNA helicase DHX29 (EC 3.6.4.13) (DEAH box protein 29) (Nucleic acid helicase DDXx) | ATP-binding RNA helicase involved in translation initiation. Part of the 43S pre-initiation complex that is required for efficient initiation on mRNAs of higher eukaryotes with structured 5'-UTRs by promoting efficient NTPase-dependent 48S complex formation. Specifically binds to the 40S ribosome near the mRNA entrance. Does not possess a processive helicase activity. {ECO:0000255|HAMAP-Rule:MF_03068, ECO:0000269|PubMed:19109895, ECO:0000269|PubMed:23706745}. |
| Q7Z591 | AKNA | S1161 | 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}. |
| Q86UX7 | FERMT3 | S337 | ochoa | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86YP4 | GATAD2A | S114 | ochoa | Transcriptional repressor p66-alpha (Hp66alpha) (GATA zinc finger domain-containing protein 2A) | Transcriptional repressor (PubMed:12183469, PubMed:16415179). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, PubMed:16415179). Efficient repression requires the presence of GATAD2B (PubMed:16415179). {ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:16415179, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| Q86YT6 | MIB1 | S416 | ochoa | E3 ubiquitin-protein ligase MIB1 (EC 2.3.2.27) (DAPK-interacting protein 1) (DIP-1) (Mind bomb homolog 1) (RING-type E3 ubiquitin transferase MIB1) (Zinc finger ZZ type with ankyrin repeat domain protein 2) | E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. {ECO:0000250, ECO:0000269|PubMed:24121310}.; FUNCTION: (Microbial infection) During adenovirus infection, mediates ubiquitination of Core-capsid bridging protein. This allows viral genome delivery into nucleus for infection. {ECO:0000269|PubMed:31851912}. |
| Q8IUQ4 | SIAH1 | S19 | 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}. |
| Q8IXJ6 | SIRT2 | S53 | ochoa | NAD-dependent protein deacetylase sirtuin-2 (EC 2.3.1.286) (NAD-dependent protein defatty-acylase sirtuin-2) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 2) (SIR2-like protein 2) | NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors (PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20543840, PubMed:20587414, PubMed:21081649, PubMed:21726808, PubMed:21949390, PubMed:22014574, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24177535, PubMed:24681946, PubMed:24769394, PubMed:24940000). Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy (PubMed:12620231, PubMed:16648462, PubMed:18249187, PubMed:18332217, PubMed:18995842, PubMed:20543840, PubMed:20587414, PubMed:21081649, PubMed:21726808, PubMed:21949390, PubMed:22014574, PubMed:22771473, PubMed:23468428, PubMed:23908241, PubMed:24177535, PubMed:24681946, PubMed:24769394, PubMed:24940000). Plays a major role in the control of cell cycle progression and genomic stability (PubMed:12697818, PubMed:16909107, PubMed:17488717, PubMed:17726514, PubMed:19282667, PubMed:23468428). Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes (PubMed:12697818, PubMed:16909107, PubMed:17488717, PubMed:17726514, PubMed:19282667, PubMed:23468428). Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis (PubMed:22014574). Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes (PubMed:23468428). Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis (PubMed:23468428). Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by KMT5A leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression (PubMed:23468428). Deacetylates KMT5A modulating KMT5A chromatin localization during the mitotic stress response (PubMed:23468428). Also deacetylates histone H3 at 'Lys-57' (H3K56ac) during the mitotic G2/M transition (PubMed:20587414). Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection (PubMed:23908241). During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function (PubMed:24940000). Deacetylates histone H4 at 'Lys-16' (H4K16ac) at the VEGFA promoter and thereby contributes to regulate expression of VEGFA, a key regulator of angiogenesis (PubMed:24940000). Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells (PubMed:18332217, PubMed:18995842). Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation (PubMed:17488717). Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination (PubMed:21949390). Involved in several cellular metabolic pathways (PubMed:20543840, PubMed:21726808, PubMed:24769394). Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability (PubMed:21726808). Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage (PubMed:24769394). Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis (PubMed:20543840). Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity (PubMed:20543840). Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells (PubMed:20543840). Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagy (PubMed:20543840). Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation (By similarity). Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia (PubMed:24681946). Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation (PubMed:21081649). Inhibits transcriptional activation by deacetylating p53/TP53 and EP300 (PubMed:18249187, PubMed:18995842). Also deacetylates EIF5A (PubMed:22771473). Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions (PubMed:24769394). Plays a role as tumor suppressor (PubMed:22014574). In addition to protein deacetylase activity, also has activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as ARF6 and KRAS, thereby regulating their association with membranes (PubMed:25704306, PubMed:29239724, PubMed:32103017). {ECO:0000250|UniProtKB:Q8VDQ8, ECO:0000269|PubMed:12620231, ECO:0000269|PubMed:12697818, ECO:0000269|PubMed:16648462, ECO:0000269|PubMed:16909107, ECO:0000269|PubMed:17488717, ECO:0000269|PubMed:17574768, ECO:0000269|PubMed:17726514, ECO:0000269|PubMed:18249187, ECO:0000269|PubMed:18332217, ECO:0000269|PubMed:18640115, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:18995842, ECO:0000269|PubMed:19282667, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:20587414, ECO:0000269|PubMed:21081649, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:21949390, ECO:0000269|PubMed:22014574, ECO:0000269|PubMed:22771473, ECO:0000269|PubMed:22819792, ECO:0000269|PubMed:23468428, ECO:0000269|PubMed:23908241, ECO:0000269|PubMed:23932781, ECO:0000269|PubMed:24177535, ECO:0000269|PubMed:24681946, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25704306, ECO:0000269|PubMed:29239724, ECO:0000269|PubMed:32103017}.; FUNCTION: [Isoform 1]: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.; FUNCTION: [Isoform 2]: Deacetylates EP300, alpha-tubulin and histone H3 and H4. {ECO:0000269|PubMed:24177535}.; FUNCTION: [Isoform 5]: Lacks deacetylation activity, at least toward known SIRT2 targets. {ECO:0000269|PubMed:24177535}. |
| Q8IXK0 | PHC2 | S591 | ochoa | Polyhomeotic-like protein 2 (hPH2) (Early development regulatory protein 2) | Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. |
| Q8IZD2 | KMT2E | S861 | psp | Inactive histone-lysine N-methyltransferase 2E (Inactive lysine N-methyltransferase 2E) (Myeloid/lymphoid or mixed-lineage leukemia protein 5) | Associates with chromatin regions downstream of transcriptional start sites of active genes and thus regulates gene transcription (PubMed:23629655, PubMed:23798402, PubMed:24130829). Chromatin interaction is mediated via the binding to tri-methylated histone H3 at 'Lys-4' (H3K4me3) (PubMed:23798402, PubMed:24130829). Key regulator of hematopoiesis involved in terminal myeloid differentiation and in the regulation of hematopoietic stem cell (HSCs) self-renewal by a mechanism that involves DNA methylation (By similarity). Also acts as an important cell cycle regulator, participating in cell cycle regulatory network machinery at multiple cell cycle stages including G1/S transition, S phase progression and mitotic entry (PubMed:14718661, PubMed:18573682, PubMed:19264965, PubMed:23629655). Recruited to E2F1 responsive promoters by HCFC1 where it stimulates tri-methylation of histone H3 at 'Lys-4' and transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). During myoblast differentiation, required to suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells (By similarity). {ECO:0000250|UniProtKB:Q3UG20, ECO:0000269|PubMed:14718661, ECO:0000269|PubMed:18573682, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:23798402, ECO:0000269|PubMed:24130829}.; FUNCTION: [Isoform NKp44L]: Cellular ligand for NCR2/NKp44, may play a role as a danger signal in cytotoxicity and NK-cell-mediated innate immunity. {ECO:0000269|PubMed:23958951}. |
| Q8N456 | LRRC18 | S82 | ochoa | Leucine-rich repeat-containing protein 18 | May be involved in the regulation of spermatogenesis and sperm maturation. {ECO:0000250}. |
| Q8N4S0 | CCDC82 | S81 | ochoa | Coiled-coil domain-containing protein 82 | None |
| Q8N9B5 | JMY | S856 | ochoa | Junction-mediating and -regulatory protein | Acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions (PubMed:30420355). In nucleus, acts as a cofactor that increases p53/TP53 response via its interaction with p300/EP300. Increases p53/TP53-dependent transcription and apoptosis, suggesting an important role in p53/TP53 stress response such as DNA damage. In cytoplasm, acts as a nucleation-promoting factor for both branched and unbranched actin filaments (PubMed:30420355). Activates the Arp2/3 complex to induce branched actin filament networks. Also catalyzes actin polymerization in the absence of Arp2/3, creating unbranched filaments (PubMed:30420355). Contributes to cell motility by controlling actin dynamics. May promote the rapid formation of a branched actin network by first nucleating new mother filaments and then activating Arp2/3 to branch off these filaments. Upon nutrient stress, directly recruited by MAP1LC3B to the phagophore membrane surfaces to promote actin assembly during autophagy (PubMed:30420355). The p53/TP53-cofactor and actin activator activities are regulated via its subcellular location (By similarity). {ECO:0000250|UniProtKB:Q9QXM1, ECO:0000269|PubMed:30420355}. |
| Q8NB49 | ATP11C | S445 | ochoa | Phospholipid-transporting ATPase IG (EC 7.6.2.1) (ATPase IQ) (ATPase class VI type 11C) (P4-ATPase flippase complex alpha subunit ATP11C) | Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane (PubMed:24904167, PubMed:25315773, PubMed:26567335, PubMed:32493773). Major PS-flippase in immune cell subsets. In erythrocyte plasma membrane, it is required to maintain PS in the inner leaflet preventing its exposure on the surface. This asymmetric distribution is critical for the survival of erythrocytes in circulation since externalized PS is a phagocytic signal for erythrocyte clearance by splenic macrophages (PubMed:26944472). Required for B cell differentiation past the pro-B cell stage (By similarity). Seems to mediate PS flipping in pro-B cells (By similarity). May be involved in the transport of cholestatic bile acids (By similarity). {ECO:0000250|UniProtKB:Q9QZW0, ECO:0000269|PubMed:24904167, ECO:0000269|PubMed:25315773, ECO:0000269|PubMed:26944472, ECO:0000269|PubMed:32493773}. |
| Q8NCN4 | RNF169 | S471 | ochoa | E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) | Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}. |
| Q8NE71 | ABCF1 | S621 | ochoa | ATP-binding cassette sub-family F member 1 (ATP-binding cassette 50) (TNF-alpha-stimulated ABC protein) | Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis. {ECO:0000269|PubMed:19570978}. |
| Q8TBE0 | BAHD1 | S121 | ochoa | Bromo adjacent homology domain-containing 1 protein (BAH domain-containing protein 1) | Heterochromatin protein that acts as a transcription repressor and has the ability to promote the formation of large heterochromatic domains. May act by recruiting heterochromatin proteins such as CBX5 (HP1 alpha), HDAC5 and MBD1. Represses IGF2 expression by binding to its CpG-rich P3 promoter and recruiting heterochromatin proteins. At specific stages of Listeria infection, in complex with TRIM28, corepresses interferon-stimulated genes, including IFNL1, IFNL2 and IFNL3. {ECO:0000269|PubMed:19666599, ECO:0000269|PubMed:21252314}. |
| Q8TC90 | CCER1 | S240 | ochoa | Coiled-coil domain-containing glutamate-rich protein 1 | Regulator of histone epigenetic modifications and chromatin compaction into the sperm head, required for histone-to-protamine (HTP) transition. HTP is a key event in which somatic histones are first replaced by testis-specific histone variants, then transition proteins (TNPs) are incorporated into the spermatid nucleus, and finally protamines (PRMs) replace the TNPs to promote chromatin condensation. {ECO:0000250|UniProtKB:Q9CQL2}. |
| Q92502 | STARD8 | S506 | ochoa | StAR-related lipid transfer protein 8 (Deleted in liver cancer 3 protein) (DLC-3) (START domain-containing protein 8) (StARD8) (START-GAP3) | Accelerates GTPase activity of RHOA and CDC42, but not RAC1. Stimulates the hydrolysis of phosphatidylinositol 4,5-bisphosphate by PLCD1. {ECO:0000269|PubMed:17976533}. |
| Q92854 | SEMA4D | S833 | ochoa | Semaphorin-4D (A8) (BB18) (GR3) (CD antigen CD100) | Cell surface receptor for PLXNB1 and PLXNB2 that plays an important role in cell-cell signaling (PubMed:20877282). Regulates GABAergic synapse development (By similarity). Promotes the development of inhibitory synapses in a PLXNB1-dependent manner (By similarity). Modulates the complexity and arborization of developing neurites in hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 mediates activation of RHOA (PubMed:19788569). Promotes the migration of cerebellar granule cells (PubMed:16055703). Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro) (PubMed:8876214). Induces endothelial cell migration through the activation of PTK2B/PYK2, SRC, and the phosphatidylinositol 3-kinase-AKT pathway (PubMed:16055703). {ECO:0000250|UniProtKB:O09126, ECO:0000269|PubMed:16055703, ECO:0000269|PubMed:19788569, ECO:0000269|PubMed:20877282, ECO:0000269|PubMed:8876214}. |
| Q969J3 | BORCS5 | S75 | ochoa | BLOC-1-related complex subunit 5 (Loss of heterozygosity 12 chromosomal region 1) (Myristoylated lysosomal protein) (Myrlysin) | 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. Thereby, it may indirectly play a role in cell spreading and motility. {ECO:0000269|PubMed:25898167}. |
| Q96B97 | SH3KBP1 | S156 | ochoa | SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) | Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}. |
| Q96F63 | CCDC97 | S275 | ochoa | Coiled-coil domain-containing protein 97 | May play a role pre-mRNA splicing through the association with the splicing factor SF3B complex which is involved in branch-site recognition. {ECO:0000269|PubMed:26344197}. |
| Q96GV9 | MACIR | S167 | ochoa | Macrophage immunometabolism regulator | Regulates the macrophage function, by enhancing the resolution of inflammation and wound repair functions mediated by M2 macrophages (PubMed:30659109). The regulation of macrophage function is, due at least in part, to its ability to inhibit glycolysis (PubMed:30659109). May also play a role in trafficking of proteins via its interaction with UNC119 and UNC119B cargo adapters: may help the release of UNC119 and UNC119B cargo or the recycling of UNC119 and UNC119B (PubMed:22085962). May play a role in ciliary membrane localization via its interaction with UNC119B and protein transport into photoreceptor cells (PubMed:22085962). {ECO:0000269|PubMed:22085962, ECO:0000269|PubMed:30659109}. |
| Q96KQ7 | EHMT2 | S211 | ochoa|psp | Histone-lysine N-methyltransferase EHMT2 (EC 2.1.1.-) (EC 2.1.1.367) (Euchromatic histone-lysine N-methyltransferase 2) (HLA-B-associated transcript 8) (Histone H3-K9 methyltransferase 3) (H3-K9-HMTase 3) (Lysine N-methyltransferase 1C) (Protein G9a) | Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000250|UniProtKB:Q9Z148, ECO:0000269|PubMed:11316813, ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:8457211}. |
| Q96NE9 | FRMD6 | S537 | ochoa | FERM domain-containing protein 6 (Willin) | None |
| Q96PV4 | PNMA5 | S128 | ochoa | Paraneoplastic antigen-like protein 5 (Tumor antigen BJ-HCC-25) | None |
| Q96Q07 | BTBD9 | S577 | ochoa | BTB/POZ domain-containing protein 9 | None |
| Q99490 | AGAP2 | S750 | ochoa | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 (AGAP-2) (Centaurin-gamma-1) (Cnt-g1) (GTP-binding and GTPase-activating protein 2) (GGAP2) (Phosphatidylinositol 3-kinase enhancer) (PIKE) | GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion. {ECO:0000269|PubMed:12640130, ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15118108, ECO:0000269|PubMed:16079295}. |
| Q99741 | CDC6 | S45 | ochoa | Cell division control protein 6 homolog (CDC6-related protein) (Cdc18-related protein) (HsCdc18) (p62(cdc6)) (HsCDC6) | Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated. |
| Q99959 | PKP2 | S71 | 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}. |
| Q9BQ70 | TCF25 | S172 | ochoa | Ribosome quality control complex subunit TCF25 (Nuclear localized protein 1) (Transcription factor 25) (TCF-25) | Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation (PubMed:30244831). In the RQC complex, required to promote formation of 'Lys-48'-linked polyubiquitin chains during ubiquitination of incompletely synthesized proteins by LTN1 (PubMed:30244831). May negatively regulate the calcineurin-NFAT signaling cascade by suppressing the activity of transcription factor NFATC4 (By similarity). May play a role in cell death control (By similarity). {ECO:0000250|UniProtKB:A0A8I6ASZ5, ECO:0000250|UniProtKB:Q8R3L2, ECO:0000269|PubMed:30244831}. |
| Q9BVJ6 | UTP14A | S81 | ochoa | U3 small nucleolar RNA-associated protein 14 homolog A (Antigen NY-CO-16) (Serologically defined colon cancer antigen 16) | May be required for ribosome biogenesis. {ECO:0000250}. |
| Q9BWH6 | RPAP1 | S1114 | ochoa | RNA polymerase II-associated protein 1 | Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. Required for interaction of the RNA polymerase II complex with acetylated histone H3. {ECO:0000269|PubMed:17643375}. |
| Q9BY89 | KIAA1671 | S1111 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYI3 | HYCC1 | S415 | ochoa | Hyccin (Down-regulated by CTNNB1 protein A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (PubMed:26571211). HYCC1 plays a key role in oligodendrocytes formation, a cell type with expanded plasma membrane that requires generation of PtdIns(4)P (PubMed:26571211). Its role in oligodendrocytes formation probably explains its importance in myelination of the central and peripheral nervous system (PubMed:16951682, PubMed:26571211). May also have a role in the beta-catenin/Lef signaling pathway (Probable). {ECO:0000269|PubMed:16951682, ECO:0000269|PubMed:26571211, ECO:0000305|PubMed:10910037}. |
| Q9C0C2 | TNKS1BP1 | S1637 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9GZX7 | AICDA | S43 | psp | Single-stranded DNA cytosine deaminase (EC 3.5.4.38) (Activation-induced cytidine deaminase) (AID) (Cytidine aminohydrolase) | Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses (PubMed:18722174, PubMed:21385873, PubMed:21518874, PubMed:27716525). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (PubMed:21496894). {ECO:0000269|PubMed:18722174, ECO:0000269|PubMed:21385873, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21518874, ECO:0000269|PubMed:27716525}. |
| Q9H0A0 | NAT10 | S675 | 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}. |
| Q9HAN9 | NMNAT1 | S135 | ochoa | Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMN/NaMN adenylyltransferase 1) (EC 2.7.7.1) (EC 2.7.7.18) (Nicotinamide-nucleotide adenylyltransferase 1) (NMN adenylyltransferase 1) (Nicotinate-nucleotide adenylyltransferase 1) (NaMN adenylyltransferase 1) | Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (PubMed:17402747). Can use triazofurin monophosphate (TrMP) as substrate (PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (PubMed:17402747). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively (PubMed:17402747). Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Also acts as a cofactor for glutamate and aspartate ADP-ribosylation by directing PARP1 catalytic activity to glutamate and aspartate residues on histones (By similarity). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (PubMed:17402747). Protects against axonal degeneration following mechanical or toxic insults (By similarity). Neural protection does not correlate with cellular NAD(+) levels but may still require enzyme activity (By similarity). {ECO:0000250|UniProtKB:Q9EPA7, ECO:0000269|PubMed:17402747, ECO:0000269|PubMed:27257257}. |
| Q9HAW4 | CLSPN | S823 | ochoa | 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}. |
| Q9HC52 | CBX8 | S352 | ochoa | Chromobox protein homolog 8 (Polycomb 3 homolog) (Pc3) (hPc3) (Rectachrome 1) | Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. {ECO:0000269|PubMed:21282530}. |
| Q9HCH5 | SYTL2 | S493 | ochoa | Synaptotagmin-like protein 2 (Breast cancer-associated antigen SGA-72M) (Exophilin-4) | Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive. {ECO:0000269|PubMed:17182843, ECO:0000269|PubMed:18266782, ECO:0000269|PubMed:18812475}. |
| Q9HDC5 | JPH1 | S157 | ochoa | Junctophilin-1 (JP-1) (Junctophilin type 1) | Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes. |
| Q9NQT8 | KIF13B | S1382 | ochoa | Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) | Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes. {ECO:0000269|PubMed:20194617}. |
| Q9NRM7 | LATS2 | S835 | psp | Serine/threonine-protein kinase LATS2 (EC 2.7.11.1) (Kinase phosphorylated during mitosis protein) (Large tumor suppressor homolog 2) (Serine/threonine-protein kinase kpm) (Warts-like kinase) | Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:18158288, PubMed:26437443, PubMed:26598551, PubMed:34404733). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:26437443, PubMed:26598551, PubMed:34404733). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:26598551, PubMed:34404733). Also phosphorylates YAP1 in response to cell contact inhibition-driven WWP1 ubiquitination of AMOTL2, which results in LATS2 activation (PubMed:34404733). Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability (PubMed:10871863). Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity (PubMed:12853976). Negative regulator of the androgen receptor (PubMed:15131260). Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities (PubMed:21952048). This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ (PubMed:21952048). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10871863, ECO:0000269|PubMed:12853976, ECO:0000269|PubMed:15131260, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:39173637}. |
| Q9NSY1 | BMP2K | S1089 | ochoa | BMP-2-inducible protein kinase (BIKe) (EC 2.7.11.1) | May be involved in osteoblast differentiation. {ECO:0000250|UniProtKB:Q91Z96}. |
| Q9NYV4 | CDK12 | S1191 | ochoa | Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) | Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| Q9NZB2 | FAM120A | S1075 | ochoa | Constitutive coactivator of PPAR-gamma-like protein 1 (Oxidative stress-associated SRC activator) (Protein FAM120A) | Component of the oxidative stress-induced survival signaling. May regulate the activation of SRC family protein kinases (PubMed:19015244). May act as a scaffolding protein enabling SRC family protein kinases to phosphorylate and activate PI3-kinase (PubMed:19015244). Binds IGF2 RNA and promotes the production of IGF2 protein (PubMed:19015244). {ECO:0000269|PubMed:19015244}. |
| Q9P0V3 | SH3BP4 | S122 | ochoa | SH3 domain-binding protein 4 (EH-binding protein 10) (Transferrin receptor-trafficking protein) | May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy. {ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:22575674}. |
| Q9P2J2 | IGSF9 | S800 | ochoa | Protein turtle homolog A (Immunoglobulin superfamily member 9A) (IgSF9A) | Functions in dendrite outgrowth and synapse maturation. {ECO:0000250}. |
| Q9UEE9 | CFDP1 | S222 | ochoa | Craniofacial development protein 1 (Bucentaur) | May play a role during embryogenesis. {ECO:0000250}. |
| Q9UGP4 | LIMD1 | S256 | 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}. |
| Q9UI08 | EVL | S369 | ochoa | Ena/VASP-like protein (Ena/vasodilator-stimulated phosphoprotein-like) | Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. EVL enhances actin nucleation and polymerization. |
| Q9UL54 | TAOK2 | S656 | ochoa | Serine/threonine-protein kinase TAO2 (EC 2.7.11.1) (Kinase from chicken homolog C) (hKFC-C) (Prostate-derived sterile 20-like kinase 1) (PSK-1) (PSK1) (Prostate-derived STE20-like kinase 1) (Thousand and one amino acid protein kinase 2) | Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17396146}. |
| Q9UPM8 | AP4E1 | S676 | ochoa | AP-4 complex subunit epsilon-1 (AP-4 adaptor complex subunit epsilon) (Adaptor-related protein complex 4 subunit epsilon-1) (Epsilon subunit of AP-4) (Epsilon-adaptin) | Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}. |
| Q9UPN9 | TRIM33 | S812 | ochoa | E3 ubiquitin-protein ligase TRIM33 (EC 2.3.2.27) (Ectodermin homolog) (RET-fused gene 7 protein) (Protein Rfg7) (RING-type E3 ubiquitin transferase TRIM33) (Transcription intermediary factor 1-gamma) (TIF1-gamma) (Tripartite motif-containing protein 33) | Acts as an E3 ubiquitin-protein ligase. Promotes SMAD4 ubiquitination, nuclear exclusion and degradation via the ubiquitin proteasome pathway. According to PubMed:16751102, does not promote a decrease in the level of endogenous SMAD4. May act as a transcriptional repressor. Inhibits the transcriptional response to TGF-beta/BMP signaling cascade. Plays a role in the control of cell proliferation. Its association with SMAD2 and SMAD3 stimulates erythroid differentiation of hematopoietic stem/progenitor (By similarity). Monoubiquitinates SMAD4 and acts as an inhibitor of SMAD4-dependent TGF-beta/BMP signaling cascade (Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade). {ECO:0000250, ECO:0000269|PubMed:10022127, ECO:0000269|PubMed:15820681, ECO:0000269|PubMed:16751102, ECO:0000269|PubMed:19135894}. |
| Q9UPT6 | MAPK8IP3 | S207 | ochoa | C-Jun-amino-terminal kinase-interacting protein 3 (JIP-3) (JNK-interacting protein 3) (JNK MAP kinase scaffold protein 3) (Mitogen-activated protein kinase 8-interacting protein 3) | 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:12189133). May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (By similarity). Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:21775604). {ECO:0000250|UniProtKB:Q9ESN9, ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:21775604}. |
| Q9UPW0 | FOXJ3 | S489 | 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}. |
| Q9Y3E2 | BOLA1 | S74 | ochoa | BolA-like protein 1 (hBolA) | Acts as a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates (Fe-S) cluster insertion into a subset of mitochondrial proteins (By similarity). Probably acts together with the monothiol glutaredoxin GLRX5 (PubMed:27532772). May protect cells against oxidative stress (PubMed:22746225). {ECO:0000250|UniProtKB:Q3E793, ECO:0000269|PubMed:22746225, ECO:0000305|PubMed:27532772}. |
| Q9Y3Z3 | SAMHD1 | S278 | ochoa | Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (dNTPase) (EC 3.1.5.-) (Dendritic cell-derived IFNG-induced protein) (DCIP) (Monocyte protein 5) (MOP-5) (SAM domain and HD domain-containing protein 1) (hSAMHD1) | Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507, PubMed:28834754, PubMed:29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23364794, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:25038827, PubMed:26101257, PubMed:26294762, PubMed:26431200, PubMed:28229507). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:24217394, PubMed:29610582). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:21613998, PubMed:21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed:23601106, PubMed:23602554, PubMed:29610582, PubMed:29670289). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed:29670289). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed:27477283, PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity). {ECO:0000250|UniProtKB:Q60710, ECO:0000269|PubMed:19525956, ECO:0000269|PubMed:21613998, ECO:0000269|PubMed:21720370, ECO:0000269|PubMed:22056990, ECO:0000269|PubMed:23364794, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:23858451, ECO:0000269|PubMed:24035396, ECO:0000269|PubMed:24217394, ECO:0000269|PubMed:24336198, ECO:0000269|PubMed:25038827, ECO:0000269|PubMed:26101257, ECO:0000269|PubMed:26294762, ECO:0000269|PubMed:26431200, ECO:0000269|PubMed:27477283, ECO:0000269|PubMed:28229507, ECO:0000269|PubMed:28834754, ECO:0000269|PubMed:29610582, ECO:0000269|PubMed:29670289}. |
| Q9Y487 | ATP6V0A2 | S154 | ochoa | V-type proton ATPase 116 kDa subunit a 2 (V-ATPase 116 kDa subunit a 2) (Lysosomal H(+)-transporting ATPase V0 subunit a 2) (TJ6) (Vacuolar proton translocating ATPase 116 kDa subunit a isoform 2) | Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Essential component of the endosomal pH-sensing machinery (PubMed:16415858). May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH (PubMed:18157129). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). {ECO:0000250|UniProtKB:Q29466, ECO:0000250|UniProtKB:Q93050, ECO:0000269|PubMed:16415858, ECO:0000269|PubMed:18157129, ECO:0000269|PubMed:28296633}. |
| Q9Y4F5 | CEP170B | S1569 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y616 | IRAK3 | S332 | ochoa | Interleukin-1 receptor-associated kinase 3 (IRAK-3) (IL-1 receptor-associated kinase M) (IRAK-M) (Inactive IL-1 receptor-associated kinase 3) | Putative inactive protein kinase which regulates signaling downstream of immune receptors including IL1R and Toll-like receptors (PubMed:10383454, PubMed:29686383). Inhibits dissociation of IRAK1 and IRAK4 from the Toll-like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex (By similarity). Upon IL33-induced lung inflammation, positively regulates expression of IL6, CSF3, CXCL2 and CCL5 mRNAs in dendritic cells (PubMed:29686383). {ECO:0000250|UniProtKB:Q8K4B2, ECO:0000269|PubMed:10383454, ECO:0000269|PubMed:29686383}. |
| Q9Y6B6 | SAR1B | S162 | ochoa | Small COPII coat GTPase SAR1B (EC 3.6.5.2) (GTP-binding protein B) (GTBPB) (Secretion-associated Ras-related GTPase 1B) | Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport. The active GTP-bound form inserts into the endoplasmic reticulum membrane where it recruits the remainder of the coat protein complex II/COPII (PubMed:23433038, PubMed:32358066, PubMed:33186557, PubMed:36369712). The coat protein complex II assembling and polymerizing on endoplasmic reticulum membrane is responsible for both the sorting of cargos and the deformation and budding of membranes into vesicles destined to the Golgi (PubMed:23433038, PubMed:32358066, PubMed:33186557). In contrast to SAR1A, SAR1B specifically interacts with the cargo receptor SURF4 to mediate the transport of lipid-carrying lipoproteins including APOB and APOA1 from the endoplasmic reticulum to the Golgi and thereby, indirectly regulates lipid homeostasis (PubMed:32358066, PubMed:33186557). In addition to its role in vesicle trafficking, can also function as a leucine sensor regulating TORC1 signaling and more indirectly cellular metabolism, growth and survival. In absence of leucine, interacts with the GATOR2 complex via MIOS and inhibits TORC1 signaling. The binding of leucine abrogates the interaction with GATOR2 and the inhibition of the TORC1 signaling. This function is completely independent of the GTPase activity of SAR1B (PubMed:34290409). {ECO:0000269|PubMed:23433038, ECO:0000269|PubMed:32358066, ECO:0000269|PubMed:33186557, ECO:0000269|PubMed:34290409, ECO:0000269|PubMed:36369712}. |
| R4GMW8 | BIVM-ERCC5 | S1523 | ochoa | DNA excision repair protein ERCC-5 | None |
| P27986 | PIK3R1 | S155 | Sugiyama | 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}. |
| Q16658 | FSCN1 | S234 | Sugiyama | Fascin (55 kDa actin-bundling protein) (Singed-like protein) (p55) | Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (PubMed:22155786). {ECO:0000269|PubMed:20137952, ECO:0000269|PubMed:20393565, ECO:0000269|PubMed:21685497, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:23184945, ECO:0000269|PubMed:9362073, ECO:0000269|PubMed:9571235}. |
| P30304 | CDC25A | S239 | iPTMNet | M-phase inducer phosphatase 1 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25A) | Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression (PubMed:12676925, PubMed:14559997, PubMed:1836978, PubMed:20360007). Directly dephosphorylates CDK1 and stimulates its kinase activity (PubMed:20360007). Also dephosphorylates CDK2 in complex with cyclin-E, in vitro (PubMed:20360007). {ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:1836978, ECO:0000269|PubMed:20360007}. |
| P61163 | ACTR1A | S331 | Sugiyama | Alpha-centractin (Centractin) (ARP1) (Actin-RPV) (Centrosome-associated actin homolog) | Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules. {ECO:0000250|UniProtKB:F2Z5G5}. |
| Q7KZF4 | SND1 | S474 | Sugiyama | Staphylococcal nuclease domain-containing protein 1 (EC 3.1.31.1) (100 kDa coactivator) (EBNA2 coactivator p100) (Tudor domain-containing protein 11) (p100 co-activator) | Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (PubMed:18453631, PubMed:28546213). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition (PubMed:28546213). Functions as a bridging factor between STAT6 and the basal transcription factor (PubMed:12234934). Plays a role in PIM1 regulation of MYB activity (PubMed:9809063). Functions as a transcriptional coactivator for STAT5 (By similarity). {ECO:0000250|UniProtKB:Q78PY7, ECO:0000269|PubMed:12234934, ECO:0000269|PubMed:18453631, ECO:0000269|PubMed:28546213, ECO:0000269|PubMed:9809063}.; FUNCTION: (Microbial infection) Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2). {ECO:0000269|PubMed:7651391}.; FUNCTION: (Microbial infection) Promotes SARS-CoV-2 RNA synthesis by binding to negative-sense RNA and the viral protein nsp9. {ECO:0000269|PubMed:37794589}. |
| O15264 | MAPK13 | S278 | Sugiyama | Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}. |
| Q6UVK1 | CSPG4 | S321 | Sugiyama | Chondroitin sulfate proteoglycan 4 (Chondroitin sulfate proteoglycan NG2) (Melanoma chondroitin sulfate proteoglycan) (Melanoma-associated chondroitin sulfate proteoglycan) | Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis. May also inhibit neurite outgrowth and growth cone collapse during axon regeneration. Cell surface receptor for collagen alpha 2(VI) which may confer cells ability to migrate on that substrate. Binds through its extracellular N-terminus growth factors, extracellular matrix proteases modulating their activity. May regulate MPP16-dependent degradation and invasion of type I collagen participating in melanoma cells invasion properties. May modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. Also functions as a signal transducing protein by binding through its cytoplasmic C-terminus scaffolding and signaling proteins. May promote retraction fiber formation and cell polarization through Rho GTPase activation. May stimulate alpha-4, beta-1 integrin-mediated adhesion and spreading by recruiting and activating a signaling cascade through CDC42, ACK1 and BCAR1. May activate FAK and ERK1/ERK2 signaling cascades. {ECO:0000269|PubMed:10587647, ECO:0000269|PubMed:11278606, ECO:0000269|PubMed:15210734}. |
| P02786 | TFRC | S159 | Sugiyama | Transferrin receptor protein 1 (TR) (TfR) (TfR1) (Trfr) (T9) (p90) (CD antigen CD71) [Cleaved into: Transferrin receptor protein 1, serum form (sTfR)] | Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity). {ECO:0000250|UniProtKB:Q62351, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus. {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.; FUNCTION: (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762, ECO:0000269|PubMed:36779763}.; FUNCTION: (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762}. |
| P08034 | GJB1 | S233 | ELM | Gap junction beta-1 protein (Connexin-32) (Cx32) (GAP junction 28 kDa liver protein) | One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. |
| P62888 | RPL30 | S75 | Sugiyama | Large ribosomal subunit protein eL30 (60S ribosomal protein L30) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| Q86VB7 | CD163 | S1084 | SIGNOR|EPSD | Scavenger receptor cysteine-rich type 1 protein M130 (Hemoglobin scavenger receptor) (CD antigen CD163) [Cleaved into: Soluble CD163 (sCD163)] | Acute phase-regulated receptor involved in clearance and endocytosis of hemoglobin/haptoglobin complexes by macrophages and may thereby protect tissues from free hemoglobin-mediated oxidative damage. May play a role in the uptake and recycling of iron, via endocytosis of hemoglobin/haptoglobin and subsequent breakdown of heme. Binds hemoglobin/haptoglobin complexes in a calcium-dependent and pH-dependent manner. Exhibits a higher affinity for complexes of hemoglobin and multimeric haptoglobin of HP*1F phenotype than for complexes of hemoglobin and dimeric haptoglobin of HP*1S phenotype. Induces a cascade of intracellular signals that involves tyrosine kinase-dependent calcium mobilization, inositol triphosphate production and secretion of IL6 and CSF1. Isoform 3 exhibits the higher capacity for ligand endocytosis and the more pronounced surface expression when expressed in cells.; FUNCTION: After shedding, the soluble form (sCD163) may play an anti-inflammatory role, and may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions. |
| P52732 | KIF11 | Y932 | Sugiyama | Kinesin-like protein KIF11 (Kinesin-like protein 1) (Kinesin-like spindle protein HKSP) (Kinesin-related motor protein Eg5) (Thyroid receptor-interacting protein 5) (TR-interacting protein 5) (TRIP-5) | Motor protein required for establishing a bipolar spindle and thus contributing to chromosome congression during mitosis (PubMed:19001501, PubMed:37728657). Required in non-mitotic cells for transport of secretory proteins from the Golgi complex to the cell surface (PubMed:23857769). {ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:23857769}. |
| P22612 | PRKACG | S41 | Sugiyama | cAMP-dependent protein kinase catalytic subunit gamma (PKA C-gamma) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus. |
| Q15785 | TOMM34 | S219 | Sugiyama | 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}. |
| P31327 | CPS1 | S1093 | Sugiyama | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| P57059 | SIK1 | S644 | Sugiyama | Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}. |
| Q05513 | PRKCZ | S148 | Sugiyama | 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}. |
| Q15569 | TESK1 | S79 | Sugiyama | Dual specificity testis-specific protein kinase 1 (EC 2.7.12.1) (Testicular protein kinase 1) | Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues (By similarity). Regulates the cellular cytoskeleton by enhancing actin stress fiber formation via phosphorylation of cofilin and by preventing microtubule breakdown via inhibition of TAOK1/MARKK kinase activity (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Positively regulates integrin-mediated cell spreading, via phosphorylation of cofilin (PubMed:15584898). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of ciliary vesicle directional trafficking to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity). {ECO:0000250|UniProtKB:O70146, ECO:0000250|UniProtKB:Q63572, ECO:0000269|PubMed:15584898, ECO:0000269|PubMed:25849865}. |
| Q8TD08 | MAPK15 | S259 | Sugiyama | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| P05362 | ICAM1 | S51 | Sugiyama | Intercellular adhesion molecule 1 (ICAM-1) (Major group rhinovirus receptor) (CD antigen CD54) | ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation. {ECO:0000269|PubMed:11173916, ECO:0000269|PubMed:17875742}.; FUNCTION: (Microbial infection) Acts as a receptor for major receptor group rhinovirus A-B capsid proteins. {ECO:0000269|PubMed:1968231, ECO:0000269|PubMed:2538243}.; FUNCTION: (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins. {ECO:0000269|PubMed:11160747, ECO:0000269|PubMed:16004874, ECO:0000269|PubMed:9539703}.; FUNCTION: (Microbial infection) Upon Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, is degraded by viral E3 ubiquitin ligase MIR2, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell. {ECO:0000269|PubMed:11413168}. |
| Q96S53 | TESK2 | S80 | Sugiyama | Dual specificity testis-specific protein kinase 2 (EC 2.7.12.1) (Testicular protein kinase 2) | Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues. Phosphorylates cofilin at 'Ser-3'. May play an important role in spermatogenesis. |
| Q92878 | RAD50 | S623 | Sugiyama | DNA repair protein RAD50 (hRAD50) (EC 3.6.-.-) | Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28134932, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex is involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), an error-free mechanism which primarily occurs during S and G2 phases (PubMed:15064416, PubMed:21757780, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The complex (1) mediates the end resection of damaged DNA, which generates proper single-stranded DNA, a key initial steps in HR, and is (2) required for the recruitment of other repair factors and efficient activation of ATM and ATR upon DNA damage (PubMed:15064416, PubMed:27889449, PubMed:28867292, PubMed:9590181, PubMed:9651580, PubMed:9705271). The MRN complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11, to initiate end resection, which is required for single-strand invasion and recombination (PubMed:11741547, PubMed:9590181, PubMed:9651580, PubMed:9705271). Within the complex, RAD50 is both required to bind DNA ends and hold them in close proximity and regulate the activity of MRE11 (PubMed:11741547, PubMed:12805565, PubMed:28134932). RAD50 provides an ATP-dependent control of MRE11 by positioning DNA ends into the MRE11 active site: ATP-binding induces a large structural change from an open form with accessible MRE11 nuclease sites into a closed form (By similarity). The MRN complex is also required for DNA damage signaling via activation of the ATM and ATR kinases: the nuclease activity of MRE11 is not required to activate ATM and ATR (PubMed:15064416, PubMed:15790808, PubMed:16622404). The MRN complex is also required for the processing of R-loops (PubMed:31537797). In telomeres the MRN complex may modulate t-loop formation (PubMed:10888888). {ECO:0000250|UniProtKB:Q9X1X1, ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:11741547, ECO:0000269|PubMed:12805565, ECO:0000269|PubMed:15064416, ECO:0000269|PubMed:15790808, ECO:0000269|PubMed:16622404, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:27889449, ECO:0000269|PubMed:28134932, ECO:0000269|PubMed:28867292, ECO:0000269|PubMed:31537797, ECO:0000269|PubMed:9590181, ECO:0000269|PubMed:9651580, ECO:0000269|PubMed:9705271}. |
| Q92900 | UPF1 | S274 | Sugiyama | Regulator of nonsense transcripts 1 (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent helicase RENT1) (Nonsense mRNA reducing factor 1) (NORF1) (Up-frameshift suppressor 1 homolog) (hUpf1) | RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs (PubMed:11163187, PubMed:16086026, PubMed:18172165, PubMed:21145460, PubMed:21419344, PubMed:24726324). Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD (PubMed:11544179, PubMed:25220460). Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD (PubMed:21419344). Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors (PubMed:12554878). UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (PubMed:18447585). Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (PubMed:16086026, PubMed:18172165). For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585, PubMed:25220460). The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (PubMed:21145460). Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (By similarity). Also capable of unwinding double-stranded DNA and translocating on single-stranded DNA (PubMed:30218034). {ECO:0000250|UniProtKB:Q9EPU0, ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:12554878, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:18447585, ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:21145460, ECO:0000269|PubMed:21419344, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:25220460, ECO:0000269|PubMed:30218034}. |
| Q9HBH9 | MKNK2 | S338 | Sugiyama | MAP kinase-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (MAP kinase signal-integrating kinase 2) (MAPK signal-integrating kinase 2) (Mnk2) | Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}. |
| Q14524 | SCN5A | S61 | 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}. |
| A0A0B4J1R7 | BORCS7-ASMT | S43 | ochoa | BLOC-1-related complex subunit 7 | None |
| A0A0J9YX86 | GOLGA8Q | S90 | ochoa | Golgin A8 family member Q | None |
| A0FGR8 | ESYT2 | S513 | ochoa | Extended synaptotagmin-2 (E-Syt2) (Chr2Syt) | Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}. |
| A0JNW5 | BLTP3B | S774 | ochoa | Bridge-like lipid transfer protein family member 3B (Syntaxin-6 Habc-interacting protein of 164 kDa) (UHRF1-binding protein 1-like) | Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:20163565, PubMed:35499567). {ECO:0000269|PubMed:20163565, ECO:0000269|PubMed:35499567}. |
| A1X283 | SH3PXD2B | S675 | ochoa | 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}. |
| A5PLL1 | ANKRD34B | S405 | ochoa | Ankyrin repeat domain-containing protein 34B | None |
| A6ND36 | FAM83G | S127 | ochoa | Protein FAM83G (Protein associated with SMAD1) | Substrate for type I BMP receptor kinase involved in regulation of some target genes of the BMP signaling pathway. Also regulates the expression of several non-BMP target genes, suggesting a role in other signaling pathways. {ECO:0000269|PubMed:24554596}. |
| A6NF01 | POM121B | S114 | ochoa | Putative nuclear envelope pore membrane protein POM 121B | Putative component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane (By similarity). {ECO:0000250}. |
| A6NMD2 | GOLGA8J | S260 | ochoa | Golgin subfamily A member 8J | None |
| A6NMY6 | ANXA2P2 | S89 | ochoa | Putative annexin A2-like protein (Annexin A2 pseudogene 2) (Lipocortin II pseudogene) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. {ECO:0000250}. |
| A6NMY6 | ANXA2P2 | S164 | ochoa | Putative annexin A2-like protein (Annexin A2 pseudogene 2) (Lipocortin II pseudogene) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. {ECO:0000250}. |
| A8CG34 | POM121C | S507 | ochoa | Nuclear envelope pore membrane protein POM 121C (Nuclear pore membrane protein 121-2) (POM121-2) (Pore membrane protein of 121 kDa C) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| A8TX70 | COL6A5 | S859 | 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}. |
| A8TX70 | COL6A5 | S2255 | 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}. |
| H0YC42 | None | S159 | ochoa | Tumor protein D52 | None |
| H3BQL2 | GOLGA8T | S260 | ochoa | Golgin subfamily A member 8T | None |
| H3BQZ7 | HNRNPUL2-BSCL2 | S543 | ochoa | Heterogeneous nuclear ribonucleoprotein U-like protein 2 | None |
| H3BSY2 | GOLGA8M | S260 | ochoa | Golgin subfamily A member 8M | None |
| I6L899 | GOLGA8R | S90 | ochoa | Golgin subfamily A member 8R | None |
| I6L899 | GOLGA8R | S260 | ochoa | Golgin subfamily A member 8R | None |
| O00170 | AIP | S132 | ochoa|psp | AH receptor-interacting protein (AIP) (Aryl-hydrocarbon receptor-interacting protein) (HBV X-associated protein 2) (XAP-2) (Immunophilin homolog ARA9) | May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.; FUNCTION: Cellular negative regulator of the hepatitis B virus (HBV) X protein. |
| O00287 | RFXAP | S193 | ochoa | Regulatory factor X-associated protein (RFX-associated protein) (RFX DNA-binding complex 36 kDa subunit) | Part of the RFX complex that binds to the X-box of MHC II promoters. |
| O00418 | EEF2K | S445 | ochoa|psp | Eukaryotic elongation factor 2 kinase (eEF-2 kinase) (eEF-2K) (EC 2.7.11.20) (Calcium/calmodulin-dependent eukaryotic elongation factor 2 kinase) | Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced. {ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:9144159}. |
| O00429 | DNM1L | S693 | psp | Dynamin-1-like protein (EC 3.6.5.5) (Dnm1p/Vps1p-like protein) (DVLP) (Dynamin family member proline-rich carboxyl-terminal domain less) (Dymple) (Dynamin-like protein) (Dynamin-like protein 4) (Dynamin-like protein IV) (HdynIV) (Dynamin-related protein 1) | Functions in mitochondrial and peroxisomal division (PubMed:11514614, PubMed:12499366, PubMed:17301055, PubMed:17460227, PubMed:17553808, PubMed:18695047, PubMed:18838687, PubMed:19342591, PubMed:19411255, PubMed:19638400, PubMed:23283981, PubMed:23530241, PubMed:23921378, PubMed:26992161, PubMed:27145208, PubMed:27145933, PubMed:27301544, PubMed:27328748, PubMed:29478834, PubMed:32439975, PubMed:32484300, PubMed:9570752, PubMed:9786947). Mediates membrane fission through oligomerization into membrane-associated tubular structures that wrap around the scission site to constrict and sever the mitochondrial membrane through a GTP hydrolysis-dependent mechanism (PubMed:23530241, PubMed:23584531, PubMed:33850055). The specific recruitment at scission sites is mediated by membrane receptors like MFF, MIEF1 and MIEF2 for mitochondrial membranes (PubMed:23283981, PubMed:23921378, PubMed:29899447). While the recruitment by the membrane receptors is GTP-dependent, the following hydrolysis of GTP induces the dissociation from the receptors and allows DNM1L filaments to curl into closed rings that are probably sufficient to sever a double membrane (PubMed:29899447). Acts downstream of PINK1 to promote mitochondrial fission in a PRKN-dependent manner (PubMed:32484300). Plays an important role in mitochondrial fission during mitosis (PubMed:19411255, PubMed:26992161, PubMed:27301544, PubMed:27328748). Through its function in mitochondrial division, ensures the survival of at least some types of postmitotic neurons, including Purkinje cells, by suppressing oxidative damage (By similarity). Required for normal brain development, including that of cerebellum (PubMed:17460227, PubMed:26992161, PubMed:27145208, PubMed:27301544, PubMed:27328748). Facilitates developmentally regulated apoptosis during neural tube formation (By similarity). Required for a normal rate of cytochrome c release and caspase activation during apoptosis; this requirement may depend upon the cell type and the physiological apoptotic cues (By similarity). Required for formation of endocytic vesicles (PubMed:20688057, PubMed:23792689, PubMed:9570752). Proposed to regulate synaptic vesicle membrane dynamics through association with BCL2L1 isoform Bcl-X(L) which stimulates its GTPase activity in synaptic vesicles; the function may require its recruitment by MFF to clathrin-containing vesicles (PubMed:17015472, PubMed:23792689). Required for programmed necrosis execution (PubMed:22265414). Rhythmic control of its activity following phosphorylation at Ser-637 is essential for the circadian control of mitochondrial ATP production (PubMed:29478834). {ECO:0000250|UniProtKB:Q8K1M6, ECO:0000269|PubMed:11514614, ECO:0000269|PubMed:12499366, ECO:0000269|PubMed:17015472, ECO:0000269|PubMed:17301055, ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:17553808, ECO:0000269|PubMed:18695047, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19342591, ECO:0000269|PubMed:19411255, ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:20688057, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23584531, ECO:0000269|PubMed:23792689, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27145933, ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29478834, ECO:0000269|PubMed:29899447, ECO:0000269|PubMed:32439975, ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:33850055, ECO:0000269|PubMed:9570752, ECO:0000269|PubMed:9786947}.; FUNCTION: [Isoform 1]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}.; FUNCTION: [Isoform 4]: Inhibits peroxisomal division when overexpressed. {ECO:0000269|PubMed:12618434}. |
| O00567 | NOP56 | S511 | ochoa | Nucleolar protein 56 (Nucleolar protein 5A) | Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs (PubMed:12777385, PubMed:15574333). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:12777385, PubMed:39570315). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:15574333, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| O14490 | DLGAP1 | S587 | ochoa | Disks large-associated protein 1 (DAP-1) (Guanylate kinase-associated protein) (hGKAP) (PSD-95/SAP90-binding protein 1) (SAP90/PSD-95-associated protein 1) (SAPAP1) | Part of the postsynaptic scaffold in neuronal cells. |
| O14523 | C2CD2L | S660 | ochoa | Phospholipid transfer protein C2CD2L (C2 domain-containing protein 2-like) (C2CD2-like) (Transmembrane protein 24) | Lipid-binding protein that transports phosphatidylinositol, the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), from its site of synthesis in the endoplasmic reticulum to the cell membrane (PubMed:28209843). It thereby maintains the pool of cell membrane phosphoinositides, which are degraded during phospholipase C (PLC) signaling (PubMed:28209843). Plays a key role in the coordination of Ca(2+) and phosphoinositide signaling: localizes to sites of contact between the endoplasmic reticulum and the cell membrane, where it tethers the two bilayers (PubMed:28209843). In response to elevation of cytosolic Ca(2+), it is phosphorylated at its C-terminus and dissociates from the cell membrane, abolishing phosphatidylinositol transport to the cell membrane (PubMed:28209843). Positively regulates insulin secretion in response to glucose: phosphatidylinositol transfer to the cell membrane allows replenishment of PI(4,5)P2 pools and calcium channel opening, priming a new population of insulin granules (PubMed:28209843). {ECO:0000269|PubMed:28209843}. |
| O14641 | DVL2 | S141 | ochoa | Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) | Plays a role in the signal transduction pathways mediated by multiple Wnt genes (PubMed:24616100). Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499, ECO:0000269|PubMed:24616100}. |
| O14745 | NHERF1 | S162 | ochoa|psp | Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (NHERF-1) (Ezrin-radixin-moesin-binding phosphoprotein 50) (EBP50) (Regulatory cofactor of Na(+)/H(+) exchanger) (Sodium-hydrogen exchanger regulatory factor 1) (Solute carrier family 9 isoform A3 regulatory factor 1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}. |
| O14745 | NHERF1 | S291 | ochoa|psp | Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (NHERF-1) (Ezrin-radixin-moesin-binding phosphoprotein 50) (EBP50) (Regulatory cofactor of Na(+)/H(+) exchanger) (Sodium-hydrogen exchanger regulatory factor 1) (Solute carrier family 9 isoform A3 regulatory factor 1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}. |
| O14770 | MEIS2 | S204 | ochoa | Homeobox protein Meis2 (Meis1-related protein 1) | Involved in transcriptional regulation. Binds to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of PBX and HOX proteins and thought to have a role in stabilization of the homeoprotein-DNA complex. Isoform 3 is required for the activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element; MEIS2 is not involved in complex DNA-binding. Probably in complex with PBX1, is involved in transcriptional regulation by KLF4. Isoform 3 and isoform 4 can bind to a EPHA8 promoter sequence containing the DNA motif 5'-CGGTCA-3'; in cooperation with a PBX protein (such as PBX2) is proposed to be involved in the transcriptional activation of EPHA8 in the developing midbrain. May be involved in regulation of myeloid differentiation. Can bind to the DNA sequence 5'-TGACAG-3'in the activator ACT sequence of the D(1A) dopamine receptor (DRD1) promoter and activate DRD1 transcription; isoform 5 cannot activate DRD1 transcription. {ECO:0000269|PubMed:10764806, ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:21746878}. |
| O14776 | TCERG1 | S833 | ochoa | Transcription elongation regulator 1 (TATA box-binding protein-associated factor 2S) (Transcription factor CA150) | Transcription factor that binds RNA polymerase II and inhibits the elongation of transcripts from target promoters. Regulates transcription elongation in a TATA box-dependent manner. Necessary for TAT-dependent activation of the human immunodeficiency virus type 1 (HIV-1) promoter. {ECO:0000269|PubMed:11604498, ECO:0000269|PubMed:9315662}. |
| O14777 | NDC80 | S50 | ochoa|psp | Kinetochore protein NDC80 homolog (Highly expressed in cancer protein) (Kinetochore protein Hec1) (HsHec1) (Kinetochore-associated protein 2) (Retinoblastoma-associated protein HEC) | Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12351790, PubMed:14654001, PubMed:14699129, PubMed:15062103, PubMed:15235793, PubMed:15239953, PubMed:15548592, PubMed:16732327, PubMed:30409912, PubMed:9315664). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:15548592, PubMed:30409912). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020). Plays a role in chromosome congression and is essential for the end-on attachment of the kinetochores to spindle microtubules (PubMed:23891108, PubMed:25743205). {ECO:0000269|PubMed:12351790, ECO:0000269|PubMed:14654001, ECO:0000269|PubMed:14699129, ECO:0000269|PubMed:15062103, ECO:0000269|PubMed:15235793, ECO:0000269|PubMed:15239953, ECO:0000269|PubMed:15548592, ECO:0000269|PubMed:16732327, ECO:0000269|PubMed:23085020, ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:25743205, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:9315664}. |
| O14791 | APOL1 | S365 | ochoa | Apolipoprotein L1 (Apolipoprotein L) (Apo-L) (ApoL) (Apolipoprotein L-I) (ApoL-I) | May play a role in lipid exchange and transport throughout the body. May participate in reverse cholesterol transport from peripheral cells to the liver. |
| O14933 | UBE2L6 | S27 | ochoa | Ubiquitin/ISG15-conjugating enzyme E2 L6 (EC 2.3.2.23) (E2 ubiquitin-conjugating enzyme L6) (Retinoic acid-induced gene B protein) (RIG-B) (UbcH8) (Ubiquitin carrier protein L6) (Ubiquitin-protein ligase L6) | Catalyzes the covalent attachment of ubiquitin or ISG15 to other proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Promotes ubiquitination and subsequent proteasomal degradation of FLT3. {ECO:0000269|PubMed:15131269, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:20508617}. |
| O15195 | VILL | S240 | ochoa | Villin-like protein | Possible tumor suppressor. |
| O15511 | ARPC5 | S77 | psp | Actin-related protein 2/3 complex subunit 5 (Arp2/3 complex 16 kDa subunit) (p16-ARC) | Component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947). {ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9230079}. |
| O15534 | PER1 | S1037 | ochoa | Period circadian protein homolog 1 (hPER1) (Circadian clock protein PERIOD 1) (Circadian pacemaker protein Rigui) | Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by BMAL1:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:24005054}. |
| O15534 | PER1 | S1040 | ochoa | Period circadian protein homolog 1 (hPER1) (Circadian clock protein PERIOD 1) (Circadian pacemaker protein Rigui) | Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by BMAL1:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:24005054}. |
| O43166 | SIPA1L1 | S1645 | ochoa | Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (High-risk human papilloma viruses E6 oncoproteins targeted protein 1) (E6-targeted protein 1) | Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}. |
| O43194 | GPR39 | S425 | ochoa | G-protein coupled receptor 39 | Zinc-sensing receptor that can sense changes in extracellular Zn(2+), mediate Zn(2+) signal transmission, and participates in the regulation of numerous physiological processes including glucose homeostasis regulation, gastrointestinal mobility, hormone secretion and cell death (PubMed:18180304). Activation by Zn(2+) in keratinocytes increases the intracellular concentration of Ca(2+) and activates the ERK/MAPK and PI3K/AKT signaling pathways leading to epithelial repair (PubMed:20522546). Plays an essential role in normal wound healing by inducing the production of cytokines including the major inflammatory cytokine IL6 via the PKC/MAPK/CEBPB pathway (By similarity). Regulates adipose tissue metabolism, especially lipolysis, and regulates the function of lipases, such as hormone-sensitive lipase and adipose triglyceride lipase (By similarity). Plays a role in the inhibition of cell death and protects against oxidative, endoplasmic reticulum and mitochondrial stress by inducing secretion of the cytoprotective pigment epithelium-derived growth factor (PEDF) and probably other protective transcripts in a GNA13/RHOA/SRE-dependent manner (PubMed:18180304). Forms dynamic heteroreceptor complexes with HTR1A and GALR1 depending on cell type or specific physiological states, resulting in signaling diversity: HTR1A-GPR39 shows additive increase in signaling along the serum response element (SRE) and NF-kappa-B pathways while GALR1 acts as an antagonist blocking SRE (PubMed:26365466). {ECO:0000250|UniProtKB:Q5U431, ECO:0000269|PubMed:18180304, ECO:0000269|PubMed:20522546, ECO:0000269|PubMed:26365466}. |
| O43290 | SART1 | S112 | ochoa | U4/U6.U5 tri-snRNP-associated protein 1 (SNU66 homolog) (hSnu66) (Squamous cell carcinoma antigen recognized by T-cells 1) (SART-1) (hSART-1) (U4/U6.U5 tri-snRNP-associated 110 kDa protein) (allergen Hom s 1) | Plays a role in mRNA splicing as a component of the U4/U6-U5 tri-snRNP, one of the building blocks of the spliceosome. May also bind to DNA. {ECO:0000269|PubMed:11350945, ECO:0000269|PubMed:25092792}. |
| O43295 | SRGAP3 | S954 | ochoa | SLIT-ROBO Rho GTPase-activating protein 3 (srGAP3) (Mental disorder-associated GAP) (Rho GTPase-activating protein 14) (WAVE-associated Rac GTPase-activating protein) (WRP) | GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons. {ECO:0000269|PubMed:12195014, ECO:0000269|PubMed:12447388}. |
| O43353 | RIPK2 | S416 | ochoa | Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. |
| O43399 | TPD52L2 | S149 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43423 | ANP32CP | S73 | ochoa | Putative uncharacterized protein ANP32CP (Acidic leucine-rich nuclear phosphoprotein 32 family member C) (Phosphoprotein 32-related protein 1) (Tumorigenic protein pp32r1) | None |
| O60269 | GPRIN2 | S264 | ochoa | G protein-regulated inducer of neurite outgrowth 2 (GRIN2) | May be involved in neurite outgrowth. {ECO:0000269|PubMed:10480904}. |
| O60282 | KIF5C | S835 | ochoa | 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}. |
| O60285 | NUAK1 | S485 | ochoa | NUAK family SNF1-like kinase 1 (EC 2.7.11.1) (AMPK-related protein kinase 5) (ARK5) (Omphalocele kinase 1) | Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171, ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}. |
| O60292 | SIPA1L3 | S1617 | ochoa | Signal-induced proliferation-associated 1-like protein 3 (SIPA1-like protein 3) (SPA-1-like protein 3) | Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217). {ECO:0000269|PubMed:26231217}. |
| O60318 | MCM3AP | S579 | ochoa | Germinal-center associated nuclear protein (GANP) (EC 2.3.1.48) (80 kDa MCM3-associated protein) (MCM3 acetylating protein) (MCM3AP) (EC 2.3.1.-) (MCM3 acetyltransferase) | [Isoform GANP]: As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (PubMed:20005110, PubMed:20384790, PubMed:22307388, PubMed:23591820). Through the acetylation of histones, affects the assembly of nucleosomes at immunoglobulin variable region genes and promotes the recruitment and positioning of transcription complex to favor DNA cytosine deaminase AICDA/AID targeting, hence promoting somatic hypermutations (PubMed:23652018). {ECO:0000269|PubMed:20005110, ECO:0000269|PubMed:20384790, ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:23591820, ECO:0000269|PubMed:23652018}.; FUNCTION: [Isoform MCM3AP]: Binds to and acetylates the replication protein MCM3. Plays a role in the initiation of DNA replication and participates in controls that ensure that DNA replication initiates only once per cell cycle (PubMed:11258703, PubMed:12226073). Through the acetylation of histones, affects the assembly of nucleosomes at immunoglobulin variable region genes and promotes the recruitment and positioning of transcription complex to favor DNA cytosine deaminase AICDA/AID targeting, hence promoting somatic hypermutations (PubMed:23652018). {ECO:0000269|PubMed:11258703, ECO:0000269|PubMed:12226073, ECO:0000269|PubMed:23652018}. |
| O60333 | KIF1B | S1603 | ochoa | Kinesin-like protein KIF1B (Klp) (EC 5.6.1.3) | Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules. {ECO:0000269|PubMed:16225668}.; FUNCTION: [Isoform 2]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde synaptic vesicle transport along axonal microtubules from the cell body to the presynapse in neuronal cells (By similarity). Functions as a downstream effector in a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells (PubMed:18334619). {ECO:0000250|UniProtKB:Q60575, ECO:0000269|PubMed:18334619}.; FUNCTION: [Isoform 3]: Has a plus-end-directed microtubule motor activity and functions as a motor for anterograde transport of mitochondria. {ECO:0000269|PubMed:16225668}. |
| O60503 | ADCY9 | S611 | ochoa | Adenylate cyclase type 9 (EC 4.6.1.1) (ATP pyrophosphate-lyase 9) (Adenylate cyclase type IX) (ACIX) (Adenylyl cyclase 9) (AC9) | Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors (PubMed:10987815, PubMed:12972952, PubMed:15879435, PubMed:9628827). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827}. |
| O60711 | LPXN | S34 | ochoa | Leupaxin | Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in integrin-mediated cell adhesion events. Suppresses the integrin-induced tyrosine phosphorylation of paxillin (PXN). May play a critical role as an adapter protein in the formation of the adhesion zone in osteoclasts. Negatively regulates B-cell antigen receptor (BCR) signaling. {ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:18451096, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:20543562}. |
| O60716 | CTNND1 | S225 | ochoa | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60716 | CTNND1 | S312 | psp | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60716 | CTNND1 | S713 | ochoa | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60832 | DKC1 | S170 | ochoa | H/ACA ribonucleoprotein complex subunit DKC1 (EC 5.4.99.-) (CBF5 homolog) (Dyskerin) (Nopp140-associated protein of 57 kDa) (Nucleolar protein NAP57) (Nucleolar protein family A member 4) (snoRNP protein DKC1) | [Isoform 1]: Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674, PubMed:32554502). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534). {ECO:0000269|PubMed:19179534, ECO:0000269|PubMed:25219674, ECO:0000269|PubMed:32554502}.; FUNCTION: [Isoform 3]: Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression. {ECO:0000269|PubMed:21820037}. |
| O75083 | WDR1 | S320 | ochoa | WD repeat-containing protein 1 (Actin-interacting protein 1) (AIP1) (NORI-1) | Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (PubMed:15629458, PubMed:27557945, PubMed:29751004). Enhances cofilin-mediated actin severing (By similarity). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (PubMed:18494608). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance (By similarity). Involved in megakaryocyte maturation and platelet shedding. Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (By similarity). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (PubMed:25792565). {ECO:0000250|UniProtKB:O88342, ECO:0000250|UniProtKB:Q9W7F2, ECO:0000269|PubMed:15629458, ECO:0000269|PubMed:18494608, ECO:0000269|PubMed:25792565, ECO:0000269|PubMed:27557945, ECO:0000269|PubMed:29751004}. |
| O75122 | CLASP2 | S1053 | ochoa|psp | CLIP-associating protein 2 (Cytoplasmic linker-associated protein 2) (Protein Orbit homolog 2) (hOrbit2) | Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules (PubMed:26003921). Involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN). Required for the polarization of the cytoplasmic microtubule arrays in migrating cells towards the leading edge of the cell. May act at the cell cortex to enhance the frequency of rescue of depolymerizing microtubules by attaching their plus-ends to cortical platforms composed of ERC1 and PHLDB2 (PubMed:16824950). This cortical microtubule stabilizing activity is regulated at least in part by phosphatidylinositol 3-kinase signaling. Also performs a similar stabilizing function at the kinetochore which is essential for the bipolar alignment of chromosomes on the mitotic spindle (PubMed:16866869, PubMed:16914514). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. {ECO:0000269|PubMed:11290329, ECO:0000269|PubMed:15631994, ECO:0000269|PubMed:16824950, ECO:0000269|PubMed:16866869, ECO:0000269|PubMed:16914514, ECO:0000269|PubMed:17543864, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:26003921}. |
| O75152 | ZC3H11A | S625 | ochoa | Zinc finger CCCH domain-containing protein 11A | Through its association with TREX complex components, may participate in the export and post-transcriptional coordination of selected mRNA transcripts, including those required to maintain the metabolic processes in embryonic cells (PubMed:22928037, PubMed:37356722). Binds RNA (PubMed:29610341, PubMed:37356722). {ECO:0000269|PubMed:22928037, ECO:0000269|PubMed:29610341, ECO:0000269|PubMed:37356722}.; FUNCTION: (Microbial infection) Plays a role in efficient growth of several nuclear-replicating viruses such as HIV-1, influenza virus or herpes simplex virus 1/HHV-1. Required for efficient viral mRNA export (PubMed:29610341). May be required for proper polyadenylation of adenovirus type 5/HAdV-5 capsid mRNA (PubMed:37356722). {ECO:0000269|PubMed:29610341, ECO:0000269|PubMed:37356722}. |
| O75154 | RAB11FIP3 | S538 | ochoa|psp | Rab11 family-interacting protein 3 (FIP3) (FIP3-Rab11) (Rab11-FIP3) (Arfophilin-1) (EF hands-containing Rab-interacting protein) (Eferin) (MU-MB-17.148) | Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery (PubMed:15601896, PubMed:16148947, PubMed:17394487, PubMed:17628206, PubMed:18511905, PubMed:19327867, PubMed:20026645, PubMed:25673879, PubMed:26258637, PubMed:31204173). Recruited by Rab11 to endosomes where it links Rab11 to dynein motor complex (PubMed:20026645). The functional Rab11-RAB11FIP3-dynein complex regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endocytic recycling compartment (ERC) during interphase of cell cycle (PubMed:17394487, PubMed:20026645). Facilitates the interaction between dynein and dynactin and activates dynein processivity (PubMed:25035494). Binding with ASAP1 is needed to regulate the pericentrosomal localization of recycling endosomes (By similarity). The Rab11-RAB11FIP3 complex is also implicated in the transport during telophase of vesicles derived from recycling endosomes to the cleavage furrow via centrosome-anchored microtubules, where the vesicles function to deliver membrane during late cytokinesis and abscission (PubMed:15601896, PubMed:16148947). The recruitment of Rab11-RAB11FIP3-containing endosomes to the cleavage furrow and tethering to the midbody is co-mediated by RAB11FIP3 interaction with ARF6-exocyst and RACGAP1-MKLP1 tethering complexes (PubMed:17628206, PubMed:18511905). Also involved in the Rab11-Rabin8-Rab8 ciliogenesis cascade by facilitating the orderly assembly of a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which directs preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:26258637, PubMed:31204173). Also promotes the activity of Rab11 and ASAP1 in the ARF4-dependent Golgi-to-cilia transport of the sensory receptor rhodopsin (PubMed:25673879). Competes with WDR44 for binding to Rab11, which controls intracellular ciliogenesis pathway (PubMed:31204173). May play a role in breast cancer cell motility by regulating actin cytoskeleton (PubMed:19327867). {ECO:0000250|UniProtKB:Q8CHD8, ECO:0000269|PubMed:15601896, ECO:0000269|PubMed:16148947, ECO:0000269|PubMed:17394487, ECO:0000269|PubMed:17628206, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19327867, ECO:0000269|PubMed:20026645, ECO:0000269|PubMed:25035494, ECO:0000269|PubMed:25673879, ECO:0000269|PubMed:26258637, ECO:0000269|PubMed:31204173}. |
| O75179 | ANKRD17 | S1457 | ochoa | Ankyrin repeat domain-containing protein 17 (Gene trap ankyrin repeat protein) (Serologically defined breast cancer antigen NY-BR-16) | Could play pivotal roles in cell cycle and DNA regulation (PubMed:19150984). Involved in innate immune defense against viruse by positively regulating the viral dsRNA receptors DDX58 and IFIH1 signaling pathways (PubMed:22328336). Involves in NOD2- and NOD1-mediated responses to bacteria suggesting a role in innate antibacterial immune pathways too (PubMed:23711367). Target of enterovirus 71 which is the major etiological agent of HFMD (hand, foot and mouth disease) (PubMed:17276651). Could play a central role for the formation and/or maintenance of the blood vessels of the circulation system (By similarity). {ECO:0000250|UniProtKB:Q99NH0, ECO:0000269|PubMed:17276651, ECO:0000269|PubMed:19150984, ECO:0000269|PubMed:22328336, ECO:0000269|PubMed:23711367}. |
| O75369 | FLNB | S81 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75369 | FLNB | S2113 | ochoa | Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) | Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro. |
| O75379 | VAMP4 | S20 | ochoa | Vesicle-associated membrane protein 4 (VAMP-4) | Involved in the pathway that functions to remove an inhibitor (probably synaptotagmin-4) of calcium-triggered exocytosis during the maturation of secretory granules. May be a marker for this sorting pathway that is critical for remodeling the secretory response of granule. |
| O75385 | ULK1 | S639 | ochoa | Serine/threonine-protein kinase ULK1 (EC 2.7.11.1) (Autophagy-related protein 1 homolog) (ATG1) (hATG1) (Unc-51-like kinase 1) | Serine/threonine-protein kinase involved in autophagy in response to starvation (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:29487085, PubMed:31123703). Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165). Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR (PubMed:21795849). Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences (PubMed:18936157). Plays a role early in neuronal differentiation and is required for granule cell axon formation (PubMed:11146101). Also phosphorylates SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to autophagy induction, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both proteolytic activation and delipidation activities of ATG4B (PubMed:28821708). {ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:20921139, ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:28821708, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:37306101}. |
| O75449 | KATNA1 | S42 | psp | Katanin p60 ATPase-containing subunit A1 (Katanin p60 subunit A1) (EC 5.6.1.1) (p60 katanin) | Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth. {ECO:0000255|HAMAP-Rule:MF_03023, ECO:0000269|PubMed:10751153, ECO:0000269|PubMed:11870226, ECO:0000269|PubMed:19287380}. |
| O75469 | NR1I2 | S200 | psp | Nuclear receptor subfamily 1 group I member 2 (Orphan nuclear receptor PAR1) (Orphan nuclear receptor PXR) (Pregnane X receptor) (Steroid and xenobiotic receptor) (SXR) | Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes. {ECO:0000269|PubMed:11297522, ECO:0000269|PubMed:11668216, ECO:0000269|PubMed:12578355, ECO:0000269|PubMed:18768384, ECO:0000269|PubMed:19297428, ECO:0000269|PubMed:9727070}. |
| O75533 | SF3B1 | S377 | ochoa | Splicing factor 3B subunit 1 (Pre-mRNA-splicing factor SF3b 155 kDa subunit) (SF3b155) (Spliceosome-associated protein 155) (SAP 155) | Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs (PubMed:12234937, PubMed:27720643, PubMed:32494006, PubMed:34822310). The 17S U2 SnRNP complex (1) directly participates in early spliceosome assembly and (2) mediates recognition of the intron branch site during pre-mRNA splicing by promoting the selection of the pre-mRNA branch-site adenosine, the nucleophile for the first step of splicing (PubMed:32494006, PubMed:34822310). Within the 17S U2 SnRNP complex, SF3B1 is part of the SF3B subcomplex, which is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence in pre-mRNA (PubMed:12234937). Sequence independent binding of SF3A and SF3B subcomplexes upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). May also be involved in the assembly of the 'E' complex (PubMed:10882114). Also acts as a component of the minor spliceosome, which is involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077, PubMed:33509932). Together with other U2 snRNP complex components may also play a role in the selective processing of microRNAs (miRNAs) from the long primary miRNA transcript, pri-miR-17-92 (By similarity). {ECO:0000250|UniProtKB:Q99NB9, ECO:0000269|PubMed:10882114, ECO:0000269|PubMed:12234937, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:27720643, ECO:0000269|PubMed:32494006, ECO:0000269|PubMed:33509932, ECO:0000269|PubMed:34822310}. |
| O75643 | SNRNP200 | S756 | ochoa | U5 small nuclear ribonucleoprotein 200 kDa helicase (EC 3.6.4.13) (Activating signal cointegrator 1 complex subunit 3-like 1) (BRR2 homolog) (U5 snRNP-specific 200 kDa protein) (U5-200KD) | Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome (PubMed:35241646). Plays a role in pre-mRNA splicing as a core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154, PubMed:30728453). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:23045696, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:35241646, ECO:0000269|PubMed:8670905, ECO:0000269|PubMed:9539711, ECO:0000305|PubMed:33509932}. |
| O75674 | TOM1L1 | S311 | 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}. |
| O75688 | PPM1B | S386 | ochoa | Protein phosphatase 1B (EC 3.1.3.16) (Protein phosphatase 2C isoform beta) (PP2C-beta) | Enzyme with a broad specificity. Dephosphorylates CDK2 and CDK6 in vitro. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser-172'. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB. {ECO:0000269|PubMed:18930133, ECO:0000269|PubMed:22750291}. |
| O75716 | STK16 | S197 | psp | Serine/threonine-protein kinase 16 (EC 2.7.11.1) (Myristoylated and palmitoylated serine/threonine-protein kinase) (MPSK) (Protein kinase PKL12) (TGF-beta-stimulated factor 1) (TSF-1) (Tyrosine-protein kinase STK16) (EC 2.7.10.2) (hPSK) | Membrane-associated protein kinase that phosphorylates on serine and threonine residues. In vitro substrates include DRG1, ENO1 and EIF4EBP1. Also autophosphorylates. May be involved in secretory vesicle trafficking or intracellular signaling. May have a role in regulating stromal-epithelial interactions that occur during ductal morphogenesis in the mammary gland. May be involved in TGF-beta signaling. Able to autophosphorylate on Tyr residue; it is however unclear whether it has tyrosine-protein kinase toward other proteins. {ECO:0000269|PubMed:10364453}. |
| O75821 | EIF3G | S264 | ochoa | Eukaryotic translation initiation factor 3 subunit G (eIF3g) (Eukaryotic translation initiation factor 3 RNA-binding subunit) (eIF-3 RNA-binding subunit) (Eukaryotic translation initiation factor 3 subunit 4) (eIF-3-delta) (eIF3 p42) (eIF3 p44) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). This subunit can bind 18S rRNA. {ECO:0000255|HAMAP-Rule:MF_03006, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| O94804 | STK10 | S454 | ochoa | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
| O94832 | MYO1D | S298 | ochoa | Unconventional myosin-Id | Unconventional myosin that functions as actin-based motor protein with ATPase activity (By similarity). Plays a role in endosomal protein trafficking, and especially in the transfer of cargo proteins from early to recycling endosomes (By similarity). Required for normal planar cell polarity in ciliated tracheal cells, for normal rotational polarity of cilia, and for coordinated, unidirectional ciliary movement in the trachea. Required for normal, polarized cilia organization in brain ependymal epithelial cells (By similarity). {ECO:0000250|UniProtKB:F1PRN2, ECO:0000250|UniProtKB:Q63357}. |
| O94880 | PHF14 | S280 | ochoa | PHD finger protein 14 | Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}. |
| O94888 | UBXN7 | S29 | ochoa | UBX domain-containing protein 7 | Ubiquitin-binding adapter that links a subset of NEDD8-associated cullin ring ligases (CRLs) to the segregase VCP/p97, to regulate turnover of their ubiquitination substrates. {ECO:0000269|PubMed:22537386}. |
| O94964 | MTCL2 | S931 | ochoa | Microtubule cross-linking factor 2 (SOGA family member 1) (Suppressor of glucose by autophagy) (Suppressor of glucose, autophagy-associated protein 1) [Cleaved into: N-terminal form; C-terminal 80 kDa form (80-kDa SOGA fragment)] | Microtubule-associated factor that enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Preferentially acts on the perinuclear microtubules accumulated around the Golgi. Associates with the Golgi membrane through the N-terminal coiled-coil region and directly binds microtubules through the C-terminal domain (By similarity). Required for faithful chromosome segregation during mitosis (PubMed:33587225). Regulates autophagy by playing a role in the reduction of glucose production in an adiponectin- and insulin-dependent manner (By similarity). {ECO:0000250|UniProtKB:E1U8D0, ECO:0000269|PubMed:33587225}. |
| O95171 | SCEL | S344 | 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. |
| O95171 | SCEL | S524 | 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. |
| O95235 | KIF20A | S668 | ochoa | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95239 | KIF4A | S1038 | ochoa | Chromosome-associated kinesin KIF4A (Chromokinesin-A) | Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (PubMed:29848660). Translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis (PubMed:15297875, PubMed:15625105). May play a role in mitotic chromosomal positioning and bipolar spindle stabilization (By similarity). {ECO:0000250|UniProtKB:P33174, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:29848660}. |
| O95239 | KIF4A | S1136 | ochoa | Chromosome-associated kinesin KIF4A (Chromokinesin-A) | Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (PubMed:29848660). Translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis (PubMed:15297875, PubMed:15625105). May play a role in mitotic chromosomal positioning and bipolar spindle stabilization (By similarity). {ECO:0000250|UniProtKB:P33174, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:29848660}. |
| O95299 | NDUFA10 | S250 | psp | NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial (Complex I-42kD) (CI-42kD) (NADH-ubiquinone oxidoreductase 42 kDa subunit) | Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. |
| O95359 | TACC2 | S749 | ochoa | Transforming acidic coiled-coil-containing protein 2 (Anti-Zuai-1) (AZU-1) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). May play a role in organizing centrosomal microtubules. May act as a tumor suppressor protein. May represent a tumor progression marker. {ECO:0000250, ECO:0000269|PubMed:10749935}. |
| O95425 | SVIL | S193 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95433 | AHSA1 | S258 | ochoa | Activator of 90 kDa heat shock protein ATPase homolog 1 (AHA1) (p38) | Acts as a co-chaperone of HSP90AA1 (PubMed:29127155). Activates the ATPase activity of HSP90AA1 leading to increase in its chaperone activity (PubMed:29127155). Competes with the inhibitory co-chaperone FNIP1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Competes with the inhibitory co-chaperone TSC1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). {ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155}. |
| O95436 | SLC34A2 | S53 | 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}. |
| O95470 | SGPL1 | S124 | ochoa | Sphingosine-1-phosphate lyase 1 (S1PL) (SP-lyase 1) (SPL 1) (hSPL) (EC 4.1.2.27) (Sphingosine-1-phosphate aldolase) | Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis (PubMed:11018465, PubMed:14570870, PubMed:24809814, PubMed:28165339). Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP (By similarity). Seems to play a role in establishing neuronal contact sites and axonal maintenance (By similarity). {ECO:0000250|UniProtKB:Q8R0X7, ECO:0000250|UniProtKB:Q9V7Y2, ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:14570870, ECO:0000269|PubMed:24809814, ECO:0000269|PubMed:28165339}. |
| O95470 | SGPL1 | S543 | ochoa | Sphingosine-1-phosphate lyase 1 (S1PL) (SP-lyase 1) (SPL 1) (hSPL) (EC 4.1.2.27) (Sphingosine-1-phosphate aldolase) | Cleaves phosphorylated sphingoid bases (PSBs), such as sphingosine-1-phosphate, into fatty aldehydes and phosphoethanolamine. Elevates stress-induced ceramide production and apoptosis (PubMed:11018465, PubMed:14570870, PubMed:24809814, PubMed:28165339). Required for global lipid homeostasis in liver and cholesterol homeostasis in fibroblasts. Involved in the regulation of pro-inflammatory response and neutrophil trafficking. Modulates neuronal autophagy via phosphoethanolamine production which regulates accumulation of aggregate-prone proteins such as APP (By similarity). Seems to play a role in establishing neuronal contact sites and axonal maintenance (By similarity). {ECO:0000250|UniProtKB:Q8R0X7, ECO:0000250|UniProtKB:Q9V7Y2, ECO:0000269|PubMed:11018465, ECO:0000269|PubMed:14570870, ECO:0000269|PubMed:24809814, ECO:0000269|PubMed:28165339}. |
| O95613 | PCNT | S1814 | ochoa | Pericentrin (Kendrin) (Pericentrin-B) | Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:30420784}. |
| O95613 | PCNT | S2485 | ochoa | Pericentrin (Kendrin) (Pericentrin-B) | Integral component of the filamentous matrix of the centrosome involved in the initial establishment of organized microtubule arrays in both mitosis and meiosis. Plays a role, together with DISC1, in the microtubule network formation. Is an integral component of the pericentriolar material (PCM). May play an important role in preventing premature centrosome splitting during interphase by inhibiting NEK2 kinase activity at the centrosome. {ECO:0000269|PubMed:10823944, ECO:0000269|PubMed:11171385, ECO:0000269|PubMed:18955030, ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:30420784}. |
| O96000 | NDUFB10 | S144 | ochoa | NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 (Complex I-PDSW) (CI-PDSW) (NADH-ubiquinone oxidoreductase PDSW subunit) | Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. Complex I has an NADH dehydrogenase activity with ubiquinone as an immediate electron acceptor and mediates the transfer of electrons from NADH to the respiratory chain. {ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:28040730}. |
| O96017 | CHEK2 | S456 | psp | Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}. |
| P00338 | LDHA | S167 | ochoa | L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}. |
| P00519 | ABL1 | S446 | 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}. |
| P00749 | PLAU | S158 | psp | Urokinase-type plasminogen activator (U-plasminogen activator) (uPA) (EC 3.4.21.73) [Cleaved into: Urokinase-type plasminogen activator long chain A; Urokinase-type plasminogen activator short chain A; Urokinase-type plasminogen activator chain B] | Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. |
| P01189 | POMC | S168 | psp | Pro-opiomelanocortin (POMC) (Corticotropin-lipotropin) [Cleaved into: NPP; Melanotropin gamma (Gamma-MSH); Potential peptide; Corticotropin (Adrenocorticotropic hormone) (ACTH); Melanocyte-stimulating hormone alpha (Alpha-MSH) (Melanotropin alpha); Corticotropin-like intermediary peptide (CLIP); Lipotropin beta (Beta-LPH); Lipotropin gamma (Gamma-LPH); Melanocyte-stimulating hormone beta (Beta-MSH) (Melanotropin beta); Beta-endorphin; Met-enkephalin] | [Corticotropin]: Stimulates the adrenal glands to release cortisol.; FUNCTION: [Melanocyte-stimulating hormone alpha]: Anorexigenic peptide. Increases the pigmentation of skin by increasing melanin production in melanocytes.; FUNCTION: [Melanocyte-stimulating hormone beta]: Increases the pigmentation of skin by increasing melanin production in melanocytes.; FUNCTION: [Beta-endorphin]: Endogenous orexigenic opiate.; FUNCTION: [Met-enkephalin]: Endogenous opiate. |
| P01236 | PRL | S194 | psp | Prolactin (PRL) | Prolactin acts primarily on the mammary gland by promoting lactation. |
| P01241 | GH1 | S176 | psp | Somatotropin (Growth hormone) (GH) (GH-N) (Growth hormone 1) (Pituitary growth hormone) | Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. |
| P01730 | CD4 | S433 | psp | T-cell surface glycoprotein CD4 (T-cell surface antigen T4/Leu-3) (CD antigen CD4) | Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. {ECO:0000269|PubMed:16951326, ECO:0000269|PubMed:24942581, ECO:0000269|PubMed:2823150, ECO:0000269|PubMed:7604010}.; FUNCTION: (Microbial infection) Primary receptor for human immunodeficiency virus-1 (HIV-1) (PubMed:12089508, PubMed:16331979, PubMed:2214026, PubMed:9641677). Down-regulated by HIV-1 Vpu (PubMed:17346169). Acts as a receptor for Human Herpes virus 7/HHV-7 (PubMed:7909607). {ECO:0000269|PubMed:12089508, ECO:0000269|PubMed:16331979, ECO:0000269|PubMed:17346169, ECO:0000269|PubMed:2214026, ECO:0000269|PubMed:7909607, ECO:0000269|PubMed:9641677}. |
| P02042 | HBD | S73 | ochoa | Hemoglobin subunit delta (Delta-globin) (Hemoglobin delta chain) | Involved in oxygen transport from the lung to the various peripheral tissues. |
| P02786 | TFRC | S19 | ochoa | 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}. |
| P02794 | FTH1 | S164 | ochoa | Ferritin heavy chain (Ferritin H subunit) (EC 1.16.3.1) (Cell proliferation-inducing gene 15 protein) [Cleaved into: Ferritin heavy chain, N-terminally processed] | Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation (PubMed:9003196). Also plays a role in delivery of iron to cells (By similarity). Mediates iron uptake in capsule cells of the developing kidney (By similarity). Delivery to lysosomes is mediated by the cargo receptor NCOA4 for autophagic degradation and release of iron (PubMed:24695223, PubMed:26436293). {ECO:0000250|UniProtKB:P09528, ECO:0000269|PubMed:24695223, ECO:0000269|PubMed:26436293, ECO:0000269|PubMed:9003196}. |
| P04075 | ALDOA | S218 | 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}. |
| P04275 | VWF | S1613 | psp | von Willebrand factor (vWF) [Cleaved into: von Willebrand antigen 2 (von Willebrand antigen II)] | Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma. |
| P05023 | ATP1A1 | S499 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P05107 | ITGB2 | S349 | ochoa | Integrin beta-2 (Cell surface adhesion glycoproteins LFA-1/CR3/p150,95 subunit beta) (Complement receptor C3 subunit beta) (CD antigen CD18) | Integrin ITGAL/ITGB2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrin ITGAL/ITGB2 is also a receptor for the secreted form of ubiquitin-like protein ISG15; the interaction is mediated by ITGAL (PubMed:29100055). Integrins ITGAM/ITGB2 and ITGAX/ITGB2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin ITGAX/ITGB2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin ITGAM/ITGB2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin ITGAM/ITGB2 is also a receptor for factor X. Integrin ITGAD/ITGB2 is a receptor for ICAM3 and VCAM1. Contributes to natural killer cell cytotoxicity (PubMed:15356110). Involved in leukocyte adhesion and transmigration of leukocytes including T-cells and neutrophils (PubMed:11812992, PubMed:28807980). Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation (PubMed:18587400). Integrin ITGAL/ITGB2 in association with ICAM3, contributes to apoptotic neutrophil phagocytosis by macrophages (PubMed:23775590). In association with alpha subunit ITGAM/CD11b, required for CD177-PRTN3-mediated activation of TNF primed neutrophils (PubMed:21193407). {ECO:0000269|PubMed:11812992, ECO:0000269|PubMed:15356110, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:21193407, ECO:0000269|PubMed:23775590, ECO:0000269|PubMed:28807980, ECO:0000269|PubMed:29100055}. |
| P06400 | RB1 | S758 | psp | Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110) | Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; FUNCTION: (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}. |
| P06400 | RB1 | S866 | ochoa | Retinoblastoma-associated protein (p105-Rb) (p110-RB1) (pRb) (Rb) (pp110) | Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle (PubMed:10499802). The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes (PubMed:10499802). Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription (PubMed:10499802). Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase (PubMed:10499802). RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C (PubMed:15084261). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases SUV39H1, KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Inhibits the intrinsic kinase activity of TAF1. Mediates transcriptional repression by SMARCA4/BRG1 by recruiting a histone deacetylase (HDAC) complex to the c-FOS promoter. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex (By similarity). {ECO:0000250|UniProtKB:P13405, ECO:0000250|UniProtKB:P33568, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:15084261}.; FUNCTION: (Microbial infection) In case of viral infections, interactions with SV40 large T antigen, HPV E7 protein or adenovirus E1A protein induce the disassembly of RB1-E2F1 complex thereby disrupting RB1's activity. {ECO:0000269|PubMed:1316611, ECO:0000269|PubMed:17974914, ECO:0000269|PubMed:18701596, ECO:0000269|PubMed:2839300, ECO:0000269|PubMed:8892909}. |
| P06733 | ENO1 | S336 | ochoa | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P07195 | LDHB | S168 | ochoa | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| P07195 | LDHB | S303 | ochoa | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| P07237 | P4HB | S32 | ochoa | Protein disulfide-isomerase (PDI) (EC 5.3.4.1) (Cellular thyroid hormone-binding protein) (Prolyl 4-hydroxylase subunit beta) (p55) | This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). {ECO:0000269|PubMed:10636893, ECO:0000269|PubMed:12485997, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:32149426}. |
| P07332 | FES | S117 | ochoa | Tyrosine-protein kinase Fes/Fps (EC 2.7.10.2) (Feline sarcoma/Fujinami avian sarcoma oncogene homolog) (Proto-oncogene c-Fes) (Proto-oncogene c-Fps) (p93c-fes) | Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28. {ECO:0000269|PubMed:11509660, ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:15485904, ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:17595334, ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:19001085, ECO:0000269|PubMed:19051325, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:2656706, ECO:0000269|PubMed:8955135}. |
| P07355 | ANXA2 | S89 | ochoa | Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity). {ECO:0000250|UniProtKB:P07356, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.; FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen. {ECO:0000269|PubMed:25139904}. |
| P07355 | ANXA2 | S164 | ochoa | Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity). {ECO:0000250|UniProtKB:P07356, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.; FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen. {ECO:0000269|PubMed:25139904}. |
| P07737 | PFN1 | S72 | psp | Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}. |
| P07864 | LDHC | S167 | ochoa | L-lactate dehydrogenase C chain (LDH-C) (EC 1.1.1.27) (Cancer/testis antigen 32) (CT32) (LDH testis subunit) (LDH-X) | Possible role in sperm motility. |
| P07900 | HSP90AA1 | S50 | 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}. |
| P07900 | HSP90AA1 | S505 | 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}. |
| P08133 | ANXA6 | S235 | 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. |
| P08133 | ANXA6 | S422 | 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 | S45 | 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}. |
| P08240 | SRPRA | S46 | ochoa | Signal recognition particle receptor subunit alpha (SR-alpha) (Docking protein alpha) (DP-alpha) | Component of the signal recognition particle (SRP) complex receptor (SR) (PubMed:16439358). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (PubMed:16675701, PubMed:34020957). Forms a guanosine 5'-triphosphate (GTP)-dependent complex with the SRP subunit SRP54 (PubMed:34020957). SRP receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER (PubMed:34020957). {ECO:0000269|PubMed:16439358, ECO:0000269|PubMed:16675701, ECO:0000269|PubMed:34020957}. |
| P08493 | MGP | S25 | psp | Matrix Gla protein (MGP) (Cell growth-inhibiting gene 36 protein) | Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation. |
| P08514 | ITGA2B | S432 | ochoa | Integrin alpha-IIb (GPalpha IIb) (GPIIb) (Platelet membrane glycoprotein IIb) (CD antigen CD41) [Cleaved into: Integrin alpha-IIb heavy chain; Integrin alpha-IIb light chain, form 1; Integrin alpha-IIb light chain, form 2] | Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain (By similarity). Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen (PubMed:9111081). This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface (By similarity). {ECO:0000250|UniProtKB:O54890, ECO:0000269|PubMed:9111081}. |
| P08758 | ANXA5 | S116 | ochoa | Annexin A5 (Anchorin CII) (Annexin V) (Annexin-5) (Calphobindin I) (CPB-I) (Endonexin II) (Lipocortin V) (Placental anticoagulant protein 4) (PP4) (Placental anticoagulant protein I) (PAP-I) (Thromboplastin inhibitor) (Vascular anticoagulant-alpha) (VAC-alpha) | This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. |
| P09874 | PARP1 | S463 | 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}. |
| P09874 | PARP1 | S519 | 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}. |
| P0CJ92 | GOLGA8H | S260 | ochoa | Golgin subfamily A member 8H | None |
| P10451 | SPP1 | S224 | ochoa|psp | Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) | Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}. |
| P10586 | PTPRF | S167 | ochoa | 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. |
| P11137 | MAP2 | S1398 | 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. |
| P11940 | PABPC1 | S120 | ochoa | Polyadenylate-binding protein 1 (PABP-1) (Poly(A)-binding protein 1) | Binds the poly(A) tail of mRNA, including that of its own transcript, and regulates processes of mRNA metabolism such as pre-mRNA splicing and mRNA stability (PubMed:11051545, PubMed:17212783, PubMed:25480299). Its function in translational initiation regulation can either be enhanced by PAIP1 or repressed by PAIP2 (PubMed:11051545, PubMed:20573744). Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo. Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). Involved in translationally coupled mRNA turnover (PubMed:11051545). 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 (PubMed:11051545). Involved in regulation of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons; for the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585). By binding to long poly(A) tails, may protect them from uridylation by ZCCHC6/ZCCHC11 and hence contribute to mRNA stability (PubMed:25480299). {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:17212783, ECO:0000269|PubMed:18447585, ECO:0000269|PubMed:20573744, ECO:0000269|PubMed:25480299, ECO:0000269|PubMed:32245947}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| P12277 | CKB | S309 | ochoa | Creatine kinase B-type (EC 2.7.3.2) (Brain creatine kinase) (B-CK) (Creatine kinase B chain) (Creatine phosphokinase B-type) (CPK-B) | Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8186255). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa (Probable). Acts as a key regulator of adaptive thermogenesis as part of the futile creatine cycle: localizes to the mitochondria of thermogenic fat cells and acts by mediating phosphorylation of creatine to initiate a futile cycle of creatine phosphorylation and dephosphorylation (By similarity). During the futile creatine cycle, creatine and N-phosphocreatine are in a futile cycle, which dissipates the high energy charge of N-phosphocreatine as heat without performing any mechanical or chemical work (By similarity). {ECO:0000250|UniProtKB:Q04447, ECO:0000269|PubMed:8186255, ECO:0000305}. |
| P12814 | ACTN1 | S91 | ochoa | Alpha-actinin-1 (Alpha-actinin cytoskeletal isoform) (F-actin cross-linking protein) (Non-muscle alpha-actinin-1) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000269|PubMed:22689882}. |
| P12882 | MYH1 | S1714 | ochoa | Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) | Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}. |
| P12883 | MYH7 | S1710 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P12931 | SRC | S97 | psp | Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src) | Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors (PubMed:34234773). Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.; FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in neurite elongation (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}. |
| P12956 | XRCC6 | S51 | psp | X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Negatively regulates apoptosis by interacting with BAX and sequestering it from the mitochondria (PubMed:15023334). Might have deubiquitination activity, acting on BAX (PubMed:18362350). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:18362350, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. |
| P12956 | XRCC6 | S477 | ochoa | X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Negatively regulates apoptosis by interacting with BAX and sequestering it from the mitochondria (PubMed:15023334). Might have deubiquitination activity, acting on BAX (PubMed:18362350). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:18362350, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. |
| P13010 | XRCC5 | S102 | ochoa | X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488}. |
| P13056 | NR2C1 | S90 | ochoa | Nuclear receptor subfamily 2 group C member 1 (Orphan nuclear receptor TR2) (Testicular receptor 2) | Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Also activator of OCT4 gene expression. May be involved in stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation. {ECO:0000269|PubMed:12093804, ECO:0000269|PubMed:17010934}. |
| P13489 | RNH1 | S84 | ochoa | Ribonuclease inhibitor (Placental ribonuclease inhibitor) (Placental RNase inhibitor) (Ribonuclease/angiogenin inhibitor 1) (RAI) | Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and angiogenin (ANG) (PubMed:12578357, PubMed:14515218, PubMed:3219362, PubMed:3243277, PubMed:3470787, PubMed:9050852). May play a role in redox homeostasis (PubMed:17292889). Required to inhibit the cytotoxic tRNA ribonuclease activity of ANG in the cytoplasm in absence of stress (PubMed:23843625, PubMed:32510170). Relocates to the nucleus in response to stress, relieving inhibition of ANG in the cytoplasm, and inhibiting the angiogenic activity of ANG in the nucleus (PubMed:23843625). {ECO:0000269|PubMed:12578357, ECO:0000269|PubMed:14515218, ECO:0000269|PubMed:17292889, ECO:0000269|PubMed:23843625, ECO:0000269|PubMed:3219362, ECO:0000269|PubMed:3243277, ECO:0000269|PubMed:32510170, ECO:0000269|PubMed:3470787, ECO:0000269|PubMed:9050852}. |
| P13533 | MYH6 | S1712 | ochoa | Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) | Muscle contraction. |
| P13535 | MYH8 | S1713 | ochoa | Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) | Muscle contraction. |
| P13639 | EEF2 | S584 | ochoa | 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}. |
| P14317 | HCLS1 | S62 | 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. |
| P14618 | PKM | S55 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P14625 | HSP90B1 | S106 | ochoa | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P14625 | HSP90B1 | S169 | ochoa | Endoplasmin (EC 3.6.4.-) (94 kDa glucose-regulated protein) (GRP-94) (Heat shock protein 90 kDa beta member 1) (Heat shock protein family C member 4) (Tumor rejection antigen 1) (gp96 homolog) | ATP-dependent chaperone involved in the processing of proteins in the endoplasmic reticulum, regulating their transport (PubMed:23572575, PubMed:39509507). Together with MESD, acts as a modulator of the Wnt pathway by promoting the folding of LRP6, a coreceptor of the canonical Wnt pathway (PubMed:23572575, PubMed:39509507). When associated with CNPY3, required for proper folding of Toll-like receptors (PubMed:11584270). Promotes folding and trafficking of TLR4 to the cell surface (PubMed:11584270). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). {ECO:0000269|PubMed:11584270, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:39509507}. |
| P14635 | CCNB1 | S370 | ochoa | G2/mitotic-specific cyclin-B1 | Essential for the control of the cell cycle at the G2/M (mitosis) transition. {ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:17495533, ECO:0000269|PubMed:27030811}. |
| P15498 | VAV1 | S215 | ochoa | Proto-oncogene vav | Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. |
| P15884 | TCF4 | S318 | ochoa | Transcription factor 4 (TCF-4) (Class B basic helix-loop-helix protein 19) (bHLHb19) (Immunoglobulin transcription factor 2) (ITF-2) (SL3-3 enhancer factor 2) (SEF-2) | Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'. {ECO:0000250}. |
| P15923 | TCF3 | S391 | ochoa | Transcription factor E2-alpha (Class B basic helix-loop-helix protein 21) (bHLHb21) (Immunoglobulin enhancer-binding factor E12/E47) (Immunoglobulin transcription factor 1) (Kappa-E2-binding factor) (Transcription factor 3) (TCF-3) (Transcription factor ITF-1) | Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition (By similarity). Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation (By similarity). Together with TCF15, required for the mesenchymal to epithelial transition (By similarity). Dimers bind DNA on E-box motifs: 5'-CANNTG-3' (By similarity). Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer (PubMed:2493990). Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region (By similarity). {ECO:0000250|UniProtKB:P15806, ECO:0000269|PubMed:2493990}.; FUNCTION: [Isoform E47]: Facilitates ATOH7 binding to DNA at the consensus sequence 5'-CAGGTG-3', and positively regulates transcriptional activity. {ECO:0000269|PubMed:31696227}. |
| P17174 | GOT1 | S66 | ochoa | Aspartate aminotransferase, cytoplasmic (cAspAT) (EC 2.6.1.1) (EC 2.6.1.3) (Cysteine aminotransferase, cytoplasmic) (Cysteine transaminase, cytoplasmic) (cCAT) (Glutamate oxaloacetate transaminase 1) (Transaminase A) | Biosynthesis of L-glutamate from L-aspartate or L-cysteine (PubMed:21900944). Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. In addition, catalyzes (2S)-2-aminobutanoate, a by-product in the cysteine biosynthesis pathway (PubMed:27827456). {ECO:0000269|PubMed:16039064, ECO:0000269|PubMed:21900944, ECO:0000269|PubMed:27827456}. |
| P17612 | PRKACA | S54 | ochoa | cAMP-dependent protein kinase catalytic subunit alpha (PKA C-alpha) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:31112131). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (PubMed:33934390). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:33934390}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}. |
| P17661 | DES | S82 | ochoa | Desmin | Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Required for nuclear membrane integrity, via anchoring at the cell tip and nuclear envelope, resulting in maintenance of microtubule-derived intracellular mechanical forces (By similarity). Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity). {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190, ECO:0000303|PubMed:25358400}. |
| P18085 | ARF4 | S137 | ochoa | ADP-ribosylation factor 4 | GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus. 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:0000269|PubMed:25673879}. |
| P18206 | VCL | S357 | 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 | S439 | 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 | S574 | 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}. |
| P18859 | ATP5PF | S65 | ochoa | ATP synthase peripheral stalk subunit F6, mitochondrial (ATPase subunit F6) (ATP synthase peripheral stalk subunit F6) | Subunit F6, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (PubMed:37244256). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). Part of the complex F(0) domain (PubMed:37244256). Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements (By similarity). {ECO:0000250|UniProtKB:P02721, ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P19338 | NCL | S482 | 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}. |
| P19484 | TFEB | S151 | ochoa | Transcription factor EB (Class E basic helix-loop-helix protein 35) (bHLHe35) | Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:30120233, PubMed:31672913, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823, PubMed:36749723, PubMed:37079666). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (PubMed:19556463, PubMed:22692423). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica: infection promotes itaconate production, leading to alkylation, resulting in nuclear localization and transcription factor activity (PubMed:35662396). Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response (PubMed:35662396). In association with ACSS2, promotes the expression of genes involved in lysosome biogenesis and both autophagy upon glucose deprivation (PubMed:28552616). {ECO:0000250|UniProtKB:Q9R210, ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:36749723, ECO:0000269|PubMed:37079666}. |
| P20042 | EIF2S2 | S67 | ochoa|psp | Eukaryotic translation initiation factor 2 subunit 2 (Eukaryotic translation initiation factor 2 subunit beta) (eIF2-beta) | Component of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:31836389). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF2B (By similarity). {ECO:0000250|UniProtKB:P05198, ECO:0000269|PubMed:31836389}. |
| P20340 | RAB6A | S117 | ochoa | Ras-related protein Rab-6A (Rab-6) (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:25962623). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:25962623). RAB6A acts as a regulator of COPI-independent retrograde transport from the Golgi apparatus towards the endoplasmic reticulum (ER) (PubMed:25962623). Has a low GTPase activity (PubMed:25962623). Recruits VPS13B to the Golgi membrane (PubMed:25492866). Plays a role in neuron projection development (Probable). {ECO:0000269|PubMed:25492866, ECO:0000269|PubMed:25962623, ECO:0000305|PubMed:25492866}. |
| P20700 | LMNB1 | S375 | ochoa | Lamin-B1 | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:28716252, PubMed:32910914). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:28716252, PubMed:32910914). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:28716252, PubMed:32910914). {ECO:0000269|PubMed:28716252, ECO:0000269|PubMed:32910914}. |
| P21333 | FLNA | S108 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | S1976 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P21333 | FLNA | S2158 | ochoa | Filamin-A (FLN-A) (Actin-binding protein 280) (ABP-280) (Alpha-filamin) (Endothelial actin-binding protein) (Filamin-1) (Non-muscle filamin) | Promotes orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton and serves as a scaffold for a wide range of cytoplasmic signaling proteins. Interaction with FLNB may allow neuroblast migration from the ventricular zone into the cortical plate. Tethers cell surface-localized furin, modulates its rate of internalization and directs its intracellular trafficking (By similarity). Involved in ciliogenesis. Plays a role in cell-cell contacts and adherens junctions during the development of blood vessels, heart and brain organs. Plays a role in platelets morphology through interaction with SYK that regulates ITAM- and ITAM-like-containing receptor signaling, resulting in by platelet cytoskeleton organization maintenance (By similarity). During the axon guidance process, required for growth cone collapse induced by SEMA3A-mediated stimulation of neurons (PubMed:25358863). {ECO:0000250, ECO:0000250|UniProtKB:Q8BTM8, ECO:0000269|PubMed:22121117, ECO:0000269|PubMed:25358863}. |
| P22314 | UBA1 | S56 | 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}. |
| P22694 | PRKACB | S54 | ochoa | cAMP-dependent protein kinase catalytic subunit beta (PKA C-beta) (EC 2.7.11.11) | Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs (PubMed:12420224, PubMed:21423175, PubMed:31112131). PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux (PubMed:12420224, PubMed:21423175). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142, ECO:0000269|PubMed:31112131}. |
| P25090 | FPR2 | S237 | 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}. |
| P25705 | ATP5F1A | S236 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P25705 | ATP5F1A | S517 | ochoa | ATP synthase F(1) complex subunit alpha, mitochondrial (ATP synthase F1 subunit alpha) | Subunit alpha, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain (Probable). ATP synthase complex consist of a soluble F(1) head domain - the catalytic core - and a membrane F(1) domain - the membrane proton channel (PubMed:37244256). These two domains are linked by a central stalk rotating inside the F(1) region and a stationary peripheral stalk (PubMed:37244256). During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation (Probable). In vivo, can only synthesize ATP although its ATP hydrolase activity can be activated artificially in vitro (By similarity). With the catalytic subunit beta (ATP5F1B), forms the catalytic core in the F(1) domain (PubMed:37244256). Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (Probable). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159). {ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:30146159, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P26639 | TARS1 | S702 | 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}. |
| P26951 | IL3RA | S348 | ochoa | Interleukin-3 receptor subunit alpha (IL-3 receptor subunit alpha) (IL-3R subunit alpha) (IL-3R-alpha) (IL-3RA) (CD antigen CD123) | Cell surface receptor for IL3 expressed on hematopoietic progenitor cells, monocytes and B-lymphocytes that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells (PubMed:10527461). Ligand stimulation rapidly induces hetrodimerization with IL3RB, phosphorylation and enzyme activity of effector proteins such as JAK2 and PI3K that play a role in signaling cell proliferation and differentiation. Activation of JAK2 leads to STAT5-mediated transcriptional program (By similarity). {ECO:0000250|UniProtKB:P26952, ECO:0000269|PubMed:10527461, ECO:0000269|PubMed:29374162}. |
| P27348 | YWHAQ | S92 | 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 | S214 | 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}. |
| P27635 | RPL10 | S54 | ochoa | Large ribosomal subunit protein uL16 (60S ribosomal protein L10) (Laminin receptor homolog) (Protein QM) (Ribosomal protein L10) (Tumor suppressor QM) | Component of the large ribosomal subunit (PubMed:26290468). Plays a role in the formation of actively translating ribosomes (PubMed:26290468). May play a role in the embryonic brain development (PubMed:25316788). {ECO:0000269|PubMed:25316788, ECO:0000269|PubMed:26290468, ECO:0000305|PubMed:12962325}. |
| P27815 | PDE4A | S567 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46) (cAMP-specific phosphodiesterase 4A) | Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:11566027, ECO:0000269|PubMed:2160582}.; FUNCTION: [Isoform 1]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 3]: Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP. {ECO:0000269|PubMed:7888306}.; FUNCTION: [Isoform 4]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:9677330}.; FUNCTION: [Isoform 6]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310, ECO:0000269|PubMed:17727341}.; FUNCTION: [Isoform 7]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:18095939}. |
| P27816 | MAP4 | S330 | ochoa | Microtubule-associated protein 4 (MAP-4) | Non-neuronal microtubule-associated protein. Promotes microtubule assembly. {ECO:0000269|PubMed:10791892, ECO:0000269|PubMed:34782749}. |
| P28908 | TNFRSF8 | S429 | ochoa | Tumor necrosis factor receptor superfamily member 8 (CD30L receptor) (Ki-1 antigen) (Lymphocyte activation antigen CD30) (CD antigen CD30) | Receptor for TNFSF8/CD30L (PubMed:8391931). May play a role in the regulation of cellular growth and transformation of activated lymphoblasts. Regulates gene expression through activation of NF-kappa-B (PubMed:8999898). {ECO:0000269|PubMed:8391931, ECO:0000269|PubMed:8999898}. |
| P29274 | ADORA2A | S374 | psp | Adenosine receptor A2a | Receptor for adenosine (By similarity). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity). {ECO:0000250|UniProtKB:P11617}. |
| P29317 | EPHA2 | S579 | 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}. |
| P29323 | EPHB2 | S575 | 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}. |
| P29350 | PTPN6 | S57 | ochoa | Tyrosine-protein phosphatase non-receptor type 6 (EC 3.1.3.48) (Hematopoietic cell protein-tyrosine phosphatase) (Protein-tyrosine phosphatase 1C) (PTP-1C) (Protein-tyrosine phosphatase SHP-1) (SH-PTP1) | Tyrosine phosphatase enzyme that plays important roles in controlling immune signaling pathways and fundamental physiological processes such as hematopoiesis (PubMed:14739280, PubMed:29925997). Dephosphorylates and negatively regulate several receptor tyrosine kinases (RTKs) such as EGFR, PDGFR and FGFR, thereby modulating their signaling activities (PubMed:21258366, PubMed:9733788). When recruited to immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors such as immunoglobulin-like transcript 2/LILRB1, programmed cell death protein 1/PDCD1, CD3D, CD22, CLEC12A and other receptors involved in immune regulation, initiates their dephosphorylation and subsequently inhibits downstream signaling events (PubMed:11907092, PubMed:14739280, PubMed:37932456, PubMed:38166031). Modulates the signaling of several cytokine receptors including IL-4 receptor (PubMed:9065461). Additionally, targets multiple cytoplasmic signaling molecules including STING1, LCK or STAT1 among others involved in diverse cellular processes including modulation of T-cell activation or cGAS-STING signaling (PubMed:34811497, PubMed:38532423). Within the nucleus, negatively regulates the activity of some transcription factors such as NFAT5 via direct dephosphorylation. Also acts as a key transcriptional regulator of hepatic gluconeogenesis by controlling recruitment of RNA polymerase II to the PCK1 promoter together with STAT5A (PubMed:37595871). {ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:11266449, ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:14739280, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:29925997, ECO:0000269|PubMed:34811497, ECO:0000269|PubMed:37595871, ECO:0000269|PubMed:37932456, ECO:0000269|PubMed:38166031, ECO:0000269|PubMed:38532423, ECO:0000269|PubMed:9065461, ECO:0000269|PubMed:9733788}. |
| P29374 | ARID4A | S1108 | ochoa | AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) | DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}. |
| P29375 | KDM5A | S287 | psp | Lysine-specific demethylase 5A (EC 1.14.11.67) (Histone demethylase JARID1A) (Jumonji/ARID domain-containing protein 1A) (Retinoblastoma-binding protein 2) (RBBP-2) ([histone H3]-trimethyl-L-lysine(4) demethylase 5A) | Histone demethylase that specifically demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (PubMed:19430464). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (PubMed:27427228). {ECO:0000250|UniProtKB:Q3UXZ9, ECO:0000269|PubMed:11358960, ECO:0000269|PubMed:15949438, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17320163, ECO:0000269|PubMed:18270511, ECO:0000269|PubMed:19430464, ECO:0000269|PubMed:27427228}. |
| P29401 | TKT | S256 | ochoa | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| P29558 | RBMS1 | S213 | ochoa | RNA-binding motif, single-stranded-interacting protein 1 (Single-stranded DNA-binding protein MSSP-1) (Suppressor of CDC2 with RNA-binding motif 2) | Single-stranded DNA binding protein that interacts with the region upstream of the MYC gene. Binds specifically to the DNA sequence motif 5'-[AT]CT[AT][AT]T-3'. Probably has a role in DNA replication. |
| P29966 | MARCKS | S52 | ochoa | Myristoylated alanine-rich C-kinase substrate (MARCKS) (Protein kinase C substrate, 80 kDa protein, light chain) (80K-L protein) (PKCSL) | Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes (PubMed:23704996, PubMed:36009319). Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis (PubMed:23704996). During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages (PubMed:37949888). Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton (By similarity). Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane (By similarity). {ECO:0000250|UniProtKB:P26645, ECO:0000250|UniProtKB:P30009, ECO:0000269|PubMed:23704996, ECO:0000269|PubMed:36009319, ECO:0000269|PubMed:37949888}. |
| P30622 | CLIP1 | S193 | ochoa | CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) | Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}. |
| P30622 | CLIP1 | S1236 | ochoa | CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) | Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}. |
| P31327 | CPS1 | S1090 | ochoa | Carbamoyl-phosphate synthase [ammonia], mitochondrial (EC 6.3.4.16) (Carbamoyl-phosphate synthetase I) (CPSase I) | Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell. |
| P31689 | DNAJA1 | S112 | ochoa | DnaJ homolog subfamily A member 1 (DnaJ protein homolog 2) (HSDJ) (Heat shock 40 kDa protein 4) (Heat shock protein J2) (HSJ-2) (Human DnaJ protein 2) (hDj-2) | Co-chaperone for HSPA8/Hsc70 (PubMed:10816573). Stimulates ATP hydrolysis, but not the folding of unfolded proteins mediated by HSPA1A (in vitro) (PubMed:24318877). Plays a role in protein transport into mitochondria via its role as co-chaperone. Functions as a co-chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis (PubMed:14752510). Promotes apoptosis in response to cellular stress mediated by exposure to anisomycin or UV (PubMed:24512202). {ECO:0000269|PubMed:10816573, ECO:0000269|PubMed:14752510, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24512202, ECO:0000269|PubMed:9192730}. |
| P31946 | YWHAB | S216 | 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 | S216 | 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}. |
| P32298 | GRK4 | S419 | psp | G protein-coupled receptor kinase 4 (EC 2.7.11.16) (G protein-coupled receptor kinase GRK4) (ITI1) | Specifically phosphorylates the activated forms of G protein-coupled receptors. GRK4-alpha can phosphorylate rhodopsin and its activity is inhibited by calmodulin; the other three isoforms do not phosphorylate rhodopsin and do not interact with calmodulin. GRK4-alpha and GRK4-gamma phosphorylate DRD3. Phosphorylates ADRB2. {ECO:0000269|PubMed:19520868, ECO:0000269|PubMed:8626439}. |
| P33176 | KIF5B | S833 | ochoa | Kinesin-1 heavy chain (Conventional kinesin heavy chain) (Ubiquitous kinesin heavy chain) (UKHC) | Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). {ECO:0000250|UniProtKB:Q2PQA9, ECO:0000250|UniProtKB:Q61768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:24088571, ECO:0000305|PubMed:22172677, ECO:0000305|PubMed:24088571}. |
| P33981 | TTK | S321 | ochoa|psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P33981 | TTK | S582 | psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P35250 | RFC2 | S30 | ochoa | Replication factor C subunit 2 (Activator 1 40 kDa subunit) (A1 40 kDa subunit) (Activator 1 subunit 2) (Replication factor C 40 kDa subunit) (RF-C 40 kDa subunit) (RFC40) | Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA (PubMed:9488738). This subunit binds ATP (By similarity). {ECO:0000250, ECO:0000269|PubMed:9488738}. |
| P35251 | RFC1 | S1093 | ochoa | Replication factor C subunit 1 (Activator 1 140 kDa subunit) (A1 140 kDa subunit) (Activator 1 large subunit) (Activator 1 subunit 1) (DNA-binding protein PO-GA) (Replication factor C 140 kDa subunit) (RF-C 140 kDa subunit) (RFC140) (Replication factor C large subunit) | Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA (PubMed:9488738). This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Can bind single- or double-stranded DNA. {ECO:0000269|PubMed:8999859, ECO:0000269|PubMed:9488738}. |
| P35367 | HRH1 | S233 | ochoa | Histamine H1 receptor (H1-R) (H1R) (HH1R) | G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity). {ECO:0000250|UniProtKB:P70174, ECO:0000269|PubMed:33828102, ECO:0000269|PubMed:8280179}. |
| P35442 | THBS2 | S238 | ochoa | Thrombospondin-2 | Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Ligand for CD36 mediating antiangiogenic properties. {ECO:0000269|PubMed:20714802}. |
| P35579 | MYH9 | S1195 | 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}. |
| P35609 | ACTN2 | S840 | ochoa | Alpha-actinin-2 (Alpha-actinin skeletal muscle isoform 2) (F-actin cross-linking protein) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. |
| P35611 | ADD1 | S532 | ochoa | Alpha-adducin (Erythrocyte adducin subunit alpha) | Membrane-cytoskeleton-associated protein that promotes the assembly of the spectrin-actin network. Binds to calmodulin. |
| P35749 | MYH11 | S1121 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P35869 | AHR | S440 | psp | Aryl hydrocarbon receptor (Ah receptor) (AhR) (Class E basic helix-loop-helix protein 76) (bHLHe76) | Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer (PubMed:23275542, PubMed:30373764, PubMed:32818467, PubMed:7961644). Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) (PubMed:23275542, PubMed:30373764, PubMed:7961644). Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (PubMed:12213388). Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) (PubMed:7961644, PubMed:33193710). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons (PubMed:34521881, PubMed:7961644). Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists (PubMed:18076143). Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands (PubMed:32818467, PubMed:32866000). Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity (PubMed:32818467). Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 (PubMed:28602820). Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 (PubMed:28602820). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28602820). {ECO:0000269|PubMed:23275542, ECO:0000269|PubMed:28602820, ECO:0000269|PubMed:30373764, ECO:0000269|PubMed:32818467, ECO:0000269|PubMed:32866000, ECO:0000269|PubMed:33193710, ECO:0000269|PubMed:34521881, ECO:0000269|PubMed:7961644, ECO:0000303|PubMed:12213388, ECO:0000303|PubMed:18076143}. |
| P36776 | LONP1 | S176 | ochoa | 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}. |
| P36897 | TGFBR1 | S187 | 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}. |
| P36897 | TGFBR1 | S189 | psp | TGF-beta receptor type-1 (TGFR-1) (EC 2.7.11.30) (Activin A receptor type II-like protein kinase of 53kD) (Activin receptor-like kinase 5) (ALK-5) (ALK5) (Serine/threonine-protein kinase receptor R4) (SKR4) (TGF-beta type I receptor) (Transforming growth factor-beta receptor type I) (TGF-beta receptor type I) (TbetaR-I) | Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis (PubMed:33914044). The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation. {ECO:0000269|PubMed:15761148, ECO:0000269|PubMed:16754747, ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:33914044, ECO:0000269|PubMed:7774578, ECO:0000269|PubMed:8752209, ECO:0000269|PubMed:8980228, ECO:0000269|PubMed:9346908}. |
| P36956 | SREBF1 | S394 | ochoa | Sterol regulatory element-binding protein 1 (SREBP-1) (Class D basic helix-loop-helix protein 1) (bHLHd1) (Sterol regulatory element-binding transcription factor 1) [Cleaved into: Processed sterol regulatory element-binding protein 1 (Transcription factor SREBF1)] | [Sterol regulatory element-binding protein 1]: Precursor of the transcription factor form (Processed sterol regulatory element-binding protein 1), which is embedded in the endoplasmic reticulum membrane (PubMed:32322062). Low sterol concentrations promote processing of this form, releasing the transcription factor form that translocates into the nucleus and activates transcription of genes involved in cholesterol biosynthesis and lipid homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:32322062}.; FUNCTION: [Processed sterol regulatory element-binding protein 1]: Key transcription factor that regulates expression of genes involved in cholesterol biosynthesis and lipid homeostasis (PubMed:12177166, PubMed:32322062, PubMed:8402897). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3') (PubMed:12177166, PubMed:8402897). Regulates the promoters of genes involved in cholesterol biosynthesis and the LDL receptor (LDLR) pathway of sterol regulation (PubMed:12177166, PubMed:32322062, PubMed:8402897). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:8402897}.; FUNCTION: [Isoform SREBP-1A]: Isoform expressed only in select tissues, which has higher transcriptional activity compared to SREBP-1C (By similarity). Able to stimulate both lipogenic and cholesterogenic gene expression (PubMed:12177166, PubMed:32497488). Has a role in the nutritional regulation of fatty acids and triglycerides in lipogenic organs such as the liver (By similarity). Required for innate immune response in macrophages by regulating lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166, ECO:0000269|PubMed:32497488}.; FUNCTION: [Isoform SREBP-1C]: Predominant isoform expressed in most tissues, which has weaker transcriptional activity compared to isoform SREBP-1A (By similarity). Primarily controls expression of lipogenic gene (PubMed:12177166). Strongly activates global lipid synthesis in rapidly growing cells (By similarity). {ECO:0000250|UniProtKB:Q9WTN3, ECO:0000269|PubMed:12177166}.; FUNCTION: [Isoform SREBP-1aDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}.; FUNCTION: [Isoform SREBP-1cDelta]: The absence of Golgi proteolytic processing requirement makes this isoform constitutively active in transactivation of lipogenic gene promoters. {ECO:0000305|PubMed:7759101}. |
| P37275 | ZEB1 | S458 | ochoa | Zinc finger E-box-binding homeobox 1 (NIL-2-A zinc finger protein) (Negative regulator of IL2) (Transcription factor 8) (TCF-8) | Acts as a transcriptional repressor. Inhibits interleukin-2 (IL-2) gene expression. Enhances or represses the promoter activity of the ATP1A1 gene depending on the quantity of cDNA and on the cell type. Represses E-cadherin promoter and induces an epithelial-mesenchymal transition (EMT) by recruiting SMARCA4/BRG1. Represses BCL6 transcription in the presence of the corepressor CTBP1. Positively regulates neuronal differentiation. Represses RCOR1 transcription activation during neurogenesis. Represses transcription by binding to the E box (5'-CANNTG-3'). In the absence of TGFB1, acts as a repressor of COL1A2 transcription via binding to the E-box in the upstream enhancer region (By similarity). {ECO:0000250|UniProtKB:Q64318, ECO:0000269|PubMed:19935649, ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. |
| P38398 | BRCA1 | S426 | 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 | S1466 | 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}. |
| P38936 | CDKN1A | S31 | ochoa | Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) (Melanoma differentiation-associated protein 6) (MDA-6) (p21) | Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Negatively regulates the CDK4- and CDK6-driven phosphorylation of RB1 in keratinocytes, thereby resulting in the release of E2F1 and subsequent transcription of E2F1-driven G1/S phase promoting genes (By similarity). {ECO:0000250|UniProtKB:P39689, ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}. |
| P39687 | ANP32A | S77 | ochoa | 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}. |
| P40425 | PBX2 | S159 | ochoa | Pre-B-cell leukemia transcription factor 2 (Homeobox protein PBX2) (Protein G17) | Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1. {ECO:0000269|PubMed:12609849}. |
| P40926 | MDH2 | S317 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P41235 | HNF4A | S190 | psp | Hepatocyte nuclear factor 4-alpha (HNF-4-alpha) (Nuclear receptor subfamily 2 group A member 1) (Transcription factor 14) (TCF-14) (Transcription factor HNF-4) | Transcriptional regulator which controls the expression of hepatic genes during the transition of endodermal cells to hepatic progenitor cells, facilitating the recruitment of RNA pol II to the promoters of target genes (PubMed:30597922). Activates the transcription of CYP2C38 (By similarity). Represses the CLOCK-BMAL1 transcriptional activity and is essential for circadian rhythm maintenance and period regulation in the liver and colon cells (PubMed:30530698). {ECO:0000250|UniProtKB:P49698, ECO:0000269|PubMed:30530698, ECO:0000269|PubMed:30597922}. |
| P41743 | PRKCI | S44 | 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}. |
| P42285 | MTREX | S687 | ochoa | Exosome RNA helicase MTR4 (EC 3.6.4.13) (ATP-dependent RNA helicase DOB1) (ATP-dependent RNA helicase SKIV2L2) (Superkiller viralicidic activity 2-like 2) (TRAMP-like complex helicase) | Catalyzes the ATP-dependent unwinding of RNA duplexes with a single-stranded 3' RNA extension (PubMed:27871484, PubMed:29844170, PubMed:29906447). Central subunit of many protein complexes, namely TRAMP-like, nuclear exosome targeting (NEXT) and poly(A) tail exosome targeting (PAXT) (PubMed:21855801, PubMed:27871484, PubMed:29844170). NEXT functions as an RNA exosome cofactor that directs a subset of non-coding short-lived RNAs for exosomal degradation. NEXT is involved in surveillance and turnover of aberrant transcripts and non-coding RNAs (PubMed:27871484, PubMed:29844170). PAXT directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor ZCCHC8, which links to RNA-binding protein adapters (PubMed:27871484). Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA (PubMed:17412707, PubMed:29107693). May be involved in pre-mRNA splicing. In the context of NEXT complex can also in vitro unwind DNA:RNA heteroduplexes with a 3' poly (A) RNA tracking strand (PubMed:29844170). Can promote unwinding and degradation of structured RNA substrates when associated with the nuclear exosome and its cofactors. Can displace a DNA strand while translocating on RNA to ultimately degrade the RNA within a DNA/RNA heteroduplex (PubMed:29906447). Plays a role in DNA damage response (PubMed:29902117). {ECO:0000269|PubMed:17412707, ECO:0000269|PubMed:21855801, ECO:0000269|PubMed:27871484, ECO:0000269|PubMed:29107693, ECO:0000269|PubMed:29844170, ECO:0000269|PubMed:29902117, ECO:0000269|PubMed:29906447}. |
| P42356 | PI4KA | S761 | ochoa | Phosphatidylinositol 4-kinase alpha (PI4-kinase alpha) (PI4K-alpha) (PtdIns-4-kinase alpha) (EC 2.7.1.67) (Phosphatidylinositol 4-Kinase III alpha) | Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate. {ECO:0000269|PubMed:10101268, ECO:0000269|PubMed:23229899}. |
| P43403 | ZAP70 | S88 | ochoa | 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}. |
| P46013 | MKI67 | S1704 | 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 | S729 | 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}. |
| P46100 | ATRX | S1244 | 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}. |
| P46527 | CDKN1B | S138 | ochoa | Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1) | Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. {ECO:0000269|PubMed:10831586, ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17254966, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:28666995}. |
| P46531 | NOTCH1 | S1791 | psp | Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). {ECO:0000269|PubMed:20616313}. |
| P46776 | RPL27A | S106 | ochoa | 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}. |
| P46939 | UTRN | S784 | ochoa | Utrophin (Dystrophin-related protein 1) (DRP-1) | May play a role in anchoring the cytoskeleton to the plasma membrane. {ECO:0000250}. |
| P46940 | IQGAP1 | S480 | ochoa|psp | 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}. |
| P48163 | ME1 | S219 | ochoa | NADP-dependent malic enzyme (NADP-ME) (EC 1.1.1.40) (Malic enzyme 1) | Catalyzes the oxidative decarboxylation of (S)-malate in the presence of NADP(+) and divalent metal ions, and decarboxylation of oxaloacetate. {ECO:0000269|PubMed:7622060, ECO:0000269|PubMed:7757881, ECO:0000269|PubMed:8187880, ECO:0000269|PubMed:8804575}. |
| P48200 | IREB2 | S177 | ochoa | Iron-responsive element-binding protein 2 (IRE-BP 2) (Iron regulatory protein 2) (IRP2) | RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA. {ECO:0000269|PubMed:7983023}. |
| P48552 | NRIP1 | S102 | ochoa | Nuclear receptor-interacting protein 1 (Nuclear factor RIP140) (Receptor-interacting protein 140) | Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors. Positive regulator of the circadian clock gene expression: stimulates transcription of BMAL1, CLOCK and CRY1 by acting as a coactivator for RORA and RORC. Involved in the regulation of ovarian function (By similarity). Plays a role in renal development (PubMed:28381549). {ECO:0000250|UniProtKB:Q8CBD1, ECO:0000269|PubMed:10364267, ECO:0000269|PubMed:11509661, ECO:0000269|PubMed:11518808, ECO:0000269|PubMed:12554755, ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:28381549, ECO:0000269|PubMed:7641693}. |
| P48637 | GSS | S149 | ochoa | Glutathione synthetase (GSH synthetase) (GSH-S) (EC 6.3.2.3) (Glutathione synthase) | Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner (PubMed:7646467, PubMed:9215686). Glutathione (gamma-glutamylcysteinylglycine, GSH) is the most abundant intracellular thiol in living aerobic cells and is required for numerous processes including the protection of cells against oxidative damage, amino acid transport, the detoxification of foreign compounds, the maintenance of protein sulfhydryl groups in a reduced state and acts as a cofactor for a number of enzymes (PubMed:10369661). Participates in ophthalmate biosynthesis in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51855, ECO:0000269|PubMed:7646467, ECO:0000269|PubMed:9215686, ECO:0000303|PubMed:10369661}. |
| P48681 | NES | S831 | ochoa | Nestin | Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}. |
| P48729 | CSNK1A1 | S242 | psp | Casein kinase I isoform alpha (CKI-alpha) (EC 2.7.11.1) (CK1) | Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (PubMed:11955436, PubMed:1409656, PubMed:18305108, PubMed:23902688). It can phosphorylate a large number of proteins (PubMed:11955436, PubMed:1409656, PubMed:18305108, PubMed:23902688). Participates in Wnt signaling (PubMed:11955436). Phosphorylates CTNNB1 at 'Ser-45' (PubMed:11955436). May phosphorylate PER1 and PER2 (By similarity). May play a role in segregating chromosomes during mitosis (PubMed:1409656). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688). Acts as a positive regulator of mTORC1 and mTORC2 signaling in response to nutrients by mediating phosphorylation of DEPTOR inhibitor (PubMed:22017875, PubMed:22017877). Acts as an inhibitor of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). {ECO:0000250|UniProtKB:Q8BK63, ECO:0000269|PubMed:11955436, ECO:0000269|PubMed:1409656, ECO:0000269|PubMed:18305108, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:23902688}. |
| P49023 | PXN | S260 | ochoa | Paxillin | Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion. {ECO:0000269|PubMed:25015296}. |
| P49591 | SARS1 | S241 | psp | Serine--tRNA ligase, cytoplasmic (EC 6.1.1.11) (Seryl-tRNA synthetase) (SerRS) (Seryl-tRNA(Ser/Sec) synthetase) | Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:36041817, PubMed:9431993). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:9431993). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423847, PubMed:19423848, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:34570399, ECO:0000269|PubMed:36041817, ECO:0000269|PubMed:9431993}. |
| P49662 | CASP4 | S280 | ochoa | Caspase-4 (CASP-4) (EC 3.4.22.57) (ICE and Ced-3 homolog 2) (ICH-2) (ICE(rel)-II) (Mih1) (Protease TX) [Cleaved into: Caspase-4 subunit p10; Caspase-4 subunit p20] | Inflammatory caspase that acts as the effector of the non-canonical inflammasome by mediating lipopolysaccharide (LPS)-induced pyroptosis (PubMed:25119034, PubMed:26375003, PubMed:32109412, PubMed:34671164, PubMed:37001519, PubMed:37993712, PubMed:37993714). Also indirectly activates the NLRP3 and NLRP6 inflammasomes (PubMed:23516580, PubMed:26375003, PubMed:32109412, PubMed:7797510). Acts as a thiol protease that cleaves a tetrapeptide after an Asp residue at position P1: catalyzes cleavage of CGAS, GSDMD and IL18 (PubMed:15326478, PubMed:23516580, PubMed:26375003, PubMed:28314590, PubMed:32109412, PubMed:37993712, PubMed:37993714, PubMed:7797510). Effector of the non-canonical inflammasome independently of NLRP3 inflammasome and CASP1: the non-canonical inflammasome promotes pyroptosis through GSDMD cleavage without involving secretion of cytokine IL1B (PubMed:25119034, PubMed:25121752, PubMed:26375003, PubMed:31268602, PubMed:32109412, PubMed:37993712, PubMed:37993714). In the non-canonical inflammasome, CASP4 is activated by direct binding to the lipid A moiety of LPS without the need of an upstream sensor (PubMed:25119034, PubMed:25121752, PubMed:29520027, PubMed:32510692, PubMed:32581219, PubMed:37993712). LPS-binding promotes CASP4 activation and CASP4-mediated cleavage of GSDMD and IL18, followed by IL18 secretion through the GSDMD pore, pyroptosis of infected cells and their extrusion into the gut lumen (PubMed:25119034, PubMed:25121752, PubMed:37993712, PubMed:37993714). Also indirectly promotes secretion of mature cytokines (IL1A and HMGB1) downstream of GSDMD-mediated pyroptosis via activation of the NLRP3 and NLRP6 inflammasomes (PubMed:26375003, PubMed:32109412). Involved in NLRP3-dependent CASP1 activation and IL1B secretion in response to non-canonical activators, such as UVB radiation or cholera enterotoxin (PubMed:22246630, PubMed:23516580, PubMed:24879791, PubMed:25964352, PubMed:26173988, PubMed:26174085, PubMed:26508369). Involved in NLRP6 inflammasome-dependent activation in response to lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, which leads to CASP1 activation and IL1B secretion (PubMed:33377178). Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). The non-canonical inflammasome is required for innate immunity to cytosolic, but not vacuolar, bacteria (By similarity). Plays a crucial role in the restriction of S.typhimurium replication in colonic epithelial cells during infection (PubMed:25121752, PubMed:25964352). Activation of the non-canonical inflammasome in brain endothelial cells can lead to excessive pyroptosis, leading to blood-brain barrier breakdown (By similarity). Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation (PubMed:25121752, PubMed:25964352, PubMed:26375003). May also act as an activator of adaptive immunity in dendritic cells, following activation by oxidized phospholipid 1-palmitoyl-2-arachidonoyl- sn-glycero-3-phosphorylcholine, an oxidized phospholipid (oxPAPC) (By similarity). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found in Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Cleavage of GSDMD is not strictly dependent on the consensus cleavage site but depends on an exosite interface on CASP4 that recognizes and binds the Gasdermin-D, C-terminal (GSDMD-CT) part (PubMed:32109412). Catalyzes cleavage and maturation of IL18; IL18 processing also depends of the exosite interface on CASP4 (PubMed:15326478, PubMed:37993712, PubMed:37993714). In contrast, it does not directly process IL1B (PubMed:7743998, PubMed:7797510, PubMed:7797592). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590). {ECO:0000250|UniProtKB:P70343, ECO:0000269|PubMed:15123740, ECO:0000269|PubMed:15326478, ECO:0000269|PubMed:22246630, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:23661706, ECO:0000269|PubMed:24879791, ECO:0000269|PubMed:25119034, ECO:0000269|PubMed:25121752, ECO:0000269|PubMed:25964352, ECO:0000269|PubMed:26173988, ECO:0000269|PubMed:26174085, ECO:0000269|PubMed:26375003, ECO:0000269|PubMed:26508369, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:29520027, ECO:0000269|PubMed:31268602, ECO:0000269|PubMed:32109412, ECO:0000269|PubMed:32510692, ECO:0000269|PubMed:32581219, ECO:0000269|PubMed:33377178, ECO:0000269|PubMed:34671164, ECO:0000269|PubMed:37001519, ECO:0000269|PubMed:37993714, ECO:0000269|PubMed:7743998, ECO:0000269|PubMed:7797510, ECO:0000269|PubMed:7797592}.; FUNCTION: (Microbial infection) In response to the Td92 surface protein of the periodontal pathogen T.denticola, activated by cathepsin CTSG which leads to production and secretion of IL1A and pyroptosis of gingival fibroblasts. {ECO:0000269|PubMed:29077095}. |
| P49711 | CTCF | S450 | ochoa | Transcriptional repressor CTCF (11-zinc finger protein) (CCCTC-binding factor) (CTCFL paralog) | Chromatin binding factor that binds to DNA sequence specific sites and regulates the 3D structure of chromatin (PubMed:18347100, PubMed:18654629, PubMed:19322193). Binds together strands of DNA, thus forming chromatin loops, and anchors DNA to cellular structures, such as the nuclear lamina (PubMed:18347100, PubMed:18654629, PubMed:19322193). Defines the boundaries between active and heterochromatic DNA via binding to chromatin insulators, thereby preventing interaction between promoter and nearby enhancers and silencers (PubMed:18347100, PubMed:18654629, PubMed:19322193). Plays a critical role in the epigenetic regulation (PubMed:16949368). Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus (PubMed:16107875, PubMed:16815976, PubMed:17827499). On the maternal allele, binding within the H19 imprinting control region (ICR) mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to IGF2 (By similarity). Mediates interchromosomal association between IGF2/H19 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory (By similarity). Regulates asynchronous replication of IGF2/H19 (By similarity). Plays a critical role in gene silencing over considerable distances in the genome (By similarity). Preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation and maintaining methylation-free zones (PubMed:18413740). Inversely, binding to target sites is prevented by CpG methylation (PubMed:18413740). Plays an important role in chromatin remodeling (PubMed:18413740). Can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping (PubMed:12191639). Causes local loss of histone acetylation and gain of histone methylation in the beta-globin locus, without affecting transcription (PubMed:12191639). When bound to chromatin, it provides an anchor point for nucleosomes positioning (PubMed:12191639). Seems to be essential for homologous X-chromosome pairing (By similarity). May participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation (PubMed:11743158). May play a role in preventing the propagation of stable methylation at the escape genes from X-inactivation (PubMed:11743158). Involved in sister chromatid cohesion (PubMed:12191639). Associates with both centromeres and chromosomal arms during metaphase and required for cohesin localization to CTCF sites (PubMed:18550811). Plays a role in the recruitment of CENPE to the pericentromeric/centromeric regions of the chromosome during mitosis (PubMed:26321640). Acts as a transcriptional repressor binding to promoters of vertebrate MYC gene and BAG1 gene (PubMed:18413740, PubMed:8649389, PubMed:9591631). Also binds to the PLK and PIM1 promoters (PubMed:12191639). Acts as a transcriptional activator of APP (PubMed:9407128). Regulates APOA1/C3/A4/A5 gene cluster and controls MHC class II gene expression (PubMed:18347100, PubMed:19322193). Plays an essential role in oocyte and preimplantation embryo development by activating or repressing transcription (By similarity). Seems to act as tumor suppressor (PubMed:12191639). {ECO:0000250|UniProtKB:Q61164, ECO:0000269|PubMed:11743158, ECO:0000269|PubMed:16107875, ECO:0000269|PubMed:16815976, ECO:0000269|PubMed:16949368, ECO:0000269|PubMed:17827499, ECO:0000269|PubMed:18347100, ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18550811, ECO:0000269|PubMed:18654629, ECO:0000269|PubMed:19322193, ECO:0000269|PubMed:26321640, ECO:0000269|PubMed:8649389, ECO:0000269|PubMed:9407128, ECO:0000269|PubMed:9591631, ECO:0000303|PubMed:12191639}. |
| P49756 | RBM25 | S683 | ochoa | RNA-binding protein 25 (Arg/Glu/Asp-rich protein of 120 kDa) (RED120) (Protein S164) (RNA-binding motif protein 25) (RNA-binding region-containing protein 7) | RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5'-splice site (5'-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5'-ss usage through the 5'-CGGGCA-3' RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5' ss in a 5'-CGGGCA-3'-dependent manner. Binds to the exonic splicing enhancer 5'-CGGGCA-3' RNA sequence located within exon 2 of the BCL2L1 pre-mRNA. Also involved in the generation of an abnormal and truncated splice form of SCN5A in heart failure. {ECO:0000269|PubMed:18663000, ECO:0000269|PubMed:21859973}. |
| P49770 | EIF2B2 | S103 | ochoa | Translation initiation factor eIF2B subunit beta (S20I15) (S20III15) (eIF2B GDP-GTP exchange factor subunit beta) | Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, PubMed:27023709, PubMed:31048492). Its guanine nucleotide exchange factor activity is repressed when bound to eIF2 complex phosphorylated on the alpha subunit, thereby limiting the amount of methionyl-initiator methionine tRNA available to the ribosome and consequently global translation is repressed (PubMed:25858979, PubMed:31048492). {ECO:0000269|PubMed:25858979, ECO:0000269|PubMed:27023709, ECO:0000269|PubMed:31048492}. |
| P49773 | HINT1 | S107 | psp | Adenosine 5'-monophosphoramidase HINT1 (EC 3.9.1.-) (Desumoylating isopeptidase HINT1) (EC 3.4.22.-) (Histidine triad nucleotide-binding protein 1) (Protein kinase C inhibitor 1) (Protein kinase C-interacting protein 1) (PKCI-1) | Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:15703176, PubMed:16835243, PubMed:17217311, PubMed:17337452, PubMed:22329685, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367). Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176, PubMed:16835243). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester (PubMed:15703176, PubMed:17337452, PubMed:22329685). Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17217311, PubMed:17337452, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367). Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide (PubMed:30772266). In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1 (PubMed:16014379, PubMed:22647378). Modulates p53/TP53 levels and p53/TP53-mediated apoptosis (PubMed:16835243). Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177). Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17 (PubMed:31088288). Deconjugates SUMO1 from RANGAP1 (By similarity). {ECO:0000250|UniProtKB:P80912, ECO:0000269|PubMed:15703176, ECO:0000269|PubMed:16014379, ECO:0000269|PubMed:16835243, ECO:0000269|PubMed:17217311, ECO:0000269|PubMed:17337452, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:22329685, ECO:0000269|PubMed:22647378, ECO:0000269|PubMed:23614568, ECO:0000269|PubMed:28691797, ECO:0000269|PubMed:29787766, ECO:0000269|PubMed:30772266, ECO:0000269|PubMed:31088288, ECO:0000269|PubMed:31990367}. |
| P49790 | NUP153 | S306 | ochoa | Nuclear pore complex protein Nup153 (153 kDa nucleoporin) (Nucleoporin Nup153) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC). {ECO:0000269|PubMed:12802065, ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22253824}.; FUNCTION: (Microbial infection) Interacts with HIV-1 caspid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro). {ECO:0000269|PubMed:23523133, ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:29997211}.; FUNCTION: (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro). {ECO:0000269|PubMed:24130490, ECO:0000269|PubMed:31913756}. |
| P49815 | TSC2 | S1346 | ochoa | Tuberin (Tuberous sclerosis 2 protein) | Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:33436626, ECO:0000269|PubMed:35772404}. |
| P50395 | GDI2 | S121 | 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}. |
| P50851 | LRBA | S1003 | ochoa | Lipopolysaccharide-responsive and beige-like anchor protein (Beige-like protein) (CDC4-like protein) | Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules (By similarity). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). {ECO:0000250|UniProtKB:Q9ESE1, ECO:0000269|PubMed:33773106}. |
| P50990 | CCT8 | S269 | 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}. |
| P50991 | CCT4 | S303 | ochoa | T-complex protein 1 subunit delta (TCP-1-delta) (EC 3.6.1.-) (CCT-delta) (Chaperonin containing T-complex polypeptide 1 subunit 4) (Stimulator of TAR RNA-binding) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P50993 | ATP1A2 | S496 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-2 (Na(+)/K(+) ATPase alpha-2 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-2) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P51114 | FXR1 | S413 | ochoa | RNA-binding protein FXR1 (FMR1 autosomal homolog 1) (hFXR1p) | mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis, muscle development and spermatogenesis (PubMed:17382880, PubMed:20417602, PubMed:30067974, PubMed:34731628, PubMed:35989368, PubMed:36306353). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:17382880, PubMed:34731628). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (By similarity). Required to activate translation of stored mRNAs during late spermatogenesis: acts by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules that recruit translation initiation factor EIF4G3 to activate translation of stored mRNAs in late spermatids (By similarity). Promotes translation of MYC transcripts by recruiting the eIF4F complex to the translation start site (PubMed:34731628). Acts as a negative regulator of inflammation in response to IL19 by promoting destabilization of pro-inflammatory transcripts (PubMed:30067974). Also acts as an inhibitor of inflammation by binding to TNF mRNA, decreasing TNF protein production (By similarity). Acts as a negative regulator of AMPA receptor GRIA2/GluA2 synthesis during long-lasting synaptic potentiation of hippocampal neurons by binding to GRIA2/GluA2 mRNA, thereby inhibiting its translation (By similarity). Regulates proliferation of adult neural stem cells by binding to CDKN1A mRNA and promoting its expression (By similarity). Acts as a regulator of sleep and synaptic homeostasis by regulating translation of transcripts in neurons (By similarity). Required for embryonic and postnatal development of muscle tissue by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules (PubMed:30770808). Involved in the nuclear pore complex localization to the nuclear envelope by preventing cytoplasmic aggregation of nucleoporins: acts by preventing ectopic phase separation of nucleoporins in the cytoplasm via a microtubule-dependent mechanism (PubMed:32706158). Plays a role in the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with PKP3 (PubMed:25225333). May also do the same for PKP2, PKP3 and DSP via its interaction with PKP1 (PubMed:25225333). Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates, crucial for processes like actomyosin reorganization (PubMed:39106863). {ECO:0000250|UniProtKB:Q61584, ECO:0000269|PubMed:17382880, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:30067974, ECO:0000269|PubMed:30770808, ECO:0000269|PubMed:32706158, ECO:0000269|PubMed:34731628, ECO:0000269|PubMed:35989368, ECO:0000269|PubMed:36306353, ECO:0000269|PubMed:39106863}. |
| P51153 | RAB13 | S111 | ochoa|psp | Ras-related protein Rab-13 (EC 3.6.5.2) (Cell growth-inhibiting gene 4 protein) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB13 is involved in endocytic recycling and regulates the transport to the plasma membrane of transmembrane proteins like the tight junction protein OCLN/occludin. Thereby, it regulates the assembly and the activity of tight junctions. Moreover, it may also regulate tight junction assembly by activating the PKA signaling pathway and by reorganizing the actin cytoskeleton through the activation of the downstream effectors PRKACA and MICALL2 respectively. Through its role in tight junction assembly, may play a role in the establishment of Sertoli cell barrier. Plays also a role in angiogenesis through regulation of endothelial cells chemotaxis. Also involved in neurite outgrowth. Has also been proposed to play a role in post-Golgi membrane trafficking from the TGN to the recycling endosome. Finally, it has been involved in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore may play a role in glucose homeostasis. {ECO:0000269|PubMed:12058051, ECO:0000269|PubMed:15096524, ECO:0000269|PubMed:15528189, ECO:0000269|PubMed:16525024, ECO:0000269|PubMed:18779367, ECO:0000269|PubMed:20008558, ECO:0000269|PubMed:35343654}. |
| P51610 | HCFC1 | S674 | ochoa | Host cell factor 1 (HCF) (HCF-1) (C1 factor) (CFF) (VCAF) (VP16 accessory protein) [Cleaved into: HCF N-terminal chain 1; HCF N-terminal chain 2; HCF N-terminal chain 3; HCF N-terminal chain 4; HCF N-terminal chain 5; HCF N-terminal chain 6; HCF C-terminal chain 1; HCF C-terminal chain 2; HCF C-terminal chain 3; HCF C-terminal chain 4; HCF C-terminal chain 5; HCF C-terminal chain 6] | Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity). {ECO:0000250|UniProtKB:D3ZN95, ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:10675337, ECO:0000269|PubMed:10779346, ECO:0000269|PubMed:12244100, ECO:0000269|PubMed:12670868, ECO:0000269|PubMed:14532282, ECO:0000269|PubMed:15190068, ECO:0000269|PubMed:16624878, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:23629655, ECO:0000269|PubMed:26416877}.; FUNCTION: (Microbial infection) In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. {ECO:0000269|PubMed:10629049, ECO:0000269|PubMed:17578910}. |
| P51668 | UBE2D1 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D1 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D1) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D1) (Stimulator of Fe transport) (SFT) (UBC4/5 homolog) (UbcH5) (Ubiquitin carrier protein D1) (Ubiquitin-conjugating enzyme E2(17)KB 1) (Ubiquitin-conjugating enzyme E2-17 kDa 1) (Ubiquitin-protein ligase D1) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:22496338). In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:20061386). Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1 (PubMed:18042044, PubMed:18359941). Ubiquitinates STUB1-associated HSP90AB1 in vitro (PubMed:18042044). Lacks inherent specificity for any particular lysine residue of ubiquitin (PubMed:18042044). Essential for viral activation of IRF3 (PubMed:19854139). Mediates polyubiquitination of CYP3A4 (PubMed:19103148). {ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18359941, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338}. |
| P51812 | RPS6KA3 | S78 | ochoa | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
| P51812 | RPS6KA3 | S375 | ochoa | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
| P52179 | MYOM1 | S1615 | ochoa | Myomesin-1 (190 kDa connectin-associated protein) (190 kDa titin-associated protein) (Myomesin family member 1) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P52292 | KPNA2 | S88 | ochoa | Importin subunit alpha-1 (Karyopherin subunit alpha-2) (RAG cohort protein 1) (SRP1-alpha) | Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1 (PubMed:28991411, PubMed:32130408, PubMed:7604027, PubMed:7754385). Binds specifically and directly to substrates containing either a simple or bipartite NLS motif (PubMed:28991411, PubMed:32130408, PubMed:7604027, PubMed:7754385). 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:7604027, PubMed:7754385). 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. 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. Mediator of PR-DUB complex component BAP1 nuclear import; acts redundantly with KPNA1 and Transportin-1/TNPO1 (PubMed:35446349). {ECO:0000269|PubMed:28991411, ECO:0000269|PubMed:32130408, ECO:0000269|PubMed:35446349, ECO:0000269|PubMed:7604027, ECO:0000269|PubMed:7754385}. |
| P52333 | JAK3 | S782 | ochoa | 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}. |
| P52630 | STAT2 | S287 | psp | Signal transducer and activator of transcription 2 (p113) | Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state (PubMed:23391734, PubMed:9020188). In addition, also has a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs (PubMed:28165510). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:23391734, PubMed:26122121, PubMed:9020188). {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121, ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142, ECO:0000269|PubMed:9020188}. |
| P52630 | STAT2 | S734 | psp | Signal transducer and activator of transcription 2 (p113) | Signal transducer and activator of transcription that mediates signaling by type I interferons (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state (PubMed:23391734, PubMed:9020188). In addition, also has a negative feedback regulatory role in the type I interferon signaling by recruiting USP18 to the type I IFN receptor subunit IFNAR2 thereby mitigating the response to type I IFNs (PubMed:28165510). Acts as a regulator of mitochondrial fission by modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' which activate and inactivate the GTPase activity of DNM1L respectively (PubMed:23391734, PubMed:26122121, PubMed:9020188). {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121, ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142, ECO:0000269|PubMed:9020188}. |
| P52948 | NUP98 | S596 | ochoa | 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 | S709 | ochoa | 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}. |
| P53794 | SLC5A3 | S632 | ochoa | Sodium/myo-inositol cotransporter (Na(+)/myo-inositol cotransporter) (Sodium/myo-inositol transporter 1) (SMIT1) (Solute carrier family 5 member 3) | Electrogenic Na(+)-coupled sugar symporter that actively transports myo-inositol and its stereoisomer scyllo-inositol across the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1 (By similarity). Maintains myo-inositol concentration gradient that defines cell volume and fluid balance during osmotic stress, in particular in the fetoplacental unit and central nervous system (By similarity). Forms coregulatory complexes with voltage-gated K(+) ion channels, allosterically altering ion selectivity, voltage dependence and gating kinetics of the channel. In turn, K(+) efflux through the channel forms a local electrical gradient that modulates electrogenic Na(+)-coupled myo-inositol influx through the transporter (PubMed:24595108, PubMed:28793216). Associates with KCNQ1-KCNE2 channel in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity) (PubMed:24595108). Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (PubMed:28793216). Provides myo-inositol precursor for biosynthesis of phosphoinositides such as PI(4,5)P2, thus indirectly affecting the activity of phosphoinositide-dependent ion channels and Ca(2+) signaling upon osmotic stress (PubMed:27217553). {ECO:0000250|UniProtKB:P31637, ECO:0000250|UniProtKB:Q9JKZ2, ECO:0000269|PubMed:24595108, ECO:0000269|PubMed:27217553, ECO:0000269|PubMed:28793216}. |
| P54296 | MYOM2 | S151 | ochoa | Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P54296 | MYOM2 | S737 | ochoa | Myomesin-2 (165 kDa connectin-associated protein) (165 kDa titin-associated protein) (M-protein) (Myomesin family member 2) | Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent. |
| P54753 | EPHB3 | S591 | 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}. |
| P54868 | HMGCS2 | S325 | ochoa | Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMG-CoA synthase) (EC 2.3.3.10) (3-hydroxy-3-methylglutaryl coenzyme A synthase) | Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate. {ECO:0000269|PubMed:11228257, ECO:0000269|PubMed:23751782, ECO:0000269|PubMed:29597274}. |
| P54920 | NAPA | S160 | ochoa | Alpha-soluble NSF attachment protein (SNAP-alpha) (N-ethylmaleimide-sensitive factor attachment protein alpha) | Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus (Probable). Together with GNA12 promotes CDH5 localization to plasma membrane (PubMed:15980433). {ECO:0000269|PubMed:15980433, ECO:0000305}. |
| P55197 | MLLT10 | S276 | ochoa | Protein AF-10 (ALL1-fused gene from chromosome 10 protein) | Probably involved in transcriptional regulation. In vitro or as fusion protein with KMT2A/MLL1 has transactivation activity. Binds to cruciform DNA. In cells, binding to unmodified histone H3 regulates DOT1L functions including histone H3 'Lys-79' dimethylation (H3K79me2) and gene activation (PubMed:26439302). {ECO:0000269|PubMed:17868029, ECO:0000269|PubMed:26439302}. |
| P55735 | SEC13 | S184 | ochoa | Protein SEC13 homolog (GATOR2 complex protein SEC13) (SEC13-like protein 1) (SEC13-related protein) | Functions as a component of the nuclear pore complex (NPC) and the COPII coat (PubMed:8972206). At the endoplasmic reticulum, SEC13 is involved in the biogenesis of COPII-coated vesicles (PubMed:8972206). Required for the exit of adipsin (CFD/ADN), an adipocyte-secreted protein from the endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q9D1M0, ECO:0000269|PubMed:8972206}.; FUNCTION: As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:25457612, PubMed:27487210, PubMed:35831510, PubMed:36528027). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:27487210, PubMed:35831510, PubMed:36528027). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25457612, PubMed:26972053, PubMed:27487210). Within the GATOR2 complex, SEC13 and SEH1L are required to stabilize the complex (PubMed:35831510). {ECO:0000269|PubMed:23723238, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26972053, ECO:0000269|PubMed:27487210, ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027}. |
| P56524 | HDAC4 | S246 | ochoa|psp | Histone deacetylase 4 (HD4) (EC 3.5.1.98) | Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1 (PubMed:27708256). {ECO:0000269|PubMed:10523670, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:27708256}. |
| P60842 | EIF4A1 | S205 | ochoa | Eukaryotic initiation factor 4A-I (eIF-4A-I) (eIF4A-I) (EC 3.6.4.13) (ATP-dependent RNA helicase eIF4A-1) | ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome (PubMed:20156963). In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. As a result, promotes cell proliferation and growth (PubMed:20156963). {ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291, ECO:0000269|PubMed:20156963}. |
| P61077 | UBE2D3 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D3 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D3) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D3) (Ubiquitin carrier protein D3) (Ubiquitin-conjugating enzyme E2(17)KB 3) (Ubiquitin-conjugating enzyme E2-17 kDa 3) (Ubiquitin-protein ligase D3) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592, PubMed:28322253). In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination (PubMed:15247280, PubMed:15496420, PubMed:18284575, PubMed:20061386, PubMed:21532592). Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation (PubMed:20347421). Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin (PubMed:10329681). Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin (PubMed:10329681). Also acts as an initiator E2, in conjunction with RNF8, for the priming of PCNA (PubMed:18948756). Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase (PubMed:18948756). Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair (PubMed:16628214). Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus (PubMed:18515077). In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53 (PubMed:12646252, PubMed:15280377). In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes (PubMed:18508924). In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (PubMed:11743028). Together with RNF135, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175). Together with ZNF598, catalyzes ubiquitination of 40S ribosomal proteins in response to ribosome collisions (PubMed:28685749). In cooperation with the GATOR2 complex, catalyzes 'Lys-6'-linked ubiquitination of NPRL2 (PubMed:36528027). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:11743028, ECO:0000269|PubMed:12646252, ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:15496420, ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:18284575, ECO:0000269|PubMed:18508924, ECO:0000269|PubMed:18515077, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:28322253, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:28685749, ECO:0000269|PubMed:36528027}. |
| P61962 | DCAF7 | S200 | psp | DDB1- and CUL4-associated factor 7 (WD repeat-containing protein 68) (WD repeat-containing protein An11 homolog) | Involved in craniofacial development. Acts upstream of the EDN1 pathway and is required for formation of the upper jaw equivalent, the palatoquadrate. The activity required for EDN1 pathway function differs between the first and second arches (By similarity). Associates with DIAPH1 and controls GLI1 transcriptional activity. Could be involved in normal and disease skin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex. {ECO:0000250, ECO:0000269|PubMed:16887337, ECO:0000269|PubMed:16949367}. |
| P61978 | HNRNPK | S127 | 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 | S219 | 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}. |
| P62081 | RPS7 | S174 | ochoa | Small ribosomal subunit protein eS7 (40S ribosomal protein S7) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for rRNA maturation (PubMed:19061985). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:19061985, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P62258 | YWHAE | S217 | 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}. |
| P62424 | RPL7A | S209 | ochoa | Large ribosomal subunit protein eL8 (60S ribosomal protein L7a) (PLA-X polypeptide) (Surfeit locus protein 3) | Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547}. |
| P62837 | UBE2D2 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D2 (EC 2.3.2.23) ((E3-independent) E2 ubiquitin-conjugating enzyme D2) (EC 2.3.2.24) (E2 ubiquitin-conjugating enzyme D2) (Ubiquitin carrier protein D2) (Ubiquitin-conjugating enzyme E2(17)KB 2) (Ubiquitin-conjugating enzyme E2-17 kDa 2) (Ubiquitin-protein ligase D2) (p53-regulated ubiquitin-conjugating enzyme 1) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins (PubMed:10329681, PubMed:18042044, PubMed:18703417, PubMed:20061386, PubMed:20403326, PubMed:20525694, PubMed:26475854, PubMed:28322253). Catalyzes 'Lys-48'-linked polyubiquitination (PubMed:10329681, PubMed:18042044, PubMed:18359941, PubMed:18703417, PubMed:20061386, PubMed:20403326, PubMed:20525694, PubMed:26475854). Mediates the selective degradation of short-lived and abnormal proteins (PubMed:10329681, PubMed:18042044, PubMed:18359941, PubMed:18703417, PubMed:20061386, PubMed:20403326, PubMed:20525694, PubMed:26475854). Functions in the E6/E6-AP-induced ubiquitination of p53/TP53 (PubMed:15280377). Mediates ubiquitination of PEX5 and SQSTM1 and autoubiquitination of STUB1 and TRAF6 (PubMed:18359941, PubMed:28322253). Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by RIGI in response to viral infection (PubMed:18703417, PubMed:20403326). Essential for viral activation of IRF3 (PubMed:19854139). {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:15280377, ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18359941, ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20403326, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:26475854, ECO:0000269|PubMed:28322253}. |
| P62851 | RPS25 | S93 | ochoa | 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}. |
| P63104 | YWHAZ | S214 | 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}. |
| P68871 | HBB | S73 | ochoa | Hemoglobin subunit beta (Beta-globin) (Hemoglobin beta chain) [Cleaved into: LVV-hemorphin-7; Spinorphin] | Involved in oxygen transport from the lung to the various peripheral tissues. {ECO:0000269|PubMed:28066926}.; FUNCTION: LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.; FUNCTION: [Spinorphin]: Functions as an endogenous inhibitor of enkephalin-degrading enzymes such as DPP3, and as a selective antagonist of the P2RX3 receptor which is involved in pain signaling, these properties implicate it as a regulator of pain and inflammation. |
| P78345 | RPP38 | S226 | ochoa | Ribonuclease P protein subunit p38 (RNaseP protein p38) | Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:10444065, PubMed:30454648, PubMed:9037013, PubMed:9630247). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465). {ECO:0000269|PubMed:10444065, ECO:0000269|PubMed:28115465, ECO:0000269|PubMed:30454648, ECO:0000269|PubMed:9037013, ECO:0000269|PubMed:9630247}. |
| P83916 | CBX1 | S129 | ochoa | Chromobox protein homolog 1 (HP1Hsbeta) (Heterochromatin protein 1 homolog beta) (HP1 beta) (Heterochromatin protein p25) (M31) (Modifier 1 protein) (p25beta) | Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane. {ECO:0000250|UniProtKB:P83917}. |
| Q01081 | U2AF1 | S59 | ochoa | Splicing factor U2AF 35 kDa subunit (U2 auxiliary factor 35 kDa subunit) (U2 small nuclear RNA auxiliary factor 1) (U2 snRNP auxiliary factor small subunit) | Plays a critical role in both constitutive and enhancer-dependent splicing by mediating protein-protein interactions and protein-RNA interactions required for accurate 3'-splice site selection. Recruits U2 snRNP to the branch point. Directly mediates interactions between U2AF2 and proteins bound to the enhancers and thus may function as a bridge between U2AF2 and the enhancer complex to recruit it to the adjacent intron. {ECO:0000269|PubMed:22158538, ECO:0000269|PubMed:25311244, ECO:0000269|PubMed:8647433}. |
| Q01658 | DR1 | S105 | ochoa | Protein Dr1 (Down-regulator of transcription 1) (Negative cofactor 2-beta) (NC2-beta) (TATA-binding protein-associated phosphoprotein) | The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. {ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:8670811}. |
| Q01814 | ATP2B2 | S1149 | ochoa | 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}. |
| Q02978 | SLC25A11 | S203 | ochoa | Mitochondrial 2-oxoglutarate/malate carrier protein (OGCP) (alpha-oxoglutarate carrier) (Solute carrier family 25 member 11) (SLC25A11) | Catalyzes the transport of 2-oxoglutarate (alpha-oxoglutarate) across the inner mitochondrial membrane in an electroneutral exchange for malate. Can also exchange 2-oxoglutarate for other dicarboxylic acids such as malonate, succinate, maleate and oxaloacetate, although with lower affinity. Contributes to several metabolic processes, including the malate-aspartate shuttle, the oxoglutarate/isocitrate shuttle, in gluconeogenesis from lactate, and in nitrogen metabolism (By similarity). Maintains mitochondrial fusion and fission events, and the organization and morphology of cristae (PubMed:21448454). Involved in the regulation of apoptosis (By similarity). Helps protect from cytotoxic-induced apoptosis by modulating glutathione levels in mitochondria (By similarity). {ECO:0000250|UniProtKB:P22292, ECO:0000250|UniProtKB:P97700, ECO:0000250|UniProtKB:Q9CR62, ECO:0000269|PubMed:21448454}. |
| Q03001 | DST | S5356 | ochoa | Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) | Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. |
| Q03188 | CENPC | S261 | 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}. |
| Q03252 | LMNB2 | S301 | ochoa | Lamin-B2 | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:33033404). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:33033404). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:33033404). {ECO:0000269|PubMed:33033404}. |
| Q03431 | PTH1R | S473 | psp | Parathyroid hormone/parathyroid hormone-related peptide receptor (PTH/PTHrP type I receptor) (PTH/PTHr receptor) (Parathyroid hormone 1 receptor) (PTH1 receptor) | G-protein-coupled receptor for parathyroid hormone (PTH) and for parathyroid hormone-related peptide (PTHLH) (PubMed:10913300, PubMed:18375760, PubMed:19674967, PubMed:27160269, PubMed:30975883, PubMed:35932760, PubMed:8397094). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (cAMP) (PubMed:30975883, PubMed:35932760). PTH1R is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:20172855, PubMed:30975883, PubMed:35932760). PTHLH dissociates from PTH1R more rapidly than PTH; as consequence, the cAMP response induced by PTHLH decays faster than the response induced by PTH (PubMed:35932760). {ECO:0000269|PubMed:10913300, ECO:0000269|PubMed:18375760, ECO:0000269|PubMed:19674967, ECO:0000269|PubMed:20172855, ECO:0000269|PubMed:27160269, ECO:0000269|PubMed:30975883, ECO:0000269|PubMed:35932760, ECO:0000269|PubMed:8397094}. |
| Q04656 | ATP7A | S147 | psp | Copper-transporting ATPase 1 (EC 7.2.2.8) (Copper pump 1) (Menkes disease-associated protein) | ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:10419525, PubMed:19453293, PubMed:19917612, PubMed:28389643, PubMed:31283225). Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway (PubMed:11092760, PubMed:28389643). Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions (PubMed:10419525, PubMed:28389643). May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (By similarity) (PubMed:28389643). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity). {ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:10419525, ECO:0000269|PubMed:11092760, ECO:0000269|PubMed:19453293, ECO:0000269|PubMed:19917612, ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:31283225}. |
| Q04656 | ATP7A | S325 | ochoa | Copper-transporting ATPase 1 (EC 7.2.2.8) (Copper pump 1) (Menkes disease-associated protein) | ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:10419525, PubMed:19453293, PubMed:19917612, PubMed:28389643, PubMed:31283225). Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway (PubMed:11092760, PubMed:28389643). Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions (PubMed:10419525, PubMed:28389643). May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (By similarity) (PubMed:28389643). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity). {ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:10419525, ECO:0000269|PubMed:11092760, ECO:0000269|PubMed:19453293, ECO:0000269|PubMed:19917612, ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:31283225}. |
| Q04656 | ATP7A | S1447 | ochoa | Copper-transporting ATPase 1 (EC 7.2.2.8) (Copper pump 1) (Menkes disease-associated protein) | ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:10419525, PubMed:19453293, PubMed:19917612, PubMed:28389643, PubMed:31283225). Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway (PubMed:11092760, PubMed:28389643). Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions (PubMed:10419525, PubMed:28389643). May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (By similarity) (PubMed:28389643). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity). {ECO:0000250|UniProtKB:Q64430, ECO:0000269|PubMed:10419525, ECO:0000269|PubMed:11092760, ECO:0000269|PubMed:19453293, ECO:0000269|PubMed:19917612, ECO:0000269|PubMed:28389643, ECO:0000269|PubMed:31283225}. |
| Q04759 | PRKCQ | S676 | ochoa|psp | Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation (PubMed:21964608). Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (PubMed:23509302). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11342610, ECO:0000269|PubMed:14988727, ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:16252004, ECO:0000269|PubMed:16356855, ECO:0000269|PubMed:16709830, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:21964608, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:8657160}. |
| Q04917 | YWHAH | S219 | 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}. |
| Q05655 | PRKCD | S359 | psp | Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}. |
| Q05655 | PRKCD | S645 | ochoa|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}. |
| Q07617 | SPAG1 | S565 | ochoa | Sperm-associated antigen 1 (HSD-3.8) (Infertility-related sperm protein Spag-1) | May play a role in the cytoplasmic assembly of the ciliary dynein arms (By similarity). May play a role in fertilization. Binds GTP and has GTPase activity. {ECO:0000250, ECO:0000269|PubMed:11517287, ECO:0000269|PubMed:1299558}. |
| Q07912 | TNK2 | S856 | ochoa | Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Tyrosine kinase non-receptor protein 2) | Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). {ECO:0000269|PubMed:10652228, ECO:0000269|PubMed:11278436, ECO:0000269|PubMed:16247015, ECO:0000269|PubMed:16257963, ECO:0000269|PubMed:16472662, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:18262180, ECO:0000269|PubMed:18435854, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:20110370, ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20383201}. |
| Q08170 | SRSF4 | S151 | ochoa | Serine/arginine-rich splicing factor 4 (Pre-mRNA-splicing factor SRP75) (SRP001LB) (Splicing factor, arginine/serine-rich 4) | Plays a role in alternative splice site selection during pre-mRNA splicing. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:15009664}. |
| Q08378 | GOLGA3 | S115 | ochoa | Golgin subfamily A member 3 (Golgi complex-associated protein of 170 kDa) (GCP170) (Golgin-160) | Golgi auto-antigen; probably involved in maintaining Golgi structure. |
| Q08499 | PDE4D | S596 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43) (cAMP-specific phosphodiesterase 4D) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:15260978, ECO:0000269|PubMed:15576036, ECO:0000269|PubMed:9371713}. |
| Q08945 | SSRP1 | S349 | ochoa | FACT complex subunit SSRP1 (Chromatin-specific transcription elongation factor 80 kDa subunit) (Facilitates chromatin transcription complex 80 kDa subunit) (FACT 80 kDa subunit) (FACTp80) (Facilitates chromatin transcription complex subunit SSRP1) (Recombination signal sequence recognition protein 1) (Structure-specific recognition protein 1) (hSSRP1) (T160) | Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). Binds specifically to double-stranded DNA and at low levels to DNA modified by the antitumor agent cisplatin. May potentiate cisplatin-induced cell death by blocking replication and repair of modified DNA. Also acts as a transcriptional coactivator for p63/TP63. {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9566881, ECO:0000269|PubMed:9836642}. |
| Q09666 | AHNAK | S501 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5397 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5500 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12802 | AKAP13 | S781 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12802 | AKAP13 | S1927 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12815 | TROAP | S421 | ochoa | Tastin (Trophinin-assisting protein) (Trophinin-associated protein) | Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation. |
| Q12888 | TP53BP1 | S78 | 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 | S105 | 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 | S294 | ochoa|psp | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12888 | TP53BP1 | S349 | ochoa | TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) | Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}. |
| Q12923 | PTPN13 | S926 | ochoa | Tyrosine-protein phosphatase non-receptor type 13 (EC 3.1.3.48) (Fas-associated protein-tyrosine phosphatase 1) (FAP-1) (PTP-BAS) (Protein-tyrosine phosphatase 1E) (PTP-E1) (hPTPE1) (Protein-tyrosine phosphatase PTPL1) | Tyrosine phosphatase which negatively regulates FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling (PubMed:15611135). May regulate phosphoinositide 3-kinase (PI3K) signaling through dephosphorylation of PIK3R2 (PubMed:23604317). {ECO:0000269|PubMed:15611135, ECO:0000269|PubMed:23604317}. |
| Q13023 | AKAP6 | S1565 | ochoa | A-kinase anchor protein 6 (AKAP-6) (A-kinase anchor protein 100 kDa) (AKAP 100) (Protein kinase A-anchoring protein 6) (PRKA6) (mAKAP) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum. May act as an adapter for assembling multiprotein complexes. |
| Q13043 | STK4 | S438 | ochoa|psp | Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. |
| Q13085 | ACACA | S78 | ochoa|psp | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13085 | ACACA | S1216 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13098 | GPS1 | S240 | ochoa | COP9 signalosome complex subunit 1 (SGN1) (Signalosome subunit 1) (G protein pathway suppressor 1) (GPS-1) (JAB1-containing signalosome subunit 1) (Protein MFH) | Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Suppresses G-protein- and mitogen-activated protein kinase-mediated signal transduction. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:9535219}. |
| Q13148 | TARDBP | S242 | 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}. |
| Q13201 | MMRN1 | S368 | ochoa | Multimerin-1 (EMILIN-4) (Elastin microfibril interface located protein 4) (Elastin microfibril interfacer 4) (Endothelial cell multimerin) [Cleaved into: Platelet glycoprotein Ia*; 155 kDa platelet multimerin (p-155) (p155)] | Carrier protein for platelet (but not plasma) factor V/Va. Plays a role in the storage and stabilization of factor V in platelets. Upon release following platelet activation, may limit platelet and plasma factor Va-dependent thrombin generation. Ligand for integrin alpha-IIb/beta-3 and integrin alpha-V/beta-3 on activated platelets, and may function as an extracellular matrix or adhesive protein. {ECO:0000269|PubMed:16363244, ECO:0000269|PubMed:19132231, ECO:0000269|PubMed:7629143}. |
| Q13233 | MAP3K1 | S67 | psp | 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}. |
| Q13242 | SRSF9 | S121 | ochoa | Serine/arginine-rich splicing factor 9 (Pre-mRNA-splicing factor SRp30C) (Splicing factor, arginine/serine-rich 9) | Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10. {ECO:0000269|PubMed:10196175, ECO:0000269|PubMed:11875052, ECO:0000269|PubMed:12024014, ECO:0000269|PubMed:12604611, ECO:0000269|PubMed:15009090, ECO:0000269|PubMed:15009664, ECO:0000269|PubMed:15695522, ECO:0000269|PubMed:7556075}. |
| Q13283 | G3BP1 | S39 | ochoa | Ras GTPase-activating protein-binding protein 1 (G3BP-1) (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent DNA helicase VIII) (hDH VIII) (GAP SH3 domain-binding protein 1) | Protein involved in various processes, such as stress granule formation and innate immunity (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:30510222, PubMed:30804210). Plays an essential role in stress granule formation (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:35977029, PubMed:36183834, PubMed:36279435, PubMed:36692217, PubMed:37379838). Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress (PubMed:12642610, PubMed:20180778, PubMed:23279204, PubMed:27022092, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:36279435, PubMed:37379838). Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations (PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:36279435, PubMed:36692217). Also acts as an ATP- and magnesium-dependent helicase: unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency (PubMed:9889278). Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA (PubMed:9889278). Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends (PubMed:9889278). Plays an essential role in innate immunity by promoting CGAS and RIGI activity (PubMed:30510222, PubMed:30804210). Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS (PubMed:30510222). Triggers the condensation of cGAS, a process probably linked to the formation of membrane-less organelles (PubMed:34779554). Also enhances RIGI-induced type I interferon production probably by helping RIGI at sensing pathogenic RNA (PubMed:30804210). May also act as a phosphorylation-dependent sequence-specific endoribonuclease in vitro: Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:12642610, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:23279204, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:30510222, ECO:0000269|PubMed:30804210, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:34779554, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:36183834, ECO:0000269|PubMed:36279435, ECO:0000269|PubMed:36692217, ECO:0000269|PubMed:37379838, ECO:0000269|PubMed:9889278}. |
| Q13310 | PABPC4 | S120 | ochoa | Polyadenylate-binding protein 4 (PABP-4) (Poly(A)-binding protein 4) (Activated-platelet protein 1) (APP-1) (Inducible poly(A)-binding protein) (iPABP) | Binds the poly(A) tail of mRNA (PubMed:8524242). Binds to SMIM26 mRNA and plays a role in its post-transcriptional regulation (PubMed:37009826). May be involved in cytoplasmic regulatory processes of mRNA metabolism. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo (By similarity). {ECO:0000250|UniProtKB:P11940, ECO:0000269|PubMed:37009826, ECO:0000269|PubMed:8524242}. |
| Q13315 | ATM | S1883 | ochoa | Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated) | Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217). May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, ECO:0000269|PubMed:9843217}. |
| Q13393 | PLD1 | S22 | ochoa | Phospholipase D1 (PLD 1) (hPLD1) (EC 3.1.4.4) (Choline phosphatase 1) (Phosphatidylcholine-hydrolyzing phospholipase D1) | Function as phospholipase selective for phosphatidylcholine (PubMed:25936805, PubMed:8530346, PubMed:9582313). Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity). {ECO:0000250|UniProtKB:Q9Z280, ECO:0000269|PubMed:25936805, ECO:0000269|PubMed:8530346, ECO:0000269|PubMed:9582313}. |
| Q13422 | IKZF1 | S368 | ochoa | DNA-binding protein Ikaros (Ikaros family zinc finger protein 1) (Lymphoid transcription factor LyF-1) | Transcription regulator of hematopoietic cell differentiation (PubMed:17934067). Binds gamma-satellite DNA (PubMed:17135265, PubMed:19141594). Plays a role in the development of lymphocytes, B- and T-cells. Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Repressor of the TDT (fikzfterminal deoxynucleotidyltransferase) gene during thymocyte differentiation. Regulates transcription through association with both HDAC-dependent and HDAC-independent complexes. Targets the 2 chromatin-remodeling complexes, NuRD and BAF (SWI/SNF), in a single complex (PYR complex), to the beta-globin locus in adult erythrocytes. Increases normal apoptosis in adult erythroid cells. Confers early temporal competence to retinal progenitor cells (RPCs) (By similarity). Function is isoform-specific and is modulated by dominant-negative inactive isoforms (PubMed:17135265, PubMed:17934067). {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, ECO:0000269|PubMed:19141594}. |
| Q13492 | PICALM | S303 | ochoa | Phosphatidylinositol-binding clathrin assembly protein (Clathrin assembly lymphoid myeloid leukemia protein) | Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly (PubMed:10436022, PubMed:16262731, PubMed:27574975). Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature (PubMed:25898166). In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 (PubMed:21808019, PubMed:22118466, PubMed:23741335). In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors (PubMed:25241929). Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF) (PubMed:24067654, PubMed:25241929). {ECO:0000269|PubMed:10436022, ECO:0000269|PubMed:16262731, ECO:0000269|PubMed:21808019, ECO:0000269|PubMed:22118466, ECO:0000269|PubMed:23741335, ECO:0000269|PubMed:24067654, ECO:0000269|PubMed:25241929, ECO:0000269|PubMed:25898166, ECO:0000269|PubMed:27574975}. |
| Q13501 | SQSTM1 | S407 | psp | Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) | Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}. |
| Q13561 | DCTN2 | S83 | ochoa | Dynactin subunit 2 (50 kDa dynein-associated polypeptide) (Dynactin complex 50 kDa subunit) (DCTN-50) (p50 dynamitin) | Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development (By similarity). {ECO:0000250|UniProtKB:A0A5G2QD80, ECO:0000250|UniProtKB:Q99KJ8}. |
| Q13813 | SPTAN1 | S1029 | ochoa | Spectrin alpha chain, non-erythrocytic 1 (Alpha-II spectrin) (Fodrin alpha chain) (Spectrin, non-erythroid alpha subunit) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. |
| Q13835 | PKP1 | S153 | ochoa | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q13905 | RAPGEF1 | S251 | ochoa | Rap guanine nucleotide exchange factor 1 (CRK SH3-binding GNRP) (Guanine nucleotide-releasing factor 2) (Protein C3G) | Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}. |
| Q14116 | IL18 | S35 | ochoa | Interleukin-18 (IL-18) (Iboctadekin) (Interferon gamma-inducing factor) (IFN-gamma-inducing factor) (Interleukin-1 gamma) (IL-1 gamma) | Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532, PubMed:37993714). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (PubMed:10653850). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744). {ECO:0000269|PubMed:10653850, ECO:0000269|PubMed:14528293, ECO:0000269|PubMed:25500532, ECO:0000269|PubMed:33883744, ECO:0000269|PubMed:37993714}. |
| Q14151 | SAFB2 | S54 | ochoa | Scaffold attachment factor B2 (SAF-B2) | Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation. |
| Q14151 | SAFB2 | S283 | ochoa | Scaffold attachment factor B2 (SAF-B2) | Binds to scaffold/matrix attachment region (S/MAR) DNA. Can function as an estrogen receptor corepressor and can also inhibit cell proliferation. |
| Q14155 | ARHGEF7 | S591 | ochoa | 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}. |
| Q14160 | SCRIB | S35 | ochoa | Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) | Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750, ECO:0000269|PubMed:27380321}. |
| Q14202 | ZMYM3 | S949 | ochoa | Zinc finger MYM-type protein 3 (Zinc finger protein 261) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q14207 | NPAT | S762 | ochoa | Protein NPAT (Nuclear protein of the ataxia telangiectasia mutated locus) (Nuclear protein of the ATM locus) (p220) | Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters. {ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:12665581, ECO:0000269|PubMed:12724424, ECO:0000269|PubMed:14585971, ECO:0000269|PubMed:14612403, ECO:0000269|PubMed:15555599, ECO:0000269|PubMed:15988025, ECO:0000269|PubMed:16131487, ECO:0000269|PubMed:17163457, ECO:0000269|PubMed:17826007, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:17974976, ECO:0000269|PubMed:9472014}. |
| Q14207 | NPAT | S1151 | ochoa | Protein NPAT (Nuclear protein of the ataxia telangiectasia mutated locus) (Nuclear protein of the ATM locus) (p220) | Required for progression through the G1 and S phases of the cell cycle and for S phase entry. Activates transcription of the histone H2A, histone H2B, histone H3 and histone H4 genes in conjunction with MIZF. Also positively regulates the ATM, MIZF and PRKDC promoters. Transcriptional activation may be accomplished at least in part by the recruitment of the NuA4 histone acetyltransferase (HAT) complex to target gene promoters. {ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:12665581, ECO:0000269|PubMed:12724424, ECO:0000269|PubMed:14585971, ECO:0000269|PubMed:14612403, ECO:0000269|PubMed:15555599, ECO:0000269|PubMed:15988025, ECO:0000269|PubMed:16131487, ECO:0000269|PubMed:17163457, ECO:0000269|PubMed:17826007, ECO:0000269|PubMed:17967892, ECO:0000269|PubMed:17974976, ECO:0000269|PubMed:9472014}. |
| Q14315 | FLNC | S2152 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14568 | HSP90AA2P | S50 | ochoa | Heat shock protein HSP 90-alpha A2 (Heat shock 90 kDa protein 1 alpha-like 3) (Heat shock protein HSP 90-alpha A2 pseudogene) (Heat shock protein family C member 2) | Putative molecular chaperone that may promote the maturation, structural maintenance and proper regulation of specific target proteins. {ECO:0000250}. |
| Q14573 | ITPR3 | S1700 | ochoa | Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 (IP3 receptor isoform 3) (IP3R-3) (InsP3R3) (Type 3 inositol 1,4,5-trisphosphate receptor) (Type 3 InsP3 receptor) | Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore participates in cellular calcium ion homeostasis (PubMed:32949214, PubMed:37898605, PubMed:8081734, PubMed:8288584). 1D-myo-inositol 1,4,5-trisphosphate binds to the ligand-free channel without altering its global conformation, yielding the low-energy resting state, then progresses through resting-to preactivated transitions to the higher energy preactivated state, which increases affinity for calcium, promoting binding of the low basal cytosolic calcium at the juxtamembrane domain (JD) site, favoring the transition through the ensemble of high-energy intermediate states along the trajectory to the fully-open activated state (PubMed:30013099, PubMed:35301323, PubMed:37898605). Upon opening, releases calcium in the cytosol where it can bind to the low-affinity cytoplasmic domain (CD) site and stabilizes the inhibited state to terminate calcium release (PubMed:30013099, PubMed:35301323, PubMed:37898605). {ECO:0000269|PubMed:30013099, ECO:0000269|PubMed:32949214, ECO:0000269|PubMed:35301323, ECO:0000269|PubMed:37898605, ECO:0000269|PubMed:8081734, ECO:0000269|PubMed:8288584}. |
| Q14586 | ZNF267 | S105 | ochoa | Zinc finger protein 267 (Zinc finger protein HZF2) | May be involved in transcriptional regulation. |
| Q14667 | BLTP2 | S1846 | ochoa | Bridge-like lipid transfer protein family member 2 (Antigen MLAA-22) (Breast cancer-overexpressed gene 1 protein) (Protein hobbit homolog) | Tube-forming lipid transport protein which binds to phosphatidylinositols and affects phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) distribution. {ECO:0000250|UniProtKB:Q9VZS7}. |
| Q14671 | PUM1 | S305 | ochoa | Pumilio homolog 1 (HsPUM) (Pumilio-1) | Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:18328718, PubMed:21397187, PubMed:21572425, PubMed:21653694). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000250|UniProtKB:Q80U78, ECO:0000269|PubMed:18328718, ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:20818387, ECO:0000269|PubMed:20860814, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:21572425, ECO:0000269|PubMed:21653694, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25768905, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:29474920}. |
| Q14674 | ESPL1 | S1073 | psp | Separin (EC 3.4.22.49) (Caspase-like protein ESPL1) (Extra spindle poles-like 1 protein) (Separase) | Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}. |
| Q14674 | ESPL1 | S1528 | ochoa | Separin (EC 3.4.22.49) (Caspase-like protein ESPL1) (Extra spindle poles-like 1 protein) (Separase) | Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms. {ECO:0000269|PubMed:10411507, ECO:0000269|PubMed:11509732}. |
| Q14678 | KANK1 | S879 | ochoa | KN motif and ankyrin repeat domain-containing protein 1 (Ankyrin repeat domain-containing protein 15) (Kidney ankyrin repeat-containing protein) | Adapter protein that links structural and signaling protein complexes positioned to guide microtubule and actin cytoskeleton dynamics during cell morphogenesis (PubMed:22084092, PubMed:24120883). At focal adhesions (FAs) rims, organizes cortical microtubule stabilizing complexes (CMSCs) and directly interacts with major FA component TLN1, forming macromolecular assemblies positioned to control microtubule-actin crosstalk at the cell edge (PubMed:24120883, PubMed:27410476). Recruits KIF21A in CMSCs at axonal growth cones and regulates axon guidance by suppressing microtubule growth without inducing microtubule disassembly once it reaches the cell cortex (PubMed:24120883). Interacts with ARFGEF1 and participates in establishing microtubule-organizing center (MTOC) orientation and directed cell movement in wound healing (PubMed:22084092). Regulates actin stress fiber formation and cell migration by inhibiting RHOA activation in response to growth factors; this function involves phosphorylation through PI3K/Akt signaling and may depend on the competitive interaction with 14-3-3 adapter proteins to sequester them from active complexes (PubMed:18458160, PubMed:25961457). Inhibits the formation of lamellipodia but not of filopodia; this function may depend on the competitive interaction with BAIAP2 to block its association with activated RAC1. Inhibits fibronectin-mediated cell spreading; this function is partially mediated by BAIAP2 (PubMed:19171758). In the nucleus, is involved in beta-catenin-dependent activation of transcription (PubMed:16968744). During cell division, may regulate DAAM1-dependent RHOA activation that signals centrosome maturation and chromosomal segregation. May also be involved in contractile ring formation during cytokinesis (By similarity). Potential tumor suppressor for renal cell carcinoma (Probable). {ECO:0000250|UniProtKB:E9Q238, ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:18458160, ECO:0000269|PubMed:19171758, ECO:0000269|PubMed:22084092, ECO:0000269|PubMed:24120883, ECO:0000269|PubMed:25961457, ECO:0000269|PubMed:27410476, ECO:0000305|PubMed:12133830}. |
| Q14684 | RRP1B | S625 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14789 | GOLGB1 | S491 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| Q14807 | KIF22 | S455 | ochoa | Kinesin-like protein KIF22 (Kinesin-like DNA-binding protein) (Kinesin-like protein 4) | Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA (By similarity). Plays a role in congression of laterally attached chromosomes in NDC80-depleted cells (PubMed:25743205). {ECO:0000250|UniProtKB:Q9I869, ECO:0000269|PubMed:25743205}. |
| Q14938 | NFIX | S239 | ochoa | Nuclear factor 1 X-type (NF1-X) (Nuclear factor 1/X) (CCAAT-box-binding transcription factor) (CTF) (Nuclear factor I/X) (NF-I/X) (NFI-X) (TGGCA-binding protein) | Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication. |
| Q14966 | ZNF638 | S1913 | ochoa | Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) | Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}. |
| Q14980 | NUMA1 | S1721 | ochoa | Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) | Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}. |
| Q14980 | NUMA1 | S1942 | ochoa | Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) | Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}. |
| Q14D04 | VEPH1 | S425 | ochoa | Ventricular zone-expressed PH domain-containing protein homolog 1 (Protein melted) | Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}. |
| Q15013 | MAD2L1BP | S37 | ochoa | MAD2L1-binding protein (Caught by MAD2 protein) (p31(comet)) | May function to silence the spindle checkpoint and allow mitosis to proceed through anaphase by binding MAD2L1 after it has become dissociated from the MAD2L1-CDC20 complex. {ECO:0000269|PubMed:18022368}. |
| Q15022 | SUZ12 | S568 | ochoa | Polycomb protein SUZ12 (Chromatin precipitated E2F target 9 protein) (ChET 9 protein) (Joined to JAZF1 protein) (Suppressor of zeste 12 protein homolog) | Polycomb group (PcG) protein. Component of the PRC2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:15231737, PubMed:15385962, PubMed:16618801, PubMed:17344414, PubMed:18285464, PubMed:28229514, PubMed:29499137, PubMed:31959557). The PRC2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:12351676, PubMed:12435631, PubMed:15099518, PubMed:15225548, PubMed:15385962, PubMed:15684044, PubMed:16431907, PubMed:18086877, PubMed:18285464). Genes repressed by the PRC2 complex include HOXC8, HOXA9, MYT1 and CDKN2A (PubMed:15231737, PubMed:16618801, PubMed:17200670, PubMed:31959557). {ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631, ECO:0000269|PubMed:15099518, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:16431907, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:17200670, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:28229514, ECO:0000269|PubMed:29499137, ECO:0000269|PubMed:31959557}. |
| Q15058 | KIF14 | S101 | ochoa | Kinesin-like protein KIF14 | Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}. |
| Q15149 | PLEC | S2833 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15327 | ANKRD1 | S213 | ochoa | Ankyrin repeat domain-containing protein 1 (Cardiac ankyrin repeat protein) (Cytokine-inducible gene C-193 protein) (Cytokine-inducible nuclear protein) | May play an important role in endothelial cell activation. May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes. Induction seems to be correlated with apoptotic cell death in hepatoma cells. {ECO:0000269|PubMed:15805281, ECO:0000269|PubMed:7730328}. |
| Q15361 | TTF1 | S253 | ochoa | Transcription termination factor 1 (TTF-1) (RNA polymerase I termination factor) (Transcription termination factor I) (TTF-I) | Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity. {ECO:0000250|UniProtKB:Q62187, ECO:0000269|PubMed:7597036}. |
| Q15361 | TTF1 | S710 | ochoa | Transcription termination factor 1 (TTF-1) (RNA polymerase I termination factor) (Transcription termination factor I) (TTF-I) | Multifunctional nucleolar protein that terminates ribosomal gene transcription, mediates replication fork arrest and regulates RNA polymerase I transcription on chromatin. Plays a dual role in rDNA regulation, being involved in both activation and silencing of rDNA transcription. Interaction with BAZ2A/TIP5 recovers DNA-binding activity. {ECO:0000250|UniProtKB:Q62187, ECO:0000269|PubMed:7597036}. |
| Q15365 | PCBP1 | S332 | ochoa | Poly(rC)-binding protein 1 (Alpha-CP1) (Heterogeneous nuclear ribonucleoprotein E1) (hnRNP E1) (Nucleic acid-binding protein SUB2.3) | Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (PubMed:15731341, PubMed:7556077, PubMed:7607214, PubMed:8152927). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity). {ECO:0000250|UniProtKB:P60335, ECO:0000269|PubMed:15731341, ECO:0000269|PubMed:7556077, ECO:0000269|PubMed:7607214, ECO:0000269|PubMed:8152927}.; FUNCTION: (Microbial infection) In case of infection by poliovirus, plays a role in initiation of viral RNA replication in concert with the viral protein 3CD. {ECO:0000269|PubMed:12414943}. |
| Q15418 | RPS6KA1 | S72 | ochoa | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q15418 | RPS6KA1 | S369 | ochoa | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q15424 | SAFB | S55 | ochoa | Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) | Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}. |
| Q15424 | SAFB | S284 | ochoa | Scaffold attachment factor B1 (SAF-B) (SAF-B1) (HSP27 estrogen response element-TATA box-binding protein) (HSP27 ERE-TATA-binding protein) | Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (PubMed:9671816). Functions as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription (PubMed:12660241). Thereby acts as a negative regulator of cell proliferation (PubMed:12660241). When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). {ECO:0000250|UniProtKB:D3YXK2, ECO:0000269|PubMed:12660241, ECO:0000269|PubMed:9671816}. |
| Q15424 | SAFB | S507 | 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}. |
| Q15648 | MED1 | S951 | ochoa | Mediator of RNA polymerase II transcription subunit 1 (Activator-recruited cofactor 205 kDa component) (ARC205) (Mediator complex subunit 1) (Peroxisome proliferator-activated receptor-binding protein) (PBP) (PPAR-binding protein) (Thyroid hormone receptor-associated protein complex 220 kDa component) (Trap220) (Thyroid receptor-interacting protein 2) (TR-interacting protein 2) (TRIP-2) (Vitamin D receptor-interacting protein complex component DRIP205) (p53 regulatory protein RB18A) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (PubMed:10406464, PubMed:11867769, PubMed:12037571, PubMed:12218053, PubMed:12556447, PubMed:14636573, PubMed:15340084, PubMed:15471764, PubMed:15989967, PubMed:16574658, PubMed:9653119). Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). {ECO:0000269|PubMed:10406464, ECO:0000269|PubMed:11867769, ECO:0000269|PubMed:12037571, ECO:0000269|PubMed:12218053, ECO:0000269|PubMed:12556447, ECO:0000269|PubMed:14636573, ECO:0000269|PubMed:15340084, ECO:0000269|PubMed:15471764, ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16574658, ECO:0000269|PubMed:24245781, ECO:0000269|PubMed:9653119}. |
| Q15678 | PTPN14 | S463 | ochoa | Tyrosine-protein phosphatase non-receptor type 14 (EC 3.1.3.48) (Protein-tyrosine phosphatase pez) | Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor. {ECO:0000269|PubMed:10934049, ECO:0000269|PubMed:12808048, ECO:0000269|PubMed:17893246, ECO:0000269|PubMed:20826270, ECO:0000269|PubMed:22233626, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:22948661}. |
| Q15678 | PTPN14 | S807 | ochoa | Tyrosine-protein phosphatase non-receptor type 14 (EC 3.1.3.48) (Protein-tyrosine phosphatase pez) | Protein tyrosine phosphatase which may play a role in the regulation of lymphangiogenesis, cell-cell adhesion, cell-matrix adhesion, cell migration, cell growth and also regulates TGF-beta gene expression, thereby modulating epithelial-mesenchymal transition. Mediates beta-catenin dephosphorylation at adhesion junctions. Acts as a negative regulator of the oncogenic property of YAP, a downstream target of the hippo pathway, in a cell density-dependent manner. May function as a tumor suppressor. {ECO:0000269|PubMed:10934049, ECO:0000269|PubMed:12808048, ECO:0000269|PubMed:17893246, ECO:0000269|PubMed:20826270, ECO:0000269|PubMed:22233626, ECO:0000269|PubMed:22525271, ECO:0000269|PubMed:22948661}. |
| Q15751 | HERC1 | S1510 | ochoa | Probable E3 ubiquitin-protein ligase HERC1 (EC 2.3.2.26) (HECT domain and RCC1-like domain-containing protein 1) (HECT-type E3 ubiquitin transferase HERC1) (p532) (p619) | Involved in membrane trafficking via some guanine nucleotide exchange factor (GEF) activity and its ability to bind clathrin. Acts as a GEF for Arf and Rab, by exchanging bound GDP for free GTP. Binds phosphatidylinositol 4,5-bisphosphate, which is required for GEF activity. May also act as a E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. {ECO:0000269|PubMed:15642342, ECO:0000269|PubMed:8861955, ECO:0000269|PubMed:9233772}. |
| Q16539 | MAPK14 | S326 | ochoa | Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}. |
| Q16659 | MAPK6 | S556 | ochoa | Mitogen-activated protein kinase 6 (MAP kinase 6) (MAPK 6) (EC 2.7.11.24) (Extracellular signal-regulated kinase 3) (ERK-3) (MAP kinase isoform p97) (p97-MAPK) | Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}. |
| Q16891 | IMMT | S390 | ochoa | MICOS complex subunit MIC60 (Cell proliferation-inducing gene 4/52 protein) (Mitochondrial inner membrane protein) (Mitofilin) (p87/89) | Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane (PubMed:22114354, PubMed:25781180, PubMed:32567732, PubMed:33130824). Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology (PubMed:22114354, PubMed:25781180, PubMed:32567732, PubMed:33130824). {ECO:0000269|PubMed:22114354, ECO:0000269|PubMed:25781180, ECO:0000269|PubMed:32567732, ECO:0000269|PubMed:33130824}. |
| Q17R91 | DIAPH2 | S820 | psp | Protein diaphanous homolog 2 (Diaphanous-related formin-2) | None |
| Q1KMD3 | HNRNPUL2 | S543 | ochoa | Heterogeneous nuclear ribonucleoprotein U-like protein 2 (Scaffold-attachment factor A2) (SAF-A2) | None |
| Q2M2I8 | AAK1 | S650 | ochoa | AP2-associated protein kinase 1 (EC 2.7.11.1) (Adaptor-associated kinase 1) | Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:11877457, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:17494869, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124). {ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:11877461, ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:21464124, ECO:0000269|PubMed:25653444}.; FUNCTION: (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue. {ECO:0000269|PubMed:25653444, ECO:0000305|PubMed:31136173}. |
| Q2M389 | WASHC4 | S1097 | ochoa | WASH complex subunit 4 (Strumpellin and WASH-interacting protein) (SWIP) (WASH complex subunit SWIP) | Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting. {ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:20498093, ECO:0000303|PubMed:21498477}. |
| Q2NKX8 | ERCC6L | S774 | ochoa | DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) | DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}. |
| Q2PPJ7 | RALGAPA2 | S1350 | ochoa | Ral GTPase-activating protein subunit alpha-2 (250 kDa substrate of Akt) (AS250) (p220) | Catalytic subunit of the heterodimeric RalGAP2 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q2VIQ3 | KIF4B | S1038 | ochoa | Chromosome-associated kinesin KIF4B (Chromokinesin-B) | Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (By similarity). Translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis (By similarity). May play a role in mitotic chromosomal positioning and bipolar spindle stabilization (By similarity). {ECO:0000250|UniProtKB:O95239, ECO:0000250|UniProtKB:P33174}. |
| Q3KQU3 | MAP7D1 | S252 | ochoa | MAP7 domain-containing protein 1 (Arginine/proline-rich coiled-coil domain-containing protein 1) (Proline/arginine-rich coiled-coil domain-containing protein 1) | Microtubule-stabilizing protein involved in the control of cell motility and neurite outgrowth. Facilitate microtubule stabilization through the maintenance of acetylated stable microtubules. {ECO:0000250|UniProtKB:A2AJI0}. |
| Q3KQU3 | MAP7D1 | S811 | ochoa | MAP7 domain-containing protein 1 (Arginine/proline-rich coiled-coil domain-containing protein 1) (Proline/arginine-rich coiled-coil domain-containing protein 1) | Microtubule-stabilizing protein involved in the control of cell motility and neurite outgrowth. Facilitate microtubule stabilization through the maintenance of acetylated stable microtubules. {ECO:0000250|UniProtKB:A2AJI0}. |
| Q3L8U1 | CHD9 | S2009 | ochoa | Chromodomain-helicase-DNA-binding protein 9 (CHD-9) (EC 3.6.4.-) (ATP-dependent helicase CHD9) (Chromatin-related mesenchymal modulator) (CReMM) (Chromatin-remodeling factor CHROM1) (Kismet homolog 2) (PPAR-alpha-interacting complex protein 320 kDa) (Peroxisomal proliferator-activated receptor A-interacting complex 320 kDa protein) | Probable ATP-dependent chromatin-remodeling factor. Acts as a transcriptional coactivator for PPARA and possibly other nuclear receptors. Has DNA-dependent ATPase activity and binds to A/T-rich DNA. Associates with A/T-rich regulatory regions in promoters of genes that participate in the differentiation of progenitors during osteogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:16095617, ECO:0000269|PubMed:16554032}. |
| Q3V6T2 | CCDC88A | S1700 | 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}. |
| Q3V6T2 | CCDC88A | S1715 | 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}. |
| Q4G0J3 | LARP7 | S300 | ochoa | La-related protein 7 (La ribonucleoprotein domain family member 7) (hLARP7) (P-TEFb-interaction protein for 7SK stability) (PIP7S) | RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function (PubMed:18249148, PubMed:32017898). Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II (PubMed:18249148, PubMed:18483487). The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:18249148, PubMed:18483487). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838). LARP7 specifically binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex (PubMed:18281698, PubMed:18483487). LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing (PubMed:32017898). Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes (PubMed:32017898). U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (PubMed:32017898). Binds U6 snRNAs with a 5'-CAGGG-3' sequence motif (PubMed:32017898). U6 snRNA processing is required for spermatogenesis (By similarity). {ECO:0000250|UniProtKB:Q05CL8, ECO:0000269|PubMed:18249148, ECO:0000269|PubMed:18281698, ECO:0000269|PubMed:18483487, ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:32017898}. |
| Q4G0N4 | NADK2 | S188 | ochoa|psp | NAD kinase 2, mitochondrial (EC 2.7.1.23) (Mitochondrial NAD kinase) (NAD kinase domain-containing protein 1, mitochondrial) | Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor. Also has weak NADH kinase activity in vitro; however NADH kinase activity is much weaker than the NAD(+) kinase activity and may not be relevant in vivo. {ECO:0000269|PubMed:23212377}. |
| Q4KWH8 | PLCH1 | S1492 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-1) (Phospholipase C-eta-1) (PLC-eta-1) (Phospholipase C-like protein 3) (PLC-L3) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by calcium-activated phosphatidylinositol-specific phospholipase C enzymes. {ECO:0000269|PubMed:15702972}. |
| Q53QZ3 | ARHGAP15 | S103 | ochoa | Rho GTPase-activating protein 15 (ArhGAP15) (Rho-type GTPase-activating protein 15) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has activity toward RAC1. Overexpression results in an increase in actin stress fibers and cell contraction. {ECO:0000269|PubMed:12650940}. |
| Q53T59 | HS1BP3 | S259 | ochoa | HCLS1-binding protein 3 (HS1-binding protein 3) (HSP1BP-3) | May be a modulator of IL-2 signaling. {ECO:0000250}. |
| Q562E7 | WDR81 | S1113 | ochoa | WD repeat-containing protein 81 | Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May also play a role in aggrephagy, the macroautophagic degradation of ubiquitinated protein aggregates. In this process, may regulate the interaction of SQSTM1 with ubiquitinated proteins and also recruit MAP1LC3C (PubMed:28404643). May also be involved in maintenance of normal mitochondrial structure and organization (By similarity). {ECO:0000250|UniProtKB:Q5ND34, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989, ECO:0000269|PubMed:28404643}. |
| Q5FWE3 | PRRT3 | S925 | ochoa | Proline-rich transmembrane protein 3 | None |
| Q5JRA6 | MIA3 | S1465 | ochoa | Transport and Golgi organization protein 1 homolog (TANGO1) (C219-reactive peptide) (D320) (Melanoma inhibitory activity protein 3) | Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum (PubMed:19269366, PubMed:27138255). Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES (PubMed:28442536). {ECO:0000269|PubMed:19269366, ECO:0000269|PubMed:27138255, ECO:0000269|PubMed:28442536}. |
| Q5JSH3 | WDR44 | S871 | ochoa | WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) | Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| Q5JSZ5 | PRRC2B | S1754 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5M775 | SPECC1 | S35 | ochoa | Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) | None |
| Q5SQI0 | ATAT1 | S237 | psp | Alpha-tubulin N-acetyltransferase 1 (Alpha-TAT) (Alpha-TAT1) (TAT) (EC 2.3.1.108) (Acetyltransferase mec-17 homolog) | Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly. {ECO:0000255|HAMAP-Rule:MF_03130, ECO:0000269|PubMed:20829795, ECO:0000269|PubMed:21068373, ECO:0000269|PubMed:24097348, ECO:0000269|PubMed:24906155}. |
| Q5SSJ5 | HP1BP3 | S377 | ochoa | Heterochromatin protein 1-binding protein 3 (Protein HP1-BP74) | Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity (PubMed:24830416). Mediates chromatin condensation during hypoxia, leading to increased tumor cell viability, radio-resistance, chemo-resistance and self-renewal (PubMed:25100860). {ECO:0000269|PubMed:24830416, ECO:0000269|PubMed:25100860}. |
| Q5SW79 | CEP170 | S450 | ochoa | Centrosomal protein of 170 kDa (Cep170) (KARP-1-binding protein) (KARP1-binding protein) | Plays a role in microtubule organization (PubMed:15616186). Required for centriole subdistal appendage assembly (PubMed:28422092). {ECO:0000269|PubMed:15616186, ECO:0000269|PubMed:28422092}. |
| Q5SYE7 | NHSL1 | S378 | ochoa | NHS-like protein 1 | None |
| Q5T011 | SZT2 | S215 | ochoa | KICSTOR complex protein SZT2 (Seizure threshold 2 protein homolog) | As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose (PubMed:28199306, PubMed:28199315). May play a role in the cellular response to oxidative stress (By similarity). {ECO:0000250|UniProtKB:A2A9C3, ECO:0000269|PubMed:28199306, ECO:0000269|PubMed:28199315}. |
| Q5T200 | ZC3H13 | S1404 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5T200 | ZC3H13 | S1433 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5T5C0 | STXBP5 | S1058 | ochoa | Syntaxin-binding protein 5 (Lethal(2) giant larvae protein homolog 3) (Tomosyn-1) | Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding (By similarity). {ECO:0000250}. |
| Q5T5Y3 | CAMSAP1 | S872 | 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}. |
| Q5T7P8 | SYT6 | S97 | ochoa | 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}. |
| Q5T8P6 | RBM26 | S588 | ochoa | RNA-binding protein 26 (CTCL tumor antigen se70-2) (RNA-binding motif protein 26) | May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}. |
| Q5TCY1 | TTBK1 | S517 | ochoa | Tau-tubulin kinase 1 (EC 2.7.11.1) (Brain-derived tau kinase) | Serine/threonine kinase which is able to phosphorylate TAU on serine, threonine and tyrosine residues. Induces aggregation of TAU. {ECO:0000269|PubMed:16923168}. |
| Q5TGY3 | AHDC1 | S846 | ochoa | Transcription factor Gibbin (AT-hook DNA-binding motif-containing protein 1) | Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis (PubMed:35585237). Directly binds promoter and enhancer regions and acts by maintaining local enhancer-promoter chromatin architecture (PubMed:35585237). Interacts with many sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes that wire surface ectoderm stratification (PubMed:35585237). {ECO:0000269|PubMed:35585237}. |
| Q5TH69 | ARFGEF3 | S2081 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (ARFGEF family member 3) | Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8, ECO:0000269|PubMed:19496786}. |
| Q5VT52 | RPRD2 | S1068 | ochoa | Regulation of nuclear pre-mRNA domain-containing protein 2 | None |
| Q5VUA4 | ZNF318 | S508 | ochoa | Zinc finger protein 318 (Endocrine regulatory protein) | [Isoform 2]: Acts as a transcriptional corepressor for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}.; FUNCTION: [Isoform 1]: Acts as a transcriptional coactivator for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}. |
| Q5VUA4 | ZNF318 | S1888 | ochoa | Zinc finger protein 318 (Endocrine regulatory protein) | [Isoform 2]: Acts as a transcriptional corepressor for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}.; FUNCTION: [Isoform 1]: Acts as a transcriptional coactivator for AR-mediated transactivation function. May act as a transcriptional regulator during spermatogenesis and, in particular, during meiotic division. {ECO:0000250|UniProtKB:Q99PP2}. |
| Q5VVJ2 | MYSM1 | S265 | ochoa | Deubiquitinase MYSM1 (2A-DUB) (EC 3.4.19.-) (Myb-like, SWIRM and MPN domain-containing protein 1) | Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response (PubMed:24062447, PubMed:26220525, PubMed:28115216). Participates in the normal programming of B-cell responses to antigen after the maturation process (By similarity). Within the cytoplasm, plays critical roles in the repression of innate immunity and autoimmunity (PubMed:33086059). Removes 'Lys-63'-linked polyubiquitins from TRAF3 and TRAF6 complexes (By similarity). Attenuates NOD2-mediated inflammation and tissue injury by promoting 'Lys-63'-linked deubiquitination of RIPK2 component (By similarity). Suppresses the CGAS-STING1 signaling pathway by cleaving STING1 'Lys-63'-linked ubiquitin chains (PubMed:33086059). In the nucleus, acts as a hematopoietic transcription regulator derepressing a range of genes essential for normal stem cell differentiation including EBF1 and PAX5 in B-cells, ID2 in NK-cell progenitor or FLT3 in dendritic cell precursors (PubMed:24062447). Deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, leading to dissociation of histone H1 from the nucleosome (PubMed:17707232). {ECO:0000250|UniProtKB:Q69Z66, ECO:0000269|PubMed:17707232, ECO:0000269|PubMed:22169041, ECO:0000269|PubMed:24062447, ECO:0000269|PubMed:26220525, ECO:0000269|PubMed:28115216, ECO:0000269|PubMed:33086059}. |
| Q5VWN6 | TASOR2 | S1717 | ochoa | Protein TASOR 2 | None |
| Q5VWQ8 | DAB2IP | S745 | 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}. |
| Q5VWQ8 | DAB2IP | S876 | 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 | S1165 | 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}. |
| Q5VZL5 | ZMYM4 | S1088 | ochoa | Zinc finger MYM-type protein 4 (Zinc finger protein 262) | Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}. |
| Q5W0B1 | OBI1 | S561 | ochoa | ORC ubiquitin ligase 1 (OBI1) (EC 2.3.2.27) (RING finger protein 219) | E3 ubiquitin ligase essential for DNA replication origin activation during S phase (PubMed:31160578). Acts as a replication origin selector which selects the origins to be fired and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase (PubMed:31160578). {ECO:0000269|PubMed:31160578}. |
| Q5XUX0 | FBXO31 | S278 | psp | F-box only protein 31 | Substrate-recognition component of the SCF(FBXO31) protein ligase complex, which specifically mediates the ubiquitination of proteins amidated at their C-terminus in response to oxidative stress, leading to their degradation by the proteasome (PubMed:39880951). FBXO31 specifically recognizes and binds C-terminal peptides bearing an amide: C-terminal amidation in response to oxidative stress takes place following protein fragmentation (PubMed:39880951). The SCF(FBXO31) also plays a role in G1 arrest following DNA damage by mediating ubiquitination of phosphorylated cyclin-D1 (CCND1), promoting its degradation by the proteasome, resulting in G1 arrest (PubMed:19412162, PubMed:29279382). The SCF(FBXO31) complex is however not a major regulator of CCND1 stability during the G1/S transition (By similarity). In response to genotoxic stress, the SCF(FBXO31) complex directs ubiquitination and degradation of phosphorylated MDM2, thereby promoting p53/TP53-mediated DNA damage response (PubMed:26124108). SCF(FBXO31) complex is required for genomic integrity by catalyzing ubiquitination and degradation of cyclin-A (CCNA1 and/or CCNA2) during the G1 phase (PubMed:31413110). In response to genotoxic stress, the SCF(FBXO31) complex directs ubiquitination and degradation of phosphorylated FBXO46 and MAP2K6 (PubMed:24936062, PubMed:30171069). SCF(FBXO31) complex promotes ubiquitination and degradation of CDT1 during the G2 phase to prevent re-replication (PubMed:24828503). The SCF(FBXO31) complex also mediates ubiquitination and degradation of DUSP6, OGT and PARD6A (PubMed:23469015, PubMed:34686346, PubMed:39894887). {ECO:0000250|UniProtKB:Q3TQF0, ECO:0000269|PubMed:19412162, ECO:0000269|PubMed:23469015, ECO:0000269|PubMed:24828503, ECO:0000269|PubMed:24936062, ECO:0000269|PubMed:26124108, ECO:0000269|PubMed:29279382, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:31413110, ECO:0000269|PubMed:34686346, ECO:0000269|PubMed:39880951, ECO:0000269|PubMed:39894887}. |
| Q641Q2 | WASHC2A | S550 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q658Y4 | FAM91A1 | S364 | 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}. |
| Q659A1 | ICE2 | S496 | ochoa | Little elongation complex subunit 2 (Interactor of little elongator complex ELL subunit 2) (NMDA receptor-regulated protein 2) | Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. {ECO:0000269|PubMed:23932780}. |
| Q674X7 | KAZN | S20 | ochoa | Kazrin | Component of the cornified envelope of keratinocytes. May be involved in the interplay between adherens junctions and desmosomes. The function in the nucleus is not known. {ECO:0000269|PubMed:15337775}. |
| Q68CZ2 | TNS3 | S337 | 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}. |
| Q6GYQ0 | RALGAPA1 | S832 | ochoa | Ral GTPase-activating protein subunit alpha-1 (GAP-related-interacting partner to E12) (GRIPE) (GTPase-activating Rap/Ran-GAP domain-like 1) (Tuberin-like protein 1) (p240) | Catalytic subunit of the heterodimeric RalGAP1 complex which acts as a GTPase activator for the Ras-like small GTPases RALA and RALB. {ECO:0000250}. |
| Q6IBW4 | NCAPH2 | S464 | ochoa | Condensin-2 complex subunit H2 (Chromosome-associated protein H2) (hCAP-H2) (Kleisin-beta) (Non-SMC condensin II complex subunit H2) | Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture (PubMed:14532007). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of chromatin bridges at anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (By similarity). Seems to have lineage-specific role in T-cell development (PubMed:14532007). {ECO:0000250|UniProtKB:Q8BSP2, ECO:0000269|PubMed:14532007}. |
| Q6IQ55 | TTBK2 | S445 | 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}. |
| Q6IQ55 | TTBK2 | S484 | 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}. |
| Q6IQ55 | TTBK2 | S817 | 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}. |
| Q6NUJ5 | PWWP2B | S291 | ochoa | PWWP domain-containing protein 2B | Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes (PubMed:30228260). Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z (PubMed:30228260). Plays a role in facilitating transcriptional elongation through regulation of histone acetylation (By similarity). Negatively regulates brown adipocyte thermogenesis by interacting with and stabilizing HDAC1 at the UCP1 gene promoter, thereby promoting histone deacetylation at the promoter leading to the repression of UCP1 expression (By similarity). {ECO:0000250|UniProtKB:Q69Z61, ECO:0000269|PubMed:30228260}. |
| Q6P1L5 | FAM117B | S508 | ochoa | Protein FAM117B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 13 protein) | None |
| Q6P2P2 | PRMT9 | S547 | ochoa | Protein arginine N-methyltransferase 9 (Protein arginine N-methyltransferase 10) (EC 2.1.1.320) | Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA). Specifically mediates the symmetrical dimethylation of SF3B2. Involved in the regulation of alternative splicing of pre-mRNA (PubMed:25737013, PubMed:25979344). {ECO:0000269|PubMed:25737013, ECO:0000269|PubMed:25979344}. |
| Q6P3S1 | DENND1B | S562 | 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}. |
| Q6P499 | NIPAL3 | S359 | ochoa | NIPA-like protein 3 | None |
| Q6P4F7 | ARHGAP11A | S604 | ochoa | Rho GTPase-activating protein 11A (Rho-type GTPase-activating protein 11A) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000269|PubMed:27957544}. |
| Q6P9A1 | ZNF530 | S130 | ochoa | Zinc finger protein 530 | May be involved in transcriptional regulation. {ECO:0000250}. |
| Q6PHR2 | ULK3 | S305 | ochoa | Serine/threonine-protein kinase ULK3 (EC 2.7.11.1) (Unc-51-like kinase 3) | Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy. {ECO:0000269|PubMed:19279323, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:20643644}. |
| Q6PIF6 | MYO7B | S934 | ochoa | Unconventional myosin-VIIb | Myosins are actin-based motor molecules with ATPase activity. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. As part of the intermicrovillar adhesion complex/IMAC plays a role in epithelial brush border differentiation, controlling microvilli organization and length (PubMed:24725409, PubMed:26812018, PubMed:32209652). May link the complex to the actin core bundle of microvilli. {ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812018, ECO:0000269|PubMed:32209652, ECO:0000305|PubMed:24725409, ECO:0000305|PubMed:26812018}. |
| Q6PJ69 | TRIM65 | S181 | psp | E3 ubiquitin-protein ligase TRIM65 (EC 2.3.2.27) (Tripartite motif-containing protein 65) | E3 ubiquitin ligase that plays a role in several processes including innate immnity, autophagy or inflammation (PubMed:28594402, PubMed:34512673). Negatively regulates miRNAs by modulating the ubiquitination and stability of TNRC6A, a protein involved in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (PubMed:24778252). This ubiquitination results in the suppressed expression of miR-138-5p leading to increased autophagy (PubMed:31160576). Upon enteroviral infection, promotes 'Lys-63'-mediated ubiquitination activation of IFIH1/MDA5 leading to innate signaling cascade (PubMed:28594402). Mechanistically, selectively recognizes MDA5 filaments that occur on dsRNAs (PubMed:33373584). Plays also a role in limitation of inflammation through different mechanisms. First, promotes 'Lys-48'-mediated ubiquitination of VCAM1 leading to its degradation and limitation of LPS-induced lung inflammation (PubMed:31310649). In addition, negatively regulates inflammasome activation by promoting 'lys48'-linked ubiquitination of NLRP3 which is critical for the inhibition of NLRP3 inflammasome activation in resting macrophages (PubMed:34512673). {ECO:0000269|PubMed:24778252, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:31160576, ECO:0000269|PubMed:31310649, ECO:0000269|PubMed:33373584, ECO:0000269|PubMed:34512673}. |
| Q6PKG0 | LARP1 | S546 | ochoa | La-related protein 1 (La ribonucleoprotein domain family member 1) | RNA-binding protein that regulates the translation of specific target mRNA species downstream of the mTORC1 complex, in function of growth signals and nutrient availability (PubMed:20430826, PubMed:23711370, PubMed:24532714, PubMed:25940091, PubMed:28650797, PubMed:28673543, PubMed:29244122). Interacts on the one hand with the 3' poly-A tails that are present in all mRNA molecules, and on the other hand with the 7-methylguanosine cap structure of mRNAs containing a 5' terminal oligopyrimidine (5'TOP) motif, which is present in mRNAs encoding ribosomal proteins and several components of the translation machinery (PubMed:23711370, PubMed:25940091, PubMed:26206669, PubMed:28379136, PubMed:28650797, PubMed:29244122). The interaction with the 5' end of mRNAs containing a 5'TOP motif leads to translational repression by preventing the binding of EIF4G1 (PubMed:25940091, PubMed:28379136, PubMed:28650797, PubMed:29244122). When mTORC1 is activated, LARP1 is phosphorylated and dissociates from the 5' untranslated region (UTR) of mRNA (PubMed:25940091, PubMed:28650797). Does not prevent binding of EIF4G1 to mRNAs that lack a 5'TOP motif (PubMed:28379136). Interacts with the free 40S ribosome subunit and with ribosomes, both monosomes and polysomes (PubMed:20430826, PubMed:24532714, PubMed:25940091, PubMed:28673543). Under normal nutrient availability, interacts primarily with the 3' untranslated region (UTR) of mRNAs encoding ribosomal proteins and increases protein synthesis (PubMed:23711370, PubMed:28650797). Associates with actively translating ribosomes and stimulates translation of mRNAs containing a 5'TOP motif, thereby regulating protein synthesis, and as a consequence, cell growth and proliferation (PubMed:20430826, PubMed:24532714). Stabilizes mRNAs species with a 5'TOP motif, which is required to prevent apoptosis (PubMed:20430826, PubMed:23711370, PubMed:25940091, PubMed:28673543). {ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:23711370, ECO:0000269|PubMed:24532714, ECO:0000269|PubMed:25940091, ECO:0000269|PubMed:26206669, ECO:0000269|PubMed:28379136, ECO:0000269|PubMed:28650797, ECO:0000269|PubMed:28673543, ECO:0000269|PubMed:29244122}.; FUNCTION: (Microbial infection) Positively regulates the replication of dengue virus (DENV). {ECO:0000269|PubMed:26735137}. |
| Q6R327 | RICTOR | S1177 | ochoa|psp | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6UWE0 | LRSAM1 | S290 | ochoa | E3 ubiquitin-protein ligase LRSAM1 (EC 2.3.2.27) (Leucine-rich repeat and sterile alpha motif-containing protein 1) (RING-type E3 ubiquitin transferase LRSAM1) (Tsg101-associated ligase) (hTAL) | E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098). {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322, ECO:0000269|PubMed:25484098}. |
| Q6UXH1 | CRELD2 | S70 | ochoa | Protein disulfide isomerase CRELD2 (EC 5.3.4.1) (Cysteine-rich with EGF-like domain protein 2) | Protein disulfide isomerase (By similarity). Might play a role in the unfolded protein response (By similarity). May regulate transport of alpha4-beta2 neuronal acetylcholine receptor (PubMed:16238698). {ECO:0000250|UniProtKB:Q9CYA0, ECO:0000269|PubMed:16238698}. |
| Q6WCQ1 | MPRIP | S381 | ochoa | Myosin phosphatase Rho-interacting protein (M-RIP) (Rho-interacting protein 3) (RIP3) (p116Rip) | Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells. {ECO:0000250|UniProtKB:P97434, ECO:0000269|PubMed:15545284, ECO:0000269|PubMed:16257966}. |
| Q6WKZ4 | RAB11FIP1 | S477 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6WKZ4 | RAB11FIP1 | S935 | ochoa | Rab11 family-interacting protein 1 (Rab11-FIP1) (Rab-coupling protein) | A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation (PubMed:26032412). {ECO:0000269|PubMed:11786538, ECO:0000269|PubMed:15181150, ECO:0000269|PubMed:15355514, ECO:0000269|PubMed:16920206, ECO:0000269|PubMed:26032412}. |
| Q6Y7W6 | GIGYF2 | S650 | ochoa | GRB10-interacting GYF protein 2 (PERQ amino acid-rich with GYF domain-containing protein 2) (Trinucleotide repeat-containing gene 15 protein) | Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931, PubMed:31439631, PubMed:35878012). In the 4EHP-GYF2 complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (PubMed:31439631). Also recruits and bridges the association of the 4EHP complex with the decapping effector protein DDX6, which is required for the ZFP36/TTP-mediated down-regulation of AU-rich mRNA (PubMed:31439631). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153). In association with EIF4E2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide (PubMed:32726578). GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist (PubMed:32726578). {ECO:0000269|PubMed:12771153, ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:31439631, ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:35878012}.; FUNCTION: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 infection, the interaction with non-structural protein 2 (nsp2) enhances GIGYF2 binding to EIF4E2 and increases repression of translation initiation of genes involved in antiviral innate immune response such as IFNB1. {ECO:0000269|PubMed:35878012}. |
| Q6YHU6 | THADA | S1015 | ochoa | tRNA (32-2'-O)-methyltransferase regulator THADA (Gene inducing thyroid adenomas protein) (Thyroid adenoma-associated protein) | Together with methyltransferase FTSJ1, methylates the 2'-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs. {ECO:0000269|PubMed:25404562}. |
| Q6ZN28 | MACC1 | S72 | ochoa | Metastasis-associated in colon cancer protein 1 (SH3 domain-containing protein 7a5) | Acts as a transcription activator for MET and as a key regulator of HGF-MET signaling. Promotes cell motility, proliferation and hepatocyte growth factor (HGF)-dependent scattering in vitro and tumor growth and metastasis in vivo. {ECO:0000269|PubMed:19098908}. |
| Q6ZS30 | NBEAL1 | S1841 | ochoa | Neurobeachin-like protein 1 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 16 protein) (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 17 protein) | None |
| Q6ZV73 | FGD6 | S692 | 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}. |
| Q6ZW13 | C16orf86 | S172 | ochoa | Uncharacterized protein C16orf86 | None |
| Q70Z35 | PREX2 | S1515 | ochoa | Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 protein (P-Rex2) (PtdIns(3,4,5)-dependent Rac exchanger 2) (DEP domain-containing protein 2) | Functions as a RAC1 guanine nucleotide exchange factor (GEF), activating Rac proteins by exchanging bound GDP for free GTP. Its activity is synergistically activated by phosphatidylinositol 3,4,5-trisphosphate and the beta gamma subunits of heterotrimeric G protein. Mediates the activation of RAC1 in a PI3K-dependent manner. May be an important mediator of Rac signaling, acting directly downstream of both G protein-coupled receptors and phosphoinositide 3-kinase. {ECO:0000269|PubMed:15304342, ECO:0000269|PubMed:15304343, ECO:0000269|PubMed:15897194}. |
| Q70Z53 | FRA10AC1 | S283 | ochoa | Protein FRA10AC1 | May be involved in pre-mRNA splicing. {ECO:0000269|PubMed:34694367}. |
| Q71F23 | CENPU | S194 | ochoa | Centromere protein U (CENP-U) (Centromere protein of 50 kDa) (CENP-50) (Interphase centromere complex protein 24) (KSHV latent nuclear antigen-interacting protein 1) (MLF1-interacting protein) (Polo-box-interacting protein 1) | Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Plays an important role in the correct PLK1 localization to the mitotic kinetochores. A scaffold protein responsible for the initial recruitment and maintenance of the kinetochore PLK1 population until its degradation. Involved in transcriptional repression. {ECO:0000269|PubMed:12941884, ECO:0000269|PubMed:16716197, ECO:0000269|PubMed:17081991}. |
| Q71RC2 | LARP4 | S569 | ochoa | La-related protein 4 (La ribonucleoprotein domain family member 4) | RNA binding protein that binds to the poly-A tract of mRNA molecules (PubMed:21098120). Associates with the 40S ribosomal subunit and with polysomes (PubMed:21098120). Plays a role in the regulation of mRNA translation (PubMed:21098120). Plays a role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987, PubMed:27615744). {ECO:0000269|PubMed:21098120, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:27615744}. |
| Q76I76 | SSH2 | S784 | ochoa | Protein phosphatase Slingshot homolog 2 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 2) (SSH-2L) (hSSH-2L) | Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein (PubMed:11832213). Required for spermatogenesis (By similarity). Involved in acrosome biogenesis, probably by regulating cofilin-mediated actin cytoskeleton remodeling during proacrosomal vesicle fusion and/or Golgi to perinuclear vesicle trafficking (By similarity). {ECO:0000250|UniProtKB:Q5SW75, ECO:0000269|PubMed:11832213}. |
| Q7KZF4 | SND1 | S126 | ochoa | Staphylococcal nuclease domain-containing protein 1 (EC 3.1.31.1) (100 kDa coactivator) (EBNA2 coactivator p100) (Tudor domain-containing protein 11) (p100 co-activator) | Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (PubMed:18453631, PubMed:28546213). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition (PubMed:28546213). Functions as a bridging factor between STAT6 and the basal transcription factor (PubMed:12234934). Plays a role in PIM1 regulation of MYB activity (PubMed:9809063). Functions as a transcriptional coactivator for STAT5 (By similarity). {ECO:0000250|UniProtKB:Q78PY7, ECO:0000269|PubMed:12234934, ECO:0000269|PubMed:18453631, ECO:0000269|PubMed:28546213, ECO:0000269|PubMed:9809063}.; FUNCTION: (Microbial infection) Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2). {ECO:0000269|PubMed:7651391}.; FUNCTION: (Microbial infection) Promotes SARS-CoV-2 RNA synthesis by binding to negative-sense RNA and the viral protein nsp9. {ECO:0000269|PubMed:37794589}. |
| Q7L9B9 | EEPD1 | S225 | ochoa | Endonuclease/exonuclease/phosphatase family domain-containing protein 1 | None |
| Q7Z2W4 | ZC3HAV1 | S635 | 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}. |
| Q7Z2Z1 | TICRR | S1583 | ochoa | Treslin (TopBP1-interacting checkpoint and replication regulator) (TopBP1-interacting, replication-stimulating protein) | Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}. |
| Q7Z3K3 | POGZ | S314 | ochoa | Pogo transposable element with ZNF domain (Suppressor of hairy wing homolog 5) (Zinc finger protein 280E) (Zinc finger protein 635) | Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms (PubMed:20562864). Promotes the repair of DNA double-strand breaks through the homologous recombination pathway (PubMed:26721387). {ECO:0000269|PubMed:20562864, ECO:0000269|PubMed:26721387}. |
| Q7Z401 | DENND4A | S900 | ochoa | C-myc promoter-binding protein (DENN domain-containing protein 4A) | Probable guanine nucleotide exchange factor (GEF) which may activate RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. According to PubMed:8056341, it may bind to ISRE-like element (interferon-stimulated response element) of MYC P2 promoter. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:8056341}. |
| Q7Z4H7 | HAUS6 | S447 | ochoa | HAUS augmin-like complex subunit 6 | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q7Z4H7 | HAUS6 | S519 | ochoa | HAUS augmin-like complex subunit 6 | Contributes to mitotic spindle assembly, maintenance of centrosome integrity and completion of cytokinesis as part of the HAUS augmin-like complex. Promotes the nucleation of microtubules from the spindle through recruitment of NEDD1 and gamma-tubulin. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19369198, ECO:0000269|PubMed:19427217}. |
| Q7Z591 | AKNA | S1133 | ochoa | Microtubule organization protein AKNA (AT-hook-containing transcription factor) | Centrosomal protein that plays a key role in cell delamination by regulating microtubule organization (By similarity). Required for the delamination and retention of neural stem cells from the subventricular zone during neurogenesis (By similarity). Also regulates the epithelial-to-mesenchymal transition in other epithelial cells (By similarity). Acts by increasing centrosomal microtubule nucleation and recruiting nucleation factors and minus-end stabilizers, thereby destabilizing microtubules at the adherens junctions and mediating constriction of the apical endfoot (By similarity). In addition, may also act as a transcription factor that specifically activates the expression of the CD40 receptor and its ligand CD40L/CD154, two cell surface molecules on lymphocytes that are critical for antigen-dependent-B-cell development (PubMed:11268217). Binds to A/T-rich promoters (PubMed:11268217). It is unclear how it can both act as a microtubule organizer and as a transcription factor; additional evidences are required to reconcile these two apparently contradictory functions (Probable). {ECO:0000250|UniProtKB:Q80VW7, ECO:0000269|PubMed:11268217, ECO:0000305}. |
| Q7Z5J4 | RAI1 | S637 | ochoa | Retinoic acid-induced protein 1 | Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}. |
| Q7Z5K2 | WAPL | S130 | ochoa | Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) | Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}. |
| Q7Z5K2 | WAPL | S254 | ochoa | Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) | Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}. |
| Q7Z5L9 | IRF2BP2 | S381 | ochoa | Interferon regulatory factor 2-binding protein 2 (IRF-2-binding protein 2) (IRF-2BP2) | Acts as a transcriptional corepressor in a IRF2-dependent manner; this repression is not mediated by histone deacetylase activities (PubMed:12799427). Represses the NFAT1-dependent transactivation of NFAT-responsive promoters (PubMed:21576369). Acts as a coactivator of VEGFA expression in cardiac and skeletal muscles (PubMed:20702774). Plays a role in immature B-cell differentiation (PubMed:27016798). {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:20702774, ECO:0000269|PubMed:21576369, ECO:0000269|PubMed:27016798}. |
| Q7Z7G8 | VPS13B | S999 | ochoa | Intermembrane lipid transfer protein VPS13B (Cohen syndrome protein 1) (Vacuolar protein sorting-associated protein 13B) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phosphatidylinositol 3-phosphate (By similarity). Functions as a tethering factor in the slow endocytic recycling pathway, to assist traffic between early and recycling endosomes (PubMed:24334764, PubMed:30962439, PubMed:32375900). Involved in the transport of proacrosomal vesicles to the nuclear dense lamina (NDL) during spermatid development (By similarity). Plays a role in the assembly of the Golgi apparatus, possibly by mediating trafficking to the Golgi membrane (PubMed:21865173). Plays a role in the development of the nervous system, and may be required for neuron projection development (PubMed:25492866, PubMed:32560273). May also play a role during adipose tissue development (PubMed:26358774). Required for maintenance of the ocular lens (By similarity). {ECO:0000250|UniProtKB:Q07878, ECO:0000250|UniProtKB:Q80TY5, ECO:0000269|PubMed:21865173, ECO:0000269|PubMed:24334764, ECO:0000269|PubMed:26358774, ECO:0000269|PubMed:30962439, ECO:0000269|PubMed:32375900, ECO:0000269|PubMed:32560273, ECO:0000305|PubMed:25492866, ECO:0000305|PubMed:32560273}. |
| Q86SQ0 | PHLDB2 | S56 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86SQ0 | PHLDB2 | S719 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86TV6 | TTC7B | S673 | ochoa | Tetratricopeptide repeat protein 7B (TPR repeat protein 7B) (Tetratricopeptide repeat protein 7-like-1) (TPR repeat protein 7-like-1) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (PubMed:26571211). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:26571211}. |
| Q86U44 | METTL3 | S243 | ochoa | N(6)-adenosine-methyltransferase catalytic subunit METTL3 (EC 2.1.1.348) (Methyltransferase-like protein 3) (hMETTL3) (N(6)-adenosine-methyltransferase 70 kDa subunit) (MT-A70) | The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some RNAs and regulates various processes such as the circadian clock, differentiation of embryonic and hematopoietic stem cells, cortical neurogenesis, response to DNA damage, differentiation of T-cells and primary miRNA processing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:27281194, PubMed:27373337, PubMed:27627798, PubMed:28297716, PubMed:29348140, PubMed:29506078, PubMed:30428350, PubMed:9409616). In the heterodimer formed with METTL14, METTL3 constitutes the catalytic core (PubMed:27281194, PubMed:27373337, PubMed:27627798). N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability, processing, translation efficiency and editing (PubMed:22575960, PubMed:24284625, PubMed:25719671, PubMed:25799998, PubMed:26321680, PubMed:26593424, PubMed:28297716, PubMed:9409616). M6A acts as a key regulator of mRNA stability: methylation is completed upon the release of mRNA into the nucleoplasm and promotes mRNA destabilization and degradation (PubMed:28637692). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization, promoting differentiation of ESCs (By similarity). M6A regulates the length of the circadian clock: acts as an early pace-setter in the circadian loop by putting mRNA production on a fast-track for facilitating nuclear processing, thereby providing an early point of control in setting the dynamics of the feedback loop (By similarity). M6A also regulates circadian regulation of hepatic lipid metabolism (PubMed:30428350). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). Also required for oogenesis (By similarity). Involved in the response to DNA damage: in response to ultraviolet irradiation, METTL3 rapidly catalyzes the formation of m6A on poly(A) transcripts at DNA damage sites, leading to the recruitment of POLK to DNA damage sites (PubMed:28297716). M6A is also required for T-cell homeostasis and differentiation: m6A methylation of transcripts of SOCS family members (SOCS1, SOCS3 and CISH) in naive T-cells promotes mRNA destabilization and degradation, promoting T-cell differentiation (By similarity). Inhibits the type I interferon response by mediating m6A methylation of IFNB (PubMed:30559377). M6A also takes place in other RNA molecules, such as primary miRNA (pri-miRNAs) (PubMed:25799998). Mediates m6A methylation of Xist RNA, thereby participating in random X inactivation: m6A methylation of Xist leads to target YTHDC1 reader on Xist and promote transcription repression activity of Xist (PubMed:27602518). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity). METTL3 mediates methylation of pri-miRNAs, marking them for recognition and processing by DGCR8 (PubMed:25799998). Acts as a positive regulator of mRNA translation independently of the methyltransferase activity: promotes translation by interacting with the translation initiation machinery in the cytoplasm (PubMed:27117702). Its overexpression in a number of cancer cells suggests that it may participate in cancer cell proliferation by promoting mRNA translation (PubMed:27117702). During human coronavirus SARS-CoV-2 infection, adds m6A modifications in SARS-CoV-2 RNA leading to decreased RIGI binding and subsequently dampening the sensing and activation of innate immune responses (PubMed:33961823). {ECO:0000250|UniProtKB:Q8C3P7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26321680, ECO:0000269|PubMed:26593424, ECO:0000269|PubMed:27117702, ECO:0000269|PubMed:27281194, ECO:0000269|PubMed:27373337, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:27627798, ECO:0000269|PubMed:28297716, ECO:0000269|PubMed:28637692, ECO:0000269|PubMed:29348140, ECO:0000269|PubMed:29506078, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:33961823, ECO:0000269|PubMed:9409616}. |
| Q86UE4 | MTDH | S496 | ochoa | Protein LYRIC (3D3/LYRIC) (Astrocyte elevated gene-1 protein) (AEG-1) (Lysine-rich CEACAM1 co-isolated protein) (Metadherin) (Metastasis adhesion protein) | Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance. {ECO:0000269|PubMed:15927426, ECO:0000269|PubMed:16452207, ECO:0000269|PubMed:18316612, ECO:0000269|PubMed:19111877}. |
| Q86V48 | LUZP1 | S518 | ochoa | Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) | F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}. |
| Q86VF7 | NRAP | S1482 | ochoa | Nebulin-related-anchoring protein (N-RAP) | May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. {ECO:0000250|UniProtKB:Q80XB4}. |
| Q86VR2 | RETREG3 | S350 | ochoa | Reticulophagy regulator 3 | Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (PubMed:33826365). Required for collagen quality control in a LIR motif-dependent manner (By similarity). Mediates NRF1-enhanced neurite outgrowth (PubMed:26040720). {ECO:0000250|UniProtKB:Q9CQV4, ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:33826365, ECO:0000269|PubMed:34338405}. |
| Q86W92 | PPFIBP1 | S464 | ochoa | Liprin-beta-1 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 1) (PTPRF-interacting protein-binding protein 1) (hSGT2) | May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}. |
| Q86WV6 | STING1 | S358 | psp | Stimulator of interferon genes protein (hSTING) (Endoplasmic reticulum interferon stimulator) (ERIS) (Mediator of IRF3 activation) (hMITA) (Transmembrane protein 173) | Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23747010, PubMed:23910378, PubMed:27801882, PubMed:29973723, PubMed:30842659, PubMed:35045565, PubMed:35388221, PubMed:36808561, PubMed:37832545, PubMed:25704810, PubMed:39255680). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:23747010, PubMed:23910378, PubMed:26229117, PubMed:30842659, PubMed:35388221, PubMed:37379839). Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state (PubMed:22394562, PubMed:25636800, PubMed:29973723, PubMed:30842653, PubMed:35045565, PubMed:35388221). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:23747010, PubMed:23910378, PubMed:26300263). The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation (PubMed:26150511). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (PubMed:30842662). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (PubMed:30842662). Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation (PubMed:37535724). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (PubMed:18724357). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23747010, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:26150511, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:36808561, ECO:0000269|PubMed:37379839, ECO:0000269|PubMed:37535724, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:39255680}.; FUNCTION: (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230). {ECO:0000269|PubMed:26405230}. |
| Q86WX3 | RPS19BP1 | S89 | ochoa | Active regulator of SIRT1 (40S ribosomal protein S19-binding protein 1) (RPS19-binding protein 1) (S19BP) | 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. Acts as a chaperone that specifically mediates the integration of RPS19 in state post-A1 (PubMed:34516797). Direct regulator of SIRT1. Enhances SIRT1-mediated deacetylation of p53/TP53, thereby participating in inhibition of p53/TP53-mediated transcriptional activity (PubMed:17964266). {ECO:0000269|PubMed:17964266, ECO:0000269|PubMed:34516797}. |
| Q86YS7 | C2CD5 | S817 | 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}. |
| Q8IVF2 | AHNAK2 | S5515 | ochoa | Protein AHNAK2 | None |
| Q8IVL1 | NAV2 | S1877 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IWU2 | LMTK2 | S559 | ochoa | Serine/threonine-protein kinase LMTK2 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase 2) (Brain-enriched kinase) (hBREK) (CDK5/p35-regulated kinase) (CPRK) (Kinase/phosphatase/inhibitor 2) (Lemur tyrosine kinase 2) (Serine/threonine-protein kinase KPI-2) | Phosphorylates PPP1C, phosphorylase b and CFTR. |
| Q8IXS8 | HYCC2 | S416 | ochoa | Hyccin 2 | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. {ECO:0000305|PubMed:26571211}. |
| Q8IYB7 | DIS3L2 | S139 | ochoa | DIS3-like exonuclease 2 (hDIS3L2) (EC 3.1.13.-) | 3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase, such as ZCCHC11/TUT4. Mediates degradation of cytoplasmic mRNAs that have been deadenylated and subsequently uridylated at their 3'. Mediates degradation of uridylated pre-let-7 miRNAs, contributing to the maintenance of embryonic stem (ES) cells. Essential for correct mitosis, and negatively regulates cell proliferation. {ECO:0000255|HAMAP-Rule:MF_03045, ECO:0000269|PubMed:23756462, ECO:0000269|PubMed:24141620}. |
| Q8IYD8 | FANCM | S1045 | psp | Fanconi anemia group M protein (Protein FACM) (EC 3.6.4.13) (ATP-dependent RNA helicase FANCM) (Fanconi anemia-associated polypeptide of 250 kDa) (FAAP250) (Protein Hef ortholog) | DNA-dependent ATPase component of the Fanconi anemia (FA) core complex (PubMed:16116422). Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:16116422, PubMed:19423727, PubMed:20347428, PubMed:20347429, PubMed:29231814). In complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA) and Holliday junction substrates (PubMed:20347428, PubMed:20347429). Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork. This activity is strongly stimulated in the presence of CENPS and CENPX (PubMed:20347429). In complex with FAAP24, efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates (PubMed:17289582). In vitro, on its own, strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA (PubMed:16116434). {ECO:0000269|PubMed:16116422, ECO:0000269|PubMed:16116434, ECO:0000269|PubMed:17289582, ECO:0000269|PubMed:19423727, ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429, ECO:0000269|PubMed:29231814}. |
| Q8IZT6 | ASPM | S253 | ochoa | Abnormal spindle-like microcephaly-associated protein (Abnormal spindle protein homolog) (Asp homolog) | Involved in mitotic spindle regulation and coordination of mitotic processes. The function in regulating microtubule dynamics at spindle poles including spindle orientation, astral microtubule density and poleward microtubule flux seems to depend on the association with the katanin complex formed by KATNA1 and KATNB1. Enhances the microtubule lattice severing activity of KATNA1 by recruiting the katanin complex to microtubules. Can block microtubule minus-end growth and reversely this function can be enhanced by the katanin complex (PubMed:28436967). May have a preferential role in regulating neurogenesis. {ECO:0000269|PubMed:12355089, ECO:0000269|PubMed:15972725, ECO:0000269|PubMed:28436967}. |
| Q8N0T1 | RBIS | S67 | ochoa | Ribosomal biogenesis factor | Trans-acting factor in ribosome biogenesis required for efficient 40S and 60S subunit production. {ECO:0000269|PubMed:26711351}. |
| Q8N1F7 | NUP93 | S75 | ochoa | Nuclear pore complex protein Nup93 (93 kDa nucleoporin) (Nucleoporin Nup93) | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling (PubMed:26878725). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:15703211, ECO:0000269|PubMed:26878725, ECO:0000269|PubMed:9348540}. |
| Q8N3A8 | PARP8 | S373 | ochoa | Protein mono-ADP-ribosyltransferase PARP8 (EC 2.4.2.-) (ADP-ribosyltransferase diphtheria toxin-like 16) (ARTD16) (Poly [ADP-ribose] polymerase 8) (PARP-8) | Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. {ECO:0000269|PubMed:25043379}. |
| Q8N3V7 | SYNPO | S467 | ochoa | Synaptopodin | Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity). {ECO:0000250}. |
| Q8N3V7 | SYNPO | S743 | ochoa | Synaptopodin | Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity). {ECO:0000250}. |
| Q8N4C6 | NIN | S1538 | ochoa | Ninein (hNinein) (Glycogen synthase kinase 3 beta-interacting protein) (GSK3B-interacting protein) | Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15190203, PubMed:23386061). May also act as a centrosome maturation factor (PubMed:11956314). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15190203). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (PubMed:15190203). Required for centriole organization and microtubule anchoring at the mother centriole (PubMed:23386061). {ECO:0000269|PubMed:11956314, ECO:0000269|PubMed:15190203, ECO:0000269|PubMed:23386061}. |
| Q8N4C8 | MINK1 | S903 | 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. |
| Q8N5V2 | NGEF | S606 | ochoa | Ephexin-1 (Eph-interacting exchange protein) (Neuronal guanine nucleotide exchange factor) | Acts as a guanine nucleotide exchange factor (GEF) which differentially activates the GTPases RHOA, RAC1 and CDC42. Plays a role in axon guidance regulating ephrin-induced growth cone collapse and dendritic spine morphogenesis. Upon activation by ephrin through EPHA4, the GEF activity switches toward RHOA resulting in its activation. Activated RHOA promotes cone retraction at the expense of RAC1- and CDC42-stimulated growth cone extension (By similarity). {ECO:0000250}. |
| Q8N7R7 | CCNYL1 | S122 | ochoa | Cyclin-Y-like protein 1 | Key regulator of Wnt signaling implicated in various biological processes including male fertility, embryonic neurogenesis and cortex development. Activates the cyclin-dependent kinase CDK16, and promotes sperm maturation. {ECO:0000250|UniProtKB:D3YUJ3}. |
| Q8N8F7 | LSMEM1 | S38 | ochoa | Leucine-rich single-pass membrane protein 1 | None |
| Q8N960 | CEP120 | S345 | ochoa | Centrosomal protein of 120 kDa (Cep120) (Coiled-coil domain-containing protein 100) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis (By similarity). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). {ECO:0000250|UniProtKB:Q7TSG1, ECO:0000269|PubMed:27185865}. |
| Q8N9M1 | C19orf47 | S395 | ochoa | Uncharacterized protein C19orf47 | None |
| Q8NB50 | ZFP62 | S345 | ochoa | Zinc finger protein 62 homolog (Zfp-62) | May play a role in differentiating skeletal muscle. {ECO:0000250}. |
| Q8NBJ4 | GOLM1 | S204 | ochoa | Golgi membrane protein 1 (Golgi membrane protein GP73) (Golgi phosphoprotein 2) | Unknown. Cellular response protein to viral infection. |
| Q8NC51 | SERBP1 | S243 | ochoa | SERPINE1 mRNA-binding protein 1 (PAI1 RNA-binding protein 1) (PAI-RBP1) (Plasminogen activator inhibitor 1 RNA-binding protein) | Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:36691768). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (By similarity). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay (PubMed:11001948). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). {ECO:0000250|UniProtKB:Q9CY58, ECO:0000269|PubMed:11001948, ECO:0000269|PubMed:28695742, ECO:0000269|PubMed:36691768}. |
| Q8NCG7 | DAGLB | S175 | ochoa | Diacylglycerol lipase-beta (DAGL-beta) (DGL-beta) (EC 3.1.1.116) (KCCR13L) (PUFA-specific triacylglycerol lipase) (EC 3.1.1.3) (Sn1-specific diacylglycerol lipase beta) | Lipase that catalyzes the hydrolysis of arachidonic acid (AA)-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further cleaved by downstream enzymes to release arachidonic acid (AA) for cyclooxygenase (COX)-mediated eicosanoid production (PubMed:14610053). Preferentially hydrolyzes DAGs at the sn-1 position in a calcium-dependent manner and has negligible activity against other lipids including monoacylglycerols and phospholipids (PubMed:14610053). Plays a key role in the regulation of 2-AG and AA pools utilized by COX1/2 to generate lipid mediators of macrophage and microglia inflammatory responses. Also functions as a polyunsaturated fatty acids-specific triacylglycerol lipase in macrophages. Plays an important role to support the metabolic and signaling demands of macrophages (By similarity). {ECO:0000250|UniProtKB:Q91WC9, ECO:0000269|PubMed:14610053}. |
| Q8NCN4 | RNF169 | S553 | ochoa | E3 ubiquitin-protein ligase RNF169 (EC 2.3.2.27) (RING finger protein 169) (RING-type E3 ubiquitin transferase RNF169) | Probable E3 ubiquitin-protein ligase that acts as a regulator of double-strand breaks (DSBs) repair following DNA damage. Functions in a non-canonical fashion to harness RNF168-mediated protein recruitment to DSB-containing chromatin, thereby contributing to regulation of DSB repair pathway utilization (PubMed:22492721, PubMed:30773093). Once recruited to DSB repair sites by recognizing and binding ubiquitin catalyzed by RNF168, competes with TP53BP1 and BRCA1 for association with RNF168-modified chromatin, thereby favouring homologous recombination repair (HRR) and single-strand annealing (SSA) instead of non-homologous end joining (NHEJ) mediated by TP53BP1 (PubMed:30104380, PubMed:30773093). E3 ubiquitin-protein ligase activity is not required for regulation of DSBs repair. {ECO:0000269|PubMed:22492721, ECO:0000269|PubMed:22733822, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:30104380, ECO:0000269|PubMed:30773093}. |
| Q8ND04 | SMG8 | S894 | 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}. |
| Q8ND24 | RNF214 | S25 | ochoa | RING finger protein 214 | None |
| Q8ND30 | PPFIBP2 | S385 | ochoa | Liprin-beta-2 (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 2) (PTPRF-interacting protein-binding protein 2) | May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}. |
| Q8ND76 | CCNY | S100 | ochoa|psp | 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}. |
| Q8ND76 | CCNY | S288 | psp | 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}. |
| Q8NE71 | ABCF1 | S595 | ochoa | ATP-binding cassette sub-family F member 1 (ATP-binding cassette 50) (TNF-alpha-stimulated ABC protein) | Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis. {ECO:0000269|PubMed:19570978}. |
| Q8NEY1 | NAV1 | S140 | 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}. |
| Q8NF91 | SYNE1 | S8277 | ochoa | Nesprin-1 (Enaptin) (KASH domain-containing protein 1) (KASH1) (Myocyte nuclear envelope protein 1) (Myne-1) (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1) | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette. {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:11792814, ECO:0000269|PubMed:18396275}. |
| Q8NFA0 | USP32 | S1421 | ochoa | Ubiquitin carboxyl-terminal hydrolase 32 (EC 3.4.19.12) (Deubiquitinating enzyme 32) (Renal carcinoma antigen NY-REN-60) (Ubiquitin thioesterase 32) (Ubiquitin-specific-processing protease 32) | Deubiquitinase that can remove conjugated ubiquitin from target proteins, such as RAB7A and LAMTOR1 (PubMed:36476874). Acts as a positive regulator of the mTORC1 signaling by mediating deubiquitination of LAMTOR1, thereby promoting the association between LAMTOR1 and the lysosomal V-ATPase complex and subsequent activation of the mTORC1 complex (PubMed:36476874). {ECO:0000269|PubMed:36476874}. |
| Q8NFC6 | BOD1L1 | S2815 | 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}. |
| Q8NFU5 | IPMK | S348 | ochoa | Inositol polyphosphate multikinase (EC 2.7.1.140) (EC 2.7.1.151) (EC 2.7.1.153) (Inositol 1,3,4,6-tetrakisphosphate 5-kinase) | Inositol phosphate kinase with a broad substrate specificity (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30420721, PubMed:30624931). Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30624931). Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (PubMed:12223481). Phosphorylates inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4) (By similarity). Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate (PubMed:28882892, PubMed:30420721). Plays an important role in MLKL-mediated necroptosis via its role in the biosynthesis of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Binding of these highly phosphorylated inositol phosphates to MLKL mediates the release of an N-terminal auto-inhibitory region, leading to activation of the kinase. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:29883610). Required for normal embryonic development, probably via its role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6) (By similarity). {ECO:0000250|UniProtKB:Q7TT16, ECO:0000269|PubMed:12027805, ECO:0000269|PubMed:12223481, ECO:0000269|PubMed:28882892, ECO:0000269|PubMed:29883610, ECO:0000269|PubMed:30420721, ECO:0000269|PubMed:30624931}. |
| Q8NFY4 | SEMA6D | S711 | ochoa | Semaphorin-6D | Shows growth cone collapsing activity on dorsal root ganglion (DRG) neurons in vitro. May be a stop signal for the DRG neurons in their target areas, and possibly also for other neurons. May also be involved in the maintenance and remodeling of neuronal connections. Ligand of TREM2 with PLXNA1 as coreceptor in dendritic cells, plays a role in the generation of immune responses and skeletal homeostasis (By similarity). {ECO:0000250|UniProtKB:Q76KF0}. |
| Q8NHP6 | MOSPD2 | S273 | ochoa | Motile sperm domain-containing protein 2 | Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and endosomes, mitochondria or Golgi through interaction with conventional- and phosphorylated-FFAT-containing organelle-bound proteins (PubMed:29858488, PubMed:33124732, PubMed:35389430). In addition, forms endoplasmic reticulum (ER)-lipid droplets (LDs) contacts through a direct protein-membrane interaction and participates in LDs homeostasis (PubMed:35389430). The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs (PubMed:35389430). Promotes migration of primary monocytes and neutrophils, in response to various chemokines (PubMed:28137892). {ECO:0000269|PubMed:28137892, ECO:0000269|PubMed:29858488, ECO:0000269|PubMed:33124732, ECO:0000269|PubMed:35389430}. |
| Q8NI08 | NCOA7 | S365 | ochoa | Nuclear receptor coactivator 7 (140 kDa estrogen receptor-associated protein) (Estrogen nuclear receptor coactivator 1) | Enhances the transcriptional activities of several nuclear receptors. Involved in the coactivation of different nuclear receptors, such as ESR1, THRB, PPARG and RARA. {ECO:0000269|PubMed:11971969}. |
| Q8TAF3 | WDR48 | S574 | ochoa | WD repeat-containing protein 48 (USP1-associated factor 1) (WD repeat endosomal protein) (p80) | Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46 (PubMed:18082604, PubMed:19075014, PubMed:26388029, PubMed:31253762). Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself (PubMed:18082604, PubMed:31253762). Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate (PubMed:19075014, PubMed:27373336). Also activates deubiquitinating activity of complexes containing USP12 (PubMed:19075014, PubMed:27373336, PubMed:27650958). In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035). Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme (PubMed:27373336, PubMed:27650958). Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination (PubMed:27239033, PubMed:27463890, PubMed:32350107). Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) (PubMed:27239033, PubMed:31253762, PubMed:32350107). DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes (PubMed:31253762, PubMed:32350107). Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:20147293). Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress (PubMed:31844045). {ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:26388029, ECO:0000269|PubMed:27239033, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:27463890, ECO:0000269|PubMed:27650958, ECO:0000269|PubMed:31253762, ECO:0000269|PubMed:31844045, ECO:0000269|PubMed:32350107}.; FUNCTION: (Microbial infection) In case of infection by Herpesvirus saimiri, may play a role in vesicular transport or membrane fusion events necessary for transport to lysosomes. Induces lysosomal vesicle formation via interaction with Herpesvirus saimiri tyrosine kinase-interacting protein (TIP). Subsequently, TIP recruits tyrosine-protein kinase LCK, resulting in down-regulation of T-cell antigen receptor TCR. May play a role in generation of enlarged endosomal vesicles via interaction with TIP (PubMed:12196293). In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1 (PubMed:18032488). {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:18032488}. |
| Q8TBA6 | GOLGA5 | S465 | ochoa | Golgin subfamily A member 5 (Cell proliferation-inducing gene 31 protein) (Golgin-84) (Protein Ret-II) (RET-fused gene 5 protein) | Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport. {ECO:0000269|PubMed:12538640, ECO:0000269|PubMed:15718469}. |
| Q8TBE0 | BAHD1 | S543 | ochoa | Bromo adjacent homology domain-containing 1 protein (BAH domain-containing protein 1) | Heterochromatin protein that acts as a transcription repressor and has the ability to promote the formation of large heterochromatic domains. May act by recruiting heterochromatin proteins such as CBX5 (HP1 alpha), HDAC5 and MBD1. Represses IGF2 expression by binding to its CpG-rich P3 promoter and recruiting heterochromatin proteins. At specific stages of Listeria infection, in complex with TRIM28, corepresses interferon-stimulated genes, including IFNL1, IFNL2 and IFNL3. {ECO:0000269|PubMed:19666599, ECO:0000269|PubMed:21252314}. |
| Q8TC07 | TBC1D15 | S203 | ochoa | TBC1 domain family member 15 (GTPase-activating protein RAB7) (GAP for RAB7) (Rab7-GAP) | Acts as a GTPase activating protein for RAB7A. Does not act on RAB4, RAB5 or RAB6 (By similarity). {ECO:0000250}. |
| Q8TC07 | TBC1D15 | S274 | ochoa | TBC1 domain family member 15 (GTPase-activating protein RAB7) (GAP for RAB7) (Rab7-GAP) | Acts as a GTPase activating protein for RAB7A. Does not act on RAB4, RAB5 or RAB6 (By similarity). {ECO:0000250}. |
| Q8TD55 | PLEKHO2 | S164 | ochoa | Pleckstrin homology domain-containing family O member 2 (PH domain-containing family O member 2) (Pleckstrin homology domain-containing family Q member 1) (PH domain-containing family Q member 1) | None |
| Q8TDF6 | RASGRP4 | S515 | ochoa | RAS guanyl-releasing protein 4 | Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP (PubMed:11880369, PubMed:11956218, PubMed:12493770, PubMed:18024961). In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway by promoting Ras-mediated activation of PIK3CG/PI3Kgamma to promote neutrophil functional responses (By similarity). In CD117(+) dendritic cells and mast cells, participates in an lipopolysaccharide (LPS)-activated signaling pathway that stimulates the production of interferon-gamma and other pro-inflammatory cytokines by natural killer (NK) cells (By similarity). May function in mast cell differentiation (PubMed:11880369, PubMed:11956218, PubMed:12493770, PubMed:18024961). Does not appear to be required for the development of B-cells, DC-cells, T-cells, or NK-cells (By similarity). {ECO:0000250|UniProtKB:Q8BTM9, ECO:0000269|PubMed:11880369, ECO:0000269|PubMed:11956218, ECO:0000269|PubMed:12493770, ECO:0000269|PubMed:18024961}. |
| Q8TDM6 | DLG5 | S296 | ochoa | Disks large homolog 5 (Discs large protein P-dlg) (Placenta and prostate DLG) | Acts as a regulator of the Hippo signaling pathway (PubMed:28087714, PubMed:28169360). Negatively regulates the Hippo signaling pathway by mediating the interaction of MARK3 with STK3/4, bringing them together to promote MARK3-dependent hyperphosphorylation and inactivation of STK3 kinase activity toward LATS1 (PubMed:28087714). Positively regulates the Hippo signaling pathway by mediating the interaction of SCRIB with STK4/MST1 and LATS1 which is important for the activation of the Hippo signaling pathway. Involved in regulating cell proliferation, maintenance of epithelial polarity, epithelial-mesenchymal transition (EMT), cell migration and invasion (PubMed:28169360). Plays an important role in dendritic spine formation and synaptogenesis in cortical neurons; regulates synaptogenesis by enhancing the cell surface localization of N-cadherin. Acts as a positive regulator of hedgehog (Hh) signaling pathway. Plays a critical role in the early point of the SMO activity cycle by interacting with SMO at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). {ECO:0000250|UniProtKB:E9Q9R9, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:28169360}. |
| Q8TDN6 | BRIX1 | S247 | ochoa | Ribosome biogenesis protein BRX1 homolog (Brix domain-containing protein 2) | Required for biogenesis of the 60S ribosomal subunit. |
| Q8TDY2 | RB1CC1 | S629 | ochoa | RB1-inducible coiled-coil protein 1 (FAK family kinase-interacting protein of 200 kDa) (FIP200) | Involved in autophagy (PubMed:21775823). Regulates early events but also late events of autophagosome formation through direct interaction with Atg16L1 (PubMed:23392225). Required for the formation of the autophagosome-like double-membrane structure that surrounds the Salmonella-containing vacuole (SCV) during S.typhimurium infection and subsequent xenophagy (By similarity). Involved in repair of DNA damage caused by ionizing radiation, which subsequently improves cell survival by decreasing apoptosis (By similarity). Inhibits PTK2/FAK1 and PTK2B/PYK2 kinase activity, affecting their downstream signaling pathways (PubMed:10769033, PubMed:12221124). Plays a role as a modulator of TGF-beta-signaling by restricting substrate specificity of RNF111 (By similarity). Functions as a DNA-binding transcription factor (PubMed:12095676). Is a potent regulator of the RB1 pathway through induction of RB1 expression (PubMed:14533007). Plays a crucial role in muscular differentiation (PubMed:12163359). Plays an indispensable role in fetal hematopoiesis and in the regulation of neuronal homeostasis (By similarity). {ECO:0000250|UniProtKB:Q9ESK9, ECO:0000269|PubMed:10769033, ECO:0000269|PubMed:12095676, ECO:0000269|PubMed:12163359, ECO:0000269|PubMed:12221124, ECO:0000269|PubMed:14533007, ECO:0000269|PubMed:21775823, ECO:0000269|PubMed:23392225}. |
| Q8TEW0 | PARD3 | S887 | 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}. |
| Q8TEW8 | PARD3B | S744 | ochoa | Partitioning defective 3 homolog B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 19 protein) (PAR3-beta) (Partitioning defective 3-like protein) (PAR3-L protein) | Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. |
| Q8TF05 | PPP4R1 | S442 | ochoa | Serine/threonine-protein phosphatase 4 regulatory subunit 1 | Regulatory subunit of serine/threonine-protein phosphatase 4. May play a role in regulation of cell division in renal glomeruli. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. Plays a role in the inhibition of TNF-induced NF-kappa-B activation by regulating the dephosphorylation of TRAF2. {ECO:0000269|PubMed:15805470}.; FUNCTION: (Microbial infection) Participates in merkel polyomavirus-mediated inhibition of NF-kappa-B by bridging viral small tumor antigen with NEMO. {ECO:0000269|PubMed:28445980}. |
| Q8TF72 | SHROOM3 | S835 | ochoa | Protein Shroom3 (Shroom-related protein) (hShrmL) | Controls cell shape changes in the neuroepithelium during neural tube closure. Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers (By similarity). Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays (By similarity). {ECO:0000250|UniProtKB:Q27IV2, ECO:0000250|UniProtKB:Q9QXN0}. |
| Q8TF72 | SHROOM3 | S1219 | ochoa | Protein Shroom3 (Shroom-related protein) (hShrmL) | Controls cell shape changes in the neuroepithelium during neural tube closure. Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers (By similarity). Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays (By similarity). {ECO:0000250|UniProtKB:Q27IV2, ECO:0000250|UniProtKB:Q9QXN0}. |
| Q8WUA4 | GTF3C2 | S147 | 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. |
| Q8WUM0 | NUP133 | S480 | ochoa | Nuclear pore complex protein Nup133 (133 kDa nucleoporin) (Nucleoporin Nup133) | Involved in poly(A)+ RNA transport. Involved in nephrogenesis (PubMed:30179222). {ECO:0000269|PubMed:11684705, ECO:0000269|PubMed:30179222}. |
| Q8WUM4 | PDCD6IP | S642 | ochoa | Programmed cell death 6-interacting protein (PDCD6-interacting protein) (ALG-2-interacting protein 1) (ALG-2-interacting protein X) (Hp95) | Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17556548, PubMed:17853893). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17556548, PubMed:17853893, PubMed:18641129). May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413). By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity). {ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:14739459, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129, ECO:0000269|PubMed:22660413}.; FUNCTION: (Microbial infection) Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function requires the interaction with CHMP4B. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as enveloped virus budding (HIV-1 and other lentiviruses). {ECO:0000269|PubMed:14505569, ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:14519844, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:18641129}. |
| Q8WW22 | DNAJA4 | S113 | ochoa | DnaJ homolog subfamily A member 4 | None |
| Q8WWI1 | LMO7 | S116 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWI1 | LMO7 | S322 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWI1 | LMO7 | S1187 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WWY3 | PRPF31 | S451 | ochoa | U4/U6 small nuclear ribonucleoprotein Prp31 (Pre-mRNA-processing factor 31) (Serologically defined breast cancer antigen NY-BR-99) (U4/U6 snRNP 61 kDa protein) (Protein 61K) (hPrp31) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11867543, PubMed:20118938, PubMed:28781166). Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:11867543). {ECO:0000269|PubMed:11867543, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:28781166}. |
| Q8WX93 | PALLD | S99 | ochoa | Palladin (SIH002) (Sarcoma antigen NY-SAR-77) | Cytoskeletal protein required for organization of normal actin cytoskeleton. Roles in establishing cell morphology, motility, cell adhesion and cell-extracellular matrix interactions in a variety of cell types. May function as a scaffolding molecule with the potential to influence both actin polymerization and the assembly of existing actin filaments into higher-order arrays. Binds to proteins that bind to either monomeric or filamentous actin. Localizes at sites where active actin remodeling takes place, such as lamellipodia and membrane ruffles. Different isoforms may have functional differences. Involved in the control of morphological and cytoskeletal changes associated with dendritic cell maturation. Involved in targeting ACTN to specific subcellular foci. {ECO:0000269|PubMed:11598191, ECO:0000269|PubMed:15147863, ECO:0000269|PubMed:17537434}. |
| Q8WXH0 | SYNE2 | S3825 | ochoa | Nesprin-2 (KASH domain-containing protein 2) (KASH2) (Nuclear envelope spectrin repeat protein 2) (Nucleus and actin connecting element protein) (Protein NUANCE) (Synaptic nuclear envelope protein 2) (Syne-2) | Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (PubMed:34818527). Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 may act redundantly. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis. Facilitates the relaxation of mechanical stress imposed by compressive actin fibers at the rupture site through its nteraction with SYN2 (PubMed:34818527). {ECO:0000250|UniProtKB:Q6ZWQ0, ECO:0000269|PubMed:12118075, ECO:0000269|PubMed:18396275, ECO:0000269|PubMed:19596800, ECO:0000269|PubMed:20724637, ECO:0000269|PubMed:22945352, ECO:0000269|PubMed:34818527}. |
| Q8WXW3 | PIBF1 | S700 | ochoa | Progesterone-induced-blocking factor 1 (PIBF) (Centrosomal protein of 90 kDa) (CEP90) | Plays a role in ciliogenesis. {ECO:0000269|PubMed:26167768}.; FUNCTION: [Isoform 1]: Pericentriolar protein required to maintain mitotic spindle pole integrity (PubMed:21224392). Required for the centrosomal accumulation of PCM1 and the recruitment of centriolar satellite proteins such as BBS4. Via association with PCM1 may be involved in primary cilia formation (PubMed:23110211). Required for CEP63 centrosomal localization and its interaction with WDR62. Together with CEP63 promotes centriole duplication. Promotes the centrosomal localization of CDK2 (PubMed:26297806). {ECO:0000269|PubMed:21224392, ECO:0000269|PubMed:23110211, ECO:0000269|PubMed:26297806}.; FUNCTION: [Isoform 4]: The secreted form is a mediator of progesterone that by acting on the phospholipase A2 enzyme interferes with arachidonic acid metabolism, induces a Th2 biased immune response, and by controlling decidual natural killer cells (NK) activity exerts an anti-abortive effect (PubMed:12516630, PubMed:14634107, PubMed:3863495). Increases the production of Th2-type cytokines by signaling via the JAK/STAT pathway. Activates STAT6 and inhibits STAT4 phosphorylation. Signaling via a not identified receptor seems to implicate IL4R and a GPI-anchored protein (PubMed:16393965, PubMed:25218441). {ECO:0000269|PubMed:12516630, ECO:0000269|PubMed:14634107, ECO:0000269|PubMed:16393965, ECO:0000269|PubMed:25218441, ECO:0000269|PubMed:3863495, ECO:0000305|PubMed:11407300}. |
| Q8WYP5 | AHCTF1 | S1827 | ochoa | Protein ELYS (Embryonic large molecule derived from yolk sac) (Protein MEL-28) (Putative AT-hook-containing transcription factor 1) | Required for the assembly of a functional nuclear pore complex (NPC) on the surface of chromosomes as nuclei form at the end of mitosis. May initiate NPC assembly by binding to chromatin and recruiting the Nup107-160 subcomplex of the NPC. Also required for the localization of the Nup107-160 subcomplex of the NPC to the kinetochore during mitosis and for the completion of cytokinesis. {ECO:0000269|PubMed:17098863, ECO:0000269|PubMed:17235358}. |
| Q92536 | SLC7A6 | S35 | ochoa | Y+L amino acid transporter 2 (Cationic amino acid transporter, y+ system) (Solute carrier family 7 member 6) (y(+)L-type amino acid transporter 2) (Y+LAT2) (y+LAT-2) | Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux route by exporting cationic amino acids such as L-arginine from inside the cells in exchange with neutral amino acids like L-leucine, L-glutamine and isoleucine, plus sodium ions and may participate in nitric oxide synthesis (PubMed:10903140, PubMed:11311135, PubMed:14603368, PubMed:15756301, PubMed:16785209, PubMed:17329401, PubMed:19562367, PubMed:31705628, PubMed:9829974). Also exchanges L-arginine with L-lysine in a sodium-independent manner (PubMed:10903140). The transport mechanism is electroneutral and operates with a stoichiometry of 1:1 (PubMed:10903140). Contributes to ammonia-induced increase of L-arginine uptake in cerebral cortical astrocytes leading to ammonia-dependent increase of nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) induction, and protein nitration (By similarity). May mediate transport of ornithine in retinal pigment epithelial (RPE) cells (PubMed:17197568). May also transport glycine betaine in a sodium dependent manner from the cumulus granulosa into the enclosed oocyte (By similarity). {ECO:0000250|UniProtKB:D3ZMM8, ECO:0000250|UniProtKB:Q8BGK6, ECO:0000269|PubMed:10903140, ECO:0000269|PubMed:11311135, ECO:0000269|PubMed:14603368, ECO:0000269|PubMed:15756301, ECO:0000269|PubMed:16785209, ECO:0000269|PubMed:17197568, ECO:0000269|PubMed:17329401, ECO:0000269|PubMed:19562367, ECO:0000269|PubMed:31705628, ECO:0000269|PubMed:9829974}. |
| Q92541 | RTF1 | S58 | ochoa | RNA polymerase-associated protein RTF1 homolog | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity). {ECO:0000250, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:20178742}. |
| Q92541 | RTF1 | S652 | ochoa | RNA polymerase-associated protein RTF1 homolog | Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity). {ECO:0000250, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:20178742}. |
| Q92545 | TMEM131 | S1495 | ochoa | Transmembrane protein 131 (Protein RW1) | Collagen binding transmembrane protein involved in collagen secretion by recruiting the ER-to-Golgi transport complex TRAPPIII (PubMed:32095531). May play a role in the immune response to viral infection. {ECO:0000250, ECO:0000269|PubMed:32095531}. |
| Q92597 | NDRG1 | S317 | ochoa | Protein NDRG1 (Differentiation-related gene 1 protein) (DRG-1) (N-myc downstream-regulated gene 1 protein) (Nickel-specific induction protein Cap43) (Reducing agents and tunicamycin-responsive protein) (RTP) (Rit42) | Stress-responsive protein involved in hormone responses, cell growth, and differentiation. Acts as a tumor suppressor in many cell types. Necessary but not sufficient for p53/TP53-mediated caspase activation and apoptosis. Has a role in cell trafficking, notably of the Schwann cell, and is necessary for the maintenance and development of the peripheral nerve myelin sheath. Required for vesicular recycling of CDH1 and TF. May also function in lipid trafficking. Protects cells from spindle disruption damage. Functions in p53/TP53-dependent mitotic spindle checkpoint. Regulates microtubule dynamics and maintains euploidy. {ECO:0000269|PubMed:15247272, ECO:0000269|PubMed:15377670, ECO:0000269|PubMed:17786215, ECO:0000269|PubMed:9766676}. |
| Q92598 | HSPH1 | S88 | ochoa | Heat shock protein 105 kDa (Antigen NY-CO-25) (Heat shock 110 kDa protein) (Heat shock protein family H member 1) | Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity). {ECO:0000250|UniProtKB:Q60446, ECO:0000250|UniProtKB:Q61699, ECO:0000269|PubMed:24318877}. |
| Q92609 | TBC1D5 | S539 | ochoa | TBC1 domain family member 5 | May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity (PubMed:19531583, PubMed:20923837). Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy (PubMed:22354992). May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (PubMed:24603492). {ECO:0000269|PubMed:19531583, ECO:0000269|PubMed:20923837, ECO:0000269|PubMed:22354992, ECO:0000269|PubMed:24603492, ECO:0000305|PubMed:19531583, ECO:0000305|PubMed:22354992, ECO:0000305|PubMed:24603492}. |
| Q92614 | MYO18A | S72 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92614 | MYO18A | S985 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92614 | MYO18A | S1942 | ochoa | Unconventional myosin-XVIIIa (Molecule associated with JAK3 N-terminus) (MAJN) (Myosin containing a PDZ domain) (Surfactant protein receptor SP-R210) (SP-R210) | May link Golgi membranes to the cytoskeleton and participate in the tensile force required for vesicle budding from the Golgi. Thereby, may play a role in Golgi membrane trafficking and could indirectly give its flattened shape to the Golgi apparatus (PubMed:19837035, PubMed:23345592). Alternatively, in concert with LURAP1 and CDC42BPA/CDC42BPB, has been involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). May be involved in the maintenance of the stromal cell architectures required for cell to cell contact (By similarity). Regulates trafficking, expression, and activation of innate immune receptors on macrophages. Plays a role to suppress inflammatory responsiveness of macrophages via a mechanism that modulates CD14 trafficking (PubMed:25965346). Acts as a receptor of surfactant-associated protein A (SFTPA1/SP-A) and plays an important role in internalization and clearance of SFTPA1-opsonized S.aureus by alveolar macrophages (PubMed:16087679, PubMed:21123169). Strongly enhances natural killer cell cytotoxicity (PubMed:27467939). {ECO:0000250|UniProtKB:Q9JMH9, ECO:0000269|PubMed:16087679, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:19837035, ECO:0000269|PubMed:21123169, ECO:0000269|PubMed:23345592, ECO:0000269|PubMed:25965346, ECO:0000269|PubMed:27467939}. |
| Q92734 | TFG | S99 | ochoa | Protein TFG (TRK-fused gene protein) | Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (PubMed:23479643, PubMed:27813252). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:21478858). {ECO:0000269|PubMed:21478858, ECO:0000269|PubMed:23479643, ECO:0000269|PubMed:27813252}. |
| Q92783 | STAM | S191 | ochoa | Signal transducing adapter molecule 1 (STAM-1) | Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes.; FUNCTION: (Microbial infection) Plays an important role in Dengue virus entry. {ECO:0000269|PubMed:29742433}. |
| Q92870 | APBB2 | S43 | ochoa | Amyloid beta precursor protein binding family B member 2 (Amyloid-beta (A4) precursor protein-binding family B member 2) (Protein Fe65-like 1) | Plays a role in the maintenance of lens transparency, and may also play a role in muscle cell strength (By similarity). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (By similarity). Activates transcription of APP (PubMed:14527950). {ECO:0000250|UniProtKB:Q9DBR4, ECO:0000269|PubMed:14527950}. |
| Q92887 | ABCC2 | S281 | ochoa | ATP-binding cassette sub-family C member 2 (EC 7.6.2.-) (EC 7.6.2.2) (EC 7.6.2.3) (Canalicular multidrug resistance protein) (Canalicular multispecific organic anion transporter 1) (Multidrug resistance-associated protein 2) | ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505). {ECO:0000269|PubMed:10220572, ECO:0000269|PubMed:10421658, ECO:0000269|PubMed:11500505, ECO:0000269|PubMed:12441801, ECO:0000269|PubMed:16332456}. |
| Q92918 | MAP4K1 | S564 | ochoa | Mitogen-activated protein kinase kinase kinase kinase 1 (EC 2.7.11.1) (Hematopoietic progenitor kinase) (MAPK/ERK kinase kinase kinase 1) (MEK kinase kinase 1) (MEKKK 1) | Serine/threonine-protein kinase, which plays a role in the response to environmental stress (PubMed:24362026). Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585). 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). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:24362026, PubMed:8824585). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity). {ECO:0000250|UniProtKB:P70218, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:8824585}. |
| Q92953 | KCNB2 | S448 | ochoa | Potassium voltage-gated channel subfamily B member 2 (Voltage-gated potassium channel subunit Kv2.2) | Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells. {ECO:0000250|UniProtKB:A6H8H5, ECO:0000250|UniProtKB:Q63099}. |
| Q92968 | PEX13 | S354 | ochoa | Peroxisomal membrane protein PEX13 (Peroxin-13) | Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (PubMed:28765278, PubMed:8858165, PubMed:9653144). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix (PubMed:28765278, PubMed:8858165, PubMed:9653144). Involved in the import of PTS1- and PTS2-type containing proteins (PubMed:8858165, PubMed:9653144). {ECO:0000250|UniProtKB:P80667, ECO:0000269|PubMed:28765278, ECO:0000269|PubMed:8858165, ECO:0000269|PubMed:9653144}. |
| Q92994 | BRF1 | S564 | ochoa | Transcription factor IIIB 90 kDa subunit (TFIIIB90) (hTFIIIB90) (B-related factor 1) (BRF-1) (hBRF) (TAF3B2) (TATA box-binding protein-associated factor, RNA polymerase III, subunit 2) | General activator of RNA polymerase which utilizes different TFIIIB complexes at structurally distinct promoters. The isoform 1 is involved in the transcription of tRNA, adenovirus VA1, 7SL and 5S RNA. Isoform 2 is required for transcription of the U6 promoter. |
| Q92997 | DVL3 | S61 | psp | Segment polarity protein dishevelled homolog DVL-3 (Dishevelled-3) (DSH homolog 3) | Involved in the signal transduction pathway mediated by multiple Wnt genes. {ECO:0000250|UniProtKB:Q61062}. |
| Q93063 | EXT2 | S371 | ochoa | Exostosin-2 (EC 2.4.1.224) (Exostosin glycosyltransferase 2) (Glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase) (Heparan sulfate co-polymerase subunit EXT1) (Multiple exostoses protein 2) | Glycosyltransferase forming with EXT1 the heterodimeric heparan sulfate polymerase which catalyzes the elongation of the heparan sulfate glycan backbone (PubMed:22660413, PubMed:36402845, PubMed:36593275). Glycan backbone extension consists in the alternating transfer of (1->4)-beta-D-GlcA and (1->4)-alpha-D-GlcNAc residues from their respective UDP-sugar donors. Both EXT1 and EXT2 are required for the full activity of the polymerase since EXT1 bears the N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity within the complex while EXT2 carries the glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity (PubMed:36402845, PubMed:36593275). Heparan sulfate proteoglycans are ubiquitous components of the extracellular matrix and play an important role in tissue homeostasis and signaling (PubMed:19344451, PubMed:22660413). {ECO:0000269|PubMed:19344451, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:36402845, ECO:0000269|PubMed:36593275}. |
| Q969R8 | ITFG2 | S104 | ochoa | KICSTOR complex protein ITFG2 (Integrin-alpha FG-GAP repeat-containing protein 2) | As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose. {ECO:0000269|PubMed:28199306}. |
| Q969S3 | ZNF622 | S174 | ochoa | Cytoplasmic 60S subunit biogenesis factor ZNF622 (Zinc finger protein 622) (Zinc finger-like protein 9) | Pre-60S-associated cytoplasmic factor involved in the cytoplasmic maturation of the 60S subunit. {ECO:0000269|PubMed:33711283}. |
| Q96A65 | EXOC4 | S254 | 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}. |
| Q96CJ1 | EAF2 | S134 | ochoa | ELL-associated factor 2 (Testosterone-regulated apoptosis inducer and tumor suppressor protein) | Acts as a transcriptional transactivator of TCEA1 elongation activity (By similarity). Acts as a transcriptional transactivator of ELL and ELL2 elongation activities. Potent inducer of apoptosis in prostatic and non-prostatic cell lines. Inhibits prostate tumor growth in vivo. {ECO:0000250, ECO:0000269|PubMed:12446457, ECO:0000269|PubMed:12907652, ECO:0000269|PubMed:16006523}. |
| Q96DG6 | CMBL | S111 | ochoa | Carboxymethylenebutenolidase homolog (EC 3.1.-.-) | Cysteine hydrolase. Can convert the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmerstatan, an angiotensin receptor blocker, in liver and intestine. May also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin. {ECO:0000269|PubMed:20177059}. |
| Q96DY7 | MTBP | S753 | ochoa | Mdm2-binding protein (hMTBP) | Inhibits cell migration in vitro and suppresses the invasive behavior of tumor cells (By similarity). May play a role in MDM2-dependent p53/TP53 homeostasis in unstressed cells. Inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability. This promotes MDM2-mediated ubiquitination of p53/TP53 and its subsequent degradation. {ECO:0000250, ECO:0000269|PubMed:15632057}. |
| Q96FQ6 | S100A16 | S36 | ochoa | Protein S100-A16 (Aging-associated gene 13 protein) (Protein S100-F) (S100 calcium-binding protein A16) | Calcium-binding protein. Binds one calcium ion per monomer (PubMed:17030513). Can promote differentiation of adipocytes (in vitro) (By similarity). Overexpression in preadipocytes increases their proliferation, enhances adipogenesis and reduces insulin-stimulated glucose uptake (By similarity). {ECO:0000250|UniProtKB:Q9D708, ECO:0000269|PubMed:17030513}. |
| Q96HA1 | POM121 | S530 | ochoa | Nuclear envelope pore membrane protein POM 121 (Nuclear envelope pore membrane protein POM 121A) (Nucleoporin Nup121) (Pore membrane protein of 121 kDa) | Essential component of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane. When overexpressed in cells induces the formation of cytoplasmic annulate lamellae (AL). {ECO:0000269|PubMed:17900573}. |
| Q96HY6 | DDRGK1 | S30 | ochoa | DDRGK domain-containing protein 1 (Dashurin) (UFM1-binding and PCI domain-containing protein 1) | Component of the UFM1 ribosome E3 ligase (UREL) complex, a multiprotein complex that catalyzes ufmylation of endoplasmic reticulum-docked proteins (PubMed:30626644, PubMed:32160526, PubMed:35753586, PubMed:36121123, PubMed:36543799, PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). The UREL complex plays a key role in ribosome recycling by mediating mono-ufmylation of the RPL26/uL24 subunit of the 60S ribosome following ribosome dissociation: ufmylation 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:37595036, PubMed:38383785, PubMed:38383789). Within the UREL complex, DDRGK1 tethers the complex to the endoplasmic reticulum membrane to restrict its activity to endoplasmic reticulum-docked ribosomes and acts as an ufmylation 'reader': following RPL26/uL24 ufmylation, DDRGK1 specifically binds to ufmylated RPL26/uL24 via its UFIM motif, resulting in stable association between the 60S ribosome and the UREL complex, followed by dissociation of the 60S ribosome subunit from the endoplasmic reticulum membrane (PubMed:36121123, PubMed:37595036, PubMed:38383785, PubMed:38383789). The UREL complex is also involved in reticulophagy in response to endoplasmic reticulum stress by promoting ufmylation of proteins such as CYB5R3 and RPN1, thereby promoting lysosomal degradation of ufmylated proteins (PubMed:32160526, PubMed:36543799). Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability (PubMed:28128204, PubMed:32160526). Acts as a regulator of immunity by promoting differentiation of B-cells into plasma cells: acts by promoting expansion of the endoplasmic reticulum and regulating the unfolded protein response (UPR) (By similarity). May also be required for TRIP4 ufmylation (PubMed:25219498). May play a role in NF-kappa-B-mediated transcription through regulation of the phosphorylation and the degradation of NFKBIA, the inhibitor of NF-kappa-B (PubMed:23675531). Plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator (PubMed:28263186). Required for stabilization and ufmylation of ATG9A (By similarity). {ECO:0000250|UniProtKB:Q80WW9, ECO:0000269|PubMed:23675531, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:28128204, ECO:0000269|PubMed:28263186, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:35753586, ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:37795761, ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}. |
| Q96I24 | FUBP3 | S162 | 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. |
| Q96IZ7 | RSRC1 | S299 | ochoa | Serine/Arginine-related protein 53 (SRrp53) (Arginine/serine-rich coiled-coil protein 1) | Has a role in alternative splicing and transcription regulation (PubMed:29522154). Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3' splice site during the second step of splicing. {ECO:0000269|PubMed:15798186, ECO:0000269|PubMed:29522154}. |
| Q96JB2 | COG3 | S531 | 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}. |
| Q96JG6 | VPS50 | S561 | ochoa | Syndetin (Coiled-coil domain-containing protein 132) (EARP/GARPII complex subunit VPS50) | Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). {ECO:0000269|PubMed:25799061}. |
| Q96JH7 | VCPIP1 | S185 | ochoa | Deubiquitinating protein VCPIP1 (EC 3.4.19.12) (Valosin-containing protein p97/p47 complex-interacting protein 1) (Valosin-containing protein p97/p47 complex-interacting protein p135) (VCP/p47 complex-interacting 135-kDa protein) | Deubiquitinating enzyme involved in DNA repair and reassembly of the Golgi apparatus and the endoplasmic reticulum following mitosis (PubMed:32649882). Necessary for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). Plays a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Mediates dissociation of the ternary complex containing STX5A, NSFL1C and VCP (By similarity). Also involved in DNA repair following phosphorylation by ATM or ATR: acts by catalyzing deubiquitination of SPRTN, thereby promoting SPRTN recruitment to chromatin and subsequent proteolytic cleavage of covalent DNA-protein cross-links (DPCs) (PubMed:32649882). Hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains (PubMed:23827681). {ECO:0000250|UniProtKB:Q8CF97, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:32649882}.; FUNCTION: (Microbial infection) Regulates the duration of C.botulinum neurotoxin type A (BoNT/A) intoxication by catalyzing deubiquitination of Botulinum neurotoxin A light chain (LC), thereby preventing LC degradation by the proteasome, and accelerating botulinum neurotoxin intoxication in patients. {ECO:0000269|PubMed:28584101}. |
| Q96JM3 | CHAMP1 | S572 | ochoa | Chromosome alignment-maintaining phosphoprotein 1 (Zinc finger protein 828) | Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore. {ECO:0000269|PubMed:21063390}. |
| Q96KB5 | PBK | S76 | ochoa | 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}. |
| Q96L93 | KIF16B | S573 | 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}. |
| Q96M11 | HYLS1 | S83 | ochoa | Centriolar and ciliogenesis-associated protein HYLS1 (Hydrolethalus syndrome protein 1) | Plays a role in ciliogenesis. {ECO:0000250|UniProtKB:A0A1L8ER70, ECO:0000250|UniProtKB:Q95X94}. |
| Q96ME7 | ZNF512 | S319 | ochoa | Zinc finger protein 512 | May be involved in transcriptional regulation. |
| Q96MY1 | NOL4L | S146 | ochoa | Nucleolar protein 4-like | None |
| Q96N67 | DOCK7 | S969 | ochoa | Dedicator of cytokinesis protein 7 | Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 'Ser-15' phosphorylation during axon formation and consequently for neuronal polarization (PubMed:16982419). As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton (PubMed:29467281). Has a role in pigmentation (By similarity). Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3 (By similarity). {ECO:0000250|UniProtKB:Q8R1A4, ECO:0000269|PubMed:16982419, ECO:0000269|PubMed:29467281}. |
| Q96NL8 | CFAP418 | S65 | ochoa | Cilia- and flagella-associated protein 418 | May be involved in photoreceptor outer segment disk morphogenesis (By similarity). {ECO:0000250|UniProtKB:Q3UJP5}. |
| Q96PE2 | ARHGEF17 | S469 | ochoa | Rho guanine nucleotide exchange factor 17 (164 kDa Rho-specific guanine-nucleotide exchange factor) (p164-RhoGEF) (p164RhoGEF) (Tumor endothelial marker 4) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. {ECO:0000269|PubMed:12071859}. |
| Q96PY5 | FMNL2 | S169 | ochoa | Formin-like protein 2 (Formin homology 2 domain-containing protein 2) | Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics. {ECO:0000269|PubMed:21834987}. |
| Q96Q15 | SMG1 | S3556 | ochoa | Serine/threonine-protein kinase SMG1 (SMG-1) (hSMG-1) (EC 2.7.11.1) (Lambda/iota protein kinase C-interacting protein) (Lambda-interacting protein) (Nonsense mediated mRNA decay-associated PI3K-related kinase SMG1) | Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ. {ECO:0000269|PubMed:11331269, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:15175154, ECO:0000269|PubMed:16452507}. |
| Q96Q89 | KIF20B | S1574 | ochoa | Kinesin-like protein KIF20B (Cancer/testis antigen 90) (CT90) (Kinesin family member 20B) (Kinesin-related motor interacting with PIN1) (M-phase phosphoprotein 1) (MPP1) | Plus-end-directed motor enzyme that is required for completion of cytokinesis (PubMed:11470801, PubMed:12740395). Required for proper midbody organization and abscission in polarized cortical stem cells. Plays a role in the regulation of neuronal polarization by mediating the transport of specific cargos. Participates in the mobilization of SHTN1 and in the accumulation of PIP3 in the growth cone of primary hippocampal neurons in a tubulin and actin-dependent manner. In the developing telencephalon, cooperates with SHTN1 to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in cerebral cortex growth (By similarity). Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000250|UniProtKB:Q80WE4, ECO:0000269|PubMed:11470801, ECO:0000269|PubMed:12740395, ECO:0000269|PubMed:17409436}. |
| Q96QT4 | TRPM7 | S1301 | ochoa | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96QT4 | TRPM7 | S1388 | ochoa | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96QT4 | TRPM7 | S1456 | psp | Transient receptor potential cation channel subfamily M member 7 (EC 2.7.11.1) (Channel-kinase 1) (Long transient receptor potential channel 7) (LTrpC-7) (LTrpC7) [Cleaved into: TRPM7 kinase, cleaved form (M7CK); TRPM7 channel, cleaved form] | Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}. |
| Q96R06 | SPAG5 | S353 | ochoa | Sperm-associated antigen 5 (Astrin) (Deepest) (Mitotic spindle-associated protein p126) (MAP126) | Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457). {ECO:0000269|PubMed:12356910, ECO:0000269|PubMed:17664331, ECO:0000269|PubMed:18055457, ECO:0000269|PubMed:18361916, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:27462074, ECO:0000305|PubMed:11724960}. |
| Q96R06 | SPAG5 | S974 | psp | Sperm-associated antigen 5 (Astrin) (Deepest) (Mitotic spindle-associated protein p126) (MAP126) | Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457). {ECO:0000269|PubMed:12356910, ECO:0000269|PubMed:17664331, ECO:0000269|PubMed:18055457, ECO:0000269|PubMed:18361916, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:27462074, ECO:0000305|PubMed:11724960}. |
| Q96RG2 | PASK | S71 | 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}. |
| Q96RV3 | PCNX1 | S323 | ochoa | Pecanex-like protein 1 (Pecanex homolog protein 1) | None |
| Q96SN8 | CDK5RAP2 | S1389 | ochoa | CDK5 regulatory subunit-associated protein 2 (CDK5 activator-binding protein C48) (Centrosome-associated protein 215) | Potential regulator of CDK5 activity via its interaction with CDK5R1 (PubMed:15164053). Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter (PubMed:19282672). Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends (PubMed:18042621, PubMed:17959831, PubMed:19553473). Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gTuRC) onto centrosomes (PubMed:18042621, PubMed:17959831, PubMed:26485573, PubMed:39321809). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q8K389, ECO:0000269|PubMed:15164053, ECO:0000269|PubMed:17959831, ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697, ECO:0000269|PubMed:39321809}. |
| Q96SN8 | CDK5RAP2 | S1663 | ochoa | CDK5 regulatory subunit-associated protein 2 (CDK5 activator-binding protein C48) (Centrosome-associated protein 215) | Potential regulator of CDK5 activity via its interaction with CDK5R1 (PubMed:15164053). Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter (PubMed:19282672). Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends (PubMed:18042621, PubMed:17959831, PubMed:19553473). Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gTuRC) onto centrosomes (PubMed:18042621, PubMed:17959831, PubMed:26485573, PubMed:39321809). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q8K389, ECO:0000269|PubMed:15164053, ECO:0000269|PubMed:17959831, ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697, ECO:0000269|PubMed:39321809}. |
| Q96T17 | MAP7D2 | S702 | ochoa | MAP7 domain-containing protein 2 | Microtubule-stabilizing protein that plays a role in the control of cell motility and neurite outgrowth via direct binding to the microtubule (By similarity). Acts as a critical cofactor for kinesin transport. In the proximal axon, regulates kinesin-1 family members, KIF5A, KIF5B and KIF5C recruitment to microtubules and contributes to kinesin-1-mediated transport in the axons (By similarity). {ECO:0000250|UniProtKB:A2AG50, ECO:0000250|UniProtKB:D4A4L4}. |
| Q96T23 | RSF1 | S660 | 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}. |
| Q96T23 | RSF1 | S1398 | ochoa | Remodeling and spacing factor 1 (Rsf-1) (HBV pX-associated protein 8) (Hepatitis B virus X-associated protein) (p325 subunit of RSF chromatin-remodeling complex) | Regulatory subunit of the ATP-dependent RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:12972596, PubMed:28801535). Binds to core histones together with SMARCA5, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Directly stimulates the ATPase activity of SMARCA1 and SMARCA5 in the RSF-1 and RSF-5 ISWI chromatin-remodeling complexes, respectively (PubMed:28801535). The RSF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the RSF-5 ISWI chromatin-remodeling complex (PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Facilitates transcription of hepatitis B virus (HBV) genes by the pX transcription activator. In case of infection by HBV, together with pX, it represses TNF-alpha induced NF-kappa-B transcription activation. Represses transcription when artificially recruited to chromatin by fusion to a heterogeneous DNA binding domain (PubMed:11788598, PubMed:11944984). {ECO:0000269|PubMed:11788598, ECO:0000269|PubMed:11944984, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:28801535}. |
| Q96T58 | SPEN | S1641 | ochoa | Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) | May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}. |
| Q96TA1 | NIBAN2 | S574 | ochoa | Protein Niban 2 (Meg-3) (Melanoma invasion by ERK) (MINERVA) (Niban-like protein 1) (Protein FAM129B) | May play a role in apoptosis suppression. May promote melanoma cell invasion in vitro. {ECO:0000269|PubMed:19362540, ECO:0000269|PubMed:21148485}. |
| Q99081 | TCF12 | S263 | ochoa | Transcription factor 12 (TCF-12) (Class B basic helix-loop-helix protein 20) (bHLHb20) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4) | Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (By similarity). May be involved in the functional network that regulates the development of the GnRH axis (PubMed:32620954). {ECO:0000250|UniProtKB:Q61286, ECO:0000269|PubMed:32620954}. |
| Q99081 | TCF12 | S333 | ochoa | Transcription factor 12 (TCF-12) (Class B basic helix-loop-helix protein 20) (bHLHb20) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4) | Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (By similarity). May be involved in the functional network that regulates the development of the GnRH axis (PubMed:32620954). {ECO:0000250|UniProtKB:Q61286, ECO:0000269|PubMed:32620954}. |
| Q99590 | SCAF11 | S565 | ochoa | Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) | Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}. |
| Q99733 | NAP1L4 | S53 | ochoa | Nucleosome assembly protein 1-like 4 (Nucleosome assembly protein 2) (NAP-2) | Acts as a histone chaperone in nucleosome assembly. {ECO:0000269|PubMed:9325046}. |
| Q99733 | NAP1L4 | S299 | ochoa | Nucleosome assembly protein 1-like 4 (Nucleosome assembly protein 2) (NAP-2) | Acts as a histone chaperone in nucleosome assembly. {ECO:0000269|PubMed:9325046}. |
| Q99741 | CDC6 | S134 | ochoa | Cell division control protein 6 homolog (CDC6-related protein) (Cdc18-related protein) (HsCdc18) (p62(cdc6)) (HsCDC6) | Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated. |
| Q99848 | EBNA1BP2 | S207 | ochoa | Probable rRNA-processing protein EBP2 (EBNA1-binding protein 2) (Nucleolar protein p40) | Required for the processing of the 27S pre-rRNA. {ECO:0000250}. |
| Q99956 | DUSP9 | S219 | ochoa | Dual specificity protein phosphatase 9 (EC 3.1.3.16) (EC 3.1.3.48) (Mitogen-activated protein kinase phosphatase 4) (MAP kinase phosphatase 4) (MKP-4) | Inactivates MAP kinases. Has a specificity for the ERK family. |
| Q9BPX3 | NCAPG | S818 | ochoa | Condensin complex subunit 3 (Chromosome-associated protein G) (Condensin subunit CAP-G) (hCAP-G) (Melanoma antigen NY-MEL-3) (Non-SMC condensin I complex subunit G) (XCAP-G homolog) | Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. {ECO:0000269|PubMed:11136719}. |
| Q9BPZ7 | MAPKAP1 | S185 | ochoa | Target of rapamycin complex 2 subunit MAPKAP1 (TORC2 subunit MAPKAP1) (Mitogen-activated protein kinase 2-associated protein 1) (Stress-activated map kinase-interacting protein 1) (SAPK-interacting protein 1) (mSIN1) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15467718, PubMed:16919458, PubMed:16962653, PubMed:17043309, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, 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:16919458, PubMed:16962653, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:16962653). Within the mTORC2 complex, MAPKAP1/SIN1 acts as a substrate adapter which recognizes and binds AGC protein kinase family members for phosphorylation by MTOR (PubMed:21806543, PubMed:28264193). 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:28264193, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (PubMed:30837283, PubMed:35926713). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation (PubMed:15988011). Inhibits HRAS and KRAS independently of mTORC2 complex (PubMed:17303383, PubMed:34380736, PubMed:35522713). Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription (PubMed:17054722). Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex (PubMed:23727834). {ECO:0000250|UniProtKB:Q8BKH7, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15988011, ECO:0000269|PubMed:16919458, ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:17043309, ECO:0000269|PubMed:17054722, ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23727834, ECO:0000269|PubMed:28264193, ECO:0000269|PubMed:28968999, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:34380736, ECO:0000269|PubMed:35522713, ECO:0000269|PubMed:35926713}.; FUNCTION: [Isoform 4]: In contrast to isoform 1, isoform 2 and isoform 6, isoform 4 is not a component of the a mTORC2 complex. {ECO:0000269|PubMed:26263164}. |
| Q9BPZ7 | MAPKAP1 | S200 | ochoa | Target of rapamycin complex 2 subunit MAPKAP1 (TORC2 subunit MAPKAP1) (Mitogen-activated protein kinase 2-associated protein 1) (Stress-activated map kinase-interacting protein 1) (SAPK-interacting protein 1) (mSIN1) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15467718, PubMed:16919458, PubMed:16962653, PubMed:17043309, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, 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:16919458, PubMed:16962653, PubMed:21806543, PubMed:28264193, PubMed:28968999, PubMed:30837283, PubMed:35926713). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:16962653). Within the mTORC2 complex, MAPKAP1/SIN1 acts as a substrate adapter which recognizes and binds AGC protein kinase family members for phosphorylation by MTOR (PubMed:21806543, PubMed:28264193). 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:28264193, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (PubMed:30837283, PubMed:35926713). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation (PubMed:15988011). Inhibits HRAS and KRAS independently of mTORC2 complex (PubMed:17303383, PubMed:34380736, PubMed:35522713). Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription (PubMed:17054722). Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex (PubMed:23727834). {ECO:0000250|UniProtKB:Q8BKH7, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15988011, ECO:0000269|PubMed:16919458, ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:17043309, ECO:0000269|PubMed:17054722, ECO:0000269|PubMed:17303383, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23727834, ECO:0000269|PubMed:28264193, ECO:0000269|PubMed:28968999, ECO:0000269|PubMed:30837283, ECO:0000269|PubMed:34380736, ECO:0000269|PubMed:35522713, ECO:0000269|PubMed:35926713}.; FUNCTION: [Isoform 4]: In contrast to isoform 1, isoform 2 and isoform 6, isoform 4 is not a component of the a mTORC2 complex. {ECO:0000269|PubMed:26263164}. |
| Q9BQI9 | NRIP2 | S96 | ochoa | Nuclear receptor-interacting protein 2 | Down-regulates transcriptional activation by nuclear receptors such as NR1F2. {ECO:0000250}. |
| Q9BQL6 | FERMT1 | S502 | ochoa | Fermitin family homolog 1 (Kindlerin) (Kindlin syndrome protein) (Kindlin-1) (Unc-112-related protein 1) | Involved in cell adhesion. Contributes to integrin activation. When coexpressed with talin, potentiates activation of ITGA2B. Required for normal keratinocyte proliferation. Required for normal polarization of basal keratinocytes in skin, and for normal cell shape. Required for normal adhesion of keratinocytes to fibronectin and laminin, and for normal keratinocyte migration to wound sites. May mediate TGF-beta 1 signaling in tumor progression. {ECO:0000269|PubMed:14634021, ECO:0000269|PubMed:17012746, ECO:0000269|PubMed:19804783}. |
| Q9BS91 | SLC35A5 | S402 | ochoa | UDP-sugar transporter protein SLC35A5 (Solute carrier family 35 member A5) | Probable UDP-sugar:UMP transmembrane antiporter involved in UDP-alpha-D-glucuronate/UDP-GlcA, UDP-GlcNAc/UDP-N-acetyl-alpha-D-glucosamine and UDP-N-acetyl-alpha-D-galactosamine/UDP-GalNAc transport from the cytosol to the lumen of the Golgi. {ECO:0000269|PubMed:2322548, ECO:0000269|PubMed:30641943}. |
| Q9BSJ8 | ESYT1 | S1067 | 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}. |
| Q9BTV7 | CABLES2 | S257 | ochoa | CDK5 and ABL1 enzyme substrate 2 (Interactor with CDK3 2) (Ik3-2) | Unknown. Probably involved in G1-S cell cycle transition. |
| Q9BVJ6 | UTP14A | S451 | ochoa | U3 small nucleolar RNA-associated protein 14 homolog A (Antigen NY-CO-16) (Serologically defined colon cancer antigen 16) | May be required for ribosome biogenesis. {ECO:0000250}. |
| Q9BWM7 | SFXN3 | S291 | ochoa | Sideroflexin-3 | Mitochondrial serine transporter that mediates transport of serine into mitochondria, an important step of the one-carbon metabolism pathway (PubMed:30442778). Mitochondrial serine is converted to glycine and formate, which then exits to the cytosol where it is used to generate the charged folates that serve as one-carbon donors (PubMed:30442778). {ECO:0000269|PubMed:30442778}. |
| Q9BWQ6 | YIPF2 | S60 | ochoa | Protein YIPF2 (YIP1 family member 2) | None |
| Q9BX66 | SORBS1 | S1227 | ochoa | Sorbin and SH3 domain-containing protein 1 (Ponsin) (SH3 domain protein 5) (SH3P12) (c-Cbl-associated protein) (CAP) | Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). {ECO:0000250|UniProtKB:Q62417}. |
| Q9BXF6 | RAB11FIP5 | S174 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BXI6 | TBC1D10A | S20 | ochoa | TBC1 domain family member 10A (EBP50-PDX interactor of 64 kDa) (EPI64 protein) (Rab27A-GAP-alpha) | GTPase-activating protein (GAP) specific for RAB27A and RAB35 (PubMed:16923811, PubMed:30905672). Does not show GAP activity for RAB2A, RAB3A and RAB4A (PubMed:16923811). {ECO:0000269|PubMed:16923811, ECO:0000269|PubMed:30905672}. |
| Q9BXL7 | CARD11 | S593 | ochoa | Caspase recruitment domain-containing protein 11 (CARD-containing MAGUK protein 1) (Carma 1) | Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement (PubMed:11278692, PubMed:11356195, PubMed:12356734). Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11356195). Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway (PubMed:28628108). {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28628108}. |
| Q9BXP5 | SRRT | S136 | ochoa | Serrate RNA effector molecule homolog (Arsenite-resistance protein 2) | Acts as a mediator between the cap-binding complex (CBC) and the primary microRNAs (miRNAs) processing machinery during cell proliferation. Contributes to the stability and delivery of capped primary miRNA transcripts to the primary miRNA processing complex containing DGCR8 and DROSHA, thereby playing a role in RNA-mediated gene silencing (RNAi) by miRNAs. Binds capped RNAs (m7GpppG-capped RNA); however interaction is probably mediated via its interaction with NCBP1/CBP80 component of the CBC complex. Involved in cell cycle progression at S phase. Does not directly confer arsenite resistance but rather modulates arsenic sensitivity. Independently of its activity on miRNAs, necessary and sufficient to promote neural stem cell self-renewal. Does so by directly binding SOX2 promoter and positively regulating its transcription (By similarity). {ECO:0000250, ECO:0000269|PubMed:19632182}. |
| Q9BXS6 | NUSAP1 | S260 | ochoa | Nucleolar and spindle-associated protein 1 (NuSAP) | Microtubule-associated protein with the capacity to bundle and stabilize microtubules (By similarity). May associate with chromosomes and promote the organization of mitotic spindle microtubules around them. {ECO:0000250, ECO:0000269|PubMed:12963707}. |
| Q9BY89 | KIAA1671 | S1441 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYD6 | MRPL1 | S297 | ochoa | Large ribosomal subunit protein uL1m (39S ribosomal protein L1, mitochondrial) (L1mt) (MRP-L1) | None |
| Q9BYM8 | RBCK1 | S331 | ochoa | RanBP-type and C3HC4-type zinc finger-containing protein 1 (EC 2.3.2.31) (HBV-associated factor 4) (Heme-oxidized IRP2 ubiquitin ligase 1) (HOIL-1) (Hepatitis B virus X-associated protein 4) (RING finger protein 54) (RING-type E3 ubiquitin transferase HOIL-1) (Ubiquitin-conjugating enzyme 7-interacting protein 3) | E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates (PubMed:12629548, PubMed:17449468, PubMed:18711448). Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination (PubMed:12629548). Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome (PubMed:17449468, PubMed:18711448). Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:17006537, PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:17006537, PubMed:19136968, PubMed:21455173, PubMed:21455180, PubMed:21455181). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). Binds polyubiquitin of different linkage types (PubMed:20005846, PubMed:21455181). {ECO:0000269|PubMed:12629548, ECO:0000269|PubMed:17006537, ECO:0000269|PubMed:17449468, ECO:0000269|PubMed:18711448, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20005846, ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:28481331}. |
| Q9BZF1 | OSBPL8 | S32 | ochoa | Oxysterol-binding protein-related protein 8 (ORP-8) (OSBP-related protein 8) | Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:26206935). Binds oxysterol, 25-hydroxycholesterol and cholesterol (PubMed:17428193, PubMed:17991739, PubMed:21698267). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:17991739, ECO:0000269|PubMed:21698267, ECO:0000269|PubMed:26206935}. |
| Q9BZF1 | OSBPL8 | S305 | ochoa | Oxysterol-binding protein-related protein 8 (ORP-8) (OSBP-related protein 8) | Lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane: specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum. Binds phosphatidylserine and PI4P in a mutually exclusive manner (PubMed:26206935). Binds oxysterol, 25-hydroxycholesterol and cholesterol (PubMed:17428193, PubMed:17991739, PubMed:21698267). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:17991739, ECO:0000269|PubMed:21698267, ECO:0000269|PubMed:26206935}. |
| Q9BZQ8 | NIBAN1 | S577 | 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}. |
| Q9C0B0 | UNK | S447 | 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}. |
| Q9C0B9 | ZCCHC2 | S564 | ochoa | Zinc finger CCHC domain-containing protein 2 | None |
| Q9C0B9 | ZCCHC2 | S804 | ochoa | Zinc finger CCHC domain-containing protein 2 | None |
| Q9C0C2 | TNKS1BP1 | S1328 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0D2 | CEP295 | S2024 | ochoa | Centrosomal protein of 295 kDa | Centriole-enriched microtubule-binding protein involved in centriole biogenesis (PubMed:20844083, PubMed:25131205, PubMed:27185865, PubMed:38154379). Essential for the generation of the distal portion of new-born centrioles in a CPAP- and CEP120-mediated elongation dependent manner during the cell cycle S/G2 phase after formation of the initiating cartwheel structure (PubMed:27185865). Required for the recruitment of centriolar proteins, such as POC1B, POC5 and CEP135, into the distal portion of centrioles (PubMed:27185865). Also required for centriole-to-centrosome conversion during mitotic progression, but is dispensable for cartwheel removal or centriole disengagement (PubMed:25131205). Binds to and stabilizes centriolar microtubule (PubMed:27185865). May be involved in ciliogenesis (PubMed:38154379). {ECO:0000269|PubMed:20844083, ECO:0000269|PubMed:25131205, ECO:0000269|PubMed:27185865, ECO:0000269|PubMed:32060285, ECO:0000269|PubMed:38154379}. |
| Q9C0D5 | TANC1 | S319 | 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 | S412 | 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}. |
| Q9H089 | LSG1 | S97 | ochoa | Large subunit GTPase 1 homolog (hLsg1) (EC 3.6.5.-) | Functions as a GTPase (PubMed:16209721). May act by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm during the 60S ribosomal subunit maturation (PubMed:31148378). {ECO:0000269|PubMed:16209721, ECO:0000269|PubMed:31148378}. |
| Q9H0K1 | SIK2 | S486 | ochoa | Serine/threonine-protein kinase SIK2 (EC 2.7.11.1) (Qin-induced kinase) (Salt-inducible kinase 2) (SIK-2) (Serine/threonine-protein kinase SNF1-like kinase 2) | Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:23322770, PubMed:26983400). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity (PubMed:21084751, PubMed:26983400). In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (PubMed:21084751, PubMed:26983400). Also plays a role in thymic T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751, ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}. |
| Q9H115 | NAPB | S160 | ochoa | Beta-soluble NSF attachment protein (SNAP-beta) (N-ethylmaleimide-sensitive factor attachment protein beta) | Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus. {ECO:0000250|UniProtKB:P28663}. |
| Q9H1A4 | ANAPC1 | S51 | ochoa | Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9H1A4 | ANAPC1 | S564 | ochoa | Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| Q9H2G2 | SLK | S354 | ochoa | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q9H2K8 | TAOK3 | S331 | ochoa | Serine/threonine-protein kinase TAO3 (EC 2.7.11.1) (Cutaneous T-cell lymphoma-associated antigen HD-CL-09) (CTCL-associated antigen HD-CL-09) (Dendritic cell-derived protein kinase) (JNK/SAPK-inhibitory kinase) (Jun kinase-inhibitory kinase) (Kinase from chicken homolog A) (hKFC-A) (Thousand and one amino acid protein 3) | Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of the MAPK8/JNK cascade and diminishes its activation in response to epidermal growth factor (EGF). Positively regulates canonical T cell receptor (TCR) signaling by preventing early PTPN6/SHP1-mediated inactivation of LCK, ensuring sustained TCR signaling that is required for optimal activation and differentiation of T cells (PubMed:30373850). Phosphorylates PTPN6/SHP1 on 'Thr-394', leading to its polyubiquitination and subsequent proteasomal degradation (PubMed:38166031). Required for cell surface expression of metalloprotease ADAM10 on type 1 transitional B cells which is necessary for their NOTCH-mediated development into marginal zone B cells (By similarity). Also required for the NOTCH-mediated terminal differentiation of splenic conventional type 2 dendritic cells (By similarity). Positively regulates osteoblast differentiation by acting as an upstream activator of the JNK pathway (PubMed:32807497). Promotes JNK signaling in hepatocytes and positively regulates hepatocyte lipid storage by inhibiting beta-oxidation and triacylglycerol secretion while enhancing lipid synthesis (PubMed:34634521). Restricts age-associated inflammation by negatively regulating differentiation of macrophages and their production of pro-inflammatory cytokines (By similarity). Plays a role in negatively regulating the abundance of regulatory T cells in white adipose tissue (By similarity). {ECO:0000250|UniProtKB:Q8BYC6, ECO:0000269|PubMed:10559204, ECO:0000269|PubMed:10924369, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:30373850, ECO:0000269|PubMed:32807497, ECO:0000269|PubMed:34634521, ECO:0000269|PubMed:38166031}. |
| Q9H2M9 | RAB3GAP2 | S916 | ochoa | Rab3 GTPase-activating protein non-catalytic subunit (RGAP-iso) (Rab3 GTPase-activating protein 150 kDa subunit) (Rab3-GAP p150) (Rab3-GAP150) (Rab3-GAP regulatory subunit) | Regulatory 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:24891604, PubMed:9733780). As part of the Rab3GAP complex, acts as a GAP for Rab3 proteins by converting active RAB3-GTP to the inactive form RAB3-GDP (By similarity). Rab3 proteins are involved in regulated exocytosis of neurotransmitters and hormones (By similarity). 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 human 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 (By similarity). May participate in neurodevelopmental processes such as proliferation, migration and differentiation before synapse formation, and non-synaptic vesicular release of neurotransmitters (By similarity). {ECO:0000250|UniProtKB:Q15042, ECO:0000269|PubMed:24891604, ECO:0000269|PubMed:26063829, ECO:0000269|PubMed:9733780}. |
| Q9H410 | DSN1 | S49 | ochoa | Kinetochore-associated protein DSN1 homolog | Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. {ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:16585270}. |
| Q9H582 | ZNF644 | S637 | ochoa | Zinc finger protein 644 (Zinc finger motif enhancer-binding protein 2) (Zep-2) | May be involved in transcriptional regulation. |
| Q9H582 | ZNF644 | S820 | ochoa | Zinc finger protein 644 (Zinc finger motif enhancer-binding protein 2) (Zep-2) | May be involved in transcriptional regulation. |
| Q9H5I5 | PIEZO2 | S1868 | ochoa | Piezo-type mechanosensitive ion channel component 2 (Protein FAM38B) | Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Expressed in sensory neurons, is essential for diverse physiological processes, including respiratory control, systemic metabolism, urinary function, and proprioception (By similarity). Mediates airway stretch sensing, enabling efficient respiration at birth and maintaining normal breathing in adults (By similarity). It regulates brown and beige adipose tissue morphology and function, preventing systemic hypermetabolism (By similarity). In the lower urinary tract, acts as a sensor in both the bladder urothelium and innervating sensory neurons being required for bladder-stretch sensing and urethral micturition reflexes, ensuring proper urinary function (PubMed:33057202). Additionally, PIEZO2 serves as the principal mechanotransducer in proprioceptors, facilitating proprioception and coordinated body movements (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). Required for Merkel-cell mechanotransduction (By similarity). Plays a major role in light-touch mechanosensation (By similarity). {ECO:0000250|UniProtKB:Q8CD54, ECO:0000269|PubMed:33057202, ECO:0000269|PubMed:37590348}. |
| Q9H6A9 | PCNX3 | S178 | ochoa | Pecanex-like protein 3 (Pecanex homolog protein 3) | None |
| Q9H792 | PEAK1 | S1248 | 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}. |
| Q9H7Z7 | PTGES2 | S90 | ochoa | Prostaglandin E synthase 2 (EC 5.3.99.3) (Membrane-associated prostaglandin E synthase-2) (mPGE synthase-2) (Microsomal prostaglandin E synthase 2) (mPGES-2) (Prostaglandin-H(2) E-isomerase) [Cleaved into: Prostaglandin E synthase 2 truncated form] | Isomerase that catalyzes the conversion of PGH2 into the more stable prostaglandin E2 (PGE2) (in vitro) (PubMed:12804604, PubMed:17585783, PubMed:18198127). The biological function and the GSH-dependent property of PTGES2 is still under debate (PubMed:17585783, PubMed:18198127). In vivo, PTGES2 could form a complex with GSH and heme and would not participate in PGE2 synthesis but would catalyze the degradation of prostaglandin E2 H2 (PGH2) to 12(S)-hydroxy-5(Z),8(E),10(E)-heptadecatrienoic acid (HHT) and malondialdehyde (MDA) (By similarity) (PubMed:17585783). {ECO:0000250|UniProtKB:Q9N0A4, ECO:0000269|PubMed:12804604, ECO:0000269|PubMed:17585783, ECO:0000269|PubMed:18198127}. |
| Q9H814 | PHAX | S149 | ochoa | Phosphorylated adapter RNA export protein (RNA U small nuclear RNA export adapter protein) | A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus (PubMed:39011894). Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner (By similarity). Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Also binds to telomerase RNA. {ECO:0000250, ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:15574333}. |
| Q9H814 | PHAX | S356 | ochoa | Phosphorylated adapter RNA export protein (RNA U small nuclear RNA export adapter protein) | A phosphoprotein adapter involved in the XPO1-mediated U snRNA export from the nucleus (PubMed:39011894). Bridge components required for U snRNA export, the cap binding complex (CBC)-bound snRNA on the one hand and the GTPase Ran in its active GTP-bound form together with the export receptor XPO1 on the other. Its phosphorylation in the nucleus is required for U snRNA export complex assembly and export, while its dephosphorylation in the cytoplasm causes export complex disassembly. It is recycled back to the nucleus via the importin alpha/beta heterodimeric import receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Its compartmentalized phosphorylation cycle may also contribute to the directionality of export. Binds strongly to m7G-capped U1 and U5 small nuclear RNAs (snRNAs) in a sequence-unspecific manner and phosphorylation-independent manner (By similarity). Also plays a role in the biogenesis of U3 small nucleolar RNA (snoRNA). Involved in the U3 snoRNA transport from nucleoplasm to Cajal bodies. Binds strongly to m7G-capped U3, U8 and U13 precursor snoRNAs and weakly to trimethylated (TMG)-capped U3, U8 and U13 snoRNAs. Also binds to telomerase RNA. {ECO:0000250, ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:15574333}. |
| Q9H8H3 | TMT1A | S69 | ochoa | Thiol S-methyltransferase TMT1A (EC 2.1.1.9) (Methyltransferase-like protein 7A) (N6-adenosine-methyltransferase TMT1A) (EC 2.1.1.348) (Protein AAM-B) (Thiol methyltransferase 1A) | Thiol S-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to alkyl and phenolic thiol-containing acceptor substrates. Together with TMT1B accounts for most of S-thiol methylation activity in the endoplasmic reticulum of hepatocytes (PubMed:37137720). Able to methylate the N6 position of adenosine residues in long non-coding RNAs (lncRNAs). May facilitate lncRNAs transfer into exosomes at the tumor-stroma interface (PubMed:34980213). Promotes osteogenic and odontogenic differentiation by regulating the expression of genes involved in stem cell differentiation and survival (PubMed:34226523, PubMed:34790668). Targeted from the endoplasmic reticulum to lipid droplets, where it recruits cellular proteins to form functional organelles (PubMed:19773358). {ECO:0000269|PubMed:19773358, ECO:0000269|PubMed:34980213, ECO:0000269|PubMed:37137720}.; FUNCTION: (Microbial infection) May be involved in the assembly and release stages of hepatitis C virus (HCV) life cycle and thus play a crucial role in HCV propagation. {ECO:0000269|PubMed:26185986}. |
| Q9H8V3 | ECT2 | S365 | ochoa | Protein ECT2 (Epithelial cell-transforming sequence 2 oncogene) | Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}. |
| Q9H8V3 | ECT2 | S410 | ochoa | Protein ECT2 (Epithelial cell-transforming sequence 2 oncogene) | Guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP. Promotes guanine nucleotide exchange on the Rho family members of small GTPases, like RHOA, RHOC, RAC1 and CDC42. Required for signal transduction pathways involved in the regulation of cytokinesis. Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Regulates the translocation of RHOA from the central spindle to the equatorial region. Plays a role in the control of mitotic spindle assembly; regulates the activation of CDC42 in metaphase for the process of spindle fibers attachment to kinetochores before chromosome congression. Involved in the regulation of epithelial cell polarity; participates in the formation of epithelial tight junctions in a polarity complex PARD3-PARD6-protein kinase PRKCQ-dependent manner. Plays a role in the regulation of neurite outgrowth. Inhibits phenobarbital (PB)-induced NR1I3 nuclear translocation. Stimulates the activity of RAC1 through its association with the oncogenic PARD6A-PRKCI complex in cancer cells, thereby acting to coordinately drive tumor cell proliferation and invasion. Also stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:10579713, ECO:0000269|PubMed:14645260, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:15545273, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16170345, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:16495035, ECO:0000269|PubMed:19129481, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21373644, ECO:0000269|PubMed:25068414, ECO:0000269|PubMed:31888991}. |
| Q9H8X2 | IPPK | S109 | ochoa | Inositol-pentakisphosphate 2-kinase (EC 2.7.1.158) (IPK1 homolog) (Inositol-1,3,4,5,6-pentakisphosphate 2-kinase) (Ins(1,3,4,5,6)P5 2-kinase) (InsP5 2-kinase) | Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate). InsP6 is involved in many processes such as mRNA export, non-homologous end-joining, endocytosis, ion channel regulation. It also protects cells from TNF-alpha-induced apoptosis. {ECO:0000269|PubMed:12084730, ECO:0000269|PubMed:15967797}. |
| Q9H999 | PANK3 | S283 | ochoa | Pantothenate kinase 3 (hPanK3) (EC 2.7.1.33) (Pantothenic acid kinase 3) | Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis. {ECO:0000269|PubMed:17631502, ECO:0000269|PubMed:20797618, ECO:0000269|PubMed:27555321, ECO:0000269|PubMed:30927326}. |
| Q9H9E3 | COG4 | S26 | ochoa | Conserved oligomeric Golgi complex subunit 4 (COG complex subunit 4) (Component of oligomeric Golgi complex 4) | Required for normal Golgi function (PubMed:19536132, PubMed:30290151). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1 (PubMed:19536132). {ECO:0000269|PubMed:19536132, ECO:0000269|PubMed:30290151}. |
| Q9H9Q4 | NHEJ1 | S55 | psp | Non-homologous end-joining factor 1 (Protein cernunnos) (XRCC4-like factor) | DNA repair protein involved in DNA non-homologous end joining (NHEJ); it is required for double-strand break (DSB) repair and V(D)J recombination and is also involved in telomere maintenance (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781, PubMed:17717001, PubMed:18158905, PubMed:18644470, PubMed:20558749, PubMed:26100018, PubMed:28369633). Plays a key role in NHEJ by promoting the ligation of various mismatched and non-cohesive ends (PubMed:17470781, PubMed:17717001, PubMed:19056826). Together with PAXX, collaborates with DNA polymerase lambda (POLL) to promote joining of non-cohesive DNA ends (PubMed:25670504, PubMed:30250067). May act in concert with XRCC5-XRCC6 (Ku) to stimulate XRCC4-mediated joining of blunt ends and several types of mismatched ends that are non-complementary or partially complementary (PubMed:16439204, PubMed:16439205, PubMed:17317666, PubMed:17470781). In some studies, has been shown to associate with XRCC4 to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22228831, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). Alternatively, it has also been shown that rather than forming filaments, a single NHEJ1 dimer interacts through both head domains with XRCC4 to promote the close alignment of DNA ends (By similarity). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582, PubMed:28500754). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Binds DNA in a length-dependent manner (PubMed:17317666, PubMed:18158905). {ECO:0000250|UniProtKB:A0A1L8ENT6, ECO:0000269|PubMed:16439204, ECO:0000269|PubMed:16439205, ECO:0000269|PubMed:17317666, ECO:0000269|PubMed:17470781, ECO:0000269|PubMed:17717001, ECO:0000269|PubMed:18158905, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:19056826, ECO:0000269|PubMed:20558749, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25670504, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28369633, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:30250067}. |
| Q9HAU0 | PLEKHA5 | S343 | ochoa | Pleckstrin homology domain-containing family A member 5 (PH domain-containing family A member 5) (Phosphoinositol 3-phosphate-binding protein 2) (PEPP-2) | None |
| Q9HAU5 | UPF2 | S285 | ochoa | Regulator of nonsense transcripts 2 (Up-frameshift suppressor 2 homolog) (hUpf2) | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core 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 UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA. {ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:18066079}. |
| Q9HAW4 | CLSPN | S721 | ochoa | 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}. |
| Q9HBA0 | TRPV4 | S189 | psp | Transient receptor potential cation channel subfamily V member 4 (TrpV4) (Osm-9-like TRP channel 4) (OTRPC4) (Transient receptor potential protein 12) (TRP12) (Vanilloid receptor-like channel 2) (Vanilloid receptor-like protein 2) (VRL-2) (Vanilloid receptor-related osmotically-activated channel) (VR-OAC) | Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:22526352, PubMed:23136043, PubMed:29899501). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18695040, PubMed:18826956, PubMed:29899501). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18695040, PubMed:18826956, PubMed:20037586, PubMed:21964574, PubMed:25256292). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (PubMed:29899501). In neurons of the central nervous system, could play a role in triggering voluntary water intake in response to increased sodium concentration in body fluid (By similarity). {ECO:0000250|UniProtKB:Q9EPK8, ECO:0000269|PubMed:11025659, ECO:0000269|PubMed:12724311, ECO:0000269|PubMed:16293632, ECO:0000269|PubMed:18587396, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:18826956, ECO:0000269|PubMed:19759329, ECO:0000269|PubMed:20037586, ECO:0000269|PubMed:21964574, ECO:0000269|PubMed:23136043, ECO:0000269|PubMed:25256292, ECO:0000269|PubMed:26249260, ECO:0000269|PubMed:29899501}.; FUNCTION: [Isoform 1]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 5]: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 2]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 4]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: [Isoform 6]: Lacks channel activity, due to impaired oligomerization and intracellular retention. {ECO:0000269|PubMed:16293632}.; FUNCTION: (Microbial infection) Facilitates hepatitis C virus (HCV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Dengue virus (DENV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}.; FUNCTION: (Microbial infection) Facilitates Zika virus (ZIKV) replication, possibly through its action on DDX3X. {ECO:0000269|PubMed:29899501}. |
| Q9HBX9 | RXFP1 | S304 | ochoa | Relaxin receptor 1 (Leucine-rich repeat-containing G-protein coupled receptor 7) (Relaxin family peptide receptor 1) | Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP. |
| Q9HC77 | CPAP | S1109 | ochoa|psp | Centrosomal P4.1-associated protein (Centromere protein J) (CENP-J) (Centrosome assembly and centriole elongation protein) (LAG-3-associated protein) (LYST-interacting protein 1) | Plays an important role in cell division and centrosome function by participating in centriole duplication (PubMed:17681131, PubMed:20531387). Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as a microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles (PubMed:15047868, PubMed:27219064, PubMed:27306797). Required for centriole elongation and for STIL-mediated centriole amplification (PubMed:22020124). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (PubMed:27306797). {ECO:0000269|PubMed:15047868, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:20531387, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27185865, ECO:0000269|PubMed:27219064, ECO:0000305|PubMed:27306797}. |
| Q9HCC0 | MCCC2 | S499 | ochoa | Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial (MCCase subunit beta) (EC 6.4.1.4) (3-methylcrotonyl-CoA carboxylase 2) (3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit) (3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta) | Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism. {ECO:0000269|PubMed:17360195}. |
| Q9HCD5 | NCOA5 | S164 | ochoa | Nuclear receptor coactivator 5 (NCoA-5) (Coactivator independent of AF-2) (CIA) | Nuclear receptor coregulator that can have both coactivator and corepressor functions. Interacts with nuclear receptors for steroids (ESR1 and ESR2) independently of the steroid binding domain (AF-2) of the ESR receptors, and with the orphan nuclear receptor NR1D2. Involved in the coactivation of nuclear steroid receptors (ER) as well as the corepression of MYC in response to 17-beta-estradiol (E2). {ECO:0000269|PubMed:15073177}. |
| Q9HCE6 | ARHGEF10L | S708 | ochoa | Rho guanine nucleotide exchange factor 10-like protein (GrinchGEF) | Acts as a guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC. {ECO:0000269|PubMed:16112081}. |
| Q9HCJ3 | RAVER2 | S622 | ochoa | Ribonucleoprotein PTB-binding 2 (Protein raver-2) | May bind single-stranded nucleic acids. {ECO:0000305}. |
| Q9HCK1 | ZDBF2 | S952 | ochoa | DBF4-type zinc finger-containing protein 2 | None |
| Q9HCM7 | FBRSL1 | S131 | ochoa | Fibrosin-1-like protein (AUTS2-like protein) (HBV X-transactivated gene 9 protein) (HBV XAg-transactivated protein 9) | None |
| Q9NQ84 | GPRC5C | S359 | 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}. |
| Q9NQT8 | KIF13B | S1795 | ochoa | Kinesin-like protein KIF13B (Kinesin-like protein GAKIN) | Involved in reorganization of the cortical cytoskeleton. Regulates axon formation by promoting the formation of extra axons. May be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes. {ECO:0000269|PubMed:20194617}. |
| Q9NQW7 | XPNPEP1 | S556 | ochoa | Xaa-Pro aminopeptidase 1 (EC 3.4.11.9) (Aminoacylproline aminopeptidase) (Cytosolic aminopeptidase P) (Soluble aminopeptidase P) (sAmp) (X-Pro aminopeptidase 1) (X-prolyl aminopeptidase 1, soluble) | Metalloaminopeptidase that catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Arg-Pro-Pro (PubMed:11106490, PubMed:18515364, PubMed:35165443). Contributes to the degradation of bradykinin (PubMed:11106490). {ECO:0000269|PubMed:11106490, ECO:0000269|PubMed:18515364, ECO:0000269|PubMed:35165443}. |
| Q9NR28 | DIABLO | S67 | psp | Diablo IAP-binding mitochondrial protein (Diablo homolog, mitochondrial) (Direct IAP-binding protein with low pI) (Second mitochondria-derived activator of caspases) (SMAC) [Cleaved into: Diablo IAP-binding mitochondrial protein, cleaved form] | Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Inhibits the activity of BIRC6/BRUCE by inhibiting its binding to caspases (PubMed:15200957, PubMed:36758104, PubMed:36758105, PubMed:36758106). {ECO:0000269|PubMed:10929711, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758105, ECO:0000269|PubMed:36758106}.; FUNCTION: [Isoform 3]: Attenuates the stability and apoptosis-inhibiting activity of XIAP/BIRC4 by promoting XIAP/BIRC4 ubiquitination and degradation through the ubiquitin-proteasome pathway. Also disrupts XIAP/BIRC4 interacting with processed caspase-9 and promotes caspase-3 activation. {ECO:0000269|PubMed:14523016}.; FUNCTION: [Isoform 1]: Defective in the capacity to down-regulate the XIAP/BIRC4 abundance. {ECO:0000269|PubMed:14523016}. |
| Q9NR45 | NANS | S248 | ochoa | N-acetylneuraminate-9-phosphate synthase (EC 2.5.1.57) (3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase) (EC 2.5.1.132) (N-acetylneuraminic acid phosphate synthase) (NANS) (Sialic acid phosphate synthase) (Sialic acid synthase) | Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) (PubMed:10749855). Also catalyzes the condensation of PEP and D-mannose 6-phosphate (Man-6-P) to produce 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate (KDN-9-P) (PubMed:10749855). Neu5Ac-9-P and KDN-9-P are the phosphorylated forms of sialic acids N-acetylneuraminic acid (Neu5Ac) and deaminoneuraminic acid (KDN), respectively (PubMed:10749855). Required for brain and skeletal development (PubMed:27213289). {ECO:0000269|PubMed:10749855, ECO:0000269|PubMed:27213289}. |
| Q9NR46 | SH3GLB2 | S203 | ochoa | Endophilin-B2 (SH3 domain-containing GRB2-like protein B2) | None |
| Q9NRA8 | EIF4ENIF1 | S541 | ochoa | Eukaryotic translation initiation factor 4E transporter (4E-T) (eIF4E transporter) (Eukaryotic translation initiation factor 4E nuclear import factor 1) | EIF4E-binding protein that regulates translation and stability of mRNAs in processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:27342281, PubMed:32354837). Plays a key role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:24335285, PubMed:32354837). Acts as a binding platform for multiple RNA-binding proteins: promotes deadenylation of mRNAs via its interaction with the CCR4-NOT complex, and blocks decapping via interaction with eIF4E (EIF4E and EIF4E2), thereby protecting deadenylated and repressed mRNAs from degradation (PubMed:27342281, PubMed:32354837). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). Promotes miRNA-mediated translational repression (PubMed:24335285, PubMed:27342281, PubMed:28487484). Required for the formation of P-bodies (PubMed:16157702, PubMed:22966201, PubMed:27342281, PubMed:32354837). Involved in mRNA translational repression mediated by the miRNA effector TNRC6B by protecting TNRC6B-targeted mRNAs from decapping and subsequent decay (PubMed:32354837). Also acts as a nucleoplasmic shuttling protein, which mediates the nuclear import of EIF4E and DDX6 by a piggy-back mechanism (PubMed:10856257, PubMed:28216671). {ECO:0000250|UniProtKB:Q9EST3, ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:28216671, ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:32354837}. |
| Q9NRD9 | DUOX1 | S634 | ochoa | Dual oxidase 1 (EC 1.11.1.-) (EC 1.6.3.1) (Large NOX 1) (Long NOX 1) (NADPH thyroid oxidase 1) (Thyroid oxidase 1) | Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. {ECO:0000269|PubMed:11514595, ECO:0000269|PubMed:12824283}. |
| Q9NRW1 | RAB6B | S117 | ochoa | Ras-related protein Rab-6B (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology (By similarity). Recruits VPS13B to the Golgi membrane (PubMed:25492866). Regulates the compacted morphology of the Golgi (PubMed:26209634). Seems to have a role in retrograde membrane traffic at the level of the Golgi complex. May function in retrograde transport in neuronal cells (PubMed:17707369). Plays a role in neuron projection development (PubMed:25492866). {ECO:0000250|UniProtKB:P20340, ECO:0000269|PubMed:17707369, ECO:0000269|PubMed:25492866, ECO:0000269|PubMed:26209634}. |
| Q9NRY5 | FAM114A2 | S270 | ochoa | Protein FAM114A2 | None |
| Q9NS56 | TOPORS | S498 | ochoa | E3 ubiquitin-protein ligase Topors (EC 2.3.2.27) (RING-type E3 ubiquitin transferase Topors) (SUMO1-protein E3 ligase Topors) (Topoisomerase I-binding RING finger protein) (Topoisomerase I-binding arginine/serine-rich protein) (Tumor suppressor p53-binding protein 3) (p53-binding protein 3) (p53BP3) | Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates p53/TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA damage-induced cell death through IKBKE sumoylation. {ECO:0000269|PubMed:15247280, ECO:0000269|PubMed:15735665, ECO:0000269|PubMed:16122737, ECO:0000269|PubMed:17803295, ECO:0000269|PubMed:18077445, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:20188669}. |
| Q9NSY1 | BMP2K | S947 | ochoa | BMP-2-inducible protein kinase (BIKe) (EC 2.7.11.1) | May be involved in osteoblast differentiation. {ECO:0000250|UniProtKB:Q91Z96}. |
| Q9NUQ6 | SPATS2L | S338 | ochoa | SPATS2-like protein (DNA polymerase-transactivated protein 6) (Stress granule and nucleolar protein) (SGNP) | None |
| Q9NW64 | RBM22 | S142 | ochoa | Pre-mRNA-splicing factor RBM22 (RNA-binding motif protein 22) (Zinc finger CCCH domain-containing protein 16) | Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30705154). Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses. {ECO:0000269|PubMed:17045351, ECO:0000269|PubMed:21122810, ECO:0000269|PubMed:22246180, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154}. |
| Q9NX46 | ADPRS | S67 | ochoa | ADP-ribosylhydrolase ARH3 (ADP-ribose glycohydrolase ARH3) (ADP-ribosylhydrolase 3) (O-acetyl-ADP-ribose deacetylase ARH3) (EC 3.5.1.-) (Poly(ADP-ribose) glycohydrolase ARH3) (EC 3.2.1.143) ([Protein ADP-ribosylarginine] hydrolase-like protein 2) ([Protein ADP-ribosylserine] hydrolase) (EC 3.2.2.-) | ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose (PubMed:21498885, PubMed:29907568, PubMed:30045870, PubMed:30401461, PubMed:30830864, PubMed:33186521, PubMed:33769608, PubMed:33894202, PubMed:34019811, PubMed:34321462, PubMed:34479984, PubMed:34625544). Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response (PubMed:28650317, PubMed:29234005, PubMed:30045870, PubMed:33186521, PubMed:34019811, PubMed:34625544). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802, PubMed:33186521, PubMed:34625544). Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds (PubMed:16278211, PubMed:33769608). Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (PubMed:16278211). Also hydrolyzes free poly(ADP-ribose) in mitochondria (PubMed:22433848). Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins (PubMed:17075046, PubMed:21498885). Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers (PubMed:21498885). {ECO:0000269|PubMed:16278211, ECO:0000269|PubMed:17075046, ECO:0000269|PubMed:21498885, ECO:0000269|PubMed:22433848, ECO:0000269|PubMed:28650317, ECO:0000269|PubMed:29234005, ECO:0000269|PubMed:29480802, ECO:0000269|PubMed:29907568, ECO:0000269|PubMed:30045870, ECO:0000269|PubMed:30401461, ECO:0000269|PubMed:30830864, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33769608, ECO:0000269|PubMed:33894202, ECO:0000269|PubMed:34019811, ECO:0000269|PubMed:34321462, ECO:0000269|PubMed:34479984, ECO:0000269|PubMed:34625544}. |
| Q9NY59 | SMPD3 | S296 | ochoa | Sphingomyelin phosphodiesterase 3 (EC 3.1.4.12) (Neutral sphingomyelinase 2) (nSMase-2) (nSMase2) (Neutral sphingomyelinase II) | Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization (PubMed:10823942, PubMed:14741383, PubMed:15051724). Binds to anionic phospholipids (APLs) such as phosphatidylserine (PS) and phosphatidic acid (PA) that modulate enzymatic activity and subcellular location. May be involved in IL-1-beta-induced JNK activation in hepatocytes (By similarity). May act as a mediator in transcriptional regulation of NOS2/iNOS via the NF-kappa-B activation under inflammatory conditions (By similarity). {ECO:0000250|UniProtKB:O35049, ECO:0000250|UniProtKB:Q9JJY3, ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:14741383, ECO:0000269|PubMed:15051724}. |
| Q9NYL2 | MAP3K20 | S568 | ochoa | Mitogen-activated protein kinase kinase kinase 20 (EC 2.7.11.25) (Human cervical cancer suppressor gene 4 protein) (HCCS-4) (Leucine zipper- and sterile alpha motif-containing kinase) (MLK-like mitogen-activated protein triple kinase) (Mitogen-activated protein kinase kinase kinase MLT) (Mixed lineage kinase 7) (Mixed lineage kinase-related kinase) (MLK-related kinase) (MRK) (Sterile alpha motif- and leucine zipper-containing kinase AZK) | Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation (PubMed:10924358, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15350844, PubMed:15737997, PubMed:18331592, PubMed:20559024, PubMed:26999302, PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JNK (MAPK8/JNK1, MAPK9/JNK2 and/or MAPK10/JNK3) and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11042189, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15172994, PubMed:15737997, PubMed:32289254, PubMed:32610081, PubMed:35857590). Activates JNK through phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7, and MAP kinase p38 gamma (MAPK12) via phosphorylation of MAP2K3/MKK3 and MAP2K6/MKK6 (PubMed:11836244, PubMed:12220515). Involved in stress associated with adrenergic stimulation: contributes to cardiac decompensation during periods of acute cardiac stress (PubMed:15350844, PubMed:21224381, PubMed:27859413). May be involved in regulation of S and G2 cell cycle checkpoint by mediating phosphorylation of CHEK2 (PubMed:15342622). {ECO:0000269|PubMed:10924358, ECO:0000269|PubMed:11042189, ECO:0000269|PubMed:11836244, ECO:0000269|PubMed:12220515, ECO:0000269|PubMed:14521931, ECO:0000269|PubMed:15172994, ECO:0000269|PubMed:15342622, ECO:0000269|PubMed:15350844, ECO:0000269|PubMed:15737997, ECO:0000269|PubMed:18331592, ECO:0000269|PubMed:20559024, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:26999302, ECO:0000269|PubMed:27859413, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}.; FUNCTION: [Isoform ZAKalpha]: Key component of the stress-activated protein kinase signaling cascade in response to ribotoxic stress or UV-B irradiation (PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts as the proximal sensor of ribosome collisions during the ribotoxic stress response (RSR): directly binds to the ribosome by inserting its flexible C-terminus into the ribosomal intersubunit space, thereby acting as a sentinel for colliding ribosomes (PubMed:32289254, PubMed:32610081). Upon ribosome collisions, activates either the stress-activated protein kinase signal transduction cascade or the integrated stress response (ISR), leading to programmed cell death or cell survival, respectively (PubMed:32610081). Dangerous levels of ribosome collisions trigger the autophosphorylation and activation of MAP3K20, which dissociates from colliding ribosomes and phosphorylates MAP kinase kinases, leading to activation of the JNK and MAP kinase p38 pathways that promote programmed cell death (PubMed:32289254, PubMed:32610081). Less dangerous levels of ribosome collisions trigger the integrated stress response (ISR): MAP3K20 activates EIF2AK4/GCN2 independently of its protein-kinase activity, promoting EIF2AK4/GCN2-mediated phosphorylation of EIF2S1/eIF-2-alpha (PubMed:32610081). Also part of the stress-activated protein kinase signaling cascade triggering the NLRP1 inflammasome in response to UV-B irradiation: ribosome collisions activate MAP3K20, which directly phosphorylates NLRP1, leading to activation of the NLRP1 inflammasome and subsequent pyroptosis (PubMed:35857590). NLRP1 is also phosphorylated by MAP kinase p38 downstream of MAP3K20 (PubMed:35857590). Also acts as a histone kinase by phosphorylating histone H3 at 'Ser-28' (H3S28ph) (PubMed:15684425). {ECO:0000269|PubMed:15684425, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}.; FUNCTION: [Isoform ZAKbeta]: Isoform that lacks the C-terminal region that mediates ribosome-binding: does not act as a sensor of ribosome collisions in response to ribotoxic stress (PubMed:32289254, PubMed:32610081, PubMed:35857590). May act as an antagonist of isoform ZAKalpha: interacts with isoform ZAKalpha, leading to decrease the expression of isoform ZAKalpha (PubMed:27859413). {ECO:0000269|PubMed:27859413, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}. |
| Q9NZ09 | UBAP1 | S265 | ochoa | Ubiquitin-associated protein 1 (UBAP-1) (Nasopharyngeal carcinoma-associated gene 20 protein) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process (PubMed:21757351, PubMed:22405001, PubMed:31203368). Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) (PubMed:21757351, PubMed:22405001). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2 (PubMed:22405001, PubMed:24284069, PubMed:31203368). {ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22405001, ECO:0000269|PubMed:24284069, ECO:0000269|PubMed:31203368}. |
| Q9NZN4 | EHD2 | S373 | ochoa | EH domain-containing protein 2 (PAST homolog 2) | ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis (By similarity). Plays a role in membrane trafficking between the plasma membrane and endosomes (PubMed:17233914). Important for the internalization of GLUT4. Required for fusion of myoblasts to skeletal muscle myotubes. Required for normal translocation of FER1L5 to the plasma membrane (By similarity). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by constraining caveolae at the cell membrane (PubMed:25588833). {ECO:0000250|UniProtKB:Q8BH64, ECO:0000269|PubMed:17233914, ECO:0000269|PubMed:25588833}. |
| Q9NZN8 | CNOT2 | S69 | ochoa | CCR4-NOT transcription complex subunit 2 (CCR4-associated factor 2) | Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Required for the CCR4-NOT complex structural integrity. Can repress transcription and may link the CCR4-NOT complex to transcriptional regulation; the repressive function may specifically involve the N-Cor repressor complex containing HDAC3, NCOR1 and NCOR2. Involved in the maintenance of embryonic stem (ES) cell identity. {ECO:0000269|PubMed:14707134, ECO:0000269|PubMed:16712523, ECO:0000269|PubMed:21299754, ECO:0000269|PubMed:22367759}. |
| Q9NZQ7 | CD274 | S184 | 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}. |
| Q9P0K7 | RAI14 | S915 | ochoa | Ankycorbin (Ankyrin repeat and coiled-coil structure-containing protein) (Novel retinal pigment epithelial cell protein) (Retinoic acid-induced protein 14) | Plays a role in actin regulation at the ectoplasmic specialization, a type of cell junction specific to testis. Important for establishment of sperm polarity and normal spermatid adhesion. May also promote integrity of Sertoli cell tight junctions at the blood-testis barrier. {ECO:0000250|UniProtKB:Q5U312}. |
| Q9P0Z9 | PIPOX | S300 | ochoa | Peroxisomal sarcosine oxidase (PSO) (EC 1.5.3.1) (EC 1.5.3.7) (L-pipecolate oxidase) (L-pipecolic acid oxidase) | Metabolizes sarcosine and L-pipecolic acid. {ECO:0000269|PubMed:10642506}. |
| Q9P227 | ARHGAP23 | S332 | ochoa | Rho GTPase-activating protein 23 (Rho-type GTPase-activating protein 23) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}. |
| Q9P266 | JCAD | S626 | ochoa | Junctional cadherin 5-associated protein (Junctional protein associated with coronary artery disease) (JCAD) | None |
| Q9P2D6 | FAM135A | S514 | ochoa | Protein FAM135A | None |
| Q9P2F5 | STOX2 | S208 | ochoa | Storkhead-box protein 2 | None |
| Q9P2N5 | RBM27 | S656 | ochoa | RNA-binding protein 27 (RNA-binding motif protein 27) | May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000269|PubMed:31950173}. |
| Q9P2T1 | GMPR2 | S26 | ochoa | GMP reductase 2 (GMPR 2) (EC 1.7.1.7) (Guanosine 5'-monophosphate oxidoreductase 2) (Guanosine monophosphate reductase 2) | Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides (PubMed:12009299, PubMed:12669231, PubMed:16359702, PubMed:22037469). Plays a role in modulating cellular differentiation (PubMed:12669231). {ECO:0000255|HAMAP-Rule:MF_03195, ECO:0000269|PubMed:12009299, ECO:0000269|PubMed:12669231, ECO:0000269|PubMed:16359702, ECO:0000269|PubMed:22037469}. |
| Q9UBS9 | SUCO | S1224 | ochoa | SUN domain-containing ossification factor (Membrane protein CH1) (Protein osteopotentia homolog) (SUN-like protein 1) | Required for bone modeling during late embryogenesis. Regulates type I collagen synthesis in osteoblasts during their postnatal maturation (By similarity). {ECO:0000250}. |
| Q9UBU7 | DBF4 | S420 | ochoa | Protein DBF4 homolog A (Activator of S phase kinase) (Chiffon homolog A) (DBF4-type zinc finger-containing protein 1) | Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. {ECO:0000269|PubMed:10373557, ECO:0000269|PubMed:10523313, ECO:0000269|PubMed:17062569}. |
| Q9UEU0 | VTI1B | S161 | ochoa | Vesicle transport through interaction with t-SNAREs homolog 1B (Vesicle transport v-SNARE protein Vti1-like 1) (Vti1-rp1) | V-SNARE that mediates vesicle transport pathways through interactions with t-SNAREs on the target membrane. These interactions are proposed to mediate aspects of the specificity of vesicle trafficking and to promote fusion of the lipid bilayers. May be concerned with increased secretion of cytokines associated with cellular senescence. {ECO:0000269|PubMed:23217709}. |
| Q9UGH3 | SLC23A2 | S70 | ochoa | Solute carrier family 23 member 2 (Na(+)/L-ascorbic acid transporter 2) (Nucleobase transporter-like 1 protein) (Sodium-dependent vitamin C transporter 2) (hSVCT2) (Yolk sac permease-like molecule 2) | Sodium/ascorbate cotransporter (PubMed:10471399, PubMed:10556521). Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate (PubMed:10471399). {ECO:0000269|PubMed:10471399, ECO:0000269|PubMed:10556521}. |
| Q9UGP4 | LIMD1 | S656 | ochoa | LIM domain-containing protein 1 | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation. {ECO:0000269|PubMed:15542589, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22286099}. |
| Q9UGU0 | TCF20 | S513 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UHB6 | LIMA1 | S326 | ochoa | LIM domain and actin-binding protein 1 (Epithelial protein lost in neoplasm) | Actin-binding protein involved in actin cytoskeleton regulation and dynamics. Increases the number and size of actin stress fibers and inhibits membrane ruffling. Inhibits actin filament depolymerization. Bundles actin filaments, delays filament nucleation and reduces formation of branched filaments (PubMed:12566430, PubMed:33999101). Acts as a negative regulator of primary cilium formation (PubMed:32496561). Plays a role in cholesterol homeostasis. Influences plasma cholesterol levels through regulation of intestinal cholesterol absorption. May act as a scaffold protein by regulating NPC1L1 transportation, an essential protein for cholesterol absorption, to the plasma membrane by recruiting MYO5B to NPC1L1, and thus facilitates cholesterol uptake (By similarity). {ECO:0000250|UniProtKB:Q9ERG0, ECO:0000269|PubMed:12566430, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:33999101}. |
| Q9UHB7 | AFF4 | S314 | ochoa | AF4/FMR2 family member 4 (ALL1-fused gene from chromosome 5q31 protein) (Protein AF-5q31) (Major CDK9 elongation factor-associated protein) | Key component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. In the SEC complex, AFF4 acts as a central scaffold that recruits other factors through direct interactions with ELL proteins (ELL, ELL2 or ELL3) and the P-TEFb complex. In case of infection by HIV-1 virus, the SEC complex is recruited by the viral Tat protein to stimulate viral gene expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:23251033}. |
| Q9UHB9 | SRP68 | S267 | ochoa | Signal recognition particle subunit SRP68 (SRP68) (Signal recognition particle 68 kDa protein) | Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (PubMed:34020957). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER (PubMed:34020957). The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER (PubMed:34020957). Binds the signal recognition particle RNA (7SL RNA), SRP72 binds to this complex subsequently (PubMed:16672232, PubMed:27899666). The SRP complex possibly participates in the elongation arrest function (By similarity). {ECO:0000250|UniProtKB:P38687, ECO:0000269|PubMed:16672232, ECO:0000269|PubMed:27899666, ECO:0000269|PubMed:34020957}. |
| Q9UHF7 | TRPS1 | S69 | ochoa | Zinc finger transcription factor Trps1 (Tricho-rhino-phalangeal syndrome type I protein) (Zinc finger protein GC79) | Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed:17391059}. |
| Q9UHG3 | PCYOX1 | S177 | ochoa | Prenylcysteine oxidase 1 (EC 1.8.3.5) (Prenylcysteine lyase) | Prenylcysteine oxidase that cleaves the thioether bond of prenyl-L-cysteines, such as farnesylcysteine and geranylgeranylcysteine (PubMed:10585463, PubMed:11078725, PubMed:12186880). Only active against free prenylcysteines and not prenylcysteine residues within prenylated proteins or peptides (By similarity). Involved in the final step in the degradation of prenylated proteins, by degrading prenylcysteines after the protein has been degraded (PubMed:10585463). {ECO:0000250|UniProtKB:F1N2K1, ECO:0000269|PubMed:10585463, ECO:0000269|PubMed:11078725, ECO:0000269|PubMed:12186880}. |
| Q9UIF8 | BAZ2B | S1467 | ochoa | Bromodomain adjacent to zinc finger domain protein 2B (hWALp4) | Regulatory subunit of the ATP-dependent BRF-1 and BRF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The BRF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the BRF-5 ISWI chromatin remodeling complex (PubMed:28801535). Chromatin reader protein, which may play a role in transcriptional regulation via interaction with ISWI (By similarity) (PubMed:10662543). Involved in positively modulating the rate of age-related behavioral deterioration (By similarity). Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with histone methyltransferase EHMT1 (By similarity). {ECO:0000250|UniProtKB:A2AUY4, ECO:0000269|PubMed:28801535, ECO:0000303|PubMed:10662543}. |
| Q9UIG0 | BAZ1B | S508 | ochoa | Tyrosine-protein kinase BAZ1B (EC 2.7.10.2) (Bromodomain adjacent to zinc finger domain protein 1B) (Williams syndrome transcription factor) (Williams-Beuren syndrome chromosomal region 10 protein) (Williams-Beuren syndrome chromosomal region 9 protein) (hWALp2) | Atypical tyrosine-protein kinase that plays a central role in chromatin remodeling and acts as a transcription regulator (PubMed:19092802). Involved in DNA damage response by phosphorylating 'Tyr-142' of histone H2AX (H2AXY142ph) (PubMed:19092802, PubMed:19234442). H2AXY142ph plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19092802, PubMed:19234442). Regulatory subunit of the ATP-dependent WICH-1 and WICH-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:11980720, PubMed:28801535). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The WICH-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the WICH-5 ISWI chromatin remodeling complex (PubMed:28801535). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the recruitment of the WICH-5 ISWI chromatin remodeling complex to replication foci during DNA replication (PubMed:15543136). {ECO:0000250|UniProtKB:Q9Z277, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:19092802, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:28801535}. |
| Q9UIW2 | PLXNA1 | S1614 | ochoa | Plexin-A1 (Semaphorin receptor NOV) | Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm. Acts as coreceptor of TREM2 for SEMA6D in dendritic cells and is involved in the generation of immune responses and skeletal homeostasis. {ECO:0000250|UniProtKB:P70206}. |
| Q9UJF2 | RASAL2 | S87 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UJM3 | ERRFI1 | S390 | ochoa | ERBB receptor feedback inhibitor 1 (Mitogen-inducible gene 6 protein) (MIG-6) | Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity). {ECO:0000250}. |
| Q9UJM3 | ERRFI1 | S391 | ochoa | ERBB receptor feedback inhibitor 1 (Mitogen-inducible gene 6 protein) (MIG-6) | Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity). {ECO:0000250}. |
| Q9UK32 | RPS6KA6 | S83 | ochoa | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| Q9UK59 | DBR1 | S499 | ochoa | Lariat debranching enzyme (EC 3.1.4.-) | Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover (PubMed:10982890, PubMed:16232320, PubMed:2435736). Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication via an RNA lariat intermediate in cDNA synthesis and have an antiviral cell-intrinsic defense function in the brainstem (PubMed:16232320, PubMed:29474921). {ECO:0000269|PubMed:10982890, ECO:0000269|PubMed:16232320, ECO:0000269|PubMed:2435736, ECO:0000269|PubMed:29474921}. |
| Q9UKL0 | RCOR1 | S127 | ochoa | REST corepressor 1 (Protein CoREST) | Essential component of the BHC complex, a corepressor complex that represses transcription of neuron-specific genes in non-neuronal cells. The BHC complex is recruited at RE1/NRSE sites by REST and acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier. In the BHC complex, it serves as a molecular beacon for the recruitment of molecular machinery, including MeCP2 and SUV39H1, that imposes silencing across a chromosomal interval. Plays a central role in demethylation of Lys-4 of histone H3 by promoting demethylase activity of KDM1A on core histones and nucleosomal substrates. It also protects KDM1A from the proteasome. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development and controls hematopoietic differentiation. {ECO:0000269|PubMed:11171972, ECO:0000269|PubMed:11516394, ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:12399542, ECO:0000269|PubMed:12493763, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16140033}. |
| Q9UKV3 | ACIN1 | S135 | 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 | S865 | 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 | S1245 | 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 | S1716 | 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}. |
| Q9UL54 | TAOK2 | S486 | ochoa | Serine/threonine-protein kinase TAO2 (EC 2.7.11.1) (Kinase from chicken homolog C) (hKFC-C) (Prostate-derived sterile 20-like kinase 1) (PSK-1) (PSK1) (Prostate-derived STE20-like kinase 1) (Thousand and one amino acid protein kinase 2) | Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17396146}. |
| Q9ULF5 | SLC39A10 | S539 | ochoa | Zinc transporter ZIP10 (Solute carrier family 39 member 10) (Zrt- and Irt-like protein 10) (ZIP-10) | Zinc-influx transporter (PubMed:17359283, PubMed:27274087, PubMed:30520657). When associated with SLC39A6, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT) (PubMed:23186163). SLC39A10-SLC39A6 heterodimers play also an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (PubMed:32797246). Plays an important for both mature B-cell maintenance and humoral immune responses (By similarity). When associated with SLC39A10, the heterodimer controls NCAM1 phosphorylation and integration into focal adhesion complexes during EMT (By similarity). {ECO:0000250|UniProtKB:Q6P5F6, ECO:0000269|PubMed:17359283, ECO:0000269|PubMed:23186163, ECO:0000269|PubMed:27274087, ECO:0000269|PubMed:30520657, ECO:0000269|PubMed:32797246}. |
| Q9ULH0 | KIDINS220 | S1531 | ochoa | Kinase D-interacting substrate of 220 kDa (Ankyrin repeat-rich membrane-spanning protein) | Promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism. Provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation. May play an important role in regulating postsynaptic signal transduction through the syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4. In cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation. Plays a role in nerve growth factor (NGF)-induced recruitment of RAPGEF2 to late endosomes and neurite outgrowth. May play a role in neurotrophin- and ephrin-mediated neuronal outgrowth and in axon guidance during neural development and in neuronal regeneration (By similarity). Modulates stress-induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway. {ECO:0000250, ECO:0000269|PubMed:18089783}. |
| Q9ULH7 | MRTFB | S896 | ochoa | Myocardin-related transcription factor B (MRTF-B) (MKL/myocardin-like protein 2) (Megakaryoblastic leukemia 2) | Acts as a transcriptional coactivator of serum response factor (SRF). Required for skeletal myogenic differentiation. {ECO:0000269|PubMed:14565952}. |
| Q9ULI0 | ATAD2B | S118 | ochoa | ATPase family AAA domain-containing protein 2B | None |
| Q9ULM3 | YEATS2 | S144 | ochoa | YEATS domain-containing protein 2 | Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4 (PubMed:18838386, PubMed:19103755, PubMed:27103431). YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}. |
| Q9ULR3 | PPM1H | S119 | ochoa | Protein phosphatase 1H (EC 3.1.3.16) | Dephosphorylates CDKN1B at 'Thr-187', thus removing a signal for proteasomal degradation. {ECO:0000269|PubMed:22586611}. |
| Q9ULU4 | ZMYND8 | S523 | ochoa | MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) | Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}. |
| Q9ULU4 | ZMYND8 | S1117 | ochoa | MYND-type zinc finger-containing chromatin reader ZMYND8 (Cutaneous T-cell lymphoma-associated antigen se14-3) (CTCL-associated antigen se14-3) (Protein kinase C-binding protein 1) (Rack7) (Transcription coregulator ZMYND8) (Zinc finger MYND domain-containing protein 8) | Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:27477906, PubMed:31965980, PubMed:36064715). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:25593309, PubMed:27732854, PubMed:30134174). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:26655721, PubMed:30134174). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:30134174, PubMed:35916866, PubMed:36064715). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928). {ECO:0000269|PubMed:25593309, ECO:0000269|PubMed:26655721, ECO:0000269|PubMed:27477906, ECO:0000269|PubMed:27732854, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:31965980, ECO:0000269|PubMed:33323928, ECO:0000269|PubMed:35916866, ECO:0000269|PubMed:36064715}. |
| Q9UMD9 | COL17A1 | S382 | ochoa | Collagen alpha-1(XVII) chain (180 kDa bullous pemphigoid antigen 2) (Bullous pemphigoid antigen 2) [Cleaved into: 120 kDa linear IgA disease antigen (120 kDa linear IgA dermatosis antigen) (Linear IgA disease antigen 1) (LAD-1); 97 kDa linear IgA disease antigen (97 kDa linear IgA bullous dermatosis antigen) (97 kDa LAD antigen) (97-LAD) (Linear IgA bullous disease antigen of 97 kDa) (LABD97)] | May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.; FUNCTION: The 120 kDa linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion. Is the target of linear IgA bullous dermatosis autoantibodies. |
| Q9UMS6 | SYNPO2 | S89 | ochoa | Synaptopodin-2 (Genethonin-2) (Myopodin) | Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336). {ECO:0000250|UniProtKB:D4A702, ECO:0000250|UniProtKB:Q91YE8, ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:23225103, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213, ECO:0000305|PubMed:16885336, ECO:0000305|PubMed:20554076}.; FUNCTION: [Isoform 1]: Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 2]: Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 3]: Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 4]: Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers. {ECO:0000269|PubMed:24005909}.; FUNCTION: [Isoform 5]: Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro. {ECO:0000269|PubMed:22915763, ECO:0000269|PubMed:24005909, ECO:0000269|PubMed:25883213}. |
| Q9UMZ2 | SYNRG | S852 | ochoa | Synergin gamma (AP1 subunit gamma-binding protein 1) (Gamma-synergin) | Plays a role in endocytosis and/or membrane trafficking at the trans-Golgi network (TGN) (PubMed:15758025). May act by linking the adapter protein complex AP-1 to other proteins (Probable). Component of clathrin-coated vesicles (PubMed:15758025). Component of the aftiphilin/p200/gamma-synergin complex, which plays roles in AP1G1/AP-1-mediated protein trafficking including the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000305|PubMed:12538641}. |
| Q9UN79 | SOX13 | S96 | ochoa | Transcription factor SOX-13 (Islet cell antigen 12) (SRY (Sex determining region Y)-box 13) (Type 1 diabetes autoantigen ICA12) | Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3' (PubMed:10871192). Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube (By similarity). Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells (By similarity). Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells (By similarity). Promotes brown adipocyte differentiation (By similarity). Inhibitor of WNT signaling (PubMed:20028982). {ECO:0000250|UniProtKB:Q04891, ECO:0000269|PubMed:10871192, ECO:0000269|PubMed:20028982}. |
| Q9UNE0 | EDAR | S273 | ochoa | Tumor necrosis factor receptor superfamily member EDAR (Anhidrotic ectodysplasin receptor 1) (Downless homolog) (EDA-A1 receptor) (Ectodermal dysplasia receptor) (Ectodysplasin-A receptor) | Receptor for EDA isoform A1, but not for EDA isoform A2. Mediates the activation of NF-kappa-B and JNK. May promote caspase-independent cell death. |
| Q9UNS1 | TIMELESS | S281 | ochoa | Protein timeless homolog (hTIM) | Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:23418588, PubMed:26344098, PubMed:31138685, PubMed:32705708, PubMed:35585232, PubMed:9856465). Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:35585232). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (PubMed:23359676). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 (PubMed:32705708). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214, PubMed:31138685). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:31138685, PubMed:9856465). May play a role as destabilizer of the PER2-CRY2 complex (PubMed:31138685). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). {ECO:0000250|UniProtKB:Q9R1X4, ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31138685, ECO:0000269|PubMed:32705708, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9856465}. |
| Q9UNW8 | GPR132 | S341 | ochoa | Probable G-protein coupled receptor 132 (G2 accumulation protein) | May be a receptor for oxidized free fatty acids derived from linoleic and arachidonic acids such as 9-hydroxyoctadecadienoic acid (9-HODE). Activates a G alpha protein, most likely G alpha(q). May be involved in apoptosis. Functions at the G2/M checkpoint to delay mitosis. May function as a sensor that monitors the oxidative states and mediates appropriate cellular responses such as secretion of paracrine signals and attenuation of proliferation. May mediate ths accumulation of intracellular inositol phosphates at acidic pH through proton-sensing activity. {ECO:0000269|PubMed:12586833, ECO:0000269|PubMed:19855098, ECO:0000269|PubMed:9770487}. |
| Q9UNZ2 | NSFL1C | S262 | ochoa | NSFL1 cofactor p47 (UBX domain-containing protein 2C) (p97 cofactor p47) | Reduces the ATPase activity of VCP (By similarity). Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis (By similarity). May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER) (By similarity). Inhibits the activity of CTSL (in vitro) (PubMed:15498563). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase (PubMed:23649807). Also, regulates spindle orientation during mitosis (PubMed:23649807). {ECO:0000250|UniProtKB:O35987, ECO:0000269|PubMed:15498563, ECO:0000269|PubMed:23649807}. |
| Q9UPM8 | AP4E1 | S847 | ochoa|psp | AP-4 complex subunit epsilon-1 (AP-4 adaptor complex subunit epsilon) (Adaptor-related protein complex 4 subunit epsilon-1) (Epsilon subunit of AP-4) (Epsilon-adaptin) | Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}. |
| Q9UPP1 | PHF8 | S722 | ochoa | Histone lysine demethylase PHF8 (EC 1.14.11.27) (EC 1.14.11.65) (PHD finger protein 8) ([histone H3]-dimethyl-L-lysine(36) demethylase PHF8) ([histone H3]-dimethyl-L-lysine(9) demethylase PHF8) | Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854, ECO:0000269|PubMed:31691806}. |
| Q9UQ35 | SRRM2 | S1349 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQB8 | BAIAP2 | S259 | ochoa | BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) | Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}. |
| Q9UQB8 | BAIAP2 | S395 | ochoa | BAR/IMD domain-containing adapter protein 2 (Brain-specific angiogenesis inhibitor 1-associated protein 2) (BAI-associated protein 2) (BAI1-associated protein 2) (Protein BAP2) (Fas ligand-associated factor 3) (FLAF3) (Insulin receptor substrate p53/p58) (IRS-58) (IRSp53/58) (Insulin receptor substrate protein of 53 kDa) (IRSp53) (Insulin receptor substrate p53) | Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions. {ECO:0000269|PubMed:11130076, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:14752106, ECO:0000269|PubMed:17115031, ECO:0000269|PubMed:19366662}. |
| Q9UQP3 | TNN | S937 | ochoa | Tenascin-N (TN-N) (Tenascin-W) (TN-W) | Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1 (By similarity) (PubMed:17909022). Involved in neurite outgrowth and cell migration in hippocampal explants (By similarity). During endochondral bone formation, inhibits proliferation and differentiation of proteoblasts mediated by canonical WNT signaling (By similarity). In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (PubMed:19884327). Expressed in most mammary tumors, may facilitate tumorigenesis by supporting the migratory behavior of breast cancer cells (PubMed:17909022). {ECO:0000250|UniProtKB:Q80YX1, ECO:0000250|UniProtKB:Q80Z71, ECO:0000269|PubMed:17909022, ECO:0000269|PubMed:19884327}. |
| Q9Y210 | TRPC6 | S903 | ochoa | Short transient receptor potential channel 6 (TrpC6) (Transient receptor protein 6) (TRP-6) | Forms a receptor-activated non-selective calcium permeant cation channel (PubMed:19936226, PubMed:23291369, PubMed:26892346, PubMed:9930701). Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C (PubMed:26892346). Seems not to be activated by intracellular calcium store depletion. {ECO:0000269|PubMed:19936226, ECO:0000269|PubMed:23291369, ECO:0000269|PubMed:26892346, ECO:0000269|PubMed:9930701}. |
| Q9Y289 | SLC5A6 | S585 | ochoa | 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}. |
| Q9Y2F5 | ICE1 | S693 | ochoa | Little elongation complex subunit 1 (Interactor of little elongator complex ELL subunit 1) | Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (PubMed:23932780). {ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23932780}. |
| Q9Y2I9 | TBC1D30 | S122 | ochoa | TBC1 domain family member 30 | May act as a GTPase-activating protein for Rab family protein(s). {ECO:0000305}. |
| Q9Y2W1 | THRAP3 | S468 | ochoa | Thyroid hormone receptor-associated protein 3 (BCLAF1 and THRAP3 family member 2) (Thyroid hormone receptor-associated protein complex 150 kDa component) (Trap150) | Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| Q9Y2X8 | UBE2D4 | S83 | ochoa | Ubiquitin-conjugating enzyme E2 D4 (EC 2.3.2.23) (E2 ubiquitin-conjugating enzyme D4) (HBUCE1) (Ubiquitin carrier protein D4) (Ubiquitin-protein ligase D4) | Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11' and 'Lys-48'-linked polyubiquitination. {ECO:0000269|PubMed:20061386}. |
| Q9Y343 | SNX24 | S122 | ochoa | Sorting nexin-24 | May be involved in several stages of intracellular trafficking. {ECO:0000250}. |
| Q9Y388 | RBMX2 | S232 | ochoa | RNA-binding motif protein, X-linked 2 | Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000305|PubMed:33509932}. |
| Q9Y3R0 | GRIP1 | S1092 | ochoa | Glutamate receptor-interacting protein 1 (GRIP-1) | May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P97879, ECO:0000269|PubMed:10197531}. |
| Q9Y426 | C2CD2 | S647 | ochoa | C2 domain-containing protein 2 (Transmembrane protein 24-like) | None |
| Q9Y446 | PKP3 | S92 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y446 | PKP3 | S698 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y462 | ZNF711 | S198 | ochoa | Zinc finger protein 711 (Zinc finger protein 6) | Transcription regulator required for brain development (PubMed:20346720). Probably acts as a transcription factor that binds to the promoter of target genes and recruits PHF8 histone demethylase, leading to activated expression of genes involved in neuron development, such as KDM5C (PubMed:20346720, PubMed:31691806). May compete with transcription factor ARX for activation of expression of KDM5C (PubMed:31691806). {ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:31691806}. |
| Q9Y490 | TLN1 | S405 | ochoa | Talin-1 | High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts. Involved in connections of major cytoskeletal structures to the plasma membrane. With KANK1 co-organize the assembly of cortical microtubule stabilizing complexes (CMSCs) positioned to control microtubule-actin crosstalk at focal adhesions (FAs) rims. {ECO:0000250|UniProtKB:P26039}. |
| Q9Y4B6 | DCAF1 | S1006 | ochoa | DDB1- and CUL4-associated factor 1 (HIV-1 Vpr-binding protein) (VprBP) (Serine/threonine-protein kinase VPRBP) (EC 2.7.11.1) (Vpr-interacting protein) | Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2 (PubMed:23063525). Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination (By similarity). Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:19287380, PubMed:23362280). The EDVP complex also mediates ubiquitination and degradation of CCP110 (PubMed:28242748, PubMed:34259627). Also acts as an atypical serine/threonine-protein kinase that specifically mediates phosphorylation of 'Thr-120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription (PubMed:24140421). H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714). By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility (By similarity). {ECO:0000250|UniProtKB:Q80TR8, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:18606781, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:20644714, ECO:0000269|PubMed:22184063, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:24140421, ECO:0000269|PubMed:28242748, ECO:0000269|PubMed:34259627}.; FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT. {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:17559673, ECO:0000269|PubMed:17609381, ECO:0000269|PubMed:17620334, ECO:0000269|PubMed:17626091, ECO:0000269|PubMed:17630831, ECO:0000269|PubMed:18524771, ECO:0000269|PubMed:24116224}.; FUNCTION: (Microbial infection) In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. {ECO:0000269|PubMed:17314515, ECO:0000269|PubMed:18464893, ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:19923175, ECO:0000269|PubMed:24336198}. |
| Q9Y4D1 | DAAM1 | S1030 | ochoa | Disheveled-associated activator of morphogenesis 1 | Binds to disheveled (Dvl) and Rho, and mediates Wnt-induced Dvl-Rho complex formation. May play a role as a scaffolding protein to recruit Rho-GDP and Rho-GEF, thereby enhancing Rho-GTP formation. Can direct nucleation and elongation of new actin filaments. Involved in building functional cilia (PubMed:16630611, PubMed:17482208). Involved in the organization of the subapical actin network in multiciliated epithelial cells (By similarity). Together with DAAM2, required for myocardial maturation and sarcomere assembly (By similarity). During cell division, may regulate RHOA activation that signals spindle orientation and chromosomal segregation. {ECO:0000250|UniProtKB:B0DOB5, ECO:0000250|UniProtKB:Q8BPM0, ECO:0000269|PubMed:16630611, ECO:0000269|PubMed:17482208}. |
| Q9Y4D2 | DAGLA | S835 | ochoa | Diacylglycerol lipase-alpha (DAGL-alpha) (DGL-alpha) (EC 3.1.1.116) (Neural stem cell-derived dendrite regulator) (Sn1-specific diacylglycerol lipase alpha) | Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) (PubMed:14610053, PubMed:23502535, PubMed:26668358). Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at the sn-2 position to biosynthesize 2-AG (PubMed:14610053, PubMed:23502535, PubMed:26668358). Has negligible activity against other lipids including monoacylglycerols and phospholipids (PubMed:14610053). Plays a key role in regulating 2-AG signaling in the central nervous system (CNS). Regulates 2-AG involved in retrograde suppression at central synapses. Supports axonal growth during development and adult neurogenesis. Plays a role for eCB signaling in the physiological regulation of anxiety and depressive behaviors. Also regulates neuroinflammatory responses in the brain, in particular, LPS-induced microglial activation (By similarity). {ECO:0000250|UniProtKB:Q6WQJ1, ECO:0000269|PubMed:14610053, ECO:0000269|PubMed:23502535, ECO:0000269|PubMed:26668358}. |
| Q9Y4E5 | ZNF451 | S838 | ochoa | E3 SUMO-protein ligase ZNF451 (EC 2.3.2.-) (Coactivator for steroid receptors) (E3 SUMO-protein transferase ZNF451) (Zinc finger protein 451) | E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins (PubMed:26524493, PubMed:26524494). Plays a role in protein SUMO2 modification in response to stress caused by DNA damage and by proteasome inhibitors (in vitro). Required for MCM4 sumoylation (By similarity). Has no activity with SUMO1 (PubMed:26524493). Preferentially transfers an additional SUMO2 chain onto the SUMO2 consensus site 'Lys-11' (PubMed:26524493). Negatively regulates transcriptional activation mediated by the SMAD4 complex in response to TGF-beta signaling. Inhibits EP300-mediated acetylation of histone H3 at 'Lys-9' (PubMed:24324267). Plays a role in regulating the transcription of AR targets (PubMed:18656483). {ECO:0000250|UniProtKB:Q8C0P7, ECO:0000269|PubMed:18656483, ECO:0000269|PubMed:24324267, ECO:0000269|PubMed:26524493, ECO:0000269|PubMed:26524494}. |
| Q9Y4F5 | CEP170B | S371 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y5K6 | CD2AP | S458 | ochoa | CD2-associated protein (Adapter protein CMS) (Cas ligand with multiple SH3 domains) | Seems to act as an adapter protein between membrane proteins and the actin cytoskeleton (PubMed:10339567). In collaboration with CBLC, modulates the rate of RET turnover and may act as regulatory checkpoint that limits the potency of GDNF on neuronal survival. Controls CBLC function, converting it from an inhibitor to a promoter of RET degradation (By similarity). May play a role in receptor clustering and cytoskeletal polarity in the junction between T-cell and antigen-presenting cell (By similarity). May anchor the podocyte slit diaphragm to the actin cytoskeleton in renal glomerolus. Also required for cytokinesis (PubMed:15800069). Plays a role in epithelial cell junctions formation (PubMed:22891260). {ECO:0000250|UniProtKB:F1LRS8, ECO:0000250|UniProtKB:Q9JLQ0, ECO:0000269|PubMed:10339567, ECO:0000269|PubMed:15800069, ECO:0000269|PubMed:22891260}. |
| Q9Y5K8 | ATP6V1D | S118 | ochoa | V-type proton ATPase subunit D (V-ATPase subunit D) (V-ATPase 28 kDa accessory protein) (Vacuolar proton pump subunit D) | Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (PubMed:21844891). {ECO:0000250|UniProtKB:P39942, ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:33065002}. |
| Q9Y5M8 | SRPRB | S209 | ochoa | Signal recognition particle receptor subunit beta (SR-beta) (Protein APMCF1) | Component of the signal recognition particle (SRP) complex receptor (SR) (By similarity). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (By similarity). May mediate the membrane association of SR (By similarity). {ECO:0000250|UniProtKB:P47758}. |
| Q9Y5M8 | SRPRB | S219 | ochoa | Signal recognition particle receptor subunit beta (SR-beta) (Protein APMCF1) | Component of the signal recognition particle (SRP) complex receptor (SR) (By similarity). Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system (By similarity). May mediate the membrane association of SR (By similarity). {ECO:0000250|UniProtKB:P47758}. |
| Q9Y5U4 | INSIG2 | S151 | psp | Insulin-induced gene 2 protein (INSIG-2) | Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR (PubMed:12242332, PubMed:16606821, PubMed:32322062). Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum (PubMed:17428920, PubMed:26160948, PubMed:32322062). In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi (PubMed:32322062). Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2 (PubMed:32322062). Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase RNF139 (PubMed:16606821, PubMed:22143767). {ECO:0000269|PubMed:12242332, ECO:0000269|PubMed:16606821, ECO:0000269|PubMed:17428920, ECO:0000269|PubMed:22143767, ECO:0000269|PubMed:26160948, ECO:0000269|PubMed:32322062}. |
| Q9Y6A5 | TACC3 | S399 | ochoa | Transforming acidic coiled-coil-containing protein 3 (ERIC-1) | Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:21297582, PubMed:23532825). May be involved in the control of cell growth and differentiation. May contribute to cancer (PubMed:14767476). {ECO:0000250|UniProtKB:Q9JJ11, ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:23532825}. |
| Q9Y6D5 | ARFGEF2 | S590 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 2 (Brefeldin A-inhibited GEP 2) (ADP-ribosylation factor guanine nucleotide-exchange factor 2) | Promotes guanine-nucleotide exchange on ARF1 and ARF3 and to a lower extent on ARF5 and ARF6. Promotes the activation of ARF1/ARF5/ARF6 through replacement of GDP with GTP. Involved in the regulation of Golgi vesicular transport. Required for the integrity of the endosomal compartment. Involved in trafficking from the trans-Golgi network (TGN) to endosomes and is required for membrane association of the AP-1 complex and GGA1. Seems to be involved in recycling of the transferrin receptor from recycling endosomes to the plasma membrane. Probably is involved in the exit of GABA(A) receptors from the endoplasmic reticulum. Involved in constitutive release of tumor necrosis factor receptor 1 via exosome-like vesicles; the function seems to involve PKA and specifically PRKAR2B. Proposed to act as A kinase-anchoring protein (AKAP) and may mediate crosstalk between Arf and PKA pathways. {ECO:0000269|PubMed:12051703, ECO:0000269|PubMed:12571360, ECO:0000269|PubMed:15385626, ECO:0000269|PubMed:16477018, ECO:0000269|PubMed:17276987, ECO:0000269|PubMed:18625701, ECO:0000269|PubMed:20360857}. |
| Q9Y6J0 | CABIN1 | S1471 | ochoa | Calcineurin-binding protein cabin-1 (Calcineurin inhibitor) (CAIN) | May be required for replication-independent chromatin assembly. May serve as a negative regulator of T-cell receptor (TCR) signaling via inhibition of calcineurin. Inhibition of activated calcineurin is dependent on both PKC and calcium signals. Acts as a negative regulator of p53/TP53 by keeping p53 in an inactive state on chromatin at promoters of a subset of it's target genes. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:9655484}. |
| Q9Y6M5 | SLC30A1 | S466 | ochoa | Proton-coupled zinc antiporter SLC30A1 (Solute carrier family 30 member 1) (Zinc transporter 1) | Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444). Forms a complex with TMC6/EVER1 and TMC8/EVER2 at the ER membrane of keratynocytes which facilitates zinc uptake into the ER (PubMed:18158319). Down-regulates the activity of transcription factors induced by zinc and cytokines (PubMed:18158319). {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:18158319, ECO:0000269|PubMed:31471319, ECO:0000269|PubMed:32441444}. |
| Q9Y6Q9 | NCOA3 | S587 | ochoa | 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. |
| Q9Y6Q9 | NCOA3 | S1048 | 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. |
| U3KPZ7 | LOC127814297 | S601 | ochoa | RNA-binding protein 27 (RNA-binding motif protein 27) | May be involved in the turnover of nuclear polyadenylated (pA+) RNA. {ECO:0000256|ARBA:ARBA00043866}. |
| P53675 | CLTCL1 | S460 | 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}. |
| Q00610 | CLTC | S460 | 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}. |
| P11586 | MTHFD1 | S129 | Sugiyama | C-1-tetrahydrofolate synthase, cytoplasmic (C1-THF synthase) (Epididymis secretory sperm binding protein) [Cleaved into: C-1-tetrahydrofolate synthase, cytoplasmic, N-terminally processed] [Includes: Methylenetetrahydrofolate dehydrogenase (EC 1.5.1.5); Methenyltetrahydrofolate cyclohydrolase (EC 3.5.4.9); Formyltetrahydrofolate synthetase (EC 6.3.4.3)] | Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate (PubMed:10828945, PubMed:18767138, PubMed:1881876). These derivatives of tetrahydrofolate are differentially required in nucleotide and amino acid biosynthesis, (6S)-10-formyltetrahydrofolate being required for purine biosynthesis while (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate is used for serine and methionine biosynthesis for instance (PubMed:18767138, PubMed:25633902). {ECO:0000269|PubMed:10828945, ECO:0000269|PubMed:18767138, ECO:0000269|PubMed:1881876, ECO:0000269|PubMed:25633902}. |
| P14314 | PRKCSH | S478 | Sugiyama | Glucosidase 2 subunit beta (80K-H protein) (Glucosidase II subunit beta) (Protein kinase C substrate 60.1 kDa protein heavy chain) (PKCSH) | Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:O08795, ECO:0000269|PubMed:10929008}. |
| Q9BY77 | POLDIP3 | S63 | EPSD|PSP | Polymerase delta-interacting protein 3 (46 kDa DNA polymerase delta interaction protein) (p46) (S6K1 Aly/REF-like target) (SKAR) | Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex. {ECO:0000269|PubMed:18423201, ECO:0000269|PubMed:22928037}. |
| P35606 | COPB2 | S204 | Sugiyama | Coatomer subunit beta' (Beta'-coat protein) (Beta'-COP) (p102) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. {ECO:0000269|PubMed:34450031}.; FUNCTION: This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner (By similarity). {ECO:0000250}. |
| Q12792 | TWF1 | S55 | Sugiyama | Twinfilin-1 (Protein A6) (Protein tyrosine kinase 9) | 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 (By similarity). {ECO:0000250}. |
| Q12931 | TRAP1 | S477 | Sugiyama | Heat shock protein 75 kDa, mitochondrial (HSP 75) (Heat shock protein family C member 5) (TNFR-associated protein 1) (Tumor necrosis factor type 1 receptor-associated protein) (TRAP-1) | Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, downstream of PINK1 and mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA. {ECO:0000269|PubMed:23525905, ECO:0000269|PubMed:23564345, ECO:0000269|PubMed:23747254}. |
| P08195 | SLC3A2 | S513 | 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}. |
| Q7KZF4 | SND1 | S473 | Sugiyama | Staphylococcal nuclease domain-containing protein 1 (EC 3.1.31.1) (100 kDa coactivator) (EBNA2 coactivator p100) (Tudor domain-containing protein 11) (p100 co-activator) | Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs (PubMed:18453631, PubMed:28546213). As part of its function in miRNA decay, regulates mRNAs involved in G1-to-S phase transition (PubMed:28546213). Functions as a bridging factor between STAT6 and the basal transcription factor (PubMed:12234934). Plays a role in PIM1 regulation of MYB activity (PubMed:9809063). Functions as a transcriptional coactivator for STAT5 (By similarity). {ECO:0000250|UniProtKB:Q78PY7, ECO:0000269|PubMed:12234934, ECO:0000269|PubMed:18453631, ECO:0000269|PubMed:28546213, ECO:0000269|PubMed:9809063}.; FUNCTION: (Microbial infection) Functions as a transcriptional coactivator for the Epstein-Barr virus nuclear antigen 2 (EBNA2). {ECO:0000269|PubMed:7651391}.; FUNCTION: (Microbial infection) Promotes SARS-CoV-2 RNA synthesis by binding to negative-sense RNA and the viral protein nsp9. {ECO:0000269|PubMed:37794589}. |
| O15075 | DCLK1 | S160 | Sugiyama | Serine/threonine-protein kinase DCLK1 (EC 2.7.11.1) (Doublecortin domain-containing protein 3A) (Doublecortin-like and CAM kinase-like 1) (Doublecortin-like kinase 1) | Probable kinase that may be involved in a calcium-signaling pathway controlling neuronal migration in the developing brain. May also participate in functions of the mature nervous system. |
| P62241 | RPS8 | S115 | Sugiyama | Small ribosomal subunit protein eS8 (40S ribosomal protein S8) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| Q8NCX0 | CCDC150 | S233 | Sugiyama | Coiled-coil domain-containing protein 150 | None |
| O43283 | MAP3K13 | S900 | 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}. |
| P61158 | ACTR3 | S232 | Sugiyama | Actin-related protein 3 (Actin-like protein 3) | 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). Plays a role in ciliogenesis (PubMed:20393563). {ECO:0000269|PubMed:17220302, ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:29058690, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:9000076}. |
| Q15293 | RCN1 | S69 | Sugiyama | Reticulocalbin-1 | May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment. |
| P43490 | NAMPT | S180 | 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}. |
| O75676 | RPS6KA4 | S507 | Sugiyama | Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| P15880 | RPS2 | S249 | Sugiyama | Small ribosomal subunit protein uS5 (40S ribosomal protein S2) (40S ribosomal protein S4) (Protein LLRep3) | Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules (PubMed:23636399). The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain (PubMed:23636399). The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel (PubMed:23636399). Plays a role in the assembly and function of the 40S ribosomal subunit (By similarity). Mutations in this protein affects the control of translational fidelity (By similarity). Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly (By similarity). {ECO:0000250|UniProtKB:P25443, ECO:0000269|PubMed:23636399}. |
| Q13596 | SNX1 | S229 | Sugiyama | Sorting nexin-1 | Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:12198132). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:19816406, PubMed:23085988). Involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin stxB. Plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi (PubMed:12198132, PubMed:15498486, PubMed:17101778, PubMed:17550970, PubMed:18088323, PubMed:21040701). Involvement in retromer-independent endocytic trafficking of P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R (PubMed:16407403, PubMed:20070609). Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901). Required for endocytosis of DRD5 upon agonist stimulation but not for basal receptor trafficking (PubMed:23152498). {ECO:0000269|PubMed:12198132, ECO:0000269|PubMed:15498486, ECO:0000269|PubMed:16407403, ECO:0000269|PubMed:17101778, ECO:0000269|PubMed:17550970, ECO:0000269|PubMed:18088323, ECO:0000269|PubMed:19816406, ECO:0000269|PubMed:20070609, ECO:0000269|PubMed:20604901, ECO:0000269|PubMed:21040701, ECO:0000269|PubMed:23085988, ECO:0000269|PubMed:23152498, ECO:0000303|PubMed:15498486}. |
| P28074 | PSMB5 | S229 | Sugiyama | Proteasome subunit beta type-5 (EC 3.4.25.1) (Macropain epsilon chain) (Multicatalytic endopeptidase complex epsilon chain) (Proteasome chain 6) (Proteasome epsilon chain) (Proteasome subunit MB1) (Proteasome subunit X) (Proteasome subunit beta-5) (beta-5) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB5 displays a chymotrypsin-like activity. {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:18502982, ECO:0000269|PubMed:18565852, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P28329 | CHAT | S594 | SIGNOR|EPSD | Choline O-acetyltransferase (CHOACTase) (ChAT) (Choline acetylase) (EC 2.3.1.6) | Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses. {ECO:0000269|PubMed:17144655}. |
| P09619 | PDGFRB | S980 | 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}. |
| Q99613 | EIF3C | S639 | Sugiyama | Eukaryotic translation initiation factor 3 subunit C (eIF3c) (Eukaryotic translation initiation factor 3 subunit 8) (eIF3 p110) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03002, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| P11362 | FGFR1 | S436 | Sugiyama | 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}. |
| P12931 | SRC | S234 | Sugiyama | Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src) | Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors (PubMed:34234773). Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.; FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in neurite elongation (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}. |
| P46779 | RPL28 | S26 | Sugiyama | Large ribosomal subunit protein eL28 (60S ribosomal protein L28) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| O60479 | DLX3 | S138 | SIGNOR|iPTMNet|EPSD | Homeobox protein DLX-3 | Transcriptional activator (By similarity). Activates transcription of GNRHR, via binding to the downstream activin regulatory element (DARE) in the gene promoter (By similarity). {ECO:0000250|UniProtKB:Q64205}. |
| P08754 | GNAI3 | S153 | Sugiyama | Guanine nucleotide-binding protein G(i) subunit alpha-3 (G(i) alpha-3) | Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal (By similarity). Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:18434541, PubMed:19478087, PubMed:8774883). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). The active GTP-bound form activates the calcium permeant TRPC5 ion channels (PubMed:37137991). {ECO:0000250|UniProtKB:P08753, ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:2535845, ECO:0000269|PubMed:37137991, ECO:0000269|PubMed:8774883}. |
| Q15056 | EIF4H | S66 | Sugiyama | Eukaryotic translation initiation factor 4H (eIF-4H) (Williams-Beuren syndrome chromosomal region 1 protein) | Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA. {ECO:0000269|PubMed:10585411, ECO:0000269|PubMed:11418588}. |
| O43747 | AP1G1 | S348 | Sugiyama | AP-1 complex subunit gamma-1 (Adaptor protein complex AP-1 subunit gamma-1) (Adaptor-related protein complex 1 subunit gamma-1) (Clathrin assembly protein complex 1 gamma-1 large chain) (Gamma1-adaptin) (Golgi adaptor HA1/AP1 adaptin subunit gamma-1) | 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. 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. In association with AFTPH/aftiphilin in the aftiphilin/p200/gamma-synergin complex, involved in the trafficking of transferrin from early to recycling endosomes, and the membrane trafficking of furin and the lysosomal enzyme cathepsin D between the trans-Golgi network (TGN) and endosomes (PubMed:15758025). {ECO:0000269|PubMed:15758025, ECO:0000269|PubMed:34102099}. |
| P17612 | PRKACA | S260 | GPS6 | cAMP-dependent protein kinase catalytic subunit alpha (PKA C-alpha) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:31112131). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (PubMed:33934390). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:33934390}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}. |
| P22612 | PRKACG | S54 | Sugiyama | cAMP-dependent protein kinase catalytic subunit gamma (PKA C-gamma) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus. |
| Q92896 | GLG1 | S1091 | Sugiyama | Golgi apparatus protein 1 (CFR-1) (Cysteine-rich fibroblast growth factor receptor) (E-selectin ligand 1) (ESL-1) (Golgi sialoglycoprotein MG-160) | Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils). {ECO:0000269|PubMed:8985126}. |
| P14868 | DARS1 | S369 | 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}. |
| Q86XZ4 | SPATS2 | S166 | Sugiyama | Spermatogenesis-associated serine-rich protein 2 (Serine-rich spermatocytes and round spermatid 59 kDa protein) (p59scr) | None |
| Q9UBU9 | NXF1 | S223 | Sugiyama | Nuclear RNA export factor 1 (Tip-associated protein) (Tip-associating protein) (mRNA export factor TAP) | Involved in the nuclear export of mRNA species bearing retroviral constitutive transport elements (CTE) and in the export of mRNA from the nucleus to the cytoplasm (TAP/NFX1 pathway) (PubMed:10924507). The NXF1-NXT1 heterodimer is involved in the export of HSP70 mRNA in conjunction with ALYREF/THOC4 and THOC5 components of the TREX complex (PubMed:18364396, PubMed:19165146, PubMed:9660949). ALYREF/THOC4-bound mRNA is thought to be transferred to the NXF1-NXT1 heterodimer for export (PubMed:18364396, PubMed:19165146, PubMed:9660949). Also involved in nuclear export of m6A-containing mRNAs: interaction between SRSF3 and YTHDC1 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). {ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:18364396, ECO:0000269|PubMed:19165146, ECO:0000269|PubMed:28984244, ECO:0000269|PubMed:9660949}. |
| P47756 | CAPZB | S90 | Sugiyama | F-actin-capping protein subunit beta (CapZ beta) | F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:A9XFX6, ECO:0000269|PubMed:21834987}. |
| Q69YN4 | VIRMA | S1432 | Sugiyama | Protein virilizer homolog | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:24981863, PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs in the 3'-UTR near the stop codon: recruits the catalytic core components METTL3 and METTL14, thereby guiding m6A methylation at specific sites (PubMed:29507755). Required for mRNA polyadenylation via its role in selective m6A methylation: m6A methylation of mRNAs in the 3'-UTR near the stop codon correlating with alternative polyadenylation (APA) (PubMed:29507755). {ECO:0000269|PubMed:24981863, ECO:0000269|PubMed:29507755}. |
| Q8WX92 | NELFB | S542 | Sugiyama | Negative elongation factor B (NELF-B) (Cofactor of BRCA1) | Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:12612062). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (PubMed:10199401). May be able to induce chromatin unfolding (PubMed:11739404). Essential for early embryogenesis; plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) by preventing unscheduled expression of developmental genes (By similarity). Plays a key role in establishing the responsiveness of stem cells to developmental cues; facilitates plasticity and cell fate commitment in ESCs by establishing the appropriate expression level of signaling molecules (By similarity). Supports the transcription of genes involved in energy metabolism in cardiomyocytes; facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes (By similarity). {ECO:0000250|UniProtKB:Q8C4Y3, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:11739404, ECO:0000269|PubMed:12612062}.; FUNCTION: (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II (PubMed:23884411). In vitro, binds weakly to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1 (PubMed:23884411). {ECO:0000269|PubMed:23884411}. |
| P36894 | BMPR1A | S216 | Sugiyama | Bone morphogenetic protein receptor type-1A (BMP type-1A receptor) (BMPR-1A) (EC 2.7.11.30) (Activin receptor-like kinase 3) (ALK-3) (Serine/threonine-protein kinase receptor R5) (SKR5) (CD antigen CD292) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP2, BMP4, GDF5 and GDF6. Positively regulates chondrocyte differentiation through GDF5 interaction. Mediates induction of adipogenesis by GDF6. May promote the expression of HAMP, potentially via its interaction with BMP2 (By similarity). {ECO:0000250|UniProtKB:P36895}. |
| Q99996 | AKAP9 | S3816 | Sugiyama | A-kinase anchor protein 9 (AKAP-9) (A-kinase anchor protein 350 kDa) (AKAP 350) (hgAKAP 350) (A-kinase anchor protein 450 kDa) (AKAP 450) (AKAP 120-like protein) (Centrosome- and Golgi-localized PKN-associated protein) (CG-NAP) (Protein hyperion) (Protein kinase A-anchoring protein 9) (PRKA9) (Protein yotiao) | Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus (PubMed:10202149, PubMed:15047863). Required for microtubule nucleation at the cis-side of the Golgi apparatus (PubMed:15047863, PubMed:19242490). Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase (PubMed:25657325). In complex with PDE4DIP isoform 13/MMG8/SMYLE, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with PDE4DIP isoform 13/MMG8/SMYLE, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery (PubMed:29162697). {ECO:0000269|PubMed:10202149, ECO:0000269|PubMed:15047863, ECO:0000269|PubMed:19242490, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:29162697}.; FUNCTION: [Isoform 4]: Associated with the N-methyl-D-aspartate receptor and is specifically found in the neuromuscular junction (NMJ) as well as in neuronal synapses, suggesting a role in the organization of postsynaptic specializations. {ECO:0000269|PubMed:9482789}. |
| Q9H1I8 | ASCC2 | S549 | Sugiyama | Activating signal cointegrator 1 complex subunit 2 (ASC-1 complex subunit p100) (Trip4 complex subunit p100) | Ubiquitin-binding protein involved in DNA repair and rescue of stalled ribosomes (PubMed:29144457, PubMed:32099016, PubMed:32579943, PubMed:36302773). Plays a role in DNA damage repair as component of the ASCC complex (PubMed:29144457). Recruits ASCC3 and ALKBH3 to sites of DNA damage by binding to polyubiquitinated proteins that have 'Lys-63'-linked polyubiquitin chains (PubMed:29144457). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). Involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (PubMed:32099016, PubMed:32579943, PubMed:36302773). Specifically recognizes and binds RPS20/uS10 ubiquitinated by ZNF598, promoting recruitment of the RQT (ribosome quality control trigger) complex on stalled ribosomes, followed by disassembly of stalled ribosomes (PubMed:36302773). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:29144457, ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773}. |
| P48736 | PIK3CG | S496 | Sugiyama | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PI3-kinase subunit gamma) (PI3K-gamma) (PI3Kgamma) (PtdIns-3-kinase subunit gamma) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma) (PtdIns-3-kinase subunit p110-gamma) (p110gamma) (Phosphoinositide-3-kinase catalytic gamma polypeptide) (Serine/threonine protein kinase PIK3CG) (EC 2.7.11.1) (p120-PI3K) | Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contributes to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis. In neutrophils, participates in a phospholipase C-activating N-formyl peptide-activated GPCR (G protein-coupled receptor) signaling pathway downstream of RASGRP4-mediated Ras-activation, to promote neutrophil functional responses (By similarity). {ECO:0000250|UniProtKB:Q9JHG7, ECO:0000269|PubMed:11277933, ECO:0000269|PubMed:12163475, ECO:0000269|PubMed:15135396, ECO:0000269|PubMed:15294162, ECO:0000269|PubMed:16094730, ECO:0000269|PubMed:16123124, ECO:0000269|PubMed:21393242, ECO:0000269|PubMed:31554793, ECO:0000269|PubMed:33054089, ECO:0000269|PubMed:7624799}. |
| P47224 | RABIF | S39 | Sugiyama | Guanine nucleotide exchange factor MSS4 (Rab-interacting factor) | Guanine-nucleotide-releasing protein that acts on members of the SEC4/YPT1/RAB subfamily. Stimulates GDP release from both YPT1, RAB3A and RAB10, but is less active on these proteins than on the SEC4 protein (PubMed:31540829). Might play a general role in vesicular transport. {ECO:0000269|PubMed:31540829}. |
| P51957 | NEK4 | S526 | Sugiyama | Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) | Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}. |
| Q9Y3S2 | ZNF330 | S25 | Sugiyama | Zinc finger protein 330 (Nucleolar autoantigen 36) (Nucleolar cysteine-rich protein) | None |
| P09960 | LTA4H | S486 | Sugiyama | Leukotriene A-4 hydrolase (LTA-4 hydrolase) (EC 3.3.2.6) (Leukotriene A(4) hydrolase) (Tripeptide aminopeptidase LTA4H) (EC 3.4.11.4) | Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Also has aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:18804029, PubMed:20813919). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090). {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:2244921, ECO:0000269|PubMed:24591641}. |
| Q9UJX3 | ANAPC7 | S64 | GPS6|EPSD | Anaphase-promoting complex subunit 7 (APC7) (Cyclosome subunit 7) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). APC7 is not required for the assembly of the APC/C complex, but has an enzyme-substrate adapter activity mediating the processive ubiquitination of specific substrates (PubMed:34942119). Involved in brain development through the specific ubiquitination and clearance of MKI67 from constitutive heterochromatin after neuronal progenitors exit mitosis (PubMed:34942119). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:34942119}. |
| O75128 | COBL | S1171 | Sugiyama | Protein cordon-bleu | Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. {ECO:0000250, ECO:0000269|PubMed:21816349}. |
| P54760 | EPHB4 | S735 | 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}. |
| Q96E11 | MRRF | S227 | Sugiyama | Ribosome-recycling factor, mitochondrial (RRF) (mtRRF) (Ribosome-releasing factor, mitochondrial) | Responsible for the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis (PubMed:19716793, PubMed:33878294). Acts in collaboration with GFM2 (PubMed:33878294). Promotes mitochondrial ribosome recycling by dissolution of intersubunit contacts (PubMed:33878294). {ECO:0000269|PubMed:19716793, ECO:0000269|PubMed:33878294}. |
| P49917 | LIG4 | S672 | SIGNOR | DNA ligase 4 (EC 6.5.1.1) (DNA ligase IV) (Polydeoxyribonucleotide synthase [ATP] 4) | DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242410, PubMed:9809069). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242). {ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:23523427, ECO:0000269|PubMed:24984242, ECO:0000269|PubMed:29980672, ECO:0000269|PubMed:33586762, ECO:0000269|PubMed:8798671, ECO:0000269|PubMed:9242410, ECO:0000269|PubMed:9809069}. |
| Q13310 | PABPC4 | S212 | Sugiyama | Polyadenylate-binding protein 4 (PABP-4) (Poly(A)-binding protein 4) (Activated-platelet protein 1) (APP-1) (Inducible poly(A)-binding protein) (iPABP) | Binds the poly(A) tail of mRNA (PubMed:8524242). Binds to SMIM26 mRNA and plays a role in its post-transcriptional regulation (PubMed:37009826). May be involved in cytoplasmic regulatory processes of mRNA metabolism. Can probably bind to cytoplasmic RNA sequences other than poly(A) in vivo (By similarity). {ECO:0000250|UniProtKB:P11940, ECO:0000269|PubMed:37009826, ECO:0000269|PubMed:8524242}. |
| O60763 | USO1 | S805 | Sugiyama | General vesicular transport factor p115 (Protein USO1 homolog) (Transcytosis-associated protein) (TAP) (Vesicle-docking protein) | General vesicular transport factor required for intercisternal transport in the Golgi stack; it is required for transcytotic fusion and/or subsequent binding of the vesicles to the target membrane. May well act as a vesicular anchor by interacting with the target membrane and holding the vesicular and target membranes in proximity. {ECO:0000250|UniProtKB:P41542}. |
| Q13873 | BMPR2 | S194 | Sugiyama | Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}. |
| Q15349 | RPS6KA2 | S366 | 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}. |
| Q15349 | RPS6KA2 | S454 | 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}. |
| Q15418 | RPS6KA1 | S457 | Sugiyama | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
| Q8IVD9 | NUDCD3 | S193 | Sugiyama | NudC domain-containing protein 3 | None |
| Q16512 | PKN1 | S156 | Sugiyama | Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) | PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. |
| P50395 | GDI2 | S43 | 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}. |
| Q9BV86 | NTMT1 | S181 | Sugiyama | N-terminal Xaa-Pro-Lys N-methyltransferase 1 (EC 2.1.1.244) (Alpha N-terminal protein methyltransferase 1A) (Methyltransferase-like protein 11A) (N-terminal RCC1 methyltransferase) (X-Pro-Lys N-terminal protein methyltransferase 1A) (NTM1A) [Cleaved into: N-terminal Xaa-Pro-Lys N-methyltransferase 1, N-terminally processed] | Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of the exposed alpha-amino group of the Ala, Gly or Ser residue in the [Ala/Gly/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Some of the substrates may be primed by NTMT2-mediated monomethylation (PubMed:24090352). Catalyzes the trimethylation of the N-terminal Gly in CENPA (after removal of Met-1). Responsible for the N-terminal methylation of KLHL31, MYL2, MYL3, RB1, RCC1, RPL23A and SET. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on RCC1. {ECO:0000269|PubMed:20481588, ECO:0000269|PubMed:20668449, ECO:0000269|PubMed:24090352, ECO:0000269|PubMed:26543159}. |
| Q16644 | MAPKAPK3 | S46 | Sugiyama | 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}. |
| Q9BQS8 | FYCO1 | S425 | Sugiyama | FYVE and coiled-coil domain-containing protein 1 (Zinc finger FYVE domain-containing protein 7) | May mediate microtubule plus end-directed vesicle transport. {ECO:0000269|PubMed:20100911}. |
| Q9GZM8 | NDEL1 | S95 | PSP | Nuclear distribution protein nudE-like 1 (Protein Nudel) (Mitosin-associated protein 1) | Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also 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 ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). Plays a role, together with DISC1, in the regulation of neurite outgrowth (By similarity). May act as a RAB9A/B effector that tethers RAB9-associated late endosomes to the dynein motor for their retrograde transport to the trans-Golgi network (PubMed:34793709). {ECO:0000250|UniProtKB:Q78PB6, ECO:0000250|UniProtKB:Q9ERR1, ECO:0000269|PubMed:12556484, ECO:0000269|PubMed:14970193, ECO:0000269|PubMed:16291865, ECO:0000269|PubMed:17600710, ECO:0000269|PubMed:34793709}. |
| Q5S007 | LRRK2 | S1345 | EPSD|PSP | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q5S007 | LRRK2 | S1467 | 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}. |
| Q5S007 | LRRK2 | S1647 | 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}. |
| Q5S007 | LRRK2 | S1853 | 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}. |
| Q5S007 | LRRK2 | S2257 | 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}. |
| O15355 | PPM1G | S354 | 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 |
| Q6XUX3 | DSTYK | S575 | 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}. |
| P22314 | UBA1 | S460 | Sugiyama | Ubiquitin-like modifier-activating enzyme 1 (EC 6.2.1.45) (Protein A1S9) (Ubiquitin-activating enzyme E1) | Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1447181, PubMed:1606621, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). {ECO:0000269|PubMed:1447181, ECO:0000269|PubMed:1606621, ECO:0000269|PubMed:22456334, ECO:0000269|PubMed:33108101}. |
| P30876 | POLR2B | S467 | Sugiyama | DNA-directed RNA polymerase II subunit RPB2 (EC 2.7.7.6) (3'-5' exoribonuclease) (EC 3.1.13.-) (DNA-directed RNA polymerase II 140 kDa polypeptide) (DNA-directed RNA polymerase II subunit B) (RNA polymerase II subunit 2) (RNA polymerase II subunit B2) (RNA-directed RNA polymerase II subunit RPB2) (EC 2.7.7.48) | Catalytic core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates (By similarity) (PubMed:27193682, PubMed:30190596, PubMed:9852112). Pol II-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol II pre-initiation complex (PIC) is recruited to DNA promoters, with focused-type promoters containing either the initiator (Inr) element, or the TATA-box found in cell-type specific genes and dispersed-type promoters that often contain hypomethylated CpG islands usually found in housekeeping genes. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (PubMed:27193682, PubMed:30190596, PubMed:9852112). Forms Pol II active center together with the largest subunit POLR2A/RPB1. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR2A/RPB1 most likely contributing a Mg(2+)-coordinating DxDGD motif and POLR2B/RPB2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg(2+) ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. The reversible pyrophosphorolysis can occur at high pyrophosphate concentrations (By similarity) (PubMed:30190596, PubMed:9852112). Can proofread the nascent RNA transcript by means of a 3' -> 5' exonuclease activity. If a ribonucleotide is mis-incorporated, backtracks along the template DNA and cleaves the phosphodiester bond releasing the mis-incorporated 5'-ribonucleotide (By similarity) (PubMed:8381534). {ECO:0000250|UniProtKB:A5PJW8, ECO:0000269|PubMed:27193682, ECO:0000269|PubMed:30190596, ECO:0000269|PubMed:8381534, ECO:0000269|PubMed:9852112}.; FUNCTION: RNA-dependent RNA polymerase that catalyzes the extension of a non-coding RNA (ncRNA) at the 3'-end using the four ribonucleoside triphosphates as substrates. An internal ncRNA sequence near the 3'-end serves as a template in a single-round Pol II-mediated RNA polymerization reaction. May decrease the stability of ncRNAs that repress Pol II-mediated gene transcription. {ECO:0000269|PubMed:23395899}. |
| Q8IWZ3 | ANKHD1 | S1429 | Sugiyama | Ankyrin repeat and KH domain-containing protein 1 (HIV-1 Vpr-binding ankyrin repeat protein) (Multiple ankyrin repeats single KH domain) (hMASK) | May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}. |
| Q8N568 | DCLK2 | S385 | 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}. |
| Q8NG66 | NEK11 | S39 | Sugiyama | Serine/threonine-protein kinase Nek11 (EC 2.7.11.1) (Never in mitosis A-related kinase 11) (NimA-related protein kinase 11) | Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. Controls degradation of CDC25A by directly phosphorylating it on residues whose phosphorylation is required for BTRC-mediated polyubiquitination and degradation. {ECO:0000269|PubMed:12154088, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422}. |
| Q9BQ39 | DDX50 | S145 | Sugiyama | ATP-dependent RNA helicase DDX50 (EC 3.6.4.13) (DEAD box protein 50) (Gu-beta) (Nucleolar protein Gu2) | ATP-dependent RNA helicase that may play a role in various aspects of RNA metabolism including pre-mRNA splicing or ribosomal RNA production (PubMed:12027455). Also acts as a viral restriction factor and promotes the activation of the NF-kappa-B and IRF3 signaling pathways following its stimulation with viral RNA or infection with RNA and DNA viruses (PubMed:35215908). For instance, decreases vaccinia virus, herpes simplex virus, Zika virus or dengue virus replication during the early stage of infection (PubMed:28181036, PubMed:35215908). Mechanistically, acts via the adapter TICAM1 and independently of the DDX1-DDX21-DHX36 helicase complex to induce the production of interferon-beta (PubMed:35215908). {ECO:0000269|PubMed:12027455, ECO:0000269|PubMed:28181036, ECO:0000269|PubMed:35215908}. |
| Q9NR30 | DDX21 | S194 | 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}. |
| P27824 | CANX | S74 | Sugiyama | Calnexin (IP90) (Major histocompatibility complex class I antigen-binding protein p88) (p90) | Calcium-binding protein that interacts with newly synthesized monoglucosylated glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at the synapse. |
| Q00610 | CLTC | S1147 | 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}. |
| Q04864 | REL | S274 | Sugiyama | Proto-oncogene c-Rel | Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator. |
| Q15043 | SLC39A14 | S56 | Sugiyama | Metal cation symporter ZIP14 (LIV-1 subfamily of ZIP zinc transporter 4) (LZT-Hs4) (Solute carrier family 39 member 14) (Zrt- and Irt-like protein 14) (ZIP-14) | Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15642354, PubMed:27231142, PubMed:29621230). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (By similarity). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (By similarity). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (By similarity). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (By similarity). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (PubMed:31699897). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (By similarity). Also functions in the extracellular uptake of free iron. May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages (PubMed:23052185). {ECO:0000250|UniProtKB:Q75N73, ECO:0000269|PubMed:15642354, ECO:0000269|PubMed:20682781, ECO:0000269|PubMed:23052185, ECO:0000269|PubMed:27231142, ECO:0000269|PubMed:27703010, ECO:0000269|PubMed:29621230, ECO:0000269|PubMed:31028174, ECO:0000269|PubMed:31699897}. |
| Q96GD4 | AURKB | S62 | Sugiyama | Aurora kinase B (EC 2.7.11.1) (Aurora 1) (Aurora- and IPL1-like midbody-associated protein 1) (AIM-1) (Aurora/IPL1-related kinase 2) (ARK-2) (Aurora-related kinase 2) (STK-1) (Serine/threonine-protein kinase 12) (Serine/threonine-protein kinase 5) (Serine/threonine-protein kinase aurora-B) | Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:29449677). 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 (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (PubMed:11756469, PubMed:11784863, PubMed:11856369, PubMed:12689593, PubMed:14602875, PubMed:16103226, PubMed:21658950). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity). Phosphorylates ATXN10 which promotes phosphorylation of ATXN10 by PLK1 and may play a role in the regulation of cytokinesis and stimulating the proteasomal degradation of ATXN10 (PubMed:25666058). {ECO:0000250|UniProtKB:O70126, ECO:0000269|PubMed:11516652, ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:11784863, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12458200, ECO:0000269|PubMed:12686604, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14602875, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21658950, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:24814515, ECO:0000269|PubMed:25666058, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:29449677, ECO:0000269|PubMed:33542149}. |
| Q96J92 | WNK4 | S316 | Sugiyama | Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4) | Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:16832045). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16832045, PubMed:22989884). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (By similarity). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (By similarity). Also inhibits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (By similarity). May also phosphorylate NEDD4L (PubMed:20525693). {ECO:0000250|UniProtKB:Q80UE6, ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:22989884}. |
| P14868 | DARS1 | S192 | 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}. |
| P47914 | RPL29 | S26 | Sugiyama | Large ribosomal subunit protein eL29 (60S ribosomal protein L29) (Cell surface heparin-binding protein HIP) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P01130 | LDLR | S286 | Sugiyama | Low-density lipoprotein receptor (LDL receptor) | Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization (PubMed:30443021). {ECO:0000269|PubMed:3005267, ECO:0000269|PubMed:30443021, ECO:0000269|PubMed:6091915}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. {ECO:0000269|PubMed:10535997, ECO:0000269|PubMed:12615904}.; FUNCTION: (Microbial infection) Acts as a receptor for Vesicular stomatitis virus. {ECO:0000269|PubMed:23589850}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. {ECO:0000269|PubMed:11100124}.; FUNCTION: (Microbial infection) Acts as a receptor for Crimean-Congo hemorrhagic fever virus (CCHFV). {ECO:0000269|PubMed:38182887}.; FUNCTION: (Microbial infection) Acts as a receptor for many Alphavirus, including Getah virus (GETV), Ross river virus (RRV) and Semliki Forest virus. {ECO:0000269|PubMed:38245515}. |
| Q9Y2U5 | MAP3K2 | S21 | Sugiyama | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| Q9BYP7 | WNK3 | S422 | Sugiyama | Serine/threonine-protein kinase WNK3 (EC 2.7.11.1) (Protein kinase lysine-deficient 3) (Protein kinase with no lysine 3) | Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922). WNK3 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:22989884). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16275911, PubMed:16275913). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (PubMed:17975670). May also phosphorylate NEDD4L (PubMed:20525693). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (PubMed:16357011, PubMed:17673510). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17673510, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:36318922}. |
| Q15751 | HERC1 | S440 | Sugiyama | Probable E3 ubiquitin-protein ligase HERC1 (EC 2.3.2.26) (HECT domain and RCC1-like domain-containing protein 1) (HECT-type E3 ubiquitin transferase HERC1) (p532) (p619) | Involved in membrane trafficking via some guanine nucleotide exchange factor (GEF) activity and its ability to bind clathrin. Acts as a GEF for Arf and Rab, by exchanging bound GDP for free GTP. Binds phosphatidylinositol 4,5-bisphosphate, which is required for GEF activity. May also act as a E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. {ECO:0000269|PubMed:15642342, ECO:0000269|PubMed:8861955, ECO:0000269|PubMed:9233772}. |
| Q9UK32 | RPS6KA6 | S465 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| Q9UKI8 | TLK1 | S226 | Sugiyama | Serine/threonine-protein kinase tousled-like 1 (EC 2.7.11.1) (PKU-beta) (Tousled-like kinase 1) | Rapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S-phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'. {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:10588641, ECO:0000269|PubMed:11314006, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:9427565}. |
| P49736 | MCM2 | S187 | Sugiyama | DNA replication licensing factor MCM2 (EC 3.6.4.12) (Minichromosome maintenance protein 2 homolog) (Nuclear protein BM28) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (PubMed:8175912). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (PubMed:26196677). {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:8175912}. |
| Q96PH1 | NOX5 | S548 | SIGNOR | NADPH oxidase 5 (EC 1.6.3.-) | Calcium-dependent NADPH oxidase that catalyzes the generation of superoxide from molecular oxygen utilizing NADPH as an electron donor (PubMed:12686516). May play a role in cell growth and apoptosis (PubMed:12686516). {ECO:0000269|PubMed:12686516}.; FUNCTION: [Isoform v2]: Calcium-dependent NADPH oxidase that catalyzes the generation of superoxide from molecular oxygen utilizing NADPH as an electron donor (PubMed:11483596, PubMed:14982937, PubMed:17275676, PubMed:17587483, PubMed:21642394, PubMed:22387196, PubMed:22427510, PubMed:24505490, PubMed:36653838). Involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contributes to endothelial response to thrombin (PubMed:17275676). Regulates redox-dependent processes in lymphocytes and spermatozoa (PubMed:11483596). {ECO:0000269|PubMed:11483596, ECO:0000269|PubMed:14982937, ECO:0000269|PubMed:17275676, ECO:0000269|PubMed:17587483, ECO:0000269|PubMed:21642394, ECO:0000269|PubMed:22387196, ECO:0000269|PubMed:22427510, ECO:0000269|PubMed:24505490, ECO:0000269|PubMed:36653838}.; FUNCTION: [Isoform v1]: Calcium-dependent NADPH oxidase that catalyzes the generation of superoxide from molecular oxygen utilizing NADPH as an electron donor. {ECO:0000269|PubMed:21319793, ECO:0000269|PubMed:22427510}.; FUNCTION: [Isoform v5]: This isoform lacks calcium-binding domains and was showed to present a NADPH oxidase activity in a calcium-independent manner (PubMed:17275676, PubMed:36653838). May be involved in endothelial generation of reactive oxygen species (ROS), proliferation and angiogenesis and contribute to endothelial response to thrombin (PubMed:17275676). However another study showed an absence of oxidase activity (PubMed:22427510). Subject to rapid degradation (PubMed:36653838). {ECO:0000269|PubMed:17275676, ECO:0000269|PubMed:22427510, ECO:0000269|PubMed:36653838}.; FUNCTION: [Isoform v3]: Lacks calcium-dependent NADPH oxidase activity. {ECO:0000269|PubMed:22427510}.; FUNCTION: [Isoform v4]: Lacks calcium-dependent NADPH oxidase activity. {ECO:0000269|PubMed:22427510}. |
| Q9BYP7 | WNK3 | S289 | Sugiyama | Serine/threonine-protein kinase WNK3 (EC 2.7.11.1) (Protein kinase lysine-deficient 3) (Protein kinase with no lysine 3) | Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922). WNK3 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:22989884). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16275911, PubMed:16275913). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (PubMed:17975670). May also phosphorylate NEDD4L (PubMed:20525693). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (PubMed:16357011, PubMed:17673510). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17673510, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:36318922}. |
| Q9H4A3 | WNK1 | S363 | Sugiyama | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9Y3S1 | WNK2 | S337 | Sugiyama | Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Antigen NY-CO-43) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Serologically defined colon cancer antigen 43) | Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (PubMed:17667937, PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (PubMed:17667937, PubMed:18593598). {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}. |
| Q9Y3S1 | WNK2 | S472 | Sugiyama | Serine/threonine-protein kinase WNK2 (EC 2.7.11.1) (Antigen NY-CO-43) (Protein kinase lysine-deficient 2) (Protein kinase with no lysine 2) (Serologically defined colon cancer antigen 43) | Serine/threonine-protein kinase component of the WNK2-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation (PubMed:17667937, PubMed:18593598, PubMed:21733846). The WNK2-SPAK/OSR1 kinase cascade is composed of WNK2, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (By similarity). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, regulating their activity (By similarity). Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively (PubMed:21733846). Activates SLC12A2, SCNN1A, SCNN1B, SCNN1D and SGK1 and inhibits SLC12A5 (PubMed:21733846). Negatively regulates the EGF-induced activation of the ERK/MAPK-pathway and the downstream cell cycle progression (PubMed:17667937, PubMed:18593598). Affects MAPK3/MAPK1 activity by modulating the activity of MAP2K1 and this modulation depends on phosphorylation of MAP2K1 by PAK1 (PubMed:17667937, PubMed:18593598). WNK2 acts by interfering with the activity of PAK1 by controlling the balance of the activity of upstream regulators of PAK1 activity, RHOA and RAC1, which display reciprocal activity (PubMed:17667937, PubMed:18593598). {ECO:0000250|UniProtKB:Q9H4A3, ECO:0000269|PubMed:17667937, ECO:0000269|PubMed:18593598, ECO:0000269|PubMed:21733846}. |
| A0A087X0R7 | SENP3-EIF4A1 | S285 | ochoa | SENP3-EIF4A1 readthrough (NMD candidate) | None |
| A0A0A6YYK5 | None | S191 | ochoa | Uncharacterized protein | None |
| H0YHG0 | None | S481 | ochoa | DnaJ homolog subfamily C member 14 (Nuclear protein Hcc-1) (SAP domain-containing ribonucleoprotein) | Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export. {ECO:0000256|ARBA:ARBA00054093}.; FUNCTION: Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface. {ECO:0000256|ARBA:ARBA00055510}. |
| O14745 | NHERF1 | S77 | psp | Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (NHERF-1) (Ezrin-radixin-moesin-binding phosphoprotein 50) (EBP50) (Regulatory cofactor of Na(+)/H(+) exchanger) (Sodium-hydrogen exchanger regulatory factor 1) (Solute carrier family 9 isoform A3 regulatory factor 1) | Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}. |
| O15344 | MID1 | S213 | ochoa | E3 ubiquitin-protein ligase Midline-1 (EC 2.3.2.27) (Midin) (Putative transcription factor XPRF) (RING finger protein 59) (RING finger protein Midline-1) (RING-type E3 ubiquitin transferase Midline-1) (Tripartite motif-containing protein 18) | Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination. {ECO:0000269|PubMed:10400985, ECO:0000269|PubMed:11685209, ECO:0000269|PubMed:22613722}. |
| O43581 | SYT7 | S105 | ochoa | Synaptotagmin-7 (IPCA-7) (Prostate cancer-associated protein 7) (Synaptotagmin VII) (SytVII) | Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain (By similarity). Ca(2+) induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (By similarity). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (PubMed:11342594). Ca(2+)-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (By similarity). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (By similarity). In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)-triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes (By similarity). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (By similarity). Probably mediates synaptic facilitation by directly increasing the probability of release (By similarity). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (By similarity). Also acts as a regulator of Ca(2+)-dependent insulin and glucagon secretion in beta-cells (By similarity). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (By similarity). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity). {ECO:0000250|UniProtKB:Q62747, ECO:0000250|UniProtKB:Q9R0N7, ECO:0000269|PubMed:11342594, ECO:0000269|PubMed:15811535}. |
| O43829 | ZBTB14 | S233 | ochoa | Zinc finger and BTB domain-containing protein 14 (Zinc finger protein 161 homolog) (Zfp-161) (Zinc finger protein 478) (Zinc finger protein 5 homolog) (ZF5) (Zfp-5) (hZF5) | Transcriptional activator of the dopamine transporter (DAT), binding it's promoter at the consensus sequence 5'-CCTGCACAGTTCACGGA-3'. Binds to 5'-d(GCC)(n)-3' trinucleotide repeats in promoter regions and acts as a repressor of the FMR1 gene. Transcriptional repressor of MYC and thymidine kinase promoters. {ECO:0000269|PubMed:17714511}. |
| O60216 | RAD21 | S185 | 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}. |
| O60353 | FZD6 | S674 | ochoa | Frizzled-6 (Fz-6) (hFz6) | Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q61089}. |
| O60427 | FADS1 | S87 | ochoa | Acyl-CoA (8-3)-desaturase (EC 1.14.19.44) (Delta(5) fatty acid desaturase) (D5D) (Delta(5) desaturase) (Delta-5 desaturase) (Fatty acid desaturase 1) | [Isoform 1]: Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 5 located between a preexisting double bond and the carboxyl end of the fatty acyl chain. Involved in biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors. Specifically, desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to generate arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3), respectively (PubMed:10601301, PubMed:10769175). As a rate limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived eicosanoid biosynthesis, controls the metabolism of inflammatory lipids like prostaglandin E2, critical for efficient acute inflammatory response and maintenance of epithelium homeostasis. Contributes to membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major acyl chain esterified into phospholipids. In particular, regulates phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory cytokine production in T-cells (By similarity). Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of LA (18:2n-6) (By similarity). {ECO:0000250|UniProtKB:Q920L1, ECO:0000250|UniProtKB:Q920R3, ECO:0000269|PubMed:10601301, ECO:0000269|PubMed:10769175}.; FUNCTION: [Isoform 2]: Does not exhibit any catalytic activity toward 20:3n-6, but it may enhance FADS2 activity. {ECO:0000250|UniProtKB:A4UVI1}. |
| O60716 | CTNND1 | S288 | ochoa|psp | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O60716 | CTNND1 | S847 | ochoa | Catenin delta-1 (Cadherin-associated Src substrate) (CAS) (p120 catenin) (p120(ctn)) (p120(cas)) | Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:18343367, ECO:0000269|PubMed:20371349}. |
| O75083 | WDR1 | S473 | ochoa | WD repeat-containing protein 1 (Actin-interacting protein 1) (AIP1) (NORI-1) | Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (PubMed:15629458, PubMed:27557945, PubMed:29751004). Enhances cofilin-mediated actin severing (By similarity). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (PubMed:18494608). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance (By similarity). Involved in megakaryocyte maturation and platelet shedding. Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (By similarity). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (PubMed:25792565). {ECO:0000250|UniProtKB:O88342, ECO:0000250|UniProtKB:Q9W7F2, ECO:0000269|PubMed:15629458, ECO:0000269|PubMed:18494608, ECO:0000269|PubMed:25792565, ECO:0000269|PubMed:27557945, ECO:0000269|PubMed:29751004}. |
| O75113 | N4BP1 | S328 | ochoa | NEDD4-binding protein 1 (N4BP1) (EC 3.1.-.-) | Potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation. Acts as a key negative regulator of select cytokine and chemokine responses elicited by TRIF-independent Toll-like receptors (TLRs), thereby limiting inflammatory cytokine responses to minor insults. In response to more threatening pathogens, cleaved by CASP8 downstream of TLR3 or TLR4, leading to its inactivation, thereby allowing production of inflammatory cytokines (By similarity). Acts as a restriction factor against some viruses, such as HIV-1: restricts HIV-1 replication by binding to HIV-1 mRNAs and mediating their degradation via its ribonuclease activity (PubMed:31133753). Also acts as an inhibitor of the E3 ubiquitin-protein ligase ITCH: acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates (By similarity). {ECO:0000250|UniProtKB:Q6A037, ECO:0000269|PubMed:31133753}. |
| O75146 | HIP1R | S592 | ochoa | Huntingtin-interacting protein 1-related protein (HIP1-related protein) (Huntingtin-interacting protein 12) (HIP-12) | Component of clathrin-coated pits and vesicles, that may link the endocytic machinery to the actin cytoskeleton. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. {ECO:0000269|PubMed:11889126, ECO:0000269|PubMed:14732715}. |
| O75376 | NCOR1 | S1117 | ochoa | Nuclear receptor corepressor 1 (N-CoR) (N-CoR1) | Mediates transcriptional repression by certain nuclear receptors (PubMed:20812024). Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:Q60974, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:20812024}. |
| O75475 | PSIP1 | S434 | ochoa | PC4 and SFRS1-interacting protein (CLL-associated antigen KW-7) (Dense fine speckles 70 kDa protein) (DFS 70) (Lens epithelium-derived growth factor) (Transcriptional coactivator p75/p52) | Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis. Isoform 2 is a more general and stronger transcriptional coactivator. Isoform 2 may also act as an adapter to coordinate pre-mRNA splicing. Cellular cofactor for lentiviral integration. {ECO:0000269|PubMed:15642333}. |
| O75717 | WDHD1 | S333 | ochoa | WD repeat and HMG-box DNA-binding protein 1 (Acidic nucleoplasmic DNA-binding protein 1) (And-1) | Core replisome component that acts as a replication initiation factor. Binds directly to the CMG complex and functions as a hub to recruit additional proteins to the replication fork. {ECO:0000269|PubMed:19805216, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}. |
| O76039 | CDKL5 | S343 | ochoa | Cyclin-dependent kinase-like 5 (EC 2.7.11.22) (Serine/threonine-protein kinase 9) | Mediates phosphorylation of MECP2 (PubMed:15917271, PubMed:16935860). May regulate ciliogenesis (PubMed:29420175). {ECO:0000269|PubMed:15917271, ECO:0000269|PubMed:16935860, ECO:0000269|PubMed:29420175}. |
| O95071 | UBR5 | S191 | psp | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95251 | KAT7 | S205 | ochoa | Histone acetyltransferase KAT7 (EC 2.3.1.48) (Histone acetyltransferase binding to ORC1) (Lysine acetyltransferase 7) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 2) (MYST-2) | Catalytic subunit of histone acetyltransferase HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby regulating various processes, such as gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance and embryonic development (PubMed:16387653, PubMed:21753189, PubMed:24065767, PubMed:26620551, PubMed:31767635, PubMed:31827282). Some complexes also catalyze acetylation of histone H4 at 'Lys-5', 'Lys-8' and 'Lys-12' (H4K5ac, H4K8ac and H4K12ac, respectively), regulating DNA replication initiation, regulating DNA replication initiation (PubMed:10438470, PubMed:19187766, PubMed:20129055, PubMed:24065767). Specificity of the HBO1 complexes is determined by the scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE (JADE1, JADE2 and JADE3) scaffold direct KAT7/HBO1 specificity towards histone H4 (PubMed:19187766, PubMed:20129055, PubMed:24065767, PubMed:26620551). H3K14ac promotes transcriptional elongation by facilitating the processivity of RNA polymerase II (PubMed:31827282). Acts as a key regulator of hematopoiesis by forming a complex with BRD1/BRPF2, directing KAT7/HBO1 specificity towards H3K14ac and promoting erythroid differentiation (PubMed:21753189). H3K14ac is also required for T-cell development (By similarity). KAT7/HBO1-mediated acetylation facilitates two consecutive steps, licensing and activation, in DNA replication initiation: H3K14ac facilitates the activation of replication origins, and histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac) facilitates chromatin loading of MCM complexes, promoting DNA replication licensing (PubMed:10438470, PubMed:11278932, PubMed:18832067, PubMed:19187766, PubMed:20129055, PubMed:21856198, PubMed:24065767, PubMed:26620551). Acts as a positive regulator of centromeric CENPA assembly: recruited to centromeres and mediates histone acetylation, thereby preventing centromere inactivation mediated by SUV39H1, possibly by increasing histone turnover/exchange (PubMed:27270040). Involved in nucleotide excision repair: phosphorylation by ATR in response to ultraviolet irradiation promotes its localization to DNA damage sites, where it mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites (PubMed:28719581). Acts as an inhibitor of NF-kappa-B independently of its histone acetyltransferase activity (PubMed:16997280). {ECO:0000250|UniProtKB:Q5SVQ0, ECO:0000269|PubMed:10438470, ECO:0000269|PubMed:11278932, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:16997280, ECO:0000269|PubMed:18832067, ECO:0000269|PubMed:19187766, ECO:0000269|PubMed:20129055, ECO:0000269|PubMed:21753189, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:26620551, ECO:0000269|PubMed:27270040, ECO:0000269|PubMed:28719581, ECO:0000269|PubMed:31767635, ECO:0000269|PubMed:31827282}.; FUNCTION: Plays a central role in the maintenance of leukemia stem cells in acute myeloid leukemia (AML) (PubMed:31827282). Acts by mediating acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby facilitating the processivity of RNA polymerase II to maintain the high expression of key genes, such as HOXA9 and HOXA10 that help to sustain the functional properties of leukemia stem cells (PubMed:31827282). {ECO:0000269|PubMed:31827282}. |
| O95425 | SVIL | S938 | ochoa | Supervillin (Archvillin) (p205/p250) | [Isoform 1]: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.; FUNCTION: [Isoform 2]: May be involved in modulation of focal adhesions. Supervillin-mediated down-regulation of focal adhesions involves binding to TRIP6. Plays a role in cytokinesis through KIF14 interaction (By similarity). {ECO:0000250|UniProtKB:O46385}. |
| O95758 | PTBP3 | S169 | ochoa | Polypyrimidine tract-binding protein 3 (Regulator of differentiation 1) (Rod1) | RNA-binding protein that mediates pre-mRNA alternative splicing regulation. Plays a role in the regulation of cell proliferation, differentiation and migration. Positive regulator of EPO-dependent erythropoiesis. Participates in cell differentiation regulation by repressing tissue-specific exons. Promotes FAS exon 6 skipping. Binds RNA, preferentially to both poly(G) and poly(U). {ECO:0000269|PubMed:10207106, ECO:0000269|PubMed:18335065, ECO:0000269|PubMed:19441079, ECO:0000269|PubMed:20937273}. |
| P01241 | GH1 | S134 | psp | Somatotropin (Growth hormone) (GH) (GH-N) (Growth hormone 1) (Pituitary growth hormone) | Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues. |
| P02545 | LMNA | S303 | ochoa | Prelamin-A/C [Cleaved into: Lamin-A/C (70 kDa lamin) (Renal carcinoma antigen NY-REN-32)] | [Lamin-A/C]: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:2188730, PubMed:22431096, PubMed:2344612, PubMed:23666920, PubMed:24741066, PubMed:31434876, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:24741066, PubMed:31548606, PubMed:37788673, PubMed:37832547). Lamin A and C also regulate matrix stiffness by conferring nuclear mechanical properties (PubMed:23990565, PubMed:25127216). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:2188730, PubMed:2344612). Lamin A and C are present in equal amounts in the lamina of mammals (PubMed:10080180, PubMed:10580070, PubMed:10587585, PubMed:10814726, PubMed:11799477, PubMed:12075506, PubMed:12927431, PubMed:15317753, PubMed:18551513, PubMed:18611980, PubMed:22431096, PubMed:23666920, PubMed:31548606). Also invoved in DNA repair: recruited by DNA repair proteins XRCC4 and IFFO1 to the DNA double-strand breaks (DSBs) to prevent chromosome translocation by immobilizing broken DNA ends (PubMed:31548606). Required for normal development of peripheral nervous system and skeletal muscle and for muscle satellite cell proliferation (PubMed:10080180, PubMed:10814726, PubMed:11799477, PubMed:18551513, PubMed:22431096). Required for osteoblastogenesis and bone formation (PubMed:12075506, PubMed:15317753, PubMed:18611980). Also prevents fat infiltration of muscle and bone marrow, helping to maintain the volume and strength of skeletal muscle and bone (PubMed:10587585). Required for cardiac homeostasis (PubMed:10580070, PubMed:12927431, PubMed:18611980, PubMed:23666920). {ECO:0000269|PubMed:10080180, ECO:0000269|PubMed:10580070, ECO:0000269|PubMed:10587585, ECO:0000269|PubMed:10814726, ECO:0000269|PubMed:11799477, ECO:0000269|PubMed:12075506, ECO:0000269|PubMed:12927431, ECO:0000269|PubMed:15317753, ECO:0000269|PubMed:18551513, ECO:0000269|PubMed:18611980, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22431096, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23666920, ECO:0000269|PubMed:23990565, ECO:0000269|PubMed:24741066, ECO:0000269|PubMed:25127216, ECO:0000269|PubMed:31434876, ECO:0000269|PubMed:31548606, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547}.; FUNCTION: [Prelamin-A/C]: Prelamin-A/C can accelerate smooth muscle cell senescence (PubMed:20458013). It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (PubMed:20458013). {ECO:0000269|PubMed:20458013}. |
| P02686 | MBP | S26 | 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}. |
| P05023 | ATP1A1 | S484 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P06733 | ENO1 | S157 | ochoa | Alpha-enolase (EC 4.2.1.11) (2-phospho-D-glycerate hydro-lyase) (C-myc promoter-binding protein) (Enolase 1) (MBP-1) (MPB-1) (Non-neural enolase) (NNE) (Phosphopyruvate hydratase) (Plasminogen-binding protein) | Glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate (PubMed:1369209, PubMed:29775581). In addition to glycolysis, involved in various processes such as growth control, hypoxia tolerance and allergic responses (PubMed:10802057, PubMed:12666133, PubMed:2005901, PubMed:29775581). May also function in the intravascular and pericellular fibrinolytic system due to its ability to serve as a receptor and activator of plasminogen on the cell surface of several cell-types such as leukocytes and neurons (PubMed:12666133). Stimulates immunoglobulin production (PubMed:1369209). {ECO:0000269|PubMed:10802057, ECO:0000269|PubMed:12666133, ECO:0000269|PubMed:1369209, ECO:0000269|PubMed:2005901, ECO:0000269|PubMed:29775581}.; FUNCTION: [Isoform MBP-1]: Binds to the myc promoter and acts as a transcriptional repressor. May be a tumor suppressor. {ECO:0000269|PubMed:10082554}. |
| P06748 | NPM1 | S43 | ochoa | Nucleophosmin (NPM) (Nucleolar phosphoprotein B23) (Nucleolar protein NO38) (Numatrin) | Involved in diverse cellular processes such as ribosome biogenesis, centrosome duplication, protein chaperoning, histone assembly, cell proliferation, and regulation of tumor suppressors p53/TP53 and ARF. Binds ribosome presumably to drive ribosome nuclear export. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. Acts as a chaperonin for the core histones H3, H2B and H4. Stimulates APEX1 endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA but inhibits APEX1 endonuclease activity on AP single-stranded RNA. May exert a control of APEX1 endonuclease activity within nucleoli devoted to repair AP on rDNA and the removal of oxidized rRNA molecules. In concert with BRCA2, regulates centrosome duplication. Regulates centriole duplication: phosphorylation by PLK2 is able to trigger centriole replication. Negatively regulates the activation of EIF2AK2/PKR and suppresses apoptosis through inhibition of EIF2AK2/PKR autophosphorylation. Antagonizes the inhibitory effect of ATF5 on cell proliferation and relieves ATF5-induced G2/M blockade (PubMed:22528486). In complex with MYC enhances the transcription of MYC target genes (PubMed:25956029). May act as chaperonin or cotransporter in the nucleolar localization of transcription termination factor TTF1 (By similarity). {ECO:0000250|UniProtKB:Q61937, ECO:0000269|PubMed:12882984, ECO:0000269|PubMed:16107701, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:18809582, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:22002061, ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:25956029}. |
| P08670 | VIM | S278 | 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}. |
| P0C7T5 | ATXN1L | S216 | ochoa | Ataxin-1-like (Brother of ataxin-1) (Brother of ATXN1) | Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor. Binds to the HEY promoter and might assist, along with NCOR2, RBPJ-mediated repression (PubMed:21475249). Can suppress ATXN1 cytotoxicity in spinocerebellar ataxia type 1 (SCA1). In concert with CIC and ATXN1, involved in brain development (By similarity). {ECO:0000250|UniProtKB:P0C7T6, ECO:0000269|PubMed:21475249}. |
| P10809 | HSPD1 | S398 | 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}. |
| P11055 | MYH3 | S1479 | ochoa | Myosin-3 (Muscle embryonic myosin heavy chain) (Myosin heavy chain 3) (Myosin heavy chain, fast skeletal muscle, embryonic) (SMHCE) | Muscle contraction. |
| P12883 | MYH7 | S1478 | ochoa | Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}. |
| P12956 | XRCC6 | S237 | ochoa | X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Negatively regulates apoptosis by interacting with BAX and sequestering it from the mitochondria (PubMed:15023334). Might have deubiquitination activity, acting on BAX (PubMed:18362350). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:18362350, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. |
| P13533 | MYH6 | S1480 | ochoa | Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) | Muscle contraction. |
| P13569 | CFTR | S790 | psp | Cystic fibrosis transmembrane conductance regulator (CFTR) (ATP-binding cassette sub-family C member 7) (Channel conductance-controlling ATPase) (EC 5.6.1.6) (cAMP-dependent chloride channel) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:12727866, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:29393851, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}. |
| P13796 | LCP1 | S418 | 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}. |
| P14316 | IRF2 | S148 | ochoa | Interferon regulatory factor 2 (IRF-2) | Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) and represses those genes. Also acts as an activator for several genes including H4 and IL7. Constitutively binds to the ISRE promoter to activate IL7. Involved in cell cycle regulation through binding the site II (HiNF-M) promoter region of H4 and activating transcription during cell growth. Antagonizes IRF1 transcriptional activation. {ECO:0000269|PubMed:12738767, ECO:0000269|PubMed:15226432, ECO:0000269|PubMed:18514056, ECO:0000269|PubMed:9540062}. |
| P14618 | PKM | S205 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P15924 | DSP | S1658 | ochoa | Desmoplakin (DP) (250/210 kDa paraneoplastic pemphigus antigen) | Major high molecular weight protein of desmosomes. Regulates profibrotic gene expression in cardiomyocytes via activation of the MAPK14/p38 MAPK signaling cascade and increase in TGFB1 protein abundance (By similarity). {ECO:0000250|UniProtKB:F1LMV6}. |
| P16066 | NPR1 | S538 | psp | Atrial natriuretic peptide receptor 1 (EC 4.6.1.2) (Atrial natriuretic peptide receptor type A) (ANP-A) (ANPR-A) (NPR-A) (Guanylate cyclase A) (GC-A) | Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis (PubMed:39543315). Plays an essential role in the regulation of endothelial cell senescence and vascular aging (PubMed:36016499). Upon activation by ANP or BNP, stimulates the production of cyclic guanosine monophosphate (cGMP) that promotes vascular tone and volume homeostasis by activation of protein kinase cGMP-dependent 1/PRKG1 and subsequently PRKAA1, thereby controlling blood pressure and maintaining cardiovascular homeostasis (PubMed:36016499). {ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:36016499, ECO:0000269|PubMed:39543315}. |
| P16615 | ATP2A2 | S555 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) | This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:12542527, PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}.; FUNCTION: [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. {ECO:0000250|UniProtKB:O55143}. |
| P16885 | PLCG2 | S1236 | 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}. |
| P16949 | STMN1 | S63 | ochoa|psp | Stathmin (Leukemia-associated phosphoprotein p18) (Metablastin) (Oncoprotein 18) (Op18) (Phosphoprotein p19) (pp19) (Prosolin) (Protein Pr22) (pp17) | Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Phosphorylation at Ser-16 may be required for axon formation during neurogenesis. Involved in the control of the learned and innate fear (By similarity). {ECO:0000250}. |
| P18146 | EGR1 | S301 | psp | Early growth response protein 1 (EGR-1) (AT225) (Nerve growth factor-induced protein A) (NGFI-A) (Transcription factor ETR103) (Transcription factor Zif268) (Zinc finger protein 225) (Zinc finger protein Krox-24) | Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, PubMed:25999311). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (By similarity). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (By similarity). {ECO:0000250|UniProtKB:P08046, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:25999311}. |
| P22090 | RPS4Y1 | S32 | ochoa | Small ribosomal subunit protein eS4, Y isoform 1 (40S ribosomal protein S4) | None |
| P22415 | USF1 | S262 | psp | Upstream stimulatory factor 1 (Class B basic helix-loop-helix protein 11) (bHLHb11) (Major late transcription factor 1) | Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. |
| P23327 | HRC | S96 | ochoa|psp | Sarcoplasmic reticulum histidine-rich calcium-binding protein | May play a role in the regulation of calcium sequestration or release in the SR of skeletal and cardiac muscle. |
| P23497 | SP100 | S223 | ochoa | Nuclear autoantigen Sp-100 (Nuclear dot-associated Sp100 protein) (Speckled 100 kDa) | Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation. {ECO:0000269|PubMed:11909962, ECO:0000269|PubMed:14647468, ECO:0000269|PubMed:15247905, ECO:0000269|PubMed:15592518, ECO:0000269|PubMed:15767676, ECO:0000269|PubMed:16177824, ECO:0000269|PubMed:17245429, ECO:0000269|PubMed:21274506, ECO:0000269|PubMed:21880768}. |
| P29728 | OAS2 | S73 | ochoa | 2'-5'-oligoadenylate synthase 2 ((2-5')oligo(A) synthase 2) (2-5A synthase 2) (EC 2.7.7.84) (p69 OAS / p71 OAS) (p69OAS / p71OAS) | Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:10464285, PubMed:9880569). Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation (PubMed:10464285, PubMed:11682059, PubMed:9880569). Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:10464285, PubMed:9880569). Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL (PubMed:21142819). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation (PubMed:21142819). May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates (By similarity). Non-infected lobules would not be affected, allowing efficient pup feeding during infection (By similarity). {ECO:0000250|UniProtKB:E9Q9A9, ECO:0000269|PubMed:10464285, ECO:0000269|PubMed:11682059, ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:9880569, ECO:0000303|PubMed:21142819}. |
| P35579 | MYH9 | S1915 | 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 | S998 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P38398 | BRCA1 | S434 | 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}. |
| P39748 | FEN1 | S210 | ochoa | Flap endonuclease 1 (FEN-1) (EC 3.1.-.-) (DNase IV) (Flap structure-specific endonuclease 1) (Maturation factor 1) (MF1) (hFEN-1) | Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}. |
| P42858 | HTT | S2382 | ochoa | Huntingtin (Huntington disease protein) (HD protein) [Cleaved into: Huntingtin, myristoylated N-terminal fragment] | [Huntingtin]: May play a role in microtubule-mediated transport or vesicle function.; FUNCTION: [Huntingtin, myristoylated N-terminal fragment]: Promotes the formation of autophagic vesicles. {ECO:0000269|PubMed:24459296}. |
| P46060 | RANGAP1 | S24 | ochoa | Ran GTPase-activating protein 1 (RanGAP1) | GTPase activator for RAN (PubMed:16428860, PubMed:8146159, PubMed:8896452). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:27160050, PubMed:8896452). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). {ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}. |
| P46934 | NEDD4 | S888 | ochoa | E3 ubiquitin-protein ligase NEDD4 (EC 2.3.2.26) (Cell proliferation-inducing gene 53 protein) (HECT-type E3 ubiquitin transferase NEDD4) (Neural precursor cell expressed developmentally down-regulated protein 4) (NEDD-4) | 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. Specifically ubiquitinates 'Lys-63' in target proteins (PubMed:19920177, PubMed:21399620, PubMed:23644597). Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes (By similarity). Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes (PubMed:21765395). Promotes ubiquitination of RAPGEF2 (PubMed:11598133). According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD (By similarity). Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development (By similarity). Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 (PubMed:20086093). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Ubiquitinates DAZAP2, leading to its proteasomal degradation (PubMed:11342538). Ubiquitinates POLR2A (PubMed:19920177). Functions as a platform to recruit USP13 to form an NEDD4-USP13 deubiquitination complex that plays a critical role in cleaving the 'Lys-48'-linked ubiquitin chains of VPS34 and then stabilizing VPS34, thus promoting the formation of autophagosomes (PubMed:32101753). {ECO:0000250|UniProtKB:P46935, ECO:0000269|PubMed:11342538, ECO:0000269|PubMed:11598133, ECO:0000269|PubMed:17218260, ECO:0000269|PubMed:18562292, ECO:0000269|PubMed:21399620, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:23644597, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:32101753}.; FUNCTION: (Microbial infection) Involved in the ubiquitination of Ebola virus protein VP40 which plays a role in viral budding. {ECO:0000269|PubMed:12559917, ECO:0000269|PubMed:18305167}. |
| P46939 | UTRN | S2482 | ochoa | Utrophin (Dystrophin-related protein 1) (DRP-1) | May play a role in anchoring the cytoskeleton to the plasma membrane. {ECO:0000250}. |
| P49642 | PRIM1 | S310 | ochoa | DNA primase small subunit (EC 2.7.7.102) (DNA primase 49 kDa subunit) (p49) | Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex - primosome/replisome) which play an essential role in the initiation of DNA synthesis (PubMed:17893144, PubMed:24043831, PubMed:25550159, PubMed:26975377, PubMed:31479243, PubMed:33060134, PubMed:9268648, PubMed:9705292). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:17893144). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:17893144). Synthesizes 9-mer RNA primers (also known as the 'unit length' RNA primers). Incorporates only ribonucleotides in the presence of ribo- and deoxy-nucleotide triphosphates (rNTPs, dNTPs) (PubMed:26975377). Requires template thymine or cytidine to start the RNA primer synthesis, with an adenine or guanine at its 5'-end (PubMed:25550159, PubMed:26975377). Binds single stranded DNA (By similarity). {ECO:0000250|UniProtKB:P09884, ECO:0000250|UniProtKB:P20664, ECO:0000269|PubMed:17893144, ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377, ECO:0000269|PubMed:33060134, ECO:0000269|PubMed:9268648, ECO:0000269|PubMed:9705292}. |
| P49757 | NUMB | S295 | ochoa|psp | Protein numb homolog (h-Numb) (Protein S171) | Regulates clathrin-mediated receptor endocytosis (PubMed:18657069). Plays a role in the process of neurogenesis (By similarity). Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate (By similarity). Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity (By similarity). May also mediate local repair of brain ventricular wall damage (By similarity). {ECO:0000250|UniProtKB:Q9QZS3, ECO:0000269|PubMed:18657069}. |
| P49841 | GSK3B | S147 | psp | Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1) | Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:11430833, PubMed:12554650, PubMed:14690523, PubMed:16484495, PubMed:1846781, PubMed:20937854, PubMed:9072970). Requires primed phosphorylation of the majority of its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:8397507). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:8397507). Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (PubMed:14690523). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (By similarity). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed:22514281). Phosphorylates SNAI1, leading to its ubiquitination and proteasomal degradation (PubMed:15448698, PubMed:15647282, PubMed:25827072, PubMed:29059170). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (By similarity). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110). Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2 complex component RICTOR at 'Ser-1235' in response to endoplasmic stress, inhibiting mTORC2 (PubMed:21343617). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (By similarity). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20067585, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:29059170, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}. |
| P52272 | HNRNPM | S575 | ochoa | Heterogeneous nuclear ribonucleoprotein M (hnRNP M) | Pre-mRNA binding protein in vivo, binds avidly to poly(G) and poly(U) RNA homopolymers in vitro. Involved in splicing. Acts as a receptor for carcinoembryonic antigen in Kupffer cells, may initiate a series of signaling events leading to tyrosine phosphorylation of proteins and induction of IL-1 alpha, IL-6, IL-10 and tumor necrosis factor alpha cytokines. |
| P53621 | COPA | S434 | ochoa | 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. |
| P54132 | BLM | S602 | ochoa | RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) | ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}. |
| P58004 | SESN2 | S73 | psp | Sestrin-2 (EC 1.11.1.-) (Hypoxia-induced gene) | Functions as an intracellular leucine sensor that negatively regulates the mTORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents mTORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100, PubMed:35831510, PubMed:36528027). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via mTORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821). {ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:19113821, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24947615, ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190, ECO:0000269|PubMed:26612684, ECO:0000269|PubMed:35114100, ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027}. |
| P60228 | EIF3E | S412 | ochoa | Eukaryotic translation initiation factor 3 subunit E (eIF3e) (Eukaryotic translation initiation factor 3 subunit 6) (Viral integration site protein INT-6 homolog) (eIF-3 p48) | 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). Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway (PubMed:17468741). May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins (PubMed:17310990, PubMed:17324924). {ECO:0000255|HAMAP-Rule:MF_03004, ECO:0000269|PubMed:17310990, ECO:0000269|PubMed:17324924, ECO:0000269|PubMed:17468741, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| P62314 | SNRPD1 | S73 | ochoa | Small nuclear ribonucleoprotein Sm D1 (Sm-D1) (Sm-D autoantigen) (snRNP core protein D1) | Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:23333303, PubMed:25555158, PubMed:26912367, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:32494006). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:26912367, PubMed:28076346, PubMed:28502770, PubMed:28781166). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077). May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through non-specific electrostatic contacts with RNA (PubMed:23333303). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:15146077, ECO:0000269|PubMed:18984161, ECO:0000269|PubMed:19325628, ECO:0000269|PubMed:23333303, ECO:0000269|PubMed:25555158, ECO:0000269|PubMed:26912367, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:32494006, ECO:0000305|PubMed:23333303}. |
| P62701 | RPS4X | S32 | ochoa | Small ribosomal subunit protein eS4, X isoform (40S ribosomal protein S4) (SCR10) (Single copy abundant mRNA protein) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P62820 | RAB1A | S114 | ochoa | Ras-related protein Rab-1A (EC 3.6.5.2) (YPT1-related protein) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:20639577, PubMed:20861236, PubMed:21303926, PubMed:22939626). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:20639577, PubMed:20861236, PubMed:21303926, PubMed:22939626). RAB1A regulates vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment and on to the cell surface, and plays a role in IL-8 and growth hormone secretion (PubMed:21303926). Required to modulate the compacted morphology of the Golgi (PubMed:26209634). Regulates the level of CASR present at the cell membrane (PubMed:20861236). Plays a role in cell adhesion and cell migration, via its role in protein trafficking (PubMed:20639577). Plays a role in autophagosome assembly and cellular defense reactions against pathogenic bacteria (PubMed:22939626). Plays a role in microtubule-dependent protein transport by early endosomes and in anterograde melanosome transport (By similarity). {ECO:0000250|UniProtKB:P62821, ECO:0000269|PubMed:20639577, ECO:0000269|PubMed:20861236, ECO:0000269|PubMed:21303926, ECO:0000269|PubMed:22939626, ECO:0000269|PubMed:26209634}. |
| P63104 | YWHAZ | S99 | 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}. |
| P68104 | EEF1A1 | S21 | ochoa|psp | Elongation factor 1-alpha 1 (EF-1-alpha-1) (EC 3.6.5.-) (Elongation factor Tu) (EF-Tu) (Eukaryotic elongation factor 1 A-1) (eEF1A-1) (Leukocyte receptor cluster member 7) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623, PubMed:36638793). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:26593721, PubMed:26651998, PubMed:36123449, PubMed:36264623). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (PubMed:17177976). Also plays a role in cytoskeleton organization by promoting actin bundling (By similarity). {ECO:0000250|UniProtKB:P68105, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:26593721, ECO:0000269|PubMed:26651998, ECO:0000269|PubMed:36123449, ECO:0000269|PubMed:36264623, ECO:0000269|PubMed:36638793}.; FUNCTION: (Microbial infection) Required for the translation of viral proteins and viral replication during human coronavirus SARS-CoV-2 infection. {ECO:0000269|PubMed:33495306}. |
| P78527 | PRKDC | S314 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P78527 | PRKDC | S3021 | ochoa | DNA-dependent protein kinase catalytic subunit (DNA-PK catalytic subunit) (DNA-PKcs) (EC 2.7.11.1) (DNPK1) (Ser-473 kinase) (S473K) (p460) | Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234). Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:33854234, PubMed:34352203). Must be bound to DNA to express its catalytic properties (PubMed:11955432). Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C) (PubMed:11955432). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326, PubMed:33854234). Acts as a scaffold protein to aid the localization of DNA repair proteins to the site of damage (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion (By similarity). Also involved in modulation of transcription (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174). Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174). Recognizes the substrate consensus sequence [ST]-Q (PubMed:11955432, PubMed:12649176, PubMed:14734805, PubMed:15574326). Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (PubMed:14627815, PubMed:16046194). Phosphorylates ASF1A, DCLRE1C, c-Abl/ABL1, histone H1, HSPCA, c-jun/JUN, p53/TP53, PARP1, POU2F1, DHX9, FH, SRF, NHEJ1/XLF, XRCC1, XRCC4, XRCC5, XRCC6, WRN, MYC and RFA2 (PubMed:10026262, PubMed:10467406, PubMed:11889123, PubMed:12509254, PubMed:14599745, PubMed:14612514, PubMed:14704337, PubMed:15177042, PubMed:1597196, PubMed:16397295, PubMed:18644470, PubMed:2247066, PubMed:2507541, PubMed:26237645, PubMed:26666690, PubMed:28712728, PubMed:29478807, PubMed:30247612, PubMed:8407951, PubMed:8464713, PubMed:9139719, PubMed:9362500). Can phosphorylate C1D not only in the presence of linear DNA but also in the presence of supercoiled DNA (PubMed:9679063). Ability to phosphorylate p53/TP53 in the presence of supercoiled DNA is dependent on C1D (PubMed:9363941). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of 'Ser-473' of protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), promoting their activation (PubMed:15262962). Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism (By similarity). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Also regulates the cGAS-STING pathway by catalyzing phosphorylation of CGAS, thereby impairing CGAS oligomerization and activation (PubMed:33273464). Also regulates the cGAS-STING pathway by mediating phosphorylation of PARP1 (PubMed:35460603). {ECO:0000250|UniProtKB:P97313, ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:10467406, ECO:0000269|PubMed:11889123, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12509254, ECO:0000269|PubMed:12649176, ECO:0000269|PubMed:14599745, ECO:0000269|PubMed:14612514, ECO:0000269|PubMed:14627815, ECO:0000269|PubMed:14704337, ECO:0000269|PubMed:14734805, ECO:0000269|PubMed:15177042, ECO:0000269|PubMed:15262962, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:1597196, ECO:0000269|PubMed:16046194, ECO:0000269|PubMed:16397295, ECO:0000269|PubMed:18644470, ECO:0000269|PubMed:2247066, ECO:0000269|PubMed:2507541, ECO:0000269|PubMed:26237645, ECO:0000269|PubMed:26666690, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:29478807, ECO:0000269|PubMed:30247612, ECO:0000269|PubMed:32103174, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33854234, ECO:0000269|PubMed:34352203, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:8407951, ECO:0000269|PubMed:8464713, ECO:0000269|PubMed:9139719, ECO:0000269|PubMed:9362500, ECO:0000269|PubMed:9363941, ECO:0000269|PubMed:9679063}. |
| P81274 | GPSM2 | S408 | ochoa|psp | G-protein-signaling modulator 2 (Mosaic protein LGN) | Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202, PubMed:21816348). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). Plays a role in metaphase spindle orientation (PubMed:22327364). Also plays an important role in asymmetric cell divisions (PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their activity (By similarity). {ECO:0000250|UniProtKB:Q8VDU0, ECO:0000269|PubMed:11781568, ECO:0000269|PubMed:15632202, ECO:0000269|PubMed:21816348, ECO:0000269|PubMed:22327364}. |
| P82979 | SARNP | S168 | ochoa | SAP domain-containing ribonucleoprotein (Cytokine-induced protein of 29 kDa) (Nuclear protein Hcc-1) (Proliferation-associated cytokine-inducible protein CIP29) | Binds both single-stranded and double-stranded DNA with higher affinity for the single-stranded form. Specifically binds to scaffold/matrix attachment region DNA. Also binds single-stranded RNA. Enhances RNA unwinding activity of DDX39A. May participate in important transcriptional or translational control of cell growth, metabolism and carcinogenesis. Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15338056, PubMed:17196963, PubMed:20844015). The TREX complex is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15338056, PubMed:17196963, PubMed:20844015). Associates with DDX39B, which facilitates RNA binding of DDX39B and likely plays a role in mRNA export (PubMed:37578863). {ECO:0000269|PubMed:15338056, ECO:0000269|PubMed:17196963, ECO:0000269|PubMed:20844015, ECO:0000269|PubMed:37578863}. |
| P83111 | LACTB | S207 | ochoa | Serine beta-lactamase-like protein LACTB, mitochondrial (EC 3.4.-.-) | Mitochondrial serine protease that acts as a regulator of mitochondrial lipid metabolism (PubMed:28329758). Acts by decreasing protein levels of PISD, a mitochondrial enzyme that converts phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn), thereby affecting mitochondrial lipid metabolism (PubMed:28329758). It is unclear whether it acts directly by mediating proteolysis of PISD or by mediating proteolysis of another lipid metabolism protein (PubMed:28329758). Acts as a tumor suppressor that has the ability to inhibit proliferation of multiple types of breast cancer cells: probably by promoting decreased levels of PISD, thereby affecting mitochondrial lipid metabolism (PubMed:28329758). {ECO:0000269|PubMed:28329758}. |
| P98171 | ARHGAP4 | S498 | ochoa | Rho GTPase-activating protein 4 (Rho-GAP hematopoietic protein C1) (Rho-type GTPase-activating protein 4) (p115) | Inhibitory effect on stress fiber organization. May down-regulate Rho-like GTPase in hematopoietic cells. |
| Q02224 | CENPE | S2083 | ochoa | Centromere-associated protein E (Centromere protein E) (CENP-E) (Kinesin-7) (Kinesin-related protein CENPE) | Microtubule plus-end-directed kinetochore motor which plays an important role in chromosome congression, microtubule-kinetochore conjugation and spindle assembly checkpoint activation. Drives chromosome congression (alignment of chromosomes at the spindle equator resulting in the formation of the metaphase plate) by mediating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the establishment and maintenance of connections between kinetochores and spindle microtubules (PubMed:23891108, PubMed:25395579, PubMed:7889940). The transport of pole-proximal chromosomes towards the spindle equator is favored by microtubule tracks that are detyrosinated (PubMed:25908662). Acts as a processive bi-directional tracker of dynamic microtubule tips; after chromosomes have congressed, continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends (PubMed:23955301). Suppresses chromosome congression in NDC80-depleted cells and contributes positively to congression only when microtubules are stabilized (PubMed:25743205). Plays an important role in the formation of stable attachments between kinetochores and spindle microtubules (PubMed:17535814) The stabilization of kinetochore-microtubule attachment also requires CENPE-dependent localization of other proteins to the kinetochore including BUB1B, MAD1 and MAD2. Plays a role in spindle assembly checkpoint activation (SAC) via its interaction with BUB1B resulting in the activation of its kinase activity, which is important for activating SAC. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss (By similarity). {ECO:0000250|UniProtKB:Q6RT24, ECO:0000269|PubMed:17535814, ECO:0000269|PubMed:23891108, ECO:0000269|PubMed:23955301, ECO:0000269|PubMed:25395579, ECO:0000269|PubMed:25743205, ECO:0000269|PubMed:25908662, ECO:0000269|PubMed:7889940}. |
| Q02487 | DSC2 | S828 | ochoa | Desmocollin-2 (Cadherin family member 2) (Desmocollin-3) (Desmosomal glycoprotein II) (Desmosomal glycoprotein III) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:33596089). Promotes timely incorporation of DSG2 into desmosome intercellular junctions and promotes interaction of desmosome cell junctions with intermediate filament cytokeratin, via modulation of DSP phosphorylation (PubMed:33596089). Plays an important role in desmosome-mediated maintenance of intestinal epithelial cell intercellular adhesion strength and barrier function (PubMed:33596089). Positively regulates wound healing of intestinal mucosa via promotion of epithelial cell migration, and also plays a role in mechanotransduction of force between intestinal epithelial cells and extracellular matrix (PubMed:31967937). May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. May promote p38MAPK signaling activation that facilitates keratinocyte migration (By similarity). {ECO:0000250|UniProtKB:P55292, ECO:0000269|PubMed:31967937, ECO:0000269|PubMed:33596089}. |
| Q02790 | FKBP4 | S350 | ochoa | Peptidyl-prolyl cis-trans isomerase FKBP4 (PPIase FKBP4) (EC 5.2.1.8) (51 kDa FK506-binding protein) (FKBP51) (52 kDa FK506-binding protein) (52 kDa FKBP) (FKBP-52) (59 kDa immunophilin) (p59) (FK506-binding protein 4) (FKBP-4) (FKBP59) (HSP-binding immunophilin) (HBI) (Immunophilin FKBP52) (Rotamase) [Cleaved into: Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed] | Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Also acts as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}. |
| Q02818 | NUCB1 | S369 | ochoa | Nucleobindin-1 (CALNUC) | Major calcium-binding protein of the Golgi which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates alpha subunits of guanine nucleotide-binding proteins (G proteins) (By similarity). {ECO:0000250|UniProtKB:Q0P569, ECO:0000250|UniProtKB:Q63083}. |
| Q03252 | LMNB2 | S318 | ochoa | Lamin-B2 | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:33033404). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:33033404). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:33033404). {ECO:0000269|PubMed:33033404}. |
| Q05639 | EEF1A2 | S21 | ochoa|psp | Elongation factor 1-alpha 2 (EF-1-alpha-2) (EC 3.6.5.-) (Eukaryotic elongation factor 1 A-2) (eEF1A-2) (Statin-S1) | Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis. Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (By similarity). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (By similarity). {ECO:0000250|UniProtKB:P68104, ECO:0000250|UniProtKB:Q71V39}. |
| Q05BQ5 | MBTD1 | S309 | ochoa | MBT domain-containing protein 1 | Chromatin reader component of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A (PubMed:27153538, PubMed:32209463). The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR) (PubMed:27153538). MBTD1 specifically recognizes and binds monomethylated and dimethylated 'Lys-20' on histone H4 (H4K20me1 and H4K20me2, respectively) (PubMed:19841675, PubMed:27153538, PubMed:32209463). In the NuA4 complex, MBTD1 promotes recruitment of the complex to H4K20me marks by competing with TP53BP1 for binding to H4K20me (PubMed:27153538). Following recruitment to H4K20me at DNA breaks, the NuA4 complex catalyzes acetylation of 'Lys-15' on histone H2A (H2AK15), blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks, thereby promoting homologous recombination (HR) (PubMed:27153538). {ECO:0000269|PubMed:19841675, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:32209463}. |
| Q06787 | FMR1 | S599 | ochoa | Fragile X messenger ribonucleoprotein 1 (Fragile X messenger ribonucleoprotein) (FMRP) (Protein FMR-1) | Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of target mRNAs (PubMed:12417522, PubMed:16631377, PubMed:18653529, PubMed:19166269, PubMed:23235829, PubMed:25464849). Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (PubMed:12417522, PubMed:30765518, PubMed:31439799). Plays a role in the alternative splicing of its own mRNA (PubMed:18653529). Stabilizes the scaffolding postsynaptic density protein DLG4/PSD-95 and the myelin basic protein (MBP) mRNAs in hippocampal neurons and glial cells, respectively; this stabilization is further increased in response to metabotropic glutamate receptor (mGluR) stimulation (By similarity). Plays a role in selective delivery of a subset of dendritic mRNAs to synaptic sites in response to mGluR activation in a kinesin-dependent manner (By similarity). Undergoes liquid-liquid phase separation following phosphorylation and interaction with CAPRIN1, promoting formation of cytoplasmic ribonucleoprotein granules that concentrate mRNAs with factors that inhibit translation and mediate deadenylation of target mRNAs (PubMed:31439799). Acts as a repressor of mRNA translation in synaptic regions by mediating formation of neuronal ribonucleoprotein granules and promoting recruitmtent of EIF4EBP2 (PubMed:30765518). Plays a role as a repressor of mRNA translation during the transport of dendritic mRNAs to postsynaptic dendritic spines (PubMed:11157796, PubMed:11532944, PubMed:12594214, PubMed:23235829). Component of the CYFIP1-EIF4E-FMR1 complex which blocks cap-dependent mRNA translation initiation (By similarity). Represses mRNA translation by stalling ribosomal translocation during elongation (By similarity). Reports are contradictory with regards to its ability to mediate translation inhibition of MBP mRNA in oligodendrocytes (PubMed:23891804). Also involved in the recruitment of the RNA helicase MOV10 to a subset of mRNAs and hence regulates microRNA (miRNA)-mediated translational repression by AGO2 (PubMed:14703574, PubMed:17057366, PubMed:25464849). Facilitates the assembly of miRNAs on specific target mRNAs (PubMed:17057366). Also plays a role as an activator of mRNA translation of a subset of dendritic mRNAs at synapses (PubMed:19097999, PubMed:19166269). In response to mGluR stimulation, FMR1-target mRNAs are rapidly derepressed, allowing for local translation at synapses (By similarity). Binds to a large subset of dendritic mRNAs that encode a myriad of proteins involved in pre- and postsynaptic functions (PubMed:11157796, PubMed:11719189, PubMed:12594214, PubMed:17417632, PubMed:23235829, PubMed:24448548, PubMed:7692601). Binds to 5'-ACU[GU]-3' and/or 5'-[AU]GGA-3' RNA consensus sequences within mRNA targets, mainly at coding sequence (CDS) and 3'-untranslated region (UTR) and less frequently at 5'-UTR (PubMed:23235829). Binds to intramolecular G-quadruplex structures in the 5'- or 3'-UTRs of mRNA targets (PubMed:11719189, PubMed:18579868, PubMed:25464849, PubMed:25692235). Binds to G-quadruplex structures in the 3'-UTR of its own mRNA (PubMed:11532944, PubMed:12594214, PubMed:15282548, PubMed:18653529, PubMed:7692601). Also binds to RNA ligands harboring a kissing complex (kc) structure; this binding may mediate the association of FMR1 with polyribosomes (PubMed:15805463). Binds mRNAs containing U-rich target sequences (PubMed:12927206). Binds to a triple stem-loop RNA structure, called Sod1 stem loop interacting with FMRP (SoSLIP), in the 5'-UTR region of superoxide dismutase SOD1 mRNA (PubMed:19166269). Binds to the dendritic, small non-coding brain cytoplasmic RNA 1 (BC1); which may increase the association of the CYFIP1-EIF4E-FMR1 complex to FMR1 target mRNAs at synapses (By similarity). Plays a role in mRNA nuclear export (PubMed:31753916). Specifically recognizes and binds a subset of N6-methyladenosine (m6A)-containing mRNAs, promoting their nuclear export in a XPO1/CRM1-dependent manner (PubMed:31753916). Together with export factor NXF2, is involved in the regulation of the NXF1 mRNA stability in neurons (By similarity). Associates with export factor NXF1 mRNA-containing ribonucleoprotein particles (mRNPs) in a NXF2-dependent manner (By similarity). Binds to a subset of miRNAs in the brain (PubMed:14703574, PubMed:17057366). May associate with nascent transcripts in a nuclear protein NXF1-dependent manner (PubMed:18936162). In vitro, binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:12950170, PubMed:15381419, PubMed:7688265, PubMed:7781595, PubMed:8156595). Moreover, plays a role in the modulation of the sodium-activated potassium channel KCNT1 gating activity (PubMed:20512134). Negatively regulates the voltage-dependent calcium channel current density in soma and presynaptic terminals of dorsal root ganglion (DRG) neurons, and hence regulates synaptic vesicle exocytosis (By similarity). Modulates the voltage-dependent calcium channel CACNA1B expression at the plasma membrane by targeting the channels for proteasomal degradation (By similarity). Plays a role in regulation of MAP1B-dependent microtubule dynamics during neuronal development (By similarity). Has been shown to play a translation-independent role in the modulation of presynaptic action potential (AP) duration and neurotransmitter release via large-conductance calcium-activated potassium (BK) channels in hippocampal and cortical excitatory neurons (PubMed:25561520). May be involved in the control of DNA damage response (DDR) mechanisms through the regulation of ATR-dependent signaling pathways such as histone H2AX/H2A.x and BRCA1 phosphorylations (PubMed:24813610). Forms a cytoplasmic messenger ribonucleoprotein (mRNP) network by packaging long mRNAs, serving as a scaffold that recruits proteins and signaling molecules. This network facilitates signaling reactions by maintaining proximity between kinases and substrates (PubMed:39106863). {ECO:0000250|UniProtKB:P35922, ECO:0000250|UniProtKB:Q80WE1, ECO:0000269|PubMed:11157796, ECO:0000269|PubMed:11532944, ECO:0000269|PubMed:11719189, ECO:0000269|PubMed:12417522, ECO:0000269|PubMed:12594214, ECO:0000269|PubMed:12927206, ECO:0000269|PubMed:12950170, ECO:0000269|PubMed:14703574, ECO:0000269|PubMed:15282548, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15805463, ECO:0000269|PubMed:16631377, ECO:0000269|PubMed:17057366, ECO:0000269|PubMed:17417632, ECO:0000269|PubMed:18579868, ECO:0000269|PubMed:18653529, ECO:0000269|PubMed:18936162, ECO:0000269|PubMed:19097999, ECO:0000269|PubMed:19166269, ECO:0000269|PubMed:20512134, ECO:0000269|PubMed:23235829, ECO:0000269|PubMed:23891804, ECO:0000269|PubMed:24448548, ECO:0000269|PubMed:24813610, ECO:0000269|PubMed:25464849, ECO:0000269|PubMed:25561520, ECO:0000269|PubMed:25692235, ECO:0000269|PubMed:30765518, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:31753916, ECO:0000269|PubMed:39106863, ECO:0000269|PubMed:7688265, ECO:0000269|PubMed:7692601, ECO:0000269|PubMed:7781595, ECO:0000269|PubMed:8156595}.; FUNCTION: [Isoform 10]: Binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). {ECO:0000269|PubMed:24204304}.; FUNCTION: [Isoform 6]: Binds to RNA homomer; preferentially on poly(G) and to a lesser extent on poly(U), but not on poly(A) or poly(C) (PubMed:24204304). May bind to RNA in Cajal bodies (PubMed:24204304). {ECO:0000269|PubMed:24204304}.; FUNCTION: (Microbial infection) Acts as a positive regulator of influenza A virus (IAV) replication. Required for the assembly and nuclear export of the viral ribonucleoprotein (vRNP) components. {ECO:0000269|PubMed:24514761}. |
| Q08378 | GOLGA3 | S467 | ochoa | Golgin subfamily A member 3 (Golgi complex-associated protein of 170 kDa) (GCP170) (Golgin-160) | Golgi auto-antigen; probably involved in maintaining Golgi structure. |
| Q0ZGT2 | NEXN | S442 | ochoa | Nexilin (F-actin-binding protein) (Nelin) | Involved in regulating cell migration through association with the actin cytoskeleton. Has an essential role in the maintenance of Z line and sarcomere integrity. {ECO:0000269|PubMed:12053183, ECO:0000269|PubMed:15823560, ECO:0000269|PubMed:19881492}. |
| Q12986 | NFX1 | S980 | ochoa | Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) | Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}. |
| Q13136 | PPFIA1 | S448 | ochoa | Liprin-alpha-1 (LAR-interacting protein 1) (LIP-1) (Protein tyrosine phosphatase receptor type f polypeptide-interacting protein alpha-1) (PTPRF-interacting protein alpha-1) | May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:7796809}. |
| Q13426 | XRCC4 | S237 | ochoa | DNA repair protein XRCC4 (hXRCC4) (X-ray repair cross-complementing protein 4) [Cleaved into: Protein XRCC4, C-terminus (XRCC4/C)] | [DNA repair protein XRCC4]: DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:16412978, PubMed:17124166, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25742519, PubMed:25934149, PubMed:26100018, PubMed:26774286, PubMed:8548796). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014, PubMed:9242410). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831, PubMed:9242410). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785). {ECO:0000269|PubMed:10757784, ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:15385968, ECO:0000269|PubMed:16412978, ECO:0000269|PubMed:17124166, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:19837014, ECO:0000269|PubMed:20852255, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:21982441, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25597996, ECO:0000269|PubMed:25742519, ECO:0000269|PubMed:25934149, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28453785, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:8548796, ECO:0000269|PubMed:9242410}.; FUNCTION: [Protein XRCC4, C-terminus]: Acts as an activator of the phospholipid scramblase activity of XKR4 (PubMed:33725486). This form, which is generated upon caspase-3 (CASP3) cleavage, translocates into the cytoplasm and interacts with XKR4, thereby promoting phosphatidylserine scramblase activity of XKR4 and leading to phosphatidylserine exposure on apoptotic cell surface (PubMed:33725486). {ECO:0000269|PubMed:33725486}. |
| Q13506 | NAB1 | S356 | ochoa | NGFI-A-binding protein 1 (EGR-1-binding protein 1) (Transcriptional regulatory protein p54) | Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2. {ECO:0000250}. |
| Q13813 | SPTAN1 | S484 | 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. |
| Q14008 | CKAP5 | S845 | ochoa | Cytoskeleton-associated protein 5 (Colonic and hepatic tumor overexpressed gene protein) (Ch-TOG) | Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as a processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:23532825). Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments (PubMed:27156448). {ECO:0000269|PubMed:12569123, ECO:0000269|PubMed:18809577, ECO:0000269|PubMed:21297582, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23532825, ECO:0000269|PubMed:27156448, ECO:0000269|PubMed:9570755}. |
| Q14160 | SCRIB | S1508 | ochoa|psp | Protein scribble homolog (Scribble) (hScrib) (Protein LAP4) | Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:16965391, PubMed:18641685, PubMed:18716323, PubMed:19041750, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Plays a role in cell directional movement, cell orientation, cell sheet organization and Golgi complex polarization at the cell migration front (By similarity). Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May regulate cell invasion via MAPK-mediated cell migration and adhesion (PubMed:18641685, PubMed:18716323). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity (PubMed:15182672). {ECO:0000250|UniProtKB:A0A8P0N4K0, ECO:0000250|UniProtKB:Q80U72, ECO:0000269|PubMed:15182672, ECO:0000269|PubMed:16344308, ECO:0000269|PubMed:16965391, ECO:0000269|PubMed:18641685, ECO:0000269|PubMed:18716323, ECO:0000269|PubMed:19041750, ECO:0000269|PubMed:27380321}. |
| Q14676 | MDC1 | S1797 | ochoa | Mediator of DNA damage checkpoint protein 1 (Nuclear factor with BRCT domains 1) | Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}. |
| Q14684 | RRP1B | S630 | ochoa | Ribosomal RNA processing protein 1 homolog B (RRP1-like protein B) | Positively regulates DNA damage-induced apoptosis by acting as a transcriptional coactivator of proapoptotic target genes of the transcriptional activator E2F1 (PubMed:20040599). Likely to play a role in ribosome biogenesis by targeting serine/threonine protein phosphatase PP1 to the nucleolus (PubMed:20926688). Involved in regulation of mRNA splicing (By similarity). Inhibits SIPA1 GTPase activity (By similarity). Involved in regulating expression of extracellular matrix genes (By similarity). Associates with chromatin and may play a role in modulating chromatin structure (PubMed:19710015). {ECO:0000250|UniProtKB:Q91YK2, ECO:0000269|PubMed:19710015, ECO:0000269|PubMed:20040599, ECO:0000269|PubMed:20926688}.; FUNCTION: (Microbial infection) Following influenza A virus (IAV) infection, promotes viral mRNA transcription by facilitating the binding of IAV RNA-directed RNA polymerase to capped mRNA. {ECO:0000269|PubMed:26311876}. |
| Q14789 | GOLGB1 | S1753 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| Q14980 | NUMA1 | S162 | ochoa | Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) | Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}. |
| Q14BN4 | SLMAP | S480 | ochoa | Sarcolemmal membrane-associated protein (Sarcolemmal-associated protein) | Associates with the striatin-interacting phosphatase and kinase (STRIPAK) core complex, forming the extended (SIKE1:SLMAP)STRIPAK complex (PubMed:29063833, PubMed:30622739). The (SIKE1:SLMAP)STRIPAK complex dephosphorylates STK3 leading to the inhibition of Hippo signaling and the control of cell growth (PubMed:29063833, PubMed:30622739). May play a role during myoblast fusion (By similarity). {ECO:0000250|UniProtKB:Q3URD3, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739}. |
| Q15021 | NCAPD2 | S608 | ochoa | Condensin complex subunit 1 (Chromosome condensation-related SMC-associated protein 1) (Chromosome-associated protein D2) (hCAP-D2) (Non-SMC condensin I complex subunit D2) (XCAP-D2 homolog) | Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. May target the condensin complex to DNA via its C-terminal domain (PubMed:11136719). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of non-centromeric ultrafine DNA bridges during anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (PubMed:27737959). {ECO:0000269|PubMed:11136719, ECO:0000269|PubMed:27737959}. |
| Q15390 | MTFR1 | S124 | ochoa | Mitochondrial fission regulator 1 (Chondrocyte protein with a poly-proline region) | May play a role in mitochondrial aerobic respiration. May also regulate mitochondrial organization and fission (By similarity). {ECO:0000250}. |
| Q15642 | TRIP10 | S477 | ochoa | Cdc42-interacting protein 4 (Protein Felic) (Salt tolerant protein) (hSTP) (Thyroid receptor-interacting protein 10) (TR-interacting protein 10) (TRIP-10) | Required for translocation of GLUT4 to the plasma membrane in response to insulin signaling (By similarity). Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Binds to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promotes membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by recruiting WASL/N-WASP which in turn activates the Arp2/3 complex. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Required for the formation of podosomes, actin-rich adhesion structures specific to monocyte-derived cells. May be required for the lysosomal retention of FASLG/FASL. {ECO:0000250, ECO:0000269|PubMed:11069762, ECO:0000269|PubMed:16318909, ECO:0000269|PubMed:16326391}. |
| Q15858 | SCN9A | S1853 | ochoa | Sodium channel protein type 9 subunit alpha (Neuroendocrine sodium channel) (hNE-Na) (Peripheral sodium channel 1) (PN1) (Sodium channel protein type IX subunit alpha) (Voltage-gated sodium channel subunit alpha Nav1.7) | Pore-forming subunit of Nav1.7, 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:15385606, PubMed:16988069, PubMed:17145499, PubMed:17167479, PubMed:19369487, PubMed:24311784, PubMed:25240195, PubMed:26680203, PubMed:7720699). Nav1.7 plays a crucial role in controlling the excitability and action potential propagation from nociceptor neurons, thereby contributing to the sensory perception of pain (PubMed:17145499, PubMed:17167479, PubMed:19369487, PubMed:24311784). {ECO:0000269|PubMed:15178348, ECO:0000269|PubMed:15385606, ECO:0000269|PubMed:16988069, ECO:0000269|PubMed:17145499, ECO:0000269|PubMed:17167479, ECO:0000269|PubMed:19369487, ECO:0000269|PubMed:24311784, ECO:0000269|PubMed:25240195, ECO:0000269|PubMed:26680203, ECO:0000269|PubMed:7720699}. |
| Q16659 | MAPK6 | S451 | ochoa | Mitogen-activated protein kinase 6 (MAP kinase 6) (MAPK 6) (EC 2.7.11.24) (Extracellular signal-regulated kinase 3) (ERK-3) (MAP kinase isoform p97) (p97-MAPK) | Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}. |
| Q16822 | PCK2 | S34 | ochoa | Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PEPCK-M) (EC 4.1.1.32) (Phosphoenolpyruvate carboxykinase 2, mitochondrial) (mtPCK2) | Mitochondrial phosphoenolpyruvate carboxykinase that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle (PubMed:28955899). Can play an active role in glyceroneogenesis and gluconeogenesis (PubMed:28955899). {ECO:0000269|PubMed:28955899}. |
| Q16825 | PTPN21 | S637 | ochoa | Tyrosine-protein phosphatase non-receptor type 21 (EC 3.1.3.48) (Protein-tyrosine phosphatase D1) | None |
| Q16891 | IMMT | S103 | ochoa|psp | MICOS complex subunit MIC60 (Cell proliferation-inducing gene 4/52 protein) (Mitochondrial inner membrane protein) (Mitofilin) (p87/89) | Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane (PubMed:22114354, PubMed:25781180, PubMed:32567732, PubMed:33130824). Plays an important role in the maintenance of the MICOS complex stability and the mitochondrial cristae morphology (PubMed:22114354, PubMed:25781180, PubMed:32567732, PubMed:33130824). {ECO:0000269|PubMed:22114354, ECO:0000269|PubMed:25781180, ECO:0000269|PubMed:32567732, ECO:0000269|PubMed:33130824}. |
| Q1MSJ5 | CSPP1 | S77 | ochoa | Centrosome and spindle pole-associated protein 1 | May play a role in cell-cycle-dependent microtubule organization. {ECO:0000269|PubMed:16826565}. |
| Q2M2I3 | FAM83E | S387 | ochoa | Protein FAM83E | May play a role in MAPK signaling. {ECO:0000303|PubMed:24736947}. |
| Q32MZ4 | LRRFIP1 | S768 | ochoa | Leucine-rich repeat flightless-interacting protein 1 (LRR FLII-interacting protein 1) (GC-binding factor 2) (TAR RNA-interacting protein) | Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:10364563, ECO:0000269|PubMed:14522076, ECO:0000269|PubMed:16199883, ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:9705290}. |
| Q5H943 | CT83 | S85 | ochoa | Kita-kyushu lung cancer antigen 1 (KK-LC-1) (Cancer/testis antigen 83) | None |
| Q5JR59 | MTUS2 | S1302 | ochoa | Microtubule-associated tumor suppressor candidate 2 (Cardiac zipper protein) (Microtubule plus-end tracking protein TIP150) (Tracking protein of 150 kDa) | Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules. May regulate the dynamics of microtubules at their growing distal tip. {ECO:0000269|PubMed:19543227}. |
| Q5JTW2 | CEP78 | S453 | ochoa | Centrosomal protein of 78 kDa (Cep78) | Centriole wall protein that localizes to mature centrioles and regulates centriole and cilia biogenesis (PubMed:27246242, PubMed:27588451, PubMed:28242748, PubMed:34259627). Involved in centrosome duplication: required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles (PubMed:27246242). Involved in cilium biogenesis and controls cilium length (PubMed:27588451). Acts as a regulator of protein stability by preventing ubiquitination of centrosomal proteins, such as CCP110 and tektins (PubMed:28242748, PubMed:34259627). Associates with the EDVP complex, preventing ubiquitination and degradation of CCP110 (PubMed:28242748, PubMed:34259627). Promotes deubiquitination of tektin proteins (TEKT1, TEKT2, TEK3, TEKT4 and TEKT5) via its interaction with USP16 (By similarity). {ECO:0000250|UniProtKB:Q6IRU7, ECO:0000269|PubMed:27246242, ECO:0000269|PubMed:27588451, ECO:0000269|PubMed:28242748, ECO:0000269|PubMed:34259627}. |
| Q5JUK3 | KCNT1 | S407 | psp | Potassium channel subfamily T member 1 (KCa4.1) (KNa1.1) (Sodium and chloride-activated ATP-sensitive potassium channel Slo2.2) | Sodium-activated K(+) channel (PubMed:37494189). Acts as an important mediator of neuronal membrane excitability (PubMed:37494189). Contributes to the delayed outward currents (By similarity). Regulates neuronal bursting in sensory neurons (By similarity). Contributes to synaptic development and plasticity (By similarity). {ECO:0000250|UniProtKB:Q6ZPR4, ECO:0000250|UniProtKB:Q9Z258, ECO:0000269|PubMed:37494189}. |
| Q5M775 | SPECC1 | S437 | ochoa | Cytospin-B (Nuclear structure protein 5) (NSP5) (Sperm antigen HCMOGT-1) (Sperm antigen with calponin homology and coiled-coil domains 1) | None |
| Q5T5Y3 | CAMSAP1 | S1042 | 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}. |
| Q5T655 | CFAP58 | S146 | ochoa | Cilia- and flagella-associated protein 58 (Coiled-coil domain-containing protein 147) | Has an essential role in the assembly and organization of the sperm flagellar axoneme (PubMed:32791035). Required for the elongation of the primary cilium and sperm flagellar midpiece via modulation of the Notch signaling pathway (By similarity). {ECO:0000250|UniProtKB:B2RW38, ECO:0000269|PubMed:32791035}. |
| Q5TGY3 | AHDC1 | S829 | ochoa | Transcription factor Gibbin (AT-hook DNA-binding motif-containing protein 1) | Transcription factor required for the proper patterning of the epidermis, which plays a key role in early epithelial morphogenesis (PubMed:35585237). Directly binds promoter and enhancer regions and acts by maintaining local enhancer-promoter chromatin architecture (PubMed:35585237). Interacts with many sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes that wire surface ectoderm stratification (PubMed:35585237). {ECO:0000269|PubMed:35585237}. |
| Q5THJ4 | VPS13D | S3802 | 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}. |
| Q5TZA2 | CROCC | S1900 | ochoa | Rootletin (Ciliary rootlet coiled-coil protein) | Major structural component of the ciliary rootlet, a cytoskeletal-like structure in ciliated cells which originates from the basal body at the proximal end of a cilium and extends proximally toward the cell nucleus (By similarity). Furthermore, is required for the correct positioning of the cilium basal body relative to the cell nucleus, to allow for ciliogenesis (PubMed:27623382). Contributes to centrosome cohesion before mitosis (PubMed:16203858). {ECO:0000250|UniProtKB:Q8CJ40, ECO:0000269|PubMed:16203858, ECO:0000269|PubMed:27623382}. |
| Q5VST9 | OBSCN | S2964 | ochoa | Obscurin (EC 2.7.11.1) (Obscurin-RhoGEF) (Obscurin-myosin light chain kinase) (Obscurin-MLCK) | Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662). {ECO:0000250|UniProtKB:A2AAJ9, ECO:0000269|PubMed:11448995, ECO:0000269|PubMed:16205939, ECO:0000269|PubMed:28826662}. |
| Q5VTE0 | EEF1A1P5 | S21 | 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}. |
| Q5VTQ0 | TTC39B | S126 | ochoa | Tetratricopeptide repeat protein 39B (TPR repeat protein 39B) | Regulates high density lipoprotein (HDL) cholesterol metabolism by promoting the ubiquitination and degradation of the oxysterols receptors LXR (NR1H2 and NR1H3). {ECO:0000250|UniProtKB:Q8BYY4}. |
| Q5W0B1 | OBI1 | S595 | ochoa | ORC ubiquitin ligase 1 (OBI1) (EC 2.3.2.27) (RING finger protein 219) | E3 ubiquitin ligase essential for DNA replication origin activation during S phase (PubMed:31160578). Acts as a replication origin selector which selects the origins to be fired and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase (PubMed:31160578). {ECO:0000269|PubMed:31160578}. |
| Q641Q2 | WASHC2A | S890 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| Q6IBW4 | NCAPH2 | S127 | ochoa | Condensin-2 complex subunit H2 (Chromosome-associated protein H2) (hCAP-H2) (Kleisin-beta) (Non-SMC condensin II complex subunit H2) | Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture (PubMed:14532007). May promote the resolution of double-strand DNA catenanes (intertwines) between sister chromatids. Condensin-mediated compaction likely increases tension in catenated sister chromatids, providing directionality for type II topoisomerase-mediated strand exchanges toward chromatid decatenation. Required for decatenation of chromatin bridges at anaphase. Early in neurogenesis, may play an essential role to ensure accurate mitotic chromosome condensation in neuron stem cells, ultimately affecting neuron pool and cortex size (By similarity). Seems to have lineage-specific role in T-cell development (PubMed:14532007). {ECO:0000250|UniProtKB:Q8BSP2, ECO:0000269|PubMed:14532007}. |
| Q6P3S1 | DENND1B | S579 | 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}. |
| Q6PL18 | ATAD2 | S170 | ochoa | ATPase family AAA domain-containing protein 2 (EC 3.6.1.-) (AAA nuclear coregulator cancer-associated protein) (ANCCA) | May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells. {ECO:0000269|PubMed:17998543}. |
| Q6UWE0 | LRSAM1 | S494 | ochoa | E3 ubiquitin-protein ligase LRSAM1 (EC 2.3.2.27) (Leucine-rich repeat and sterile alpha motif-containing protein 1) (RING-type E3 ubiquitin transferase LRSAM1) (Tsg101-associated ligase) (hTAL) | E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098). {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322, ECO:0000269|PubMed:25484098}. |
| Q6UWF9 | FAM180A | S112 | ochoa | Protein FAM180A | None |
| Q6ZMQ8 | AATK | S520 | ochoa | Serine/threonine-protein kinase LMTK1 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase) (AATYK) (Brain apoptosis-associated tyrosine kinase) (CDK5-binding protein) (Lemur tyrosine kinase 1) (p35-binding protein) (p35BP) | May be involved in neuronal differentiation. {ECO:0000269|PubMed:10837911}. |
| Q6ZVD8 | PHLPP2 | S307 | ochoa | PH domain leucine-rich repeat-containing protein phosphatase 2 (EC 3.1.3.16) (PH domain leucine-rich repeat-containing protein phosphatase-like) (PHLPP-like) | Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). {ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:20513427, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}. |
| Q6ZVD8 | PHLPP2 | S1210 | ochoa | PH domain leucine-rich repeat-containing protein phosphatase 2 (EC 3.1.3.16) (PH domain leucine-rich repeat-containing protein phosphatase-like) (PHLPP-like) | Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). {ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:20513427, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}. |
| Q71DI3 | H3C15 | S87 | ochoa | Histone H3.2 (H3-clustered histone 13) (H3-clustered histone 14) (H3-clustered histone 15) (Histone H3/m) (Histone H3/o) | Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| Q76FK4 | NOL8 | S714 | ochoa | Nucleolar protein 8 (Nucleolar protein Nop132) | Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells. {ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:15132771, ECO:0000269|PubMed:16963496}. |
| Q7L2E3 | DHX30 | S380 | ochoa | ATP-dependent RNA helicase DHX30 (EC 3.6.4.13) (DEAH box protein 30) | RNA-dependent helicase (PubMed:29100085). Plays an important role in the assembly of the mitochondrial large ribosomal subunit (PubMed:25683715, PubMed:29100085). Required for optimal function of the zinc-finger antiviral protein ZC3HAV1 (By similarity). Associates with mitochondrial DNA (PubMed:18063578). Involved in nervous system development and differentiation through its involvement in the up-regulation of a number of genes which are required for neurogenesis, including GSC, NCAM1, neurogenin, and NEUROD (By similarity). {ECO:0000250|UniProtKB:Q5BJS0, ECO:0000250|UniProtKB:Q99PU8, ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:25683715, ECO:0000269|PubMed:29100085}. |
| Q7Z569 | BRAP | S286 | ochoa | BRCA1-associated protein (EC 2.3.2.27) (BRAP2) (Impedes mitogenic signal propagation) (IMP) (RING finger protein 52) (RING-type E3 ubiquitin transferase BRAP2) (Renal carcinoma antigen NY-REN-63) | Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination resulting in the release of inhibition of Raf/MEK complex formation. May also act as a cytoplasmic retention protein with a role in regulating nuclear transport. {ECO:0000269|PubMed:14724641, ECO:0000303|PubMed:10777491}. |
| Q7Z628 | NET1 | S78 | ochoa | Neuroepithelial cell-transforming gene 1 protein (Proto-oncogene p65 Net1) (Rho guanine nucleotide exchange factor 8) | Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPase. May be involved in activation of the SAPK/JNK pathway Stimulates genotoxic stress-induced RHOB activity in breast cancer cells leading to their cell death. {ECO:0000269|PubMed:21373644}. |
| Q86SQ7 | SDCCAG8 | S71 | ochoa | Serologically defined colon cancer antigen 8 (Antigen NY-CO-8) (Centrosomal colon cancer autoantigen protein) (hCCCAP) | Plays a role in the establishment of cell polarity and epithelial lumen formation (By similarity). Also plays an essential role in ciliogenesis and subsequent Hedgehog signaling pathway that requires the presence of intact primary cilia for pathway activation. Mechanistically, interacts with and mediates RABEP2 centrosomal localization which is critical for ciliogenesis (PubMed:27224062). {ECO:0000250|UniProtKB:Q80UF4, ECO:0000269|PubMed:27224062}. |
| Q86UD3 | MARCHF3 | S53 | ochoa | E3 ubiquitin-protein ligase MARCHF3 (EC 2.3.2.27) (Membrane-associated RING finger protein 3) (Membrane-associated RING-CH protein III) (MARCH-III) (RING finger protein 173) (RING-type E3 ubiquitin transferase MARCHF3) | E3 ubiquitin-protein ligase which may be involved in endosomal trafficking. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. {ECO:0000250|UniProtKB:Q5XIE5}. |
| Q86YR5 | GPSM1 | S413 | ochoa | G-protein-signaling modulator 1 (Activator of G-protein signaling 3) | Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction. {ECO:0000269|PubMed:11024022, ECO:0000269|PubMed:12642577}. |
| Q8IWU2 | LMTK2 | S616 | ochoa | Serine/threonine-protein kinase LMTK2 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase 2) (Brain-enriched kinase) (hBREK) (CDK5/p35-regulated kinase) (CPRK) (Kinase/phosphatase/inhibitor 2) (Lemur tyrosine kinase 2) (Serine/threonine-protein kinase KPI-2) | Phosphorylates PPP1C, phosphorylase b and CFTR. |
| Q8IY92 | SLX4 | S287 | ochoa | Structure-specific endonuclease subunit SLX4 (BTB/POZ domain-containing protein 12) | Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks. {ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19596236}. |
| Q8IYI6 | EXOC8 | S35 | ochoa | Exocyst complex component 8 (Exocyst complex 84 kDa subunit) | Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. |
| Q8IZH2 | XRN1 | S1046 | 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}. |
| Q8N137 | CNTROB | S36 | psp | Centrobin (Centrosomal BRCA2-interacting protein) (LYST-interacting protein 8) | Required for centriole duplication. Inhibition of centriole duplication leading to defects in cytokinesis. {ECO:0000269|PubMed:16275750}. |
| Q8N1G4 | LRRC47 | S315 | ochoa | Leucine-rich repeat-containing protein 47 | None |
| Q8N1W1 | ARHGEF28 | S735 | ochoa | Rho guanine nucleotide exchange factor 28 (190 kDa guanine nucleotide exchange factor) (p190-RhoGEF) (p190RhoGEF) (Rho guanine nucleotide exchange factor) | Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Also functions in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity). {ECO:0000250}. |
| Q8N490 | PNKD | S128 | psp | Probable thioesterase PNKD (EC 3.1.2.-) (Myofibrillogenesis regulator 1) (MR-1) (Paroxysmal nonkinesiogenic dyskinesia protein) (Trans-activated by hepatitis C virus core protein 2) | Probable thioesterase that may play a role in cellular detoxification processes; it likely acts on a yet-unknown alpha-hydroxythioester substrate (Probable). In vitro, it is able to catalyze the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid at very low rate, though this reaction is not physiologically relevant in vivo (PubMed:21487022). {ECO:0000269|PubMed:21487022, ECO:0000305|PubMed:21487022}. |
| Q8N4C6 | NIN | S1783 | ochoa | Ninein (hNinein) (Glycogen synthase kinase 3 beta-interacting protein) (GSK3B-interacting protein) | Centrosomal protein required in the positioning and anchorage of the microtubule minus-end in epithelial cells (PubMed:15190203, PubMed:23386061). May also act as a centrosome maturation factor (PubMed:11956314). May play a role in microtubule nucleation, by recruiting the gamma-tubulin ring complex to the centrosome (PubMed:15190203). Overexpression does not perturb nucleation or elongation of microtubules but suppresses release of microtubules (PubMed:15190203). Required for centriole organization and microtubule anchoring at the mother centriole (PubMed:23386061). {ECO:0000269|PubMed:11956314, ECO:0000269|PubMed:15190203, ECO:0000269|PubMed:23386061}. |
| Q8N680 | ZBTB2 | S178 | ochoa | Zinc finger and BTB domain-containing protein 2 | May be involved in transcriptional regulation. |
| Q8NDX1 | PSD4 | S604 | ochoa | PH and SEC7 domain-containing protein 4 (Exchange factor for ADP-ribosylation factor guanine nucleotide factor 6 B) (Exchange factor for ARF6 B) (Pleckstrin homology and SEC7 domain-containing protein 4) (Telomeric of interleukin-1 cluster protein) | Guanine nucleotide exchange factor for ARF6 and ARL14/ARF7. Through ARL14 activation, controls the movement of MHC class II-containing vesicles along the actin cytoskeleton in dendritic cells. Involved in membrane recycling. Interacts with several phosphatidylinositol phosphate species, including phosphatidylinositol 3,4-bisphosphate, phosphatidylinositol 3,5-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:12082148, ECO:0000269|PubMed:21458045}. |
| Q8NEG4 | FAM83F | S316 | ochoa | Protein FAM83F | None |
| Q8NEY1 | NAV1 | S654 | 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}. |
| Q8NEZ3 | WDR19 | S893 | ochoa | WD repeat-containing protein 19 (Intraflagellar transport 144 homolog) | As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly (PubMed:20889716). Essential for functional IFT-A assembly and ciliary entry of GPCRs (PubMed:20889716). Associates with the BBSome complex to mediate ciliary transport (By similarity). {ECO:0000250|UniProtKB:Q3UGF1, ECO:0000269|PubMed:20889716}. |
| Q8NFC6 | BOD1L1 | S277 | 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}. |
| Q8NFH8 | REPS2 | S631 | ochoa | RalBP1-associated Eps domain-containing protein 2 (Partner of RalBP1) (RalBP1-interacting protein 2) | Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors as part of the Ral signaling pathway (PubMed:10393179, PubMed:12771942, PubMed:9422736). By controlling growth factor receptors endocytosis may regulate cell survival (PubMed:12771942). Through ASAP1 may regulate cell adhesion and migration (PubMed:12149250). {ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:12149250, ECO:0000269|PubMed:12771942, ECO:0000269|PubMed:9422736}. |
| Q8TDR2 | STK35 | S385 | ochoa|psp | Serine/threonine-protein kinase 35 (EC 2.7.11.1) (CLP-36-interacting kinase 1) (CLIK-1) (PDLIM1-interacting kinase 1) (Serine/threonine-protein kinase 35 L1) | None |
| Q8TF40 | FNIP1 | S169 | ochoa | Folliculin-interacting protein 1 | Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed:17028174, PubMed:18663353, PubMed:24081491, PubMed:37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed:24081491). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity). Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent inactivation of TFEB and TFE3 (PubMed:37079666). Together with FLCN, regulates autophagy: following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed:25126726). In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2, inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 (PubMed:27353360, PubMed:30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed:27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress, the conserved Cys degron is reduced, leading to recognition and polyubiquitylation by the CRL2(FEM1B) complex, followed by proteasomal (By similarity). Required for B-cell development (PubMed:32905580). {ECO:0000250|UniProtKB:Q68FD7, ECO:0000250|UniProtKB:Q9P278, ECO:0000269|PubMed:17028174, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:32905580, ECO:0000269|PubMed:37079666}. |
| Q8WUM9 | SLC20A1 | S318 | ochoa | Sodium-dependent phosphate transporter 1 (Gibbon ape leukemia virus receptor 1) (GLVR-1) (Leukemia virus receptor 1 homolog) (Phosphate transporter 1) (PiT-1) (Solute carrier family 20 member 1) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:16790504, PubMed:17494632, PubMed:19726692, PubMed:7929240, PubMed:8041748). May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification (PubMed:11009570). Essential for cell proliferation but this function is independent of its phosphate transporter activity (PubMed:19726692). {ECO:0000269|PubMed:11009570, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:19726692, ECO:0000269|PubMed:7929240, ECO:0000269|PubMed:8041748}.; FUNCTION: (Microbial infection) May function as a retroviral receptor as it confers human cells susceptibility to infection to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine leukemia virus (10A1 MLV). {ECO:0000269|PubMed:12097582, ECO:0000269|PubMed:1309898, ECO:0000269|PubMed:2078500, ECO:0000269|PubMed:7966619}. |
| Q8WVV4 | POF1B | S364 | ochoa | Protein POF1B (Premature ovarian failure protein 1B) | Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development. {ECO:0000269|PubMed:16773570, ECO:0000269|PubMed:21940798}. |
| Q8WVV4 | POF1B | S497 | ochoa | Protein POF1B (Premature ovarian failure protein 1B) | Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development. {ECO:0000269|PubMed:16773570, ECO:0000269|PubMed:21940798}. |
| Q92547 | TOPBP1 | S879 | ochoa | DNA topoisomerase 2-binding protein 1 (DNA topoisomerase II-beta-binding protein 1) (TopBP1) (DNA topoisomerase II-binding protein 1) | Scaffold protein that acts as a key protein-protein adapter in DNA replication and DNA repair (PubMed:10498869, PubMed:11395493, PubMed:11714696, PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:33592542, PubMed:35597237, PubMed:37674080). Composed of multiple BRCT domains, which specifically recognize and bind phosphorylated proteins, bringing proteins together into functional combinations (PubMed:17575048, PubMed:20545769, PubMed:21777809, PubMed:26811421, PubMed:30898438, PubMed:31135337, PubMed:35597237, PubMed:37674080). Required for DNA replication initiation but not for the formation of pre-replicative complexes or the elongation stages (By similarity). Necessary for the loading of replication factors onto chromatin, including GMNC, CDC45, DNA polymerases and components of the GINS complex (By similarity). Plays a central role in DNA repair by bridging proteins and promoting recruitment of proteins to DNA damage sites (PubMed:30898438, PubMed:35597237, PubMed:37674080). Involved in double-strand break (DSB) repair via homologous recombination in S-phase by promoting the exchange between the DNA replication factor A (RPA) complex and RAD51 (PubMed:26811421, PubMed:35597237). Mechanistically, TOPBP1 is recruited to DNA damage sites in S-phase via interaction with phosphorylated HTATSF1, and promotes the loading of RAD51, thereby facilitating RAD51 nucleofilaments formation and RPA displacement, followed by homologous recombination (PubMed:35597237). Involved in microhomology-mediated end-joining (MMEJ) DNA repair by promoting recruitment of polymerase theta (POLQ) to DNA damage sites during mitosis (PubMed:37674080). MMEJ is an alternative non-homologous end-joining (NHEJ) machinery that takes place during mitosis to repair DSBs in DNA that originate in S-phase (PubMed:37674080). Recognizes and binds POLQ phosphorylated by PLK1, enabling its recruitment to DSBs for subsequent repair (PubMed:37674080). Involved in G1 DNA damage checkpoint by acting as a molecular adapter that couples TP53BP1 and the 9-1-1 complex (PubMed:31135337). In response to DNA damage, triggers the recruitment of checkpoint signaling proteins on chromatin, which activate the CHEK1 signaling pathway and block S-phase progression (PubMed:16530042, PubMed:21777809). Acts as an activator of the kinase activity of ATR (PubMed:16530042, PubMed:21777809). Also required for chromosomal stability when DSBs occur during mitosis by forming filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Together with CIP2A, plays an essential role in the response to genome instability generated by the presence of acentric chromosome fragments derived from shattered chromosomes within micronuclei (PubMed:35121901, PubMed:35842428, PubMed:37165191, PubMed:37316668). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, the CIP2A-TOPBP1 complex tethers chromosome fragments during mitosis to ensure clustered segregation of the fragments to a single daughter cell nucleus, facilitating re-ligation with limited chromosome scattering and loss (PubMed:37165191, PubMed:37316668). Recruits the SWI/SNF chromatin remodeling complex to E2F1-responsive promoters, thereby down-regulating E2F1 activity and inhibiting E2F1-dependent apoptosis during G1/S transition and after DNA damage (PubMed:12697828, PubMed:15075294). {ECO:0000250|UniProtKB:Q800K6, ECO:0000269|PubMed:10498869, ECO:0000269|PubMed:11395493, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:12697828, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:16530042, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:35121901, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:35842428, ECO:0000269|PubMed:37165191, ECO:0000269|PubMed:37316668, ECO:0000269|PubMed:37674080}. |
| Q92674 | CENPI | S520 | ochoa | Centromere protein I (CENP-I) (FSH primary response protein 1) (Follicle-stimulating hormone primary response protein) (Interphase centromere complex protein 19) (Leucine-rich primary response protein 1) | Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. Required for the localization of CENPF, MAD1L1 and MAD2 (MAD2L1 or MAD2L2) to kinetochores. Involved in the response of gonadal tissues to follicle-stimulating hormone. {ECO:0000269|PubMed:12640463, ECO:0000269|PubMed:16622420}. |
| Q93045 | STMN2 | S97 | ochoa|psp | Stathmin-2 (Superior cervical ganglion-10 protein) (Protein SCG10) | Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone (By similarity). {ECO:0000250}. |
| Q96BY6 | DOCK10 | S1318 | 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}. |
| Q96CT7 | CCDC124 | S194 | ochoa | Coiled-coil domain-containing protein 124 | Ribosome-binding protein involved in ribosome hibernation: associates with translationally inactive ribosomes and stabilizes the nonrotated conformation of the 80S ribosome, thereby promoting ribosome preservation and storage (PubMed:32687489). Also required for proper progression of late cytokinetic stages (PubMed:23894443). {ECO:0000269|PubMed:23894443, ECO:0000269|PubMed:32687489}. |
| Q96D71 | REPS1 | S767 | ochoa | RalBP1-associated Eps domain-containing protein 1 (RalBP1-interacting protein 1) | May coordinate the cellular actions of activated EGF receptors and Ral-GTPases. {ECO:0000250}. |
| Q96ED9 | HOOK2 | S442 | ochoa | Protein Hook homolog 2 (h-hook2) (hHK2) | Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Contributes to the establishment and maintenance of centrosome function. May function in the positioning or formation of aggresomes, which are pericentriolar accumulations of misfolded proteins, proteasomes and chaperones. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). {ECO:0000269|PubMed:17140400, ECO:0000269|PubMed:17540036, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}. |
| Q96EP5 | DAZAP1 | S20 | ochoa | DAZ-associated protein 1 (Deleted in azoospermia-associated protein 1) | RNA-binding protein, which may be required during spermatogenesis. |
| Q96L93 | KIF16B | S1104 | 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}. |
| Q96MX3 | ZNF48 | S316 | ochoa | Zinc finger protein 48 (Zinc finger protein 553) | May be involved in transcriptional regulation. |
| Q96PU5 | NEDD4L | S184 | ochoa | 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}. |
| Q96SD1 | DCLRE1C | S553 | psp | Protein artemis (EC 3.1.-.-) (DNA cross-link repair 1C protein) (Protein A-SCID) (SNM1 homolog C) (hSNM1C) (SNM1-like protein) | Nuclease involved in DNA non-homologous end joining (NHEJ); required for double-strand break repair and V(D)J recombination (PubMed:11336668, PubMed:11955432, PubMed:12055248, PubMed:14744996, PubMed:15071507, PubMed:15574326, PubMed:15936993). Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments (PubMed:11336668, PubMed:11955432, PubMed:14744996). V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs) (PubMed:11336668, PubMed:11955432, PubMed:14744996). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends (PubMed:11336668, PubMed:11955432, PubMed:14744996). These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively (PubMed:11336668, PubMed:11955432, PubMed:14744996). This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC (PubMed:11955432, PubMed:15071507, PubMed:15574326, PubMed:15936993). The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint (PubMed:11955432). Also required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ (PubMed:15456891, PubMed:15468306, PubMed:15574327, PubMed:15811628). {ECO:0000269|PubMed:11336668, ECO:0000269|PubMed:11955432, ECO:0000269|PubMed:12055248, ECO:0000269|PubMed:14744996, ECO:0000269|PubMed:15071507, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15468306, ECO:0000269|PubMed:15574326, ECO:0000269|PubMed:15574327, ECO:0000269|PubMed:15811628, ECO:0000269|PubMed:15936993}. |
| Q96ST2 | IWS1 | S69 | ochoa | Protein IWS1 homolog (IWS1-like protein) | Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. {ECO:0000269|PubMed:17184735, ECO:0000269|PubMed:17234882, ECO:0000269|PubMed:19141475}. |
| Q96T51 | RUFY1 | S319 | ochoa | RUN and FYVE domain-containing protein 1 (FYVE-finger protein EIP1) (La-binding protein 1) (Rab4-interacting protein) (Zinc finger FYVE domain-containing protein 12) | Activating adapter involved in cargo sorting from early/recycling endosomes. Regulates retrieval of proteins from endosomes to the trans-Golgi network through interaction with the dynein-dynactin complex (PubMed:36282215). Dual effector of RAB4B and RAB14, mediates a cooperative interaction allowing endosomal tethering and fusion (PubMed:20534812). Binds phospholipid vesicles containing phosphatidylinositol 3-phosphate and participates in early endosomal trafficking (PubMed:14617813). In oocytes, self-assembles to form a protein matrix which hold together endolysosomes, autophagosomes and proteasomes and generate non-membrane-bound compartments called endo-lysosomal vesicular assemblies (ELVAs). In immature oocytes, ELVAs sequester ubiquitinated protein aggregates and degrade them upon oocyte maturation (By similarity). {ECO:0000250|UniProtKB:Q8BIJ7, ECO:0000269|PubMed:14617813, ECO:0000269|PubMed:20534812, ECO:0000269|PubMed:36282215}. |
| Q99615 | DNAJC7 | S207 | ochoa | 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}. |
| Q99959 | PKP2 | S34 | 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}. |
| Q9BT81 | SOX7 | S139 | ochoa | Transcription factor SOX-7 | Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors (By similarity). May be required for the survival of both hematopoietic and endothelial precursors during specification (By similarity). Competes with GATA4 for binding and activation of the FGF3 promoter (By similarity). Represses Wnt/beta-catenin-stimulated transcription, probably by targeting CTNNB1 to proteasomal degradation. Binds the DNA sequence 5'-AACAAT-3'. {ECO:0000250, ECO:0000269|PubMed:18819930}. |
| Q9BV73 | CEP250 | S264 | ochoa | Centrosome-associated protein CEP250 (250 kDa centrosomal protein) (Cep250) (Centrosomal Nek2-associated protein 1) (C-Nap1) (Centrosomal protein 2) | Plays an important role in centrosome cohesion during interphase (PubMed:30404835, PubMed:36282799). Recruits CCDC102B to the proximal ends of centrioles (PubMed:30404835). Maintains centrosome cohesion by forming intercentriolar linkages (PubMed:36282799). Accumulates at the proximal end of each centriole, forming supramolecular assemblies with viscous material properties that promote organelle cohesion (PubMed:36282799). May be involved in ciliogenesis (PubMed:28005958). {ECO:0000269|PubMed:28005958, ECO:0000269|PubMed:30404835, ECO:0000269|PubMed:36282799}. |
| Q9BXF6 | RAB11FIP5 | S553 | ochoa | Rab11 family-interacting protein 5 (Rab11-FIP5) (Gamma-SNAP-associated factor 1) (Gaf-1) (Phosphoprotein pp75) (Rab11-interacting protein Rip11) | Rab effector involved in protein trafficking from apical recycling endosomes to the apical plasma membrane. Involved in insulin granule exocytosis. May regulate V-ATPase intracellular transport in response to extracellular acidosis. {ECO:0000269|PubMed:11163216, ECO:0000269|PubMed:20717956}. |
| Q9BZF9 | UACA | S1353 | ochoa | Uveal autoantigen with coiled-coil domains and ankyrin repeats | Regulates APAF1 expression and plays an important role in the regulation of stress-induced apoptosis. Promotes apoptosis by regulating three pathways, apoptosome up-regulation, LGALS3/galectin-3 down-regulation and NF-kappa-B inactivation. Regulates the redistribution of APAF1 into the nucleus after proapoptotic stress. Down-regulates the expression of LGALS3 by inhibiting NFKB1 (By similarity). {ECO:0000250}.; FUNCTION: Modulates isoactin dynamics to regulate the morphological alterations required for cell growth and motility. Interaction with ARF6 may modulate cell shape and motility after injury. May be involved in multiple neurite formation (By similarity). {ECO:0000250|UniProtKB:Q8CGB3, ECO:0000250|UniProtKB:Q8HYY4}. |
| Q9BZR8 | BCL2L14 | S135 | ochoa | Apoptosis facilitator Bcl-2-like protein 14 (Bcl2-L-14) (Apoptosis regulator Bcl-G) | Plays a role in apoptosis. |
| Q9H0U4 | RAB1B | S111 | ochoa | Ras-related protein Rab-1B (EC 3.6.5.2) | The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:20545908, PubMed:9437002, PubMed:23236136). 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:9437002). Plays a role in the initial events of the autophagic vacuole development which take place at specialized regions of the endoplasmic reticulum (PubMed:20545908). Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments (By similarity). Required to modulate the compacted morphology of the Golgi (PubMed:26209634). Promotes the recruitment of lipid phosphatase MTMR6 to the endoplasmic reticulum-Golgi intermediate compartment (By similarity). {ECO:0000250|UniProtKB:P10536, ECO:0000269|PubMed:20545908, ECO:0000269|PubMed:23236136, ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:9437002}. |
| Q9H299 | SH3BGRL3 | S22 | ochoa | SH3 domain-binding glutamic acid-rich-like protein 3 (SH3 domain-binding protein 1) (SH3BP-1) (TNF inhibitory protein B1) (TIP-B1) | Could act as a modulator of glutaredoxin biological activity (Probable). May play a role in cytoskeleton organization (PubMed:34380438). {ECO:0000269|PubMed:34380438, ECO:0000305|PubMed:15907482}. |
| Q9H2P0 | ADNP | S363 | ochoa | Activity-dependent neuroprotector homeobox protein (Activity-dependent neuroprotective protein) | May be involved in transcriptional regulation. May mediate some of the neuroprotective peptide VIP-associated effects involving normal growth and cancer proliferation. Positively modulates WNT-beta-catenin/CTNN1B signaling, acting by regulating phosphorylation of, and thereby stabilizing, CTNNB1. May be required for neural induction and neuronal differentiation. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q9Z103}. |
| Q9H2Y7 | ZNF106 | S508 | 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}. |
| Q9H3D4 | TP63 | S68 | psp | Tumor protein 63 (p63) (Chronic ulcerative stomatitis protein) (CUSP) (Keratinocyte transcription factor KET) (Transformation-related protein 63) (TP63) (Tumor protein p73-like) (p73L) (p40) (p51) | Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter. {ECO:0000269|PubMed:11641404, ECO:0000269|PubMed:12374749, ECO:0000269|PubMed:12446779, ECO:0000269|PubMed:12446784, ECO:0000269|PubMed:20123734, ECO:0000269|PubMed:22197488, ECO:0000269|PubMed:9774969}. |
| Q9H3Q1 | CDC42EP4 | S105 | ochoa | Cdc42 effector protein 4 (Binder of Rho GTPases 4) | Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation, when overexpressed in fibroblasts. |
| Q9H3U1 | UNC45A | S175 | ochoa | Protein unc-45 homolog A (Unc-45A) (GCUNC-45) (Smooth muscle cell-associated protein 1) (SMAP-1) | Acts as a co-chaperone for HSP90. Prevents the stimulation of HSP90AB1 ATPase activity by AHSA1. Positive factor in promoting PGR function in the cell. May be necessary for proper folding of myosin (Potential). Necessary for normal cell proliferation. Necessary for normal myotube formation and myosin accumulation during muscle cell development. May play a role in erythropoiesis in stroma cells in the spleen (By similarity). {ECO:0000250, ECO:0000269|PubMed:12119110, ECO:0000269|PubMed:16478993, ECO:0000305}. |
| Q9H4L4 | SENP3 | S355 | ochoa | Sentrin-specific protease 3 (EC 3.4.22.-) (SUMO-1-specific protease 3) (Sentrin/SUMO-specific protease SENP3) | Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:16608850, PubMed:32832608, PubMed:36050397). Deconjugates SUMO2 from MEF2D, which increases its transcriptional activation capability (PubMed:15743823). Deconjugates SUMO2 and SUMO3 from CDCA8 (PubMed:18946085). Redox sensor that, when redistributed into nucleoplasm, can act as an effector to enhance HIF1A transcriptional activity by desumoylating EP300 (PubMed:19680224). Required for rRNA processing through deconjugation of SUMO2 and SUMO3 from nucleophosmin, NPM1 (PubMed:19015314). Plays a role in the regulation of sumoylation status of ZNF148 (PubMed:18259216). Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Deconjugates SUMO2 from KAT5 (PubMed:32832608). Catalyzes desumoylation of MRE11 (PubMed:36050397). {ECO:0000269|PubMed:15743823, ECO:0000269|PubMed:16608850, ECO:0000269|PubMed:18259216, ECO:0000269|PubMed:18946085, ECO:0000269|PubMed:19015314, ECO:0000269|PubMed:19680224, ECO:0000269|PubMed:22872859, ECO:0000269|PubMed:32832608, ECO:0000269|PubMed:36050397}. |
| Q9H4L5 | OSBPL3 | S330 | ochoa | Oxysterol-binding protein-related protein 3 (ORP-3) (OSBP-related protein 3) | Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193). {ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:18270267, ECO:0000269|PubMed:25447204}. |
| Q9H6R4 | NOL6 | S121 | ochoa | Nucleolar protein 6 (Nucleolar RNA-associated protein) (Nrap) | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. {ECO:0000269|PubMed:11895476, ECO:0000269|PubMed:34516797}. |
| Q9H8K7 | PAAT | S302 | ochoa | ATPase PAAT (EC 3.6.1.-) (Protein associated with ABC transporters) (PAAT) | ATPase that regulates mitochondrial ABC transporters ABCB7, ABCB8/MITOSUR and ABCB10 (PubMed:25063848). Regulates mitochondrial ferric concentration and heme biosynthesis and plays a role in the maintenance of mitochondrial homeostasis and cell survival (PubMed:25063848). {ECO:0000269|PubMed:25063848}. |
| Q9HD20 | ATP13A1 | S935 | ochoa | Endoplasmic reticulum transmembrane helix translocase (EC 7.4.2.-) (Endoplasmic reticulum P5A-ATPase) | Endoplasmic reticulum translocase required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum (PubMed:32973005, PubMed:36264797). Acts as a dislocase that mediates the ATP-dependent extraction of mislocalized mitochondrial transmembrane proteins from the endoplasmic reticulum membrane (PubMed:32973005). Specifically binds mitochondrial tail-anchored transmembrane proteins: has an atypically large substrate-binding pocket that recognizes and binds moderately hydrophobic transmembranes with short hydrophilic lumenal domains (PubMed:32973005). {ECO:0000269|PubMed:32973005, ECO:0000269|PubMed:36264797}. |
| Q9NPG3 | UBN1 | S142 | ochoa | Ubinuclein-1 (HIRA-binding protein) (Protein VT4) (Ubiquitously expressed nuclear protein) | Acts as a novel regulator of senescence. Involved in the formation of senescence-associated heterochromatin foci (SAHF), which represses expression of proliferation-promoting genes. Binds to proliferation-promoting genes. May be required for replication-independent chromatin assembly. {ECO:0000269|PubMed:14718166, ECO:0000269|PubMed:19029251}. |
| Q9NQS7 | INCENP | S357 | ochoa | Inner centromere protein | Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules (PubMed:12925766, PubMed:15316025, PubMed:27332895). The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC (PubMed:27332895). Required for localization of CBX5 to mitotic centromeres (PubMed:21346195). Controls the kinetochore localization of BUB1 (PubMed:16760428). {ECO:0000250|UniProtKB:P53352, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:21346195, ECO:0000269|PubMed:27332895}. |
| Q9NQW6 | ANLN | S562 | 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}. |
| Q9NR45 | NANS | S253 | ochoa | N-acetylneuraminate-9-phosphate synthase (EC 2.5.1.57) (3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase) (EC 2.5.1.132) (N-acetylneuraminic acid phosphate synthase) (NANS) (Sialic acid phosphate synthase) (Sialic acid synthase) | Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P) (PubMed:10749855). Also catalyzes the condensation of PEP and D-mannose 6-phosphate (Man-6-P) to produce 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate (KDN-9-P) (PubMed:10749855). Neu5Ac-9-P and KDN-9-P are the phosphorylated forms of sialic acids N-acetylneuraminic acid (Neu5Ac) and deaminoneuraminic acid (KDN), respectively (PubMed:10749855). Required for brain and skeletal development (PubMed:27213289). {ECO:0000269|PubMed:10749855, ECO:0000269|PubMed:27213289}. |
| Q9NRA8 | EIF4ENIF1 | S417 | ochoa | Eukaryotic translation initiation factor 4E transporter (4E-T) (eIF4E transporter) (Eukaryotic translation initiation factor 4E nuclear import factor 1) | EIF4E-binding protein that regulates translation and stability of mRNAs in processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:27342281, PubMed:32354837). Plays a key role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:24335285, PubMed:32354837). Acts as a binding platform for multiple RNA-binding proteins: promotes deadenylation of mRNAs via its interaction with the CCR4-NOT complex, and blocks decapping via interaction with eIF4E (EIF4E and EIF4E2), thereby protecting deadenylated and repressed mRNAs from degradation (PubMed:27342281, PubMed:32354837). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). Promotes miRNA-mediated translational repression (PubMed:24335285, PubMed:27342281, PubMed:28487484). Required for the formation of P-bodies (PubMed:16157702, PubMed:22966201, PubMed:27342281, PubMed:32354837). Involved in mRNA translational repression mediated by the miRNA effector TNRC6B by protecting TNRC6B-targeted mRNAs from decapping and subsequent decay (PubMed:32354837). Also acts as a nucleoplasmic shuttling protein, which mediates the nuclear import of EIF4E and DDX6 by a piggy-back mechanism (PubMed:10856257, PubMed:28216671). {ECO:0000250|UniProtKB:Q9EST3, ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:28216671, ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:32354837}. |
| Q9NWF9 | RNF216 | S346 | ochoa | E3 ubiquitin-protein ligase RNF216 (EC 2.3.2.27) (RING finger protein 216) (RING-type E3 ubiquitin transferase RNF216) (Triad domain-containing protein 3) (Ubiquitin-conjugating enzyme 7-interacting protein 1) (Zinc finger protein inhibiting NF-kappa-B) | [Isoform 1]: E3 ubiquitin ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their ubiquitination (PubMed:34998453). Plays a role in the regulation of antiviral responses by promoting the degradation of TRAF3, TLR4 and TLR9 (PubMed:15107846, PubMed:19893624). In turn, down-regulates NF-kappa-B and IRF3 activation as well as beta interferon production. Also participates in the regulation of autophagy by ubiquitinating BECN1 leading to its degradation and autophagy inhibition (PubMed:25484083). Plays a role in ARC-dependent synaptic plasticity by mediating ARC ubiquitination resulting in its rapid proteasomal degradation (PubMed:24945773). Plays aso an essential role in spermatogenesis and male fertility (By similarity). Mechanistically, regulates meiosis by promoting the degradation of PRKACB through the ubiquitin-mediated lysosome pathway (By similarity). Modulates the gonadotropin-releasing hormone signal pathway by affecting the stability of STAU2 that is required for the microtubule-dependent transport of neuronal RNA from the cell body to the dendrite (By similarity). {ECO:0000250|UniProtKB:P58283, ECO:0000269|PubMed:15107846, ECO:0000269|PubMed:19893624, ECO:0000269|PubMed:24945773, ECO:0000269|PubMed:25484083, ECO:0000269|PubMed:34998453}.; FUNCTION: [Isoform 3]: Inhibits TNF and IL-1 mediated activation of NF-kappa-B. Promotes TNF and RIP mediated apoptosis. {ECO:0000269|PubMed:11854271}. |
| Q9NYF8 | BCLAF1 | S502 | ochoa | Bcl-2-associated transcription factor 1 (Btf) (BCLAF1 and THRAP3 family member 1) | Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:18794151}. |
| Q9P0K7 | RAI14 | S479 | ochoa | Ankycorbin (Ankyrin repeat and coiled-coil structure-containing protein) (Novel retinal pigment epithelial cell protein) (Retinoic acid-induced protein 14) | Plays a role in actin regulation at the ectoplasmic specialization, a type of cell junction specific to testis. Important for establishment of sperm polarity and normal spermatid adhesion. May also promote integrity of Sertoli cell tight junctions at the blood-testis barrier. {ECO:0000250|UniProtKB:Q5U312}. |
| Q9P2Q2 | FRMD4A | S335 | ochoa | FERM domain-containing protein 4A | Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (By similarity). Plays a redundant role with FRMD4B in epithelial polarization (By similarity). May regulate MAPT secretion by activating ARF6-signaling (PubMed:27044754). {ECO:0000250|UniProtKB:Q8BIE6, ECO:0000269|PubMed:27044754}. |
| Q9UEE9 | CFDP1 | S221 | ochoa | Craniofacial development protein 1 (Bucentaur) | May play a role during embryogenesis. {ECO:0000250}. |
| Q9UIK4 | DAPK2 | S318 | ochoa|psp | Death-associated protein kinase 2 (DAP kinase 2) (EC 2.7.11.1) (DAP-kinase-related protein 1) (DRP-1) | Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation (PubMed:17347302). Regulates granulocytic motility by controlling cell spreading and polarization (PubMed:24163421). {ECO:0000269|PubMed:17347302, ECO:0000269|PubMed:24163421, ECO:0000269|PubMed:26047703}.; FUNCTION: Isoform 2 is not regulated by calmodulin. It can phosphorylate MYL9. It can induce membrane blebbing and autophagic cell death. |
| Q9UKF6 | CPSF3 | S659 | ochoa | Cleavage and polyadenylation specificity factor subunit 3 (EC 3.1.27.-) (Cleavage and polyadenylation specificity factor 73 kDa subunit) (CPSF 73 kDa subunit) (mRNA 3'-end-processing endonuclease CPSF-73) | Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Has endonuclease activity, and functions as an mRNA 3'-end-processing endonuclease (PubMed:30507380). Also involved in the histone 3'-end pre-mRNA processing (PubMed:30507380). U7 snRNP-dependent protein that induces both the 3'-endoribonucleolytic cleavage of histone pre-mRNAs and acts as a 5' to 3' exonuclease for degrading the subsequent downstream cleavage product (DCP) of mature histone mRNAs. Cleavage occurs after the 5'-ACCCA-3' sequence in the histone pre-mRNA leaving a 3'hydroxyl group on the upstream fragment containing the stem loop (SL) and 5' phosphate on the downstream cleavage product (DCP) starting with CU nucleotides. The U7-dependent 5' to 3' exonuclease activity is processive and degrades the DCP RNA substrate even after complete removal of the U7-binding site. Binds to the downstream cleavage product (DCP) of histone pre-mRNAs and the cleaved DCP RNA substrate in a U7 snRNP dependent manner. Required for entering/progressing through S-phase of the cell cycle (PubMed:30507380). Required for the selective processing of microRNAs (miRNAs) during embryonic stem cell differentiation via its interaction with ISY1 (By similarity). Required for the biogenesis of all miRNAs from the pri-miR-17-92 primary transcript except miR-92a (By similarity). Only required for the biogenesis of miR-290 and miR-96 from the pri-miR-290-295 and pri-miR-96-183 primary transcripts, respectively (By similarity). {ECO:0000250|UniProtKB:Q9QXK7, ECO:0000269|PubMed:14749727, ECO:0000269|PubMed:15037765, ECO:0000269|PubMed:17128255, ECO:0000269|PubMed:18688255, ECO:0000269|PubMed:30507380}. |
| Q9UKX2 | MYH2 | S424 | ochoa | Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) | Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}. |
| Q9UKX3 | MYH13 | S1482 | ochoa | Myosin-13 (Myosin heavy chain 13) (Myosin heavy chain, skeletal muscle, extraocular) (MyHC-EO) (Myosin heavy chain, skeletal muscle, laryngeal) (MyHC-IIL) (Superfast myosin) | Fast twitching myosin mediating the high-velocity and low-tension contractions of specific striated muscles. {ECO:0000269|PubMed:23908353}. |
| Q9ULD2 | MTUS1 | S958 | ochoa | Microtubule-associated tumor suppressor 1 (AT2 receptor-binding protein) (Angiotensin-II type 2 receptor-interacting protein) (Mitochondrial tumor suppressor 1) | Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}. |
| Q9ULD2 | MTUS1 | S1203 | ochoa | Microtubule-associated tumor suppressor 1 (AT2 receptor-binding protein) (Angiotensin-II type 2 receptor-interacting protein) (Mitochondrial tumor suppressor 1) | Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. {ECO:0000269|PubMed:12692079, ECO:0000269|PubMed:19794912}. |
| Q9ULH1 | ASAP1 | S493 | 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}. |
| Q9ULJ3 | ZBTB21 | S285 | ochoa | Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) | Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}. |
| Q9Y277 | VDAC3 | S165 | ochoa | Non-selective voltage-gated ion channel VDAC3 (VDAC-3) (hVDAC3) (Outer mitochondrial membrane protein porin 3) | Non-selective voltage-gated ion channel that mediates the transport of anions and cations through the mitochondrion outer membrane and plasma membrane (PubMed:31935282). Forms a high-conducting channel with a stable open state and a voltage-induced closure with a mild preference for anions over cations (PubMed:31935282). Involved in male fertility and sperm mitochondrial sheath formation (By similarity). {ECO:0000250|UniProtKB:Q60931, ECO:0000269|PubMed:31935282}. |
| Q9Y2X7 | GIT1 | S417 | ochoa | ARF GTPase-activating protein GIT1 (ARF GAP GIT1) (Cool-associated and tyrosine-phosphorylated protein 1) (CAT-1) (CAT1) (G protein-coupled receptor kinase-interactor 1) (GRK-interacting protein 1) (p95-APP1) | GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}. |
| Q9Y365 | STARD10 | S246 | ochoa | START domain-containing protein 10 (StARD10) (Antigen NY-CO-28) (PCTP-like protein) (PCTP-L) (Serologically defined colon cancer antigen 28) (StAR-related lipid transfer protein 10) | May play metabolic roles in sperm maturation or fertilization (By similarity). Phospholipid transfer protein that preferentially selects lipid species containing a palmitoyl or stearoyl chain on the sn-1 and an unsaturated fatty acyl chain (18:1 or 18:2) on the sn-2 position. Able to transfer phosphatidylcholine (PC) and phosphatidyetanolamline (PE) between membranes. {ECO:0000250, ECO:0000269|PubMed:15911624}. |
| Q9Y3T6 | R3HCC1 | S236 | ochoa | R3H and coiled-coil domain-containing protein 1 | None |
| Q9Y490 | TLN1 | S1021 | 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}. |
| Q9Y5B9 | SUPT16H | S365 | ochoa | FACT complex subunit SPT16 (Chromatin-specific transcription elongation factor 140 kDa subunit) (FACT 140 kDa subunit) (FACTp140) (Facilitates chromatin transcription complex subunit SPT16) (hSPT16) | Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. The FACT complex is probably also involved in phosphorylation of 'Ser-392' of p53/TP53 via its association with CK2 (casein kinase II). {ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:12934006, ECO:0000269|PubMed:16713563, ECO:0000269|PubMed:9489704, ECO:0000269|PubMed:9836642}. |
| Q9Y6K9 | IKBKG | S196 | ochoa | NF-kappa-B essential modulator (NEMO) (FIP-3) (IkB kinase-associated protein 1) (IKKAP1) (Inhibitor of nuclear factor kappa-B kinase subunit gamma) (I-kappa-B kinase subunit gamma) (IKK-gamma) (IKKG) (IkB kinase subunit gamma) (NF-kappa-B essential modifier) | Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:14695475, PubMed:20724660, PubMed:21518757, PubMed:9751060). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:19185524, PubMed:21606507, PubMed:27777308, PubMed:33567255). Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:19185524, PubMed:21606507, PubMed:27777308). Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3 (PubMed:19854139). Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (PubMed:20724660). {ECO:0000269|PubMed:14695475, ECO:0000269|PubMed:16547522, ECO:0000269|PubMed:18287044, ECO:0000269|PubMed:19033441, ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20724660, ECO:0000269|PubMed:21518757, ECO:0000269|PubMed:21606507, ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:33567255, ECO:0000269|PubMed:9751060}.; FUNCTION: (Microbial infection) Also considered to be a mediator for HTLV-1 Tax oncoprotein activation of NF-kappa-B. {ECO:0000269|PubMed:10364167, ECO:0000269|PubMed:11064457}. |
| Q9Y6R0 | NUMBL | S324 | ochoa | Numb-like protein (Numb-related protein) (Numb-R) | Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF-kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and degradation of TRAF6 in cortical neurons. {ECO:0000269|PubMed:18299187, ECO:0000269|PubMed:20079715}. |
| P35613 | BSG | S279 | Sugiyama | Basigin (5F7) (Collagenase stimulatory factor) (Extracellular matrix metalloproteinase inducer) (EMMPRIN) (Hepatoma-associated antigen) (HAb18G) (Leukocyte activation antigen M6) (OK blood group antigen) (Tumor cell-derived collagenase stimulatory factor) (TCSF) (CD antigen CD147) | [Isoform 1]: Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes (PubMed:21620857). {ECO:0000250|UniProtKB:P18572, ECO:0000269|PubMed:21620857, ECO:0000269|PubMed:25957687}.; FUNCTION: [Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2. {ECO:0000269|PubMed:22080952}.; FUNCTION: [Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (PubMed:11688976, PubMed:11943775). Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane (PubMed:17127621, PubMed:21778275, PubMed:28666119). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (PubMed:25825981). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells (PubMed:19837976). Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) (PubMed:11992541, PubMed:12553375, PubMed:15833850). {ECO:0000269|PubMed:11688976, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:11992541, ECO:0000269|PubMed:12553375, ECO:0000269|PubMed:15833850, ECO:0000269|PubMed:17127621, ECO:0000269|PubMed:19837976, ECO:0000269|PubMed:21778275, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:28666119}.; FUNCTION: [Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3 (PubMed:22080952, PubMed:26195724). Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866). {ECO:0000269|PubMed:22080952, ECO:0000269|PubMed:26195724, ECO:0000269|PubMed:28409866}.; FUNCTION: [Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:15688292}.; FUNCTION: [Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA. {ECO:0000269|PubMed:11353871}.; FUNCTION: [Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is not required for SARS-CoV-2 infection. {ECO:0000269|PubMed:33432067, ECO:0000303|PubMed:32307653}.; FUNCTION: [Isoform 2]: (Microbial infection) Acts as a receptor for measles virus. {ECO:0000269|PubMed:20147391}.; FUNCTION: [Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells. {ECO:0000269|PubMed:29739904}. |
| Q99816 | TSG101 | S232 | Sugiyama | Tumor susceptibility gene 101 protein (ESCRT-I complex subunit TSG101) | Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may also play a role in the extracellular release of microvesicles that differ from the exosomes (PubMed:22315426). {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:21070952, ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:22660413}. |
| Q9Y2B0 | CNPY2 | S127 | Sugiyama | Protein canopy homolog 2 (MIR-interacting saposin-like protein) (Putative secreted protein Zsig9) (Transmembrane protein 4) | Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation. |
| P12270 | TPR | S135 | Sugiyama | Nucleoprotein TPR (Megator) (NPC-associated intranuclear protein) (Translocated promoter region protein) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:11952838, PubMed:22253824). Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:9864356}. |
| Q8IX12 | CCAR1 | S1091 | Sugiyama | 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}. |
| O43252 | PAPSS1 | S231 | Sugiyama | Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPS synthase 1) (PAPSS 1) (Sulfurylase kinase 1) (SK 1) (SK1) [Includes: Sulfate adenylyltransferase (EC 2.7.7.4) (ATP-sulfurylase) (Sulfate adenylate transferase) (SAT); Adenylyl-sulfate kinase (EC 2.7.1.25) (3'-phosphoadenosine-5'-phosphosulfate synthase) (APS kinase) (Adenosine-5'-phosphosulfate 3'-phosphotransferase) (Adenylylsulfate 3'-phosphotransferase)] | Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway (PubMed:14747722, PubMed:9576487, PubMed:9648242, PubMed:9668121). Required for normal biosynthesis of sulfated L-selectin ligands in endothelial cells (PubMed:9576487). {ECO:0000269|PubMed:14747722, ECO:0000269|PubMed:9576487, ECO:0000269|PubMed:9648242, ECO:0000269|PubMed:9668121}. |
| Q9Y3R0 | GRIP1 | S734 | SIGNOR | Glutamate receptor-interacting protein 1 (GRIP-1) | May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity). {ECO:0000250|UniProtKB:P97879, ECO:0000269|PubMed:10197531}. |
| Q99961 | SH3GL1 | S108 | Sugiyama | Endophilin-A2 (EEN fusion partner of MLL) (Endophilin-2) (Extra eleven-nineteen leukemia fusion gene protein) (EEN) (SH3 domain protein 2B) (SH3 domain-containing GRB2-like protein 1) | Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). {ECO:0000250}. |
| O95259 | KCNH1 | S952 | Sugiyama | Voltage-gated delayed rectifier potassium channel KCNH1 (Ether-a-go-go potassium channel 1) (EAG channel 1) (h-eag) (hEAG1) (Potassium voltage-gated channel subfamily H member 1) (Voltage-gated potassium channel subunit Kv10.1) | Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel that mediates outward-rectifying potassium currents which, on depolarization, reaches a steady-state level and do not inactivate (PubMed:10880439, PubMed:11943152, PubMed:22732247, PubMed:25420144, PubMed:25556795, PubMed:25915598, PubMed:27005320, PubMed:27325704, PubMed:27618660, PubMed:30149017, PubMed:9738473). The activation kinetics depend on the prepulse potential and external divalent cation concentration (PubMed:11943152). With negative prepulses, the current activation is delayed and slowed down several fold, whereas more positive prepulses speed up activation (PubMed:11943152). The time course of activation is biphasic with a fast and a slowly activating current component (PubMed:11943152). Activates at more positive membrane potentials and exhibit a steeper activation curve (PubMed:11943152). Channel properties are modulated by subunit assembly (PubMed:11943152). Mediates IK(NI) current in myoblasts (PubMed:9738473). Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (PubMed:23881642). {ECO:0000269|PubMed:10880439, ECO:0000269|PubMed:11943152, ECO:0000269|PubMed:22732247, ECO:0000269|PubMed:23881642, ECO:0000269|PubMed:25420144, ECO:0000269|PubMed:25556795, ECO:0000269|PubMed:25915598, ECO:0000269|PubMed:27005320, ECO:0000269|PubMed:27325704, ECO:0000269|PubMed:27618660, ECO:0000269|PubMed:30149017, ECO:0000269|PubMed:9738473}. |
| P55769 | SNU13 | S29 | Sugiyama | NHP2-like protein 1 (High mobility group-like nuclear protein 2 homolog 1) (OTK27) (SNU13 homolog) (hSNU13) (U4/U6.U5 small nuclear ribonucleoprotein SNU13) (U4/U6.U5 tri-snRNP 15.5 kDa protein) [Cleaved into: NHP2-like protein 1, N-terminally processed] | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28781166). Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly (PubMed:10545122, PubMed:17412961). The protein undergoes a conformational change upon RNA-binding (PubMed:10545122, PubMed:17412961, PubMed:28781166). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:39570315). {ECO:0000269|PubMed:10545122, ECO:0000269|PubMed:17412961, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| O60664 | PLIN3 | S76 | Sugiyama | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| Q16401 | PSMD5 | S98 | Sugiyama | 26S proteasome non-ATPase regulatory subunit 5 (26S protease subunit S5 basic) (26S proteasome subunit S5B) | Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD5:PSMC2:PSMC1:PSMD2 module which probably assembles with a PSMD10:PSMC4:PSMC5:PAAF1 module followed by dissociation of PSMD5. {ECO:0000269|PubMed:19412159, ECO:0000269|PubMed:19490896}. |
| Q96J02 | ITCH | S162 | SIGNOR | E3 ubiquitin-protein ligase Itchy homolog (Itch) (EC 2.3.2.26) (Atrophin-1-interacting protein 4) (AIP4) (HECT-type E3 ubiquitin transferase Itchy homolog) (NFE2-associated polypeptide 1) (NAPP1) | Acts as an Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11046148, PubMed:14602072, PubMed:15051726, PubMed:16387660, PubMed:17028573, PubMed:18718448, PubMed:18718449, PubMed:19116316, PubMed:19592251, PubMed:19881509, PubMed:20068034, PubMed:20392206, PubMed:20491914, PubMed:23146885, PubMed:24790097, PubMed:25631046). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the negative regulation of MAVS-dependent cellular antiviral responses (PubMed:19881509). Ubiquitinates MAVS through 'Lys-48'-linked conjugation resulting in MAVS proteasomal degradation (PubMed:19881509). Following ligand stimulation, regulates sorting of Wnt receptor FZD4 to the degradative endocytic pathway probably by modulating PI42KA activity (PubMed:23146885). Ubiquitinates PI4K2A and negatively regulates its catalytic activity (PubMed:23146885). Ubiquitinates chemokine receptor CXCR4 and regulates sorting of CXCR4 to the degradative endocytic pathway following ligand stimulation by ubiquitinating endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:14602072, PubMed:23146885, PubMed:34927784). Targets DTX1 for lysosomal degradation and controls NOTCH1 degradation, in the absence of ligand, through 'Lys-29'-linked polyubiquitination (PubMed:17028573, PubMed:18628966, PubMed:23886940). Ubiquitinates SNX9 (PubMed:20491914). Ubiquitinates MAP3K7 through 'Lys-48'-linked conjugation (By similarity). Together with UBR5, involved in the regulation of apoptosis and reactive oxygen species levels through the ubiquitination and proteasomal degradation of TXNIP: catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP (PubMed:20068034, PubMed:29378950). ITCH synthesizes 'Lys-63'-linked chains, while UBR5 is branching multiple 'Lys-48'-linked chains of substrate initially modified (PubMed:29378950). Mediates the antiapoptotic activity of epidermal growth factor through the ubiquitination and proteasomal degradation of p15 BID (PubMed:20392206). Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Inhibits the replication of influenza A virus (IAV) via ubiquitination of IAV matrix protein 1 (M1) through 'Lys-48'-linked conjugation resulting in M1 proteasomal degradation (PubMed:30328013). Ubiquitinates NEDD9/HEF1, resulting in proteasomal degradation of NEDD9/HEF1 (PubMed:15051726). {ECO:0000250|UniProtKB:Q8C863, ECO:0000269|PubMed:14602072, ECO:0000269|PubMed:15051726, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:17028573, ECO:0000269|PubMed:18628966, ECO:0000269|PubMed:18718448, ECO:0000269|PubMed:18718449, ECO:0000269|PubMed:19116316, ECO:0000269|PubMed:19131965, ECO:0000269|PubMed:19592251, ECO:0000269|PubMed:19881509, ECO:0000269|PubMed:20068034, ECO:0000269|PubMed:20392206, ECO:0000269|PubMed:20491914, ECO:0000269|PubMed:23146885, ECO:0000269|PubMed:23886940, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:30328013}. |
| Q13464 | ROCK1 | S418 | 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}. |
| P25205 | MCM3 | S41 | Sugiyama | DNA replication licensing factor MCM3 (EC 3.6.4.12) (DNA polymerase alpha holoenzyme-associated protein P1) (P1-MCM3) (RLF subunit beta) (p102) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (Probable). {ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000305|PubMed:35585232}. |
| Q12906 | ILF3 | S36 | Sugiyama | Interleukin enhancer-binding factor 3 (Double-stranded RNA-binding protein 76) (DRBP76) (M-phase phosphoprotein 4) (MPP4) (Nuclear factor associated with dsRNA) (NFAR) (Nuclear factor of activated T-cells 90 kDa) (NF-AT-90) (Translational control protein 80) (TCP80) | RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651, PubMed:34110282). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552). {ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:28625552, ECO:0000269|PubMed:9442054}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3. {ECO:0000269|PubMed:26891316}. |
| Q14164 | IKBKE | S582 | Sugiyama | Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i) | Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1. {ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265}. |
| Q9Y5J9 | TIMM8B | S50 | Sugiyama | Mitochondrial import inner membrane translocase subunit Tim8 B (DDP-like protein) (Deafness dystonia protein 2) | Probable mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity). {ECO:0000250}. |
| P00966 | ASS1 | S189 | 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}. |
| Q16658 | FSCN1 | S259 | Sugiyama | Fascin (55 kDa actin-bundling protein) (Singed-like protein) (p55) | Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (PubMed:22155786). {ECO:0000269|PubMed:20137952, ECO:0000269|PubMed:20393565, ECO:0000269|PubMed:21685497, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:23184945, ECO:0000269|PubMed:9362073, ECO:0000269|PubMed:9571235}. |
| O95721 | SNAP29 | S210 | Sugiyama | Synaptosomal-associated protein 29 (SNAP-29) (Soluble 29 kDa NSF attachment protein) (Vesicle-membrane fusion protein SNAP-29) | SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions. {ECO:0000269|PubMed:23217709, ECO:0000269|PubMed:25686250, ECO:0000269|PubMed:25686604}. |
| Q6EMK4 | VASN | S488 | Sugiyama | Vasorin (Protein slit-like 2) | May act as an inhibitor of TGF-beta signaling. {ECO:0000269|PubMed:15247411}. |
| Q6FI81 | CIAPIN1 | S170 | Sugiyama | Anamorsin (Cytokine-induced apoptosis inhibitor 1) (Fe-S cluster assembly protein DRE2 homolog) | Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1 (PubMed:23596212). NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit (By similarity). Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells (By similarity). {ECO:0000250|UniProtKB:P36152, ECO:0000250|UniProtKB:Q8WTY4, ECO:0000255|HAMAP-Rule:MF_03115, ECO:0000269|PubMed:23596212}. |
| P00451 | F8 | S1656 | SIGNOR | Coagulation factor VIII (Antihemophilic factor) (AHF) (Procoagulant component) [Cleaved into: Factor VIIIa heavy chain, 200 kDa isoform; Factor VIIIa heavy chain, 92 kDa isoform; Factor VIII B chain; Factor VIIIa light chain] | Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa. |
| Q9BYP7 | WNK3 | S424 | Sugiyama | Serine/threonine-protein kinase WNK3 (EC 2.7.11.1) (Protein kinase lysine-deficient 3) (Protein kinase with no lysine 3) | Serine/threonine-protein kinase component of the WNK3-SPAK/OSR1 kinase cascade, which plays an important role in the regulation of electrolyte homeostasis and regulatory volume increase in response to hyperosmotic stress (PubMed:16275911, PubMed:16275913, PubMed:16501604, PubMed:22989884, PubMed:36318922). WNK3 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK3 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK3-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:22989884). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A4/KCC1, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16275911, PubMed:16275913). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A4/KCC1, SLC12A5/KCC2 and SLC12A6/KCC3 inhibits its activity, blocking ion efflux (PubMed:16275911, PubMed:16275913, PubMed:16357011, PubMed:19470686, PubMed:21613606). Phosphorylates WNK4, possibly regulating the activity of SLC12A3/NCC (PubMed:17975670). May also phosphorylate NEDD4L (PubMed:20525693). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as KCNJ1 and SLC26A9 (PubMed:16357011, PubMed:17673510). Increases Ca(2+) influx mediated by TRPV5 and TRPV6 by enhancing their membrane expression level via a kinase-dependent pathway (PubMed:18768590). {ECO:0000269|PubMed:16275911, ECO:0000269|PubMed:16275913, ECO:0000269|PubMed:16357011, ECO:0000269|PubMed:16501604, ECO:0000269|PubMed:17673510, ECO:0000269|PubMed:17975670, ECO:0000269|PubMed:18768590, ECO:0000269|PubMed:19470686, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:36318922}. |
| Q14524 | SCN5A | S1865 | 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}. |
| A0A0U1RQV5 | None | S27 | ochoa | Eukaryotic translation initiation factor 6 | None |
| O00139 | KIF2A | S207 | ochoa | Kinesin-like protein KIF2A (Kinesin-2) (hK2) | Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity. {ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:17538014, ECO:0000269|PubMed:18411309, ECO:0000269|PubMed:30785839}. |
| O00267 | SUPT5H | S744 | ochoa | Transcription elongation factor SPT5 (hSPT5) (DRB sensitivity-inducing factor 160 kDa subunit) (DSIF p160) (DRB sensitivity-inducing factor large subunit) (DSIF large subunit) (Tat-cotransactivator 1 protein) (Tat-CT1 protein) | Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A (PubMed:10075709, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter (PubMed:10075709, PubMed:10199401, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex (PubMed:10075709, PubMed:10199401, PubMed:10421630, PubMed:10757782, PubMed:10912001, PubMed:11112772, PubMed:11553615, PubMed:12653964, PubMed:12718890, PubMed:15136722, PubMed:15380072, PubMed:9450929, PubMed:9857195). DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II (PubMed:16214896). TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme (PubMed:16214896). Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites (PubMed:16214896). Following phosphorylation by CDK9, DSIF can also positively regulate transcriptional elongation (PubMed:16427012). Required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat (PubMed:10393184, PubMed:10454543, PubMed:11809800, PubMed:9514752). DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences (PubMed:11112772, PubMed:14701750). {ECO:0000269|PubMed:10075709, ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10421630, ECO:0000269|PubMed:10454543, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11553615, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:12653964, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15136722, ECO:0000269|PubMed:15380072, ECO:0000269|PubMed:16214896, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:9450929, ECO:0000269|PubMed:9514752, ECO:0000269|PubMed:9857195}. |
| O00764 | PDXK | S261 | ochoa | Pyridoxal kinase (EC 2.7.1.35) (Pyridoxine kinase) | Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (Probable) (PubMed:10987144, PubMed:17766369, PubMed:19351586, PubMed:31187503, PubMed:9099727). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions. {ECO:0000269|PubMed:10987144, ECO:0000269|PubMed:17766369, ECO:0000269|PubMed:19351586, ECO:0000269|PubMed:31187503, ECO:0000269|PubMed:9099727, ECO:0000305}. |
| O14641 | DVL2 | S227 | ochoa | Segment polarity protein dishevelled homolog DVL-2 (Dishevelled-2) (DSH homolog 2) | Plays a role in the signal transduction pathways mediated by multiple Wnt genes (PubMed:24616100). Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:19252499, ECO:0000269|PubMed:24616100}. |
| O14686 | KMT2D | S2016 | ochoa | Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}. |
| O14965 | AURKA | S53 | ochoa | Aurora kinase A (EC 2.7.11.1) (Aurora 2) (Aurora/IPL1-related kinase 1) (ARK-1) (Aurora-related kinase 1) (Breast tumor-amplified kinase) (Ipl1- and aurora-related kinase 1) (Serine/threonine-protein kinase 15) (Serine/threonine-protein kinase 6) (Serine/threonine-protein kinase Ayk1) (Serine/threonine-protein kinase aurora-A) | Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735). {ECO:0000250|UniProtKB:A0A8I3S724, ECO:0000269|PubMed:11039908, ECO:0000269|PubMed:11551964, ECO:0000269|PubMed:12390251, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:14523000, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15128871, ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:15987997, ECO:0000269|PubMed:17125279, ECO:0000269|PubMed:17360485, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19668197, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:27192185, ECO:0000269|PubMed:27335426, ECO:0000269|PubMed:28218735}. |
| O15503 | INSIG1 | S190 | 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}. |
| O43298 | ZBTB43 | S200 | ochoa | Zinc finger and BTB domain-containing protein 43 (Zinc finger and BTB domain-containing protein 22B) (Zinc finger protein 297B) (ZnF-x) | May be involved in transcriptional regulation. |
| O43303 | CCP110 | S854 | ochoa | Centriolar coiled-coil protein of 110 kDa (Centrosomal protein of 110 kDa) (CP110) (Cep110) | Necessary for centrosome duplication at different stages of procentriole formation. Acts as a key negative regulator of ciliogenesis in collaboration with CEP97 by capping the mother centriole thereby preventing cilia formation (PubMed:17681131, PubMed:17719545, PubMed:23486064, PubMed:30375385, PubMed:35301795). Also involved in promoting ciliogenesis. May play a role in the assembly of the mother centriole subdistal appendages (SDA) thereby effecting the fusion of recycling endosomes to basal bodies during cilia formation (By similarity). Required for correct spindle formation and has a role in regulating cytokinesis and genome stability via cooperation with CALM1 and CETN2 (PubMed:16760425). {ECO:0000250|UniProtKB:Q7TSH4, ECO:0000269|PubMed:12361598, ECO:0000269|PubMed:16760425, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:17719545, ECO:0000269|PubMed:23486064, ECO:0000269|PubMed:30375385, ECO:0000269|PubMed:35301795}. |
| O43765 | SGTA | S88 | ochoa | Small glutamine-rich tetratricopeptide repeat-containing protein alpha (Alpha-SGT) (Vpu-binding protein) (UBP) | Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails (PubMed:28104892). Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module (PubMed:28104892). Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins (PubMed:25535373, PubMed:28104892). It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states (PubMed:23129660, PubMed:25179605). Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex (PubMed:27193484). Binds directly to HSC70 and HSP70 and regulates their ATPase activity (PubMed:18759457). {ECO:0000269|PubMed:18759457, ECO:0000269|PubMed:23129660, ECO:0000269|PubMed:25179605, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:27193484, ECO:0000269|PubMed:28104892}.; FUNCTION: (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection via interaction with DNAJB12, DNAJB14 and HSPA8/Hsc70 (PubMed:24675744). {ECO:0000269|PubMed:24675744}. |
| O60256 | PRPSAP2 | S240 | ochoa | Phosphoribosyl pyrophosphate synthase-associated protein 2 (PRPP synthase-associated protein 2) (41 kDa phosphoribosypyrophosphate synthetase-associated protein) (PAP41) | Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis. |
| O60260 | PRKN | S101 | psp | E3 ubiquitin-protein ligase parkin (Parkin) (EC 2.3.2.31) (Parkin RBR E3 ubiquitin-protein ligase) (Parkinson juvenile disease protein 2) (Parkinson disease protein 2) | Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753, PubMed:21376232, PubMed:21532592, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:29311685, PubMed:32047033). Substrates include SYT11 and VDAC1 (PubMed:29311685, PubMed:32047033). Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2 (PubMed:10888878, PubMed:10973942, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753, PubMed:21376232, PubMed:21532592, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:24660806, PubMed:24751536). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25474007, PubMed:25621951, PubMed:32047033). Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11431533, PubMed:11590439, PubMed:15105460, PubMed:15728840, PubMed:19229105). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy (PubMed:20889974). Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:11439185, PubMed:18957282, PubMed:19029340, PubMed:19966284, PubMed:21376232, PubMed:22082830, PubMed:22396657, PubMed:23620051, PubMed:23933751, PubMed:24660806, PubMed:24784582, PubMed:24896179, PubMed:25474007, PubMed:25527291, PubMed:32047033). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:11439185, PubMed:19029340, PubMed:19801972, PubMed:19966284, PubMed:21376232, PubMed:22082830, PubMed:22396657, PubMed:23620051, PubMed:23685073, PubMed:23933751, PubMed:24896179, PubMed:25527291, PubMed:32047033, PubMed:33499712). Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin (PubMed:24660806, PubMed:24784582, PubMed:25474007, PubMed:25527291). After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:27534820, PubMed:32047033). When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:21753002, PubMed:22396657, PubMed:23620051, PubMed:23685073, PubMed:23933751, PubMed:24896179, PubMed:25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy (PubMed:25621951, PubMed:32047033). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:23620051). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:23620051). Regulates motility of damaged mitochondria via 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). Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A (PubMed:21376232). Limits the production of reactive oxygen species (ROS) (PubMed:18541373). Regulates cyclin-E during neuronal apoptosis (PubMed:12628165). In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene (PubMed:12719539). {ECO:0000269|PubMed:10888878, ECO:0000269|PubMed:10973942, ECO:0000269|PubMed:11431533, ECO:0000269|PubMed:11439185, ECO:0000269|PubMed:11590439, ECO:0000269|PubMed:12150907, ECO:0000269|PubMed:12628165, ECO:0000269|PubMed:12719539, ECO:0000269|PubMed:15105460, ECO:0000269|PubMed:15728840, ECO:0000269|PubMed:16135753, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:18541373, ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19029340, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19801972, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:21753002, ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23685073, 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:25474007, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:25621951, ECO:0000269|PubMed:27534820, ECO:0000269|PubMed:29311685, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:33499712}. |
| O60341 | KDM1A | S687 | psp | Lysine-specific histone demethylase 1A (EC 1.14.99.66) (BRAF35-HDAC complex protein BHC110) (Flavin-containing amine oxidase domain-containing protein 2) ([histone H3]-dimethyl-L-lysine(4) FAD-dependent demethylase 1A) | Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:16079795, PubMed:16140033, PubMed:16223729, PubMed:27292636). Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed (PubMed:15620353, PubMed:15811342, PubMed:16079794, PubMed:21300290). Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me (PubMed:15620353, PubMed:20389281, PubMed:21300290, PubMed:23721412). May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity (PubMed:16079794, PubMed:16140033, PubMed:16885027, PubMed:21300290, PubMed:23721412). Also acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in AR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A (PubMed:16079795). Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1 (PubMed:29691401). Demethylates methylated 'Lys-42' and methylated 'Lys-117' of SOX2 (PubMed:29358331). Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (PubMed:16079794, PubMed:16140033). Facilitates epithelial-to-mesenchymal transition by acting as an effector of SNAI1-mediated transcription repression of epithelial markers E-cadherin/CDH1, CDN7 and KRT8 (PubMed:20562920, PubMed:27292636). Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7 (PubMed:20389281). Required for the repression of GIPR expression (PubMed:34655521, PubMed:34906447). {ECO:0000269|PubMed:12032298, ECO:0000269|PubMed:15620353, ECO:0000269|PubMed:15811342, ECO:0000269|PubMed:16079794, ECO:0000269|PubMed:16079795, ECO:0000269|PubMed:16140033, ECO:0000269|PubMed:16223729, ECO:0000269|PubMed:16885027, ECO:0000269|PubMed:16956976, ECO:0000269|PubMed:17805299, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:23721412, ECO:0000269|PubMed:27292636, ECO:0000269|PubMed:29358331, ECO:0000269|PubMed:29691401, ECO:0000269|PubMed:34655521, ECO:0000269|PubMed:34906447}. |
| O75022 | LILRB3 | S522 | ochoa | Leukocyte immunoglobulin-like receptor subfamily B member 3 (LIR-3) (Leukocyte immunoglobulin-like receptor 3) (CD85 antigen-like family member A) (Immunoglobulin-like transcript 5) (ILT-5) (Monocyte inhibitory receptor HL9) (CD antigen CD85a) | May act as receptor for class I MHC antigens. Becomes activated upon coligation of LILRB3 and immune receptors, such as FCGR2B and the B-cell receptor. Down-regulates antigen-induced B-cell activation by recruiting phosphatases to its immunoreceptor tyrosine-based inhibitor motifs (ITIM). {ECO:0000250|UniProtKB:P97484}. |
| O75069 | TMCC2 | S78 | ochoa | Transmembrane and coiled-coil domains protein 2 (Cerebral protein 11) | May be involved in the regulation of the proteolytic processing of the amyloid precursor protein (APP) possibly also implicating APOE. {ECO:0000269|PubMed:21593558}. |
| O75112 | LDB3 | S508 | ochoa | LIM domain-binding protein 3 (Protein cypher) (Z-band alternatively spliced PDZ-motif protein) | May function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton. {ECO:0000305}. |
| O75151 | PHF2 | S638 | ochoa | Lysine-specific demethylase PHF2 (EC 1.14.11.-) (GRC5) (PHD finger protein 2) | Lysine demethylase that demethylates both histones and non-histone proteins (PubMed:20129925, PubMed:21167174, PubMed:21532585). Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B (PubMed:21532585). Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes (PubMed:21532585). The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA (PubMed:21532585). Involved in the activation of toll-like receptor 4 (TLR4)-target inflammatory genes in macrophages by catalyzing the demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the gene promoters (By similarity). {ECO:0000250|UniProtKB:Q9WTU0, ECO:0000269|PubMed:20129925, ECO:0000269|PubMed:21167174, ECO:0000269|PubMed:21532585}. |
| O75152 | ZC3H11A | S370 | ochoa | Zinc finger CCCH domain-containing protein 11A | Through its association with TREX complex components, may participate in the export and post-transcriptional coordination of selected mRNA transcripts, including those required to maintain the metabolic processes in embryonic cells (PubMed:22928037, PubMed:37356722). Binds RNA (PubMed:29610341, PubMed:37356722). {ECO:0000269|PubMed:22928037, ECO:0000269|PubMed:29610341, ECO:0000269|PubMed:37356722}.; FUNCTION: (Microbial infection) Plays a role in efficient growth of several nuclear-replicating viruses such as HIV-1, influenza virus or herpes simplex virus 1/HHV-1. Required for efficient viral mRNA export (PubMed:29610341). May be required for proper polyadenylation of adenovirus type 5/HAdV-5 capsid mRNA (PubMed:37356722). {ECO:0000269|PubMed:29610341, ECO:0000269|PubMed:37356722}. |
| O75676 | RPS6KA4 | S721 | ochoa | Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| O95235 | KIF20A | S683 | ochoa|psp | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95490 | ADGRL2 | S1365 | 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}. |
| O95905 | ECD | S154 | ochoa | Protein ecdysoneless homolog (Human suppressor of GCR two) (hSGT1) | Regulator of p53/TP53 stability and function. Inhibits MDM2-mediated degradation of p53/TP53 possibly by cooperating in part with TXNIP (PubMed:16849563, PubMed:23880345). May be involved transcriptional regulation. In vitro has intrinsic transactivation activity enhanced by EP300. May be a transcriptional activator required for the expression of glycolytic genes (PubMed:19919181, PubMed:9928932). Involved in regulation of cell cycle progression. Proposed to disrupt Rb-E2F binding leading to transcriptional activation of E2F proteins (PubMed:19640839). The cell cycle -regulating function may depend on its RUVBL1-mediated association with the R2TP complex (PubMed:26711270). May play a role in regulation of pre-mRNA splicing (PubMed:24722212). Participates together with DDX39A in mRNA nuclear export (PubMed:33941617). {ECO:0000269|PubMed:16849563, ECO:0000269|PubMed:19640839, ECO:0000269|PubMed:19919181, ECO:0000269|PubMed:23880345, ECO:0000269|PubMed:26711270, ECO:0000269|PubMed:33941617, ECO:0000305|PubMed:24722212, ECO:0000305|PubMed:9928932}. |
| P01111 | NRAS | S89 | psp | GTPase NRas (EC 3.6.5.2) (Transforming protein N-Ras) | Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. {ECO:0000269|PubMed:30712867}. |
| P02671 | FGA | S436 | ochoa | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P04180 | LCAT | S205 | psp | Phosphatidylcholine-sterol acyltransferase (EC 2.3.1.43) (1-alkyl-2-acetylglycerophosphocholine esterase) (EC 3.1.1.47) (Lecithin-cholesterol acyltransferase) (Phospholipid-cholesterol acyltransferase) (Platelet-activating factor acetylhydrolase) (PAF acetylhydrolase) | Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs) (PubMed:10329423, PubMed:19065001, PubMed:26195816). The cholesterol ester is then transported back to the liver. Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines (PubMed:8820107). Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms (PubMed:10722751). Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:8016111). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF (PubMed:8016111). Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters (PubMed:24620755). {ECO:0000269|PubMed:10329423, ECO:0000269|PubMed:10722751, ECO:0000269|PubMed:12354767, ECO:0000269|PubMed:14636062, ECO:0000269|PubMed:19065001, ECO:0000269|PubMed:24620755, ECO:0000269|PubMed:26195816, ECO:0000269|PubMed:8016111, ECO:0000269|PubMed:8820107}. |
| P04406 | GAPDH | S151 | ochoa | Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) (Peptidyl-cysteine S-nitrosylase GAPDH) (EC 2.6.99.-) | Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively (PubMed:11724794, PubMed:3170585). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (PubMed:11724794, PubMed:3170585). Modulates the organization and assembly of the cytoskeleton (By similarity). Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (PubMed:23332158, PubMed:27387501). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis (By similarity). Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity). {ECO:0000250|UniProtKB:P04797, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:23071094, ECO:0000269|PubMed:23332158, ECO:0000269|PubMed:27387501, ECO:0000269|PubMed:3170585}. |
| P05165 | PCCA | S252 | ochoa | Propionyl-CoA carboxylase alpha chain, mitochondrial (PCCase subunit alpha) (EC 6.4.1.3) (Propanoyl-CoA:carbon dioxide ligase subunit alpha) | This is one of the 2 subunits of the biotin-dependent propionyl-CoA carboxylase (PCC), a mitochondrial enzyme involved in the catabolism of odd chain fatty acids, branched-chain amino acids isoleucine, threonine, methionine, and valine and other metabolites (PubMed:6765947, PubMed:8434582). Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-CoA/(S)-methylmalonyl-CoA (PubMed:10101253, PubMed:6765947, PubMed:8434582). Within the holoenzyme, the alpha subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, while the beta subunit then transfers the carboxyl group from carboxylated biotin to propionyl-CoA (By similarity). Propionyl-CoA carboxylase also significantly acts on butyryl-CoA/butanoyl-CoA, which is converted to ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA at a much lower rate (PubMed:6765947). Other alternative minor substrates include (2E)-butenoyl-CoA/crotonoyl-CoA (By similarity). {ECO:0000250|UniProtKB:P0DTA4, ECO:0000250|UniProtKB:Q5LUF3, ECO:0000269|PubMed:10101253, ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582}. |
| P05771 | PRKCB | S234 | ochoa | Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}. |
| P07203 | GPX1 | S34 | ochoa | Glutathione peroxidase 1 (GPx-1) (GSHPx-1) (EC 1.11.1.9) (Cellular glutathione peroxidase) (Phospholipid-hydroperoxide glutathione peroxidase GPX1) (EC 1.11.1.12) | Catalyzes the reduction of hydroperoxides in a glutathione-dependent manner thus regulating cellular redox homeostasis (PubMed:11115402, PubMed:36608588). Can reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide, as well as several fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). In platelets catalyzes the reduction of 12-hydroperoxyeicosatetraenoic acid, the primary product of the arachidonate 12-lipoxygenase pathway (PubMed:11115402). {ECO:0000269|PubMed:11115402, ECO:0000269|PubMed:36608588}. |
| P07355 | ANXA2 | S184 | ochoa | Annexin A2 (Annexin II) (Annexin-2) (Calpactin I heavy chain) (Calpactin-1 heavy chain) (Chromobindin-8) (Lipocortin II) (Placental anticoagulant protein IV) (PAP-IV) (Protein I) (p36) | Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9 (PubMed:18799458, PubMed:22848640, PubMed:24808179). Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation (By similarity). Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis (By similarity). {ECO:0000250|UniProtKB:P07356, ECO:0000269|PubMed:18799458, ECO:0000269|PubMed:22848640, ECO:0000269|PubMed:24808179}.; FUNCTION: (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen. {ECO:0000269|PubMed:25139904}. |
| P07814 | EPRS1 | S747 | 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}. |
| P08758 | ANXA5 | S230 | ochoa | Annexin A5 (Anchorin CII) (Annexin V) (Annexin-5) (Calphobindin I) (CPB-I) (Endonexin II) (Lipocortin V) (Placental anticoagulant protein 4) (PP4) (Placental anticoagulant protein I) (PAP-I) (Thromboplastin inhibitor) (Vascular anticoagulant-alpha) (VAC-alpha) | This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. |
| P09693 | CD3G | S148 | ochoa|psp | T-cell surface glycoprotein CD3 gamma chain (T-cell receptor T3 gamma chain) (CD antigen CD3g) | Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:2470098). In addition to this role of signal transduction in T-cell activation, CD3G plays an essential role in the dynamic regulation of TCR expression at the cell surface (PubMed:8187769). Indeed, constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3G. {ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:8187769, ECO:0000269|PubMed:8636209}. |
| P10451 | SPP1 | S239 | psp | Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) | Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}. |
| P11473 | VDR | S51 | psp | Vitamin D3 receptor (VDR) (1,25-dihydroxyvitamin D3 receptor) (Nuclear receptor subfamily 1 group I member 1) | Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:10678179, PubMed:15728261, PubMed:16913708, PubMed:28698609, PubMed:37478846). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638). {ECO:0000250|UniProtKB:P13053, ECO:0000269|PubMed:10678179, ECO:0000269|PubMed:12016314, ECO:0000269|PubMed:15728261, ECO:0000269|PubMed:16913708, ECO:0000269|PubMed:28698609, ECO:0000269|PubMed:32354638, ECO:0000269|PubMed:37478846}. |
| P12956 | XRCC6 | S77 | psp | X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6) | Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Also has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Has a role in chromosome translocation (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). It works in the 3'-5' direction (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Binding to DNA may be mediated by XRCC6 (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer acts as a regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:11493912, PubMed:12145306, PubMed:20493174, PubMed:2466842, PubMed:7957065, PubMed:8621488, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Negatively regulates apoptosis by interacting with BAX and sequestering it from the mitochondria (PubMed:15023334). Might have deubiquitination activity, acting on BAX (PubMed:18362350). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:18362350, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. |
| P14618 | PKM | S425 | ochoa | Pyruvate kinase PKM (EC 2.7.1.40) (Cytosolic thyroid hormone-binding protein) (CTHBP) (Opa-interacting protein 3) (OIP-3) (Pyruvate kinase 2/3) (Pyruvate kinase muscle isozyme) (Threonine-protein kinase PKM2) (EC 2.7.11.1) (Thyroid hormone-binding protein 1) (THBP1) (Tumor M2-PK) (Tyrosine-protein kinase PKM2) (EC 2.7.10.2) (p58) | Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). {ECO:0000269|PubMed:15996096, ECO:0000269|PubMed:1854723, ECO:0000269|PubMed:20847263}.; FUNCTION: [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). {ECO:0000250|UniProtKB:P52480, ECO:0000269|PubMed:17308100, ECO:0000269|PubMed:18191611, ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263, ECO:0000269|PubMed:21620138, ECO:0000269|PubMed:22056988, ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:22901803, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:26787900}.; FUNCTION: [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). {ECO:0000269|PubMed:18337823, ECO:0000269|PubMed:20847263}. |
| P15924 | DSP | S957 | 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 | S809 | ochoa | Integrin beta-4 (GP150) (CD antigen CD104) | Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}. |
| P22681 | CBL | S705 | ochoa | E3 ubiquitin-protein ligase CBL (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene) (Proto-oncogene c-Cbl) (RING finger protein 55) (RING-type E3 ubiquitin transferase CBL) (Signal transduction protein CBL) | E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, PubMed:19689429, PubMed:21596750, PubMed:28381567). Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signaling (PubMed:15190072, PubMed:18374639, PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates NECTIN1 following association between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, leading to NECTIN1 removal from cell surface (PubMed:28381567). Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis (PubMed:15190072, PubMed:18374639). Essential for osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:P22682, ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17094949, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:28381567}. |
| P23142 | FBLN1 | S147 | ochoa | Fibulin-1 (FIBL-1) | Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes. Has been implicated in a role in cellular transformation and tumor invasion, it appears to be a tumor suppressor. May play a role in haemostasis and thrombosis owing to its ability to bind fibrinogen and incorporate into clots. Could play a significant role in modulating the neurotrophic activities of APP, particularly soluble APP. {ECO:0000269|PubMed:11792823, ECO:0000269|PubMed:9393974, ECO:0000269|PubMed:9466671}. |
| P23246 | SFPQ | S491 | ochoa | Splicing factor, proline- and glutamine-rich (100 kDa DNA-pairing protein) (hPOMp100) (DNA-binding p52/p100 complex, 100 kDa subunit) (Polypyrimidine tract-binding protein-associated-splicing factor) (PSF) (PTB-associated-splicing factor) | DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA (PubMed:25765647). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as a transcriptional activator (PubMed:25765647). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as a transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF1-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000250|UniProtKB:Q8VIJ6, ECO:0000269|PubMed:10847580, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:10931916, ECO:0000269|PubMed:11259580, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:25765647, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:8045264, ECO:0000269|PubMed:8449401}. |
| P25445 | FAS | S209 | ochoa | Tumor necrosis factor receptor superfamily member 6 (Apo-1 antigen) (Apoptosis-mediating surface antigen FAS) (FASLG receptor) (CD antigen CD95) | Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase CASP8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs CASP8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro). {ECO:0000269|PubMed:19118384, ECO:0000269|PubMed:7533181, ECO:0000269|PubMed:9184224}. |
| P29374 | ARID4A | S827 | ochoa | AT-rich interactive domain-containing protein 4A (ARID domain-containing protein 4A) (Retinoblastoma-binding protein 1) (RBBP-1) | DNA-binding protein which modulates activity of several transcription factors including RB1 (retinoblastoma-associated protein) and AR (androgen receptor) (By similarity). May function as part of an mSin3A repressor complex (PubMed:14581478). Has no intrinsic transcriptional activity (By similarity). Plays a role in the regulation of epigenetic modifications at the PWS/AS imprinting center near the SNRPN promoter, where it might function as part of a complex with RB1 and ARID4B (By similarity). Involved in spermatogenesis, together with ARID4B, where it acts as a transcriptional coactivator for AR and enhances expression of genes required for sperm maturation. Regulates expression of the tight junction protein CLDN3 in the testis, which is important for integrity of the blood-testis barrier (By similarity). Plays a role in myeloid homeostasis where it regulates the histone methylation state of bone marrow cells and expression of various genes involved in hematopoiesis. May function as a leukemia suppressor (By similarity). {ECO:0000250|UniProtKB:F8VPQ2, ECO:0000269|PubMed:14581478}. |
| P30622 | CLIP1 | S1371 | ochoa | CAP-Gly domain-containing linker protein 1 (Cytoplasmic linker protein 1) (Cytoplasmic linker protein 170 alpha-2) (CLIP-170) (Reed-Sternberg intermediate filament-associated protein) (Restin) | Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking. {ECO:0000269|PubMed:12433698, ECO:0000269|PubMed:17563362, ECO:0000269|PubMed:17889670}. |
| P35606 | COPB2 | S847 | ochoa | Coatomer subunit beta' (Beta'-coat protein) (Beta'-COP) (p102) | The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. {ECO:0000269|PubMed:34450031}.; FUNCTION: This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner (By similarity). {ECO:0000250}. |
| P40227 | CCT6A | S200 | ochoa | T-complex protein 1 subunit zeta (TCP-1-zeta) (EC 3.6.1.-) (Acute morphine dependence-related protein 2) (CCT-zeta-1) (Chaperonin containing T-complex polypeptide 1 subunit 6A) (HTR3) (Tcp20) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). {ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P46013 | MKI67 | S969 | 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}. |
| P46779 | RPL28 | S37 | ochoa | Large ribosomal subunit protein eL28 (60S ribosomal protein L28) | Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000305|PubMed:12962325}. |
| P47712 | PLA2G4A | S515 | psp | Cytosolic phospholipase A2 (cPLA2) (Phospholipase A2 group IVA) [Includes: Phospholipase A2 (EC 3.1.1.4) (Phosphatidylcholine 2-acylhydrolase); Lysophospholipase (EC 3.1.1.5)] | Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (PubMed:10358058, PubMed:14709560, PubMed:16617059, PubMed:17472963, PubMed:18451993, PubMed:27642067, PubMed:7794891, PubMed:8619991, PubMed:8702602, PubMed:9425121). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:8619991, PubMed:9425121). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway (PubMed:10358058, PubMed:17472963, PubMed:18451993, PubMed:7794891, PubMed:9425121). In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids (PubMed:27642067). Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific (PubMed:7794891). Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides (PubMed:12672805). Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (PubMed:7794891). {ECO:0000250|UniProtKB:P47713, ECO:0000269|PubMed:10358058, ECO:0000269|PubMed:12672805, ECO:0000269|PubMed:14709560, ECO:0000269|PubMed:16617059, ECO:0000269|PubMed:17472963, ECO:0000269|PubMed:18451993, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7794891, ECO:0000269|PubMed:8619991, ECO:0000269|PubMed:8702602, ECO:0000269|PubMed:9425121}. |
| P48729 | CSNK1A1 | S218 | psp | Casein kinase I isoform alpha (CKI-alpha) (EC 2.7.11.1) (CK1) | Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (PubMed:11955436, PubMed:1409656, PubMed:18305108, PubMed:23902688). It can phosphorylate a large number of proteins (PubMed:11955436, PubMed:1409656, PubMed:18305108, PubMed:23902688). Participates in Wnt signaling (PubMed:11955436). Phosphorylates CTNNB1 at 'Ser-45' (PubMed:11955436). May phosphorylate PER1 and PER2 (By similarity). May play a role in segregating chromosomes during mitosis (PubMed:1409656). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688). Acts as a positive regulator of mTORC1 and mTORC2 signaling in response to nutrients by mediating phosphorylation of DEPTOR inhibitor (PubMed:22017875, PubMed:22017877). Acts as an inhibitor of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). {ECO:0000250|UniProtKB:Q8BK63, ECO:0000269|PubMed:11955436, ECO:0000269|PubMed:1409656, ECO:0000269|PubMed:18305108, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:23902688}. |
| P49116 | NR2C2 | S96 | ochoa | Nuclear receptor subfamily 2 group C member 2 (Orphan nuclear receptor TAK1) (Orphan nuclear receptor TR4) (Testicular receptor 4) | Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation. {ECO:0000250, ECO:0000269|PubMed:10347174, ECO:0000269|PubMed:10644740, ECO:0000269|PubMed:17974920, ECO:0000269|PubMed:7779113, ECO:0000269|PubMed:9556573}. |
| P49327 | FASN | S51 | 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}. |
| P49685 | GPR15 | S335 | ochoa | G-protein coupled receptor 15 (Brother of Bonzo) (BoB) | G protein-coupled receptor that plays an important role in immune homeostasis (PubMed:33758080, PubMed:38918398). Acts via its natural ligand GPR15LG, a chemokine-like polypeptide strongly expressed in gastrointestinal tissues. GPR15-GPR15LG signaling axis regulates intestinal homeostasis and inflammation through the migration of immune cells (PubMed:33758080, PubMed:38918398). Controls thereby the specific homing of T-cells, particularly FOXP3+ regulatory T-cells (Tregs), to the large intestine lamina propria (By similarity). Also required for skin localization of thymus-derived dendritic epidermal T-cells (By similarity). Plays an important role in mediating cytoprotective function as well as angiogenesis of thrombomodulin (By similarity). Mechanistically, preferentially signals through the Gi/o pathway to inhibit adenylate cyclase activity and activate a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:35510660). {ECO:0000250|UniProtKB:Q0VDU3, ECO:0000269|PubMed:33758080, ECO:0000269|PubMed:35510660, ECO:0000269|PubMed:38918398}.; FUNCTION: (Microbial infection) Acts as an alternative coreceptor with CD4 for HIV-1 infection. {ECO:0000269|PubMed:9791028}. |
| P49792 | RANBP2 | S1263 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49796 | RGS3 | S992 | ochoa | Regulator of G-protein signaling 3 (RGP3) (RGS3) | Down-regulates signaling from heterotrimeric G-proteins by increasing the GTPase activity of the alpha subunits, thereby driving them into their inactive GDP-bound form. Down-regulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. {ECO:0000269|PubMed:10749886, ECO:0000269|PubMed:11294858, ECO:0000269|PubMed:8602223, ECO:0000269|PubMed:9858594}. |
| P50479 | PDLIM4 | S208 | 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}. |
| P51116 | FXR2 | S622 | ochoa | RNA-binding protein FXR2 (FXR2P) (FMR1 autosomal homolog 2) | mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for adult hippocampal neurogenesis (By similarity). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs: mRNAs storage into membraneless compartments regulates their translation and/or stability (By similarity). Acts as a regulator of adult hippocampal neurogenesis by regulating translation and/or stability of NOG mRNA, thereby preventing NOG protein expression in the dentate gyrus (By similarity). {ECO:0000250|UniProtKB:Q61584, ECO:0000250|UniProtKB:Q9WVR4}. |
| P52895 | AKR1C2 | S166 | 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}. |
| P54259 | ATN1 | S107 | ochoa | Atrophin-1 (Dentatorubral-pallidoluysian atrophy protein) | Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats. {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:10973986}. |
| P54274 | TERF1 | S114 | psp | Telomeric repeat-binding factor 1 (NIMA-interacting protein 2) (TTAGGG repeat-binding factor 1) (Telomeric protein Pin2/TRF1) | Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. {ECO:0000269|PubMed:16166375}. |
| P54707 | ATP12A | S499 | ochoa | Potassium-transporting ATPase alpha chain 2 (HK alpha 2) (Non-gastric H(+)/K(+) ATPase subunit alpha) (EC 7.2.2.19) (Non-gastric Na(+)/K(+) ATPase subunit alpha) (EC 7.2.2.13) (Proton pump) (Sodium pump) | The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment (PubMed:11341842, PubMed:7485470, PubMed:8853415, PubMed:9774385). Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon (By similarity). In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance (PubMed:29391451). {ECO:0000250|UniProtKB:Q9Z1W8, ECO:0000269|PubMed:11341842, ECO:0000269|PubMed:29391451, ECO:0000269|PubMed:7485470, ECO:0000269|PubMed:8853415, ECO:0000269|PubMed:9774385}. |
| P56470 | LGALS4 | S229 | ochoa | Galectin-4 (Gal-4) (Antigen NY-CO-27) (L-36 lactose-binding protein) (L36LBP) (Lactose-binding lectin 4) | Galectin that binds lactose and a related range of sugars. May be involved in the assembly of adherens junctions. |
| P56537 | EIF6 | S175 | ochoa|psp | 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}. |
| P61925 | PKIA | S32 | ochoa | cAMP-dependent protein kinase inhibitor alpha (PKI-alpha) (cAMP-dependent protein kinase inhibitor, muscle/brain isoform) | Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains. |
| P62491 | RAB11A | S115 | 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}. |
| P82094 | TMF1 | S349 | 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}. |
| Q03164 | KMT2A | S1004 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q03164 | KMT2A | S1119 | ochoa | Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] | Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}. |
| Q04206 | RELA | S472 | psp | Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148}. |
| Q05209 | PTPN12 | S449 | ochoa | Tyrosine-protein phosphatase non-receptor type 12 (EC 3.1.3.48) (PTP-PEST) (Protein-tyrosine phosphatase G1) (PTPG1) | Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades (PubMed:18559503). Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2 (PubMed:17329398, PubMed:27134172). Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (PubMed:27134172). {ECO:0000269|PubMed:17329398, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:27134172}. |
| Q06710 | PAX8 | S217 | 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. |
| Q07864 | POLE | S2077 | ochoa | DNA polymerase epsilon catalytic subunit A (EC 2.7.7.7) (3'-5' exodeoxyribonuclease) (EC 3.1.11.-) (DNA polymerase II subunit A) | Catalytic component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in chromosomal DNA replication (By similarity). Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199). Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374). {ECO:0000250|UniProtKB:P21951, ECO:0000269|PubMed:10801849, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:27573199}. |
| Q08209 | PPP3CA | S438 | ochoa | Protein phosphatase 3 catalytic subunit alpha (EC 3.1.3.16) (CAM-PRP catalytic subunit) (Calcineurin A alpha) (Calmodulin-dependent calcineurin A subunit alpha isoform) (CNA alpha) (Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform) | Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T-cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679). {ECO:0000250|UniProtKB:P48452, ECO:0000250|UniProtKB:P63328, ECO:0000250|UniProtKB:P63329, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:17498738, ECO:0000269|PubMed:17502104, ECO:0000269|PubMed:18838687, ECO:0000269|PubMed:19154138, ECO:0000269|PubMed:22343722, ECO:0000269|PubMed:23468591, ECO:0000269|PubMed:26248042, ECO:0000269|PubMed:27974827, ECO:0000269|PubMed:30254215, ECO:0000269|PubMed:30611118, ECO:0000269|PubMed:30718414, ECO:0000269|PubMed:31375679, ECO:0000269|PubMed:33691586}. |
| Q12802 | AKAP13 | S1895 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12824 | SMARCB1 | S129 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (BRG1-associated factor 47) (BAF47) (Integrase interactor 1 protein) (SNF5 homolog) (hSNF5) | Core component of the BAF (hSWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. The BAF complex is able to create a stable, altered form of chromatin that constrains fewer negative supercoils than normal. This change in supercoiling would be due to the conversion of up to one-half of the nucleosomes on polynucleosomal arrays into asymmetric structures, termed altosomes, each composed of 2 histones octamers. Stimulates in vitro the remodeling activity of SMARCA4/BRG1/BAF190A. Involved in activation of CSF1 promoter. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Plays a key role in cell-cycle control and causes cell cycle arrest in G0/G1. {ECO:0000250|UniProtKB:Q9Z0H3, ECO:0000269|PubMed:10078207, ECO:0000269|PubMed:12226744, ECO:0000269|PubMed:14604992, ECO:0000269|PubMed:16267391, ECO:0000269|PubMed:16314535, ECO:0000269|PubMed:9448295}. |
| Q12967 | RALGDS | S686 | ochoa | Ral guanine nucleotide dissociation stimulator (RalGDS) (Ral guanine nucleotide exchange factor) (RalGEF) | Functions as a guanine nucleotide exchange factor (GEF) activating either RalA or RalB GTPases and plays an important role in intracellular transport. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap (By similarity). During bacterial clearance, recognizes 'Lys-33'-linked polyubiquitinated TRAF3 and subsequently mediates assembly of the exocyst complex (PubMed:27438768). {ECO:0000250|UniProtKB:Q03385, ECO:0000269|PubMed:27438768}. |
| Q13523 | PRP4K | S622 | 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}. |
| Q13568 | IRF5 | S437 | psp | Interferon regulatory factor 5 (IRF-5) | Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:11303025, PubMed:15695821, PubMed:22412986, PubMed:25326418, PubMed:32433612). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000250|UniProtKB:P56477, ECO:0000269|PubMed:11303025, ECO:0000269|PubMed:15695821, ECO:0000269|PubMed:22412986, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:33440148}. |
| Q13796 | SHROOM2 | S644 | ochoa | Protein Shroom2 (Apical-like protein) (Protein APXL) | May be involved in endothelial cell morphology changes during cell spreading. In the retinal pigment epithelium, may regulate the biogenesis of melanosomes and promote their association with the apical cell surface by inducing gamma-tubulin redistribution (By similarity). {ECO:0000250}. |
| Q14318 | FKBP8 | S323 | ochoa | Peptidyl-prolyl cis-trans isomerase FKBP8 (PPIase FKBP8) (EC 5.2.1.8) (38 kDa FK506-binding protein) (38 kDa FKBP) (FKBP-38) (hFKBP38) (FK506-binding protein 8) (FKBP-8) (FKBPR38) (Rotamase) | Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis. Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297). {ECO:0000269|PubMed:12510191, ECO:0000269|PubMed:15757646, ECO:0000269|PubMed:16176796, ECO:0000269|PubMed:28169297}. |
| Q14677 | CLINT1 | S323 | ochoa | Clathrin interactor 1 (Clathrin-interacting protein localized in the trans-Golgi region) (Clint) (Enthoprotin) (Epsin-4) (Epsin-related protein) (EpsinR) | Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly. {ECO:0000269|PubMed:12429846, ECO:0000269|PubMed:12538641}. |
| Q14690 | PDCD11 | S26 | ochoa | Protein RRP5 homolog (NF-kappa-B-binding protein) (NFBP) (Programmed cell death protein 11) | Essential for the generation of mature 18S rRNA, specifically necessary for cleavages at sites A0, 1 and 2 of the 47S precursor. Directly interacts with U3 snoRNA. {ECO:0000269|PubMed:17654514}.; FUNCTION: Involved in the biogenesis of rRNA. {ECO:0000250}. |
| Q14966 | ZNF638 | S299 | ochoa | Zinc finger protein 638 (Cutaneous T-cell lymphoma-associated antigen se33-1) (CTCL-associated antigen se33-1) (Nuclear protein 220) (Zinc finger matrin-like protein) | Transcription factor that binds to cytidine clusters in double-stranded DNA (PubMed:30487602, PubMed:8647861). Plays a key role in the silencing of unintegrated retroviral DNA: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Mediates transcriptional repression of unintegrated viral DNA by specifically binding to the cytidine clusters of retroviral DNA and mediating the recruitment of chromatin silencers, such as the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 (PubMed:30487602). Acts as an early regulator of adipogenesis by acting as a transcription cofactor of CEBPs (CEBPA, CEBPD and/or CEBPG), controlling the expression of PPARG and probably of other proadipogenic genes, such as SREBF1 (By similarity). May also regulate alternative splicing of target genes during adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q61464, ECO:0000269|PubMed:30487602, ECO:0000269|PubMed:8647861}. |
| Q15058 | KIF14 | S21 | ochoa | Kinesin-like protein KIF14 | Microtubule motor protein that binds to microtubules with high affinity through each tubulin heterodimer and has an ATPase activity (By similarity). Plays a role in many processes like cell division, cytokinesis and also in cell proliferation and apoptosis (PubMed:16648480, PubMed:24784001). During cytokinesis, targets to central spindle and midbody through its interaction with PRC1 and CIT respectively (PubMed:16431929). Regulates cell growth through regulation of cell cycle progression and cytokinesis (PubMed:24854087). During cell cycle progression acts through SCF-dependent proteasomal ubiquitin-dependent protein catabolic process which controls CDKN1B degradation, resulting in positive regulation of cyclins, including CCNE1, CCND1 and CCNB1 (PubMed:24854087). During late neurogenesis, regulates the cerebellar, cerebral cortex and olfactory bulb development through regulation of apoptosis, cell proliferation and cell division (By similarity). Also is required for chromosome congression and alignment during mitotic cell cycle process (PubMed:15843429). Regulates cell spreading, focal adhesion dynamics, and cell migration through its interaction with RADIL resulting in regulation of RAP1A-mediated inside-out integrin activation by tethering RADIL on microtubules (PubMed:23209302). {ECO:0000250|UniProtKB:L0N7N1, ECO:0000269|PubMed:15843429, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:16648480, ECO:0000269|PubMed:23209302, ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:24854087}. |
| Q15185 | PTGES3 | S44 | ochoa | Prostaglandin E synthase 3 (EC 5.3.99.3) (Cytosolic prostaglandin E2 synthase) (cPGES) (Hsp90 co-chaperone) (Progesterone receptor complex p23) (Telomerase-binding protein p23) | Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) (PubMed:10922363). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes (PubMed:11274138, PubMed:12077419). Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway (PubMed:24711448). {ECO:0000269|PubMed:10922363, ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:12077419, ECO:0000269|PubMed:24711448}. |
| Q15643 | TRIP11 | S1842 | ochoa | Thyroid receptor-interacting protein 11 (TR-interacting protein 11) (TRIP-11) (Clonal evolution-related gene on chromosome 14 protein) (Golgi-associated microtubule-binding protein 210) (GMAP-210) (Trip230) | Is a membrane tether required for vesicle tethering to Golgi. Has an essential role in the maintenance of Golgi structure and function (PubMed:25473115, PubMed:30728324). It is required for efficient anterograde and retrograde trafficking in the early secretory pathway, functioning at both the ER-to-Golgi intermediate compartment (ERGIC) and Golgi complex (PubMed:25717001). Binds the ligand binding domain of the thyroid receptor (THRB) in the presence of triiodothyronine and enhances THRB-modulated transcription. {ECO:0000269|PubMed:10189370, ECO:0000269|PubMed:25473115, ECO:0000269|PubMed:25717001, ECO:0000269|PubMed:30728324, ECO:0000269|PubMed:9256431}. |
| Q15907 | RAB11B | S115 | 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}. |
| Q16825 | PTPN21 | S795 | ochoa | Tyrosine-protein phosphatase non-receptor type 21 (EC 3.1.3.48) (Protein-tyrosine phosphatase D1) | None |
| Q16831 | UPP1 | S282 | ochoa | Uridine phosphorylase 1 (UPase 1) (UrdPase 1) (EC 2.4.2.3) | Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (PubMed:7488099). Shows broad substrate specificity and can also accept deoxyuridine and other analogous compounds (Probable). {ECO:0000269|PubMed:7488099, ECO:0000305|PubMed:13737038}. |
| Q2LD37 | BLTP1 | S4612 | ochoa | Bridge-like lipid transfer protein family member 1 (Fragile site-associated protein) | Tube-forming lipid transport protein which provides phosphatidylethanolamine for glycosylphosphatidylinositol (GPI) anchor synthesis in the endoplasmic reticulum (Probable). Plays a role in endosomal trafficking and endosome recycling. Also involved in the actin cytoskeleton and cilia structural dynamics (PubMed:30906834). Acts as a regulator of phagocytosis (PubMed:31540829). {ECO:0000269|PubMed:30906834, ECO:0000269|PubMed:31540829, ECO:0000305|PubMed:35015055, ECO:0000305|PubMed:35491307}. |
| Q4G0N8 | SLC9C1 | S219 | ochoa | Solute carrier family 9 member C1 (Na(+)/H(+) exchanger 10) (NHE-10) (Sodium/hydrogen exchanger 10) (Solute carrier family 9 member 10) (Sperm-specific Na(+)/H(+) exchanger) (sNHE) | Sperm-specific solute carrier involved in intracellular pH regulation of spermatozoa. Required for sperm motility and fertility. Involved in sperm cell hyperactivation, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for the expression and bicarbonate regulation of the soluble adenylyl cyclase (sAC) (By similarity). {ECO:0000250|UniProtKB:Q6UJY2}. |
| Q53GG5 | PDLIM3 | S250 | ochoa | PDZ and LIM domain protein 3 (Actinin-associated LIM protein) (Alpha-actinin-2-associated LIM protein) | May play a role in the organization of actin filament arrays within muscle cells. {ECO:0000250}. |
| Q5T0W9 | FAM83B | S538 | 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}. |
| Q5T200 | ZC3H13 | S1406 | ochoa | Zinc finger CCCH domain-containing protein 13 | Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing (PubMed:29507755). Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs at the 3'-UTR (By similarity). Controls embryonic stem cells (ESCs) pluripotency via its role in m6A methylation (By similarity). In the WMM complex, anchors component of the MACOM subcomplex in the nucleus (By similarity). Also required for bridging WTAP to the RNA-binding component RBM15 (RBM15 or RBM15B) (By similarity). {ECO:0000250|UniProtKB:E9Q784}. |
| Q5THK1 | PRR14L | S1482 | ochoa | Protein PRR14L (Proline rich 14-like protein) | None |
| Q5VU43 | PDE4DIP | S235 | ochoa | Myomegalin (Cardiomyopathy-associated protein 2) (Phosphodiesterase 4D-interacting protein) | Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes (By similarity). {ECO:0000250|UniProtKB:Q9WUJ3}.; FUNCTION: [Isoform 13]: Participates in microtubule dynamics, promoting microtubule assembly. Depending upon the cell context, may act at the level of the Golgi apparatus or that of the centrosome (PubMed:25217626, PubMed:27666745, PubMed:28814570, PubMed:29162697). In complex with AKAP9, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with AKAP9, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension from the centrosome to the cell periphery, a crucial process for directed cell migration, mitotic spindle orientation and cell-cycle progression (PubMed:29162697). {ECO:0000269|PubMed:25217626, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:29162697}. |
| Q5VUJ6 | LRCH2 | S315 | ochoa | Leucine-rich repeat and calponin homology domain-containing protein 2 | May play a role in the organization of the cytoskeleton. {ECO:0000250|UniProtKB:Q960C5, ECO:0000250|UniProtKB:Q96II8}. |
| Q5VV42 | CDKAL1 | S99 | ochoa | Threonylcarbamoyladenosine tRNA methylthiotransferase (EC 2.8.4.5) (CDK5 regulatory subunit-associated protein 1-like 1) (tRNA-t(6)A37 methylthiotransferase) | Catalyzes the methylthiolation of N6-threonylcarbamoyladenosine (t(6)A), leading to the formation of 2-methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine. {ECO:0000250|UniProtKB:Q91WE6}. |
| Q5VZ89 | DENND4C | S1551 | 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}. |
| Q658P3 | STEAP3 | S469 | ochoa | Metalloreductase STEAP3 (EC 1.16.1.-) (Dudulin-2) (Six-transmembrane epithelial antigen of prostate 3) (Tumor suppressor-activated pathway protein 6) (hTSAP6) (pHyde) (hpHyde) | Integral membrane protein that functions as a NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe(3+) chelate that is bound on the other side of the membrane (PubMed:26205815). Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe(3+) chelate (By similarity). Can also reduce Cu(2+) to Cu(1+) (By similarity). Mediates efficient transferrin-dependent iron uptake in erythroid cells (By similarity). May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression (By similarity). Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP (PubMed:15319436, PubMed:16651434). {ECO:0000250|UniProtKB:Q5RKL5, ECO:0000250|UniProtKB:Q687X5, ECO:0000250|UniProtKB:Q8CI59, ECO:0000269|PubMed:15319436, ECO:0000269|PubMed:16651434, ECO:0000269|PubMed:26205815}. |
| Q6DN14 | MCTP1 | S455 | ochoa | Multiple C2 and transmembrane domain-containing protein 1 | Calcium sensor which is essential for the stabilization of normal baseline neurotransmitter release and for the induction and long-term maintenance of presynaptic homeostatic plasticity. {ECO:0000250|UniProtKB:A1ZBD6}. |
| Q6NXT6 | TAPT1 | S521 | ochoa | Transmembrane anterior posterior transformation protein 1 homolog (Cytomegalovirus partial fusion receptor) | Plays a role in primary cilia formation (PubMed:26365339). May act as a downstream effector of HOXC8 possibly by transducing or transmitting extracellular information required for axial skeletal patterning during development (By similarity). May be involved in cartilage and bone development (By similarity). May play a role in the differentiation of cranial neural crest cells (By similarity). {ECO:0000250|UniProtKB:A2BIE7, ECO:0000250|UniProtKB:Q4VBD2, ECO:0000269|PubMed:26365339}.; FUNCTION: (Microbial infection) In case of infection, may act as a fusion receptor for cytomegalovirus (HCMV) strain AD169. {ECO:0000269|PubMed:10640539}. |
| Q6P6C2 | ALKBH5 | S305 | ochoa | RNA demethylase ALKBH5 (EC 1.14.11.53) (Alkylated DNA repair protein alkB homolog 5) (Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5) | Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178, PubMed:34048572, PubMed:36944332, PubMed:37257451, PubMed:37369679). Demethylates RNA by oxidative demethylation, which requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178). Demethylation of m6A mRNA affects mRNA processing, translation and export (PubMed:23177736, PubMed:34048572, PubMed:36944332, PubMed:37257451). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (PubMed:24616105). Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (By similarity). Involved in paraspeckle assembly, a nuclear membraneless organelle, by undergoing liquid-liquid phase separation (PubMed:37369679, PubMed:37474102). Paraspeckle assembly is coupled with m6A demethylation of RNAs, such as NEAT1 non-coding RNA (PubMed:37474102). Also acts as a negative regulator of T-cell development: inhibits gamma-delta T-cell proliferation via demethylation of JAG1 and NOTCH2 transcripts (By similarity). Inhibits regulatory T-cell (Treg) recruitment by mediating demethylation and destabilization of CCL28 mRNAs (By similarity). {ECO:0000250|UniProtKB:Q3TSG4, ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:24489119, ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:24778178, ECO:0000269|PubMed:34048572, ECO:0000269|PubMed:36944332, ECO:0000269|PubMed:37257451, ECO:0000269|PubMed:37369679, ECO:0000269|PubMed:37474102}. |
| Q6STE5 | SMARCD3 | S178 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 (60 kDa BRG-1/Brm-associated factor subunit C) (BRG1-associated factor 60C) (BAF60C) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Stimulates nuclear receptor mediated transcription. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6P9Z1, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:8804307, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q6ZNJ1 | NBEAL2 | S294 | ochoa | Neurobeachin-like protein 2 | Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}. |
| Q76FK4 | NOL8 | S421 | ochoa | Nucleolar protein 8 (Nucleolar protein Nop132) | Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells. {ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:15132771, ECO:0000269|PubMed:16963496}. |
| Q7Z333 | SETX | S956 | ochoa | Probable helicase senataxin (EC 3.6.4.-) (Amyotrophic lateral sclerosis 4 protein) (SEN1 homolog) (Senataxin) | Probable RNA/DNA helicase involved in diverse aspects of RNA metabolism and genomic integrity. Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription (PubMed:19515850, PubMed:21700224). Contributes to the mRNA splicing efficiency and splice site selection (PubMed:19515850). Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination (PubMed:19515850, PubMed:21700224, PubMed:26700805). Required for the 3' transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation (By similarity). Involved in DNA double-strand breaks damage response generated by oxidative stress (PubMed:17562789). In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage (PubMed:24105744). Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI) (By similarity). May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription (PubMed:21112256). Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis (PubMed:21576111). {ECO:0000250|UniProtKB:A2AKX3, ECO:0000269|PubMed:17562789, ECO:0000269|PubMed:19515850, ECO:0000269|PubMed:21112256, ECO:0000269|PubMed:21576111, ECO:0000269|PubMed:21700224, ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:26700805}. |
| Q7Z3S7 | CACNA2D4 | S498 | ochoa | Voltage-dependent calcium channel subunit alpha-2/delta-4 (Voltage-gated calcium channel subunit alpha-2/delta-4) [Cleaved into: Voltage-dependent calcium channel subunit alpha-2-4; Voltage-dependent calcium channel subunit delta-4] | The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. {ECO:0000269|PubMed:12181424}. |
| Q86SQ0 | PHLDB2 | S980 | ochoa | Pleckstrin homology-like domain family B member 2 (Protein LL5-beta) | Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}. |
| Q86TV6 | TTC7B | S666 | ochoa | Tetratricopeptide repeat protein 7B (TPR repeat protein 7B) (Tetratricopeptide repeat protein 7-like-1) (TPR repeat protein 7-like-1) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (PubMed:26571211). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:26571211}. |
| Q86U86 | PBRM1 | S383 | 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}. |
| Q86U86 | PBRM1 | S987 | 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 | S957 | 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}. |
| Q86VF7 | NRAP | S1603 | ochoa | Nebulin-related-anchoring protein (N-RAP) | May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. {ECO:0000250|UniProtKB:Q80XB4}. |
| Q86VQ0 | LCA5 | S87 | ochoa | Lebercilin (Leber congenital amaurosis 5 protein) | Involved in intraflagellar protein (IFT) transport in photoreceptor cilia. {ECO:0000250|UniProtKB:Q80ST9}. |
| Q86X27 | RALGPS2 | S443 | ochoa | Ras-specific guanine nucleotide-releasing factor RalGPS2 (Ral GEF with PH domain and SH3-binding motif 2) (RalA exchange factor RalGPS2) | Guanine nucleotide exchange factor for the small GTPase RALA. May be involved in cytoskeletal organization. May also be involved in the stimulation of transcription in a Ras-independent fashion (By similarity). {ECO:0000250}. |
| Q8IUD2 | ERC1 | S374 | ochoa | ELKS/Rab6-interacting/CAST family member 1 (ERC-1) (Rab6-interacting protein 2) | Regulatory subunit of the IKK complex. Probably recruits IkappaBalpha/NFKBIA to the complex. May be involved in the organization of the cytomatrix at the nerve terminals active zone (CAZ) which regulates neurotransmitter release. May be involved in vesicle trafficking at the CAZ. May be involved in Rab-6 regulated endosomes to Golgi transport. {ECO:0000269|PubMed:15218148}. |
| Q8IW50 | FAM219A | S47 | ochoa | Protein FAM219A | None |
| Q8IW50 | FAM219A | S102 | ochoa | Protein FAM219A | None |
| Q8IXF0 | NPAS3 | S563 | ochoa | Neuronal PAS domain-containing protein 3 (Neuronal PAS3) (Basic-helix-loop-helix-PAS protein MOP6) (Class E basic helix-loop-helix protein 12) (bHLHe12) (Member of PAS protein 6) (PAS domain-containing protein 6) | May play a broad role in neurogenesis. May control regulatory pathways relevant to schizophrenia and to psychotic illness (By similarity). {ECO:0000250}. |
| Q8IY81 | FTSJ3 | S441 | ochoa | pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3 (EC 2.1.1.-) (Protein ftsJ homolog 3) (Putative rRNA methyltransferase 3) | RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation. {ECO:0000255|HAMAP-Rule:MF_03163, ECO:0000269|PubMed:22195017}.; FUNCTION: (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2'-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system (PubMed:30626973). RNA 2'-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5 (PubMed:30626973). Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine (PubMed:30626973). Recruited to HIV-1 RNA via interaction with TARBP2/TRBP (PubMed:30626973). {ECO:0000269|PubMed:30626973}. |
| Q8IZ83 | ALDH16A1 | S488 | ochoa | Aldehyde dehydrogenase family 16 member A1 | None |
| Q8N1F7 | NUP93 | S438 | ochoa | Nuclear pore complex protein Nup93 (93 kDa nucleoporin) (Nucleoporin Nup93) | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling (PubMed:26878725). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:15703211, ECO:0000269|PubMed:26878725, ECO:0000269|PubMed:9348540}. |
| Q8N3F0 | MTURN | S58 | psp | Maturin (Maturin neural progenitor differentiation regulator protein homolog) (Protein Ells1) | Promotes megakaryocyte differentiation by enhancing ERK and JNK signaling as well as up-regulating RUNX1 and FLI1 expression (PubMed:24681962). Represses NF-kappa-B transcriptional activity by inhibiting phosphorylation of RELA at 'Ser-536' (PubMed:24681962). May be involved in early neuronal development (By similarity). {ECO:0000250|UniProtKB:Q7ZX36, ECO:0000269|PubMed:24681962}. |
| Q8N3Z6 | ZCCHC7 | S122 | ochoa | Zinc finger CCHC domain-containing protein 7 (TRAMP-like complex RNA-binding factor ZCCHC7) | None |
| Q8N5F7 | NKAP | S301 | ochoa | NF-kappa-B-activating protein | Acts as a transcriptional repressor (PubMed:14550261, PubMed:19409814, PubMed:31587868). Plays a role as a transcriptional corepressor of the Notch-mediated signaling required for T-cell development (PubMed:19409814). Also involved in the TNF and IL-1 induced NF-kappa-B activation. Associates with chromatin at the Notch-regulated SKP2 promoter. {ECO:0000269|PubMed:14550261, ECO:0000269|PubMed:19409814, ECO:0000269|PubMed:31587868}. |
| Q8NA03 | FSIP1 | S338 | ochoa | Fibrous sheath-interacting protein 1 | None |
| Q8NCD3 | HJURP | S347 | ochoa | Holliday junction recognition protein (14-3-3-associated AKT substrate) (Fetal liver-expressing gene 1 protein) (Up-regulated in lung cancer 9) | Centromeric protein that plays a central role in the incorporation and maintenance of histone H3-like variant CENPA at centromeres. Acts as a specific chaperone for CENPA and is required for the incorporation of newly synthesized CENPA molecules into nucleosomes at replicated centromeres. Prevents CENPA-H4 tetramerization and prevents premature DNA binding by the CENPA-H4 tetramer. Directly binds Holliday junctions. {ECO:0000269|PubMed:19410544, ECO:0000269|PubMed:19410545}. |
| Q8NEY1 | NAV1 | S1840 | 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}. |
| Q8TAT6 | NPLOC4 | S60 | ochoa | Nuclear protein localization protein 4 homolog (Protein NPL4) | 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 (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (PubMed:26471729). {ECO:0000250|UniProtKB:Q9ES54, ECO:0000269|PubMed:26471729}. |
| Q8TDJ6 | DMXL2 | S1149 | ochoa | DmX-like protein 2 (Rabconnectin-3) | May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles (PubMed:11809763). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (By similarity). {ECO:0000250|UniProtKB:Q8BPN8, ECO:0000269|PubMed:11809763}. |
| Q8TE99 | PXYLP1 | S376 | ochoa | 2-phosphoxylose phosphatase 1 (EC 3.1.3.-) (Acid phosphatase-like protein 2) (Xylosyl phosphatase) (epididymis luminal protein 124) | Responsible for the 2-O-dephosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature glycosaminoglycan (GAG) chains. Sulfated glycosaminoglycans (GAGs), including heparan sulfate and chondroitin sulfate, are synthesized on the so-called common GAG-protein linkage region (GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser) of core proteins, which is formed by the stepwise addition of monosaccharide residues by the respective specific glycosyltransferases. Xylose 2-O-dephosphorylation during completion of linkage region formation is a prerequisite for the initiation and efficient elongation of the repeating disaccharide region of GAG chains. {ECO:0000269|PubMed:24425863}. |
| Q8TEA7 | TBCK | S414 | ochoa | TBC domain-containing protein kinase-like protein (FERRY endosomal RAB5 effector complex subunit 1) (Fy-1) | Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary) (PubMed:37267905). 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). Also involved in the modulation of mTOR signaling and expression of mTOR complex components (PubMed:23977024, PubMed:27040691). Involved in the control of actin-cytoskeleton organization (PubMed:23977024). {ECO:0000269|PubMed:23977024, ECO:0000269|PubMed:24576458, ECO:0000269|PubMed:27040691, ECO:0000269|PubMed:37267905}. |
| Q8TF76 | HASPIN | S366 | psp | Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) | Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}. |
| Q8WU90 | ZC3H15 | S328 | ochoa | Zinc finger CCCH domain-containing protein 15 (DRG family-regulatory protein 1) (Likely ortholog of mouse immediate early response erythropoietin 4) | Protects DRG1 from proteolytic degradation (PubMed:19819225). Stimulates DRG1 GTPase activity likely by increasing the affinity for the potassium ions (PubMed:23711155). {ECO:0000269|PubMed:19819225, ECO:0000269|PubMed:23711155}. |
| Q8WUA4 | GTF3C2 | S597 | 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. |
| Q8WUY3 | PRUNE2 | S737 | ochoa | Protein prune homolog 2 (BNIP2 motif-containing molecule at the C-terminal region 1) | May play an important role in regulating differentiation, survival and aggressiveness of the tumor cells. {ECO:0000269|PubMed:16288218}. |
| Q8WVM7 | STAG1 | S1093 | ochoa | Cohesin subunit SA-1 (SCC3 homolog 1) (Stromal antigen 1) | Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. |
| Q8WWI1 | LMO7 | S1421 | ochoa | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q8WYQ5 | DGCR8 | S677 | psp | Microprocessor complex subunit DGCR8 (DiGeorge syndrome critical region 8) | Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs (PubMed:26027739, PubMed:26748718). The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding (PubMed:15531877, PubMed:15574589, PubMed:15589161, PubMed:16751099, PubMed:16906129, PubMed:16963499, PubMed:17159994). Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing (PubMed:25799998). Involved in the silencing of embryonic stem cell self-renewal (By similarity). Also plays a role in DNA repair by promoting the recruitment of RNF168 to RNF8 and MDC1 at DNA double-strand breaks and subsequently the clearance of DNA breaks (PubMed:34188037). {ECO:0000250|UniProtKB:Q9EQM6, ECO:0000269|PubMed:15531877, ECO:0000269|PubMed:15574589, ECO:0000269|PubMed:15589161, ECO:0000269|PubMed:16751099, ECO:0000269|PubMed:16906129, ECO:0000269|PubMed:16963499, ECO:0000269|PubMed:17159994, ECO:0000269|PubMed:25799998, ECO:0000269|PubMed:26027739, ECO:0000269|PubMed:26748718}. |
| Q92539 | LPIN2 | S135 | ochoa | Phosphatidate phosphatase LPIN2 (EC 3.1.3.4) (Lipin-2) | Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the endoplasmic reticulum membrane. Plays important roles in controlling the metabolism of fatty acids at different levels. Also acts as a nuclear transcriptional coactivator for PPARGC1A to modulate lipid metabolism. {ECO:0000250|UniProtKB:Q99PI5}. |
| Q92900 | UPF1 | S1100 | ochoa | Regulator of nonsense transcripts 1 (EC 3.6.4.12) (EC 3.6.4.13) (ATP-dependent helicase RENT1) (Nonsense mRNA reducing factor 1) (NORF1) (Up-frameshift suppressor 1 homolog) (hUpf1) | RNA-dependent helicase required for nonsense-mediated decay (NMD) of aberrant mRNAs containing premature stop codons and modulates the expression level of normal mRNAs (PubMed:11163187, PubMed:16086026, PubMed:18172165, PubMed:21145460, PubMed:21419344, PubMed:24726324). Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD (PubMed:11544179, PubMed:25220460). Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD (PubMed:21419344). Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors (PubMed:12554878). UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways (PubMed:18447585). Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2 (PubMed:16086026, PubMed:18172165). For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed (PubMed:18447585, PubMed:25220460). The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD (PubMed:21145460). Together with UPF2 and dependent on TDRD6, mediates the degradation of mRNA harboring long 3'UTR by inducing the NMD machinery (By similarity). Also capable of unwinding double-stranded DNA and translocating on single-stranded DNA (PubMed:30218034). {ECO:0000250|UniProtKB:Q9EPU0, ECO:0000269|PubMed:11163187, ECO:0000269|PubMed:11544179, ECO:0000269|PubMed:12554878, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:18447585, ECO:0000269|PubMed:19417104, ECO:0000269|PubMed:21145460, ECO:0000269|PubMed:21419344, ECO:0000269|PubMed:24726324, ECO:0000269|PubMed:25220460, ECO:0000269|PubMed:30218034}. |
| Q96B01 | RAD51AP1 | S146 | ochoa | RAD51-associated protein 1 (HsRAD51AP1) (RAD51-interacting protein) | Structure-specific DNA-binding protein involved in DNA repair by promoting RAD51-mediated homologous recombination (PubMed:17996710, PubMed:17996711, PubMed:20871616, PubMed:25288561, PubMed:26323318). Acts by stimulating D-Loop formation by RAD51: specifically enhances joint molecule formation through its structure-specific DNA interaction and its interaction with RAD51 (PubMed:17996710, PubMed:17996711). Binds single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures: has a strong preference for branched-DNA structures that are obligatory intermediates during joint molecule formation (PubMed:17996710, PubMed:17996711, PubMed:22375013, PubMed:9396801). Cooperates with WDR48/UAF1 to stimulate RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during homologous recombination and DNA repair (PubMed:27239033, PubMed:27463890, PubMed:32350107). WDR48/UAF1 and RAD51AP1 also have a coordinated role in DNA-binding to promote USP1-mediated deubiquitination of FANCD2 (PubMed:31253762). Also involved in meiosis by promoting DMC1-mediated homologous meiotic recombination (PubMed:21307306). Key mediator of alternative lengthening of telomeres (ALT) pathway, a homology-directed repair mechanism of telomere elongation that controls proliferation in aggressive cancers, by stimulating homologous recombination (PubMed:31400850). May also bind RNA; additional evidences are however required to confirm RNA-binding in vivo (PubMed:9396801). {ECO:0000269|PubMed:17996710, ECO:0000269|PubMed:17996711, ECO:0000269|PubMed:20871616, ECO:0000269|PubMed:21307306, ECO:0000269|PubMed:22375013, ECO:0000269|PubMed:25288561, ECO:0000269|PubMed:26323318, ECO:0000269|PubMed:27239033, ECO:0000269|PubMed:27463890, ECO:0000269|PubMed:31253762, ECO:0000269|PubMed:31400850, ECO:0000269|PubMed:32350107, ECO:0000269|PubMed:9396801}. |
| Q96B97 | SH3KBP1 | S444 | ochoa | SH3 domain-containing kinase-binding protein 1 (CD2-binding protein 3) (CD2BP3) (Cbl-interacting protein of 85 kDa) (Human Src family kinase-binding protein 1) (HSB-1) | Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through an association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may be inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Has an essential role in the stimulation of B cell activation (PubMed:29636373). {ECO:0000250, ECO:0000269|PubMed:11894095, ECO:0000269|PubMed:11894096, ECO:0000269|PubMed:12177062, ECO:0000269|PubMed:12734385, ECO:0000269|PubMed:12771190, ECO:0000269|PubMed:15090612, ECO:0000269|PubMed:15707590, ECO:0000269|PubMed:16177060, ECO:0000269|PubMed:16256071, ECO:0000269|PubMed:21275903, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:29636373}. |
| Q96GG9 | DCUN1D1 | S59 | ochoa | DCN1-like protein 1 (DCNL1) (DCUN1 domain-containing protein 1) (Defective in cullin neddylation protein 1-like protein 1) (Squamous cell carcinoma-related oncogene) | Part of an E3 ubiquitin ligase complex for neddylation (PubMed:18826954). Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (PubMed:19617556, PubMed:23201271, PubMed:23401859, PubMed:26906416). Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (PubMed:25349211, PubMed:28581483). Also acts as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity). {ECO:0000250|UniProtKB:Q9QZ73, ECO:0000269|PubMed:18826954, ECO:0000269|PubMed:19617556, ECO:0000269|PubMed:23201271, ECO:0000269|PubMed:23401859, ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26906416, ECO:0000269|PubMed:28581483}. |
| Q96HC4 | PDLIM5 | S280 | ochoa | PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) | May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}. |
| Q96JQ2 | CLMN | S838 | ochoa | Calmin (Calponin-like transmembrane domain protein) | None |
| Q96KG9 | SCYL1 | S462 | ochoa | N-terminal kinase-like protein (Coated vesicle-associated kinase of 90 kDa) (SCY1-like protein 1) (Telomerase regulation-associated protein) (Telomerase transcriptional element-interacting factor) (Teratoma-associated tyrosine kinase) | Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). {ECO:0000269|PubMed:18556652, ECO:0000269|PubMed:26581903}.; FUNCTION: [Isoform 6]: Acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region. {ECO:0000269|PubMed:15963946}. |
| Q96KP4 | CNDP2 | S299 | ochoa | Cytosolic non-specific dipeptidase (EC 3.4.13.18) (CNDP dipeptidase 2) (Glutamate carboxypeptidase-like protein 1) (Peptidase A) (Threonyl dipeptidase) | Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides (By similarity). Mediates threonyl dipeptide catabolism in a tissue-specific way (By similarity). Has high dipeptidase activity toward cysteinylglycine, an intermediate metabolite in glutathione metabolism (PubMed:12473676, PubMed:19346245). Metabolizes N-lactoyl-amino acids, both through hydrolysis to form lactic acid and amino acids, as well as through their formation by reverse proteolysis (PubMed:25964343). Plays a role in the regulation of cell cycle arrest and apoptosis (PubMed:17121880, PubMed:24395568). {ECO:0000250|UniProtKB:Q9D1A2, ECO:0000269|PubMed:12473676, ECO:0000269|PubMed:17121880, ECO:0000269|PubMed:19346245, ECO:0000269|PubMed:24395568, ECO:0000269|PubMed:25964343}. |
| Q96P20 | NLRP3 | S334 | psp | NACHT, LRR and PYD domains-containing protein 3 (EC 3.6.4.-) (Angiotensin/vasopressin receptor AII/AVP-like) (Caterpiller protein 1.1) (CLR1.1) (Cold-induced autoinflammatory syndrome 1 protein) (Cryopyrin) (PYRIN-containing APAF1-like protein 1) | Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis (PubMed:16407889, PubMed:18403674, PubMed:18604214, PubMed:23582325, PubMed:25686105, PubMed:27929086, PubMed:28656979, PubMed:28847925, PubMed:30487600, PubMed:30612879, PubMed:31086327, PubMed:31086329, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:34512673, PubMed:36442502). In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:16407889, PubMed:18403674, PubMed:27432880, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:36142182, PubMed:36442502). Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis (PubMed:23582325, PubMed:28847925, PubMed:31189953, PubMed:33231615, PubMed:34133077, PubMed:34341353). Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494). Under resting conditions, ADP-bound NLRP3 is autoinhibited (PubMed:35114687). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18403674, PubMed:18604214, PubMed:19414800, PubMed:23871209). Almost all stimuli trigger intracellular K(+) efflux (By similarity). These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex (PubMed:36442502, PubMed:39173637). Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600, PubMed:34554188). Shows ATPase activity (PubMed:17483456). {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:16407889, ECO:0000269|PubMed:17483456, ECO:0000269|PubMed:18403674, ECO:0000269|PubMed:18604214, ECO:0000269|PubMed:19414800, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:25686105, ECO:0000269|PubMed:27432880, ECO:0000269|PubMed:27929086, ECO:0000269|PubMed:28656979, ECO:0000269|PubMed:28847925, ECO:0000269|PubMed:30487600, ECO:0000269|PubMed:30612879, ECO:0000269|PubMed:31086327, ECO:0000269|PubMed:31086329, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:33231615, ECO:0000269|PubMed:34133077, ECO:0000269|PubMed:34341353, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:35114687, ECO:0000269|PubMed:36142182, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637}.; FUNCTION: Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription (By similarity). Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3' (By similarity). May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity). {ECO:0000250|UniProtKB:Q8R4B8}. |
| Q96PV7 | FAM193B | S844 | ochoa | Protein FAM193B | None |
| Q96RL7 | VPS13A | S1936 | ochoa | Intermembrane lipid transfer protein VPS13A (Chorea-acanthocytosis protein) (Chorein) (Vacuolar protein sorting-associated protein 13A) | Mediates the transfer of lipids between membranes at organelle contact sites (By similarity). Binds phospholipids (PubMed:34830155). Required for the formation or stabilization of ER-mitochondria contact sites which enable transfer of lipids between the ER and mitochondria (PubMed:30741634). Negatively regulates lipid droplet size and motility (PubMed:30741634). Required for efficient lysosomal protein degradation (PubMed:30709847). {ECO:0000250|UniProtKB:Q07878, ECO:0000269|PubMed:30709847, ECO:0000269|PubMed:30741634, ECO:0000269|PubMed:34830155}. |
| Q96SI9 | STRBP | S565 | ochoa | Spermatid perinuclear RNA-binding protein | Involved in spermatogenesis and sperm function. Plays a role in regulation of cell growth. Binds to double-stranded DNA and RNA. Binds most efficiently to poly(I:C) RNA than to poly(dI:dC) DNA. Binds also to single-stranded poly(G) RNA. Binds non-specifically to the mRNA PRM1 3'-UTR and adenovirus VA RNA (By similarity). {ECO:0000250}. |
| Q96SN8 | CDK5RAP2 | S697 | ochoa | CDK5 regulatory subunit-associated protein 2 (CDK5 activator-binding protein C48) (Centrosome-associated protein 215) | Potential regulator of CDK5 activity via its interaction with CDK5R1 (PubMed:15164053). Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter (PubMed:19282672). Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends (PubMed:18042621, PubMed:17959831, PubMed:19553473). Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gTuRC) onto centrosomes (PubMed:18042621, PubMed:17959831, PubMed:26485573, PubMed:39321809). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity). {ECO:0000250|UniProtKB:Q8K389, ECO:0000269|PubMed:15164053, ECO:0000269|PubMed:17959831, ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:19282672, ECO:0000269|PubMed:19553473, ECO:0000269|PubMed:26485573, ECO:0000269|PubMed:29162697, ECO:0000269|PubMed:39321809}. |
| Q96T88 | UHRF1 | S172 | ochoa | E3 ubiquitin-protein ligase UHRF1 (EC 2.3.2.27) (Inverted CCAAT box-binding protein of 90 kDa) (Nuclear protein 95) (Nuclear zinc finger protein Np95) (HuNp95) (hNp95) (RING finger protein 106) (RING-type E3 ubiquitin transferase UHRF1) (Transcription factor ICBP90) (Ubiquitin-like PHD and RING finger domain-containing protein 1) (hUHRF1) (Ubiquitin-like-containing PHD and RING finger domains protein 1) | Multidomain protein that acts as a key epigenetic regulator by bridging DNA methylation and chromatin modification. Specifically recognizes and binds hemimethylated DNA at replication forks via its YDG domain and recruits DNMT1 methyltransferase to ensure faithful propagation of the DNA methylation patterns through DNA replication. In addition to its role in maintenance of DNA methylation, also plays a key role in chromatin modification: through its tudor-like regions and PHD-type zinc fingers, specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3) and unmethylated at 'Arg-2' (H3R2me0), respectively, and recruits chromatin proteins. Enriched in pericentric heterochromatin where it recruits different chromatin modifiers required for this chromatin replication. Also localizes to euchromatic regions where it negatively regulates transcription possibly by impacting DNA methylation and histone modifications. Has E3 ubiquitin-protein ligase activity by mediating the ubiquitination of target proteins such as histone H3 and PML. It is still unclear how E3 ubiquitin-protein ligase activity is related to its role in chromatin in vivo. Plays a role in DNA repair by cooperating with UHRF2 to ensure recruitment of FANCD2 to interstrand cross-links (ICLs) leading to FANCD2 activation. Acts as a critical player of proper spindle architecture by catalyzing the 'Lys-63'-linked ubiquitination of KIF11, thereby controlling KIF11 localization on the spindle (PubMed:37728657). {ECO:0000269|PubMed:10646863, ECO:0000269|PubMed:15009091, ECO:0000269|PubMed:15361834, ECO:0000269|PubMed:17673620, ECO:0000269|PubMed:17967883, ECO:0000269|PubMed:19056828, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:21777816, ECO:0000269|PubMed:22945642, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:37728657}. |
| Q99623 | PHB2 | S267 | ochoa | Prohibitin-2 (B-cell receptor-associated protein BAP37) (D-prohibitin) (Repressor of estrogen receptor activity) | 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 and sex steroid hormones in the nucleus. {ECO:0000269|PubMed:10359819, ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:20959514, ECO:0000269|PubMed:24003225, ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117}.; FUNCTION: In the mitochondria, together with PHB, 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). Also regulates cytochrome-c oxidase assembly (COX) and mitochondrial respiration (PubMed:11302691, PubMed:20959514). Binding to sphingoid 1-phosphate (SPP) modulates its regulator activity (PubMed:11302691, PubMed:20959514). Has a key 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:O35129, ECO:0000269|PubMed:11302691, ECO:0000269|PubMed:20959514, ECO:0000269|PubMed:28017329, ECO:0000269|PubMed:31522117, ECO:0000305|PubMed:25904163}.; FUNCTION: In the nucleus, serves as transcriptional co-regulator (Probable). Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases. Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity (By similarity). {ECO:0000250|UniProtKB:O35129, ECO:0000305|PubMed:25904163}.; FUNCTION: In the plasma membrane, is involved in IGFBP6-induced cell migration (PubMed:24003225). Cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates. Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity). {ECO:0000250|UniProtKB:O35129, ECO:0000269|PubMed:24003225}.; FUNCTION: (Microbial infection) Involved in human enterovirus 71/EV-71 infection by enhancing the autophagy mechanism during the infection. {ECO:0000269|PubMed:32276428}. |
| Q9BX63 | BRIP1 | S917 | ochoa | Fanconi anemia group J protein (EC 5.6.2.3) (BRCA1-associated C-terminal helicase 1) (BRCA1-interacting protein C-terminal helicase 1) (BRCA1-interacting protein 1) (DNA 5'-3' helicase FANCJ) | DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of chromosomal stability (PubMed:11301010, PubMed:14983014, PubMed:16116421, PubMed:16153896, PubMed:17596542, PubMed:36608669). Acts late in the Fanconi anemia pathway, after FANCD2 ubiquitination (PubMed:14983014, PubMed:16153896). Involved in the repair of DNA double-strand breaks by homologous recombination in a manner that depends on its association with BRCA1 (PubMed:14983014, PubMed:16153896). Involved in the repair of abasic sites at replication forks by promoting the degradation of DNA-protein cross-links: acts by catalyzing unfolding of HMCES DNA-protein cross-link via its helicase activity, exposing the underlying DNA and enabling cleavage of the DNA-protein adduct by the SPRTN metalloprotease (PubMed:16116421, PubMed:36608669). Can unwind RNA:DNA substrates (PubMed:14983014). Unwinds G-quadruplex DNA; unwinding requires a 5'-single stranded tail (PubMed:18426915, PubMed:20639400). {ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:14983014, ECO:0000269|PubMed:16116421, ECO:0000269|PubMed:16153896, ECO:0000269|PubMed:17596542, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639400, ECO:0000269|PubMed:36608669}. |
| Q9BXB5 | OSBPL10 | S265 | ochoa | Oxysterol-binding protein-related protein 10 (ORP-10) (OSBP-related protein 10) | Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable) (PubMed:23934110). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110). {ECO:0000269|PubMed:17428193, ECO:0000269|PubMed:19554302, ECO:0000269|PubMed:22906437, ECO:0000269|PubMed:23934110, ECO:0000305}. |
| Q9BXM7 | PINK1 | S228 | psp | Serine/threonine-protein kinase PINK1, mitochondrial (EC 2.7.11.1) (BRPK) (PTEN-induced putative kinase protein 1) | Serine/threonine-protein kinase which acts as a sensor of mitochondrial damage and protects against mitochondrial dysfunction during cellular stress. It phosphorylates mitochondrial proteins to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:18957282, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20547144, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:24898855, PubMed:25527291, PubMed:32484300). Depending on the severity of mitochondrial damage, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN-dependent mitophagy (PubMed:14607334, PubMed:15087508, PubMed:18443288, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:22396657, PubMed:23620051, PubMed:23933751, PubMed:24898855, PubMed:32047033, PubMed:32484300). When cellular stress results in irreversible mitochondrial damage, PINK1 accumulates at the outer mitochondrial membrane (OMM) where it phosphorylates pre-existing polyubiquitin chains at 'Ser-65', recruits PRKN from the cytosol to the OMM and activates PRKN by phosphorylation at 'Ser-65'; activated PRKN then ubiquinates VDAC1 and other OMM proteins to initiate mitophagy (PubMed:14607334, PubMed:15087508, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291, PubMed:32047033). The PINK1-PRKN pathway also promotes fission of damaged mitochondria through phosphorylation and PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128). {ECO:0000250|UniProtKB:Q99MQ3, ECO:0000269|PubMed:14607334, ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:18443288, ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20547144, ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:24898855, ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:29123128, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:32484300}. |
| Q9BY77 | POLDIP3 | S244 | ochoa | Polymerase delta-interacting protein 3 (46 kDa DNA polymerase delta interaction protein) (p46) (S6K1 Aly/REF-like target) (SKAR) | Is involved in regulation of translation. Is preferentially associated with CBC-bound spliced mRNA-protein complexes during the pioneer round of mRNA translation. Contributes to enhanced translational efficiency of spliced over nonspliced mRNAs. Recruits activated ribosomal protein S6 kinase beta-1 I/RPS6KB1 to newly synthesized mRNA. Involved in nuclear mRNA export; probably mediated by association with the TREX complex. {ECO:0000269|PubMed:18423201, ECO:0000269|PubMed:22928037}. |
| Q9C0B0 | UNK | S606 | psp | RING finger protein unkempt homolog (Zinc finger CCCH domain-containing protein 5) | Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280). {ECO:0000269|PubMed:25737280}. |
| Q9C0B1 | FTO | S256 | ochoa | Alpha-ketoglutarate-dependent dioxygenase FTO (Fat mass and obesity-associated protein) (U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO) (EC 1.14.11.-) (U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO) (EC 1.14.11.-) (mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO) (m6A(m)-demethylase FTO) (EC 1.14.11.-) (mRNA N(6)-methyladenosine demethylase FTO) (EC 1.14.11.53) (tRNA N1-methyl adenine demethylase FTO) (EC 1.14.11.-) | RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:28002401, PubMed:30197295). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:30197295). M6A demethylation by FTO affects mRNA expression and stability (PubMed:30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:30197295). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:30197295). Has no activity towards 1-methylguanine (PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:18775698, PubMed:20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:28017614, PubMed:29249359). {ECO:0000250|UniProtKB:Q8BGW1, ECO:0000269|PubMed:18775698, ECO:0000269|PubMed:20376003, ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:25452335, ECO:0000269|PubMed:26287746, ECO:0000269|PubMed:26457839, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:28002401, ECO:0000269|PubMed:28017614, ECO:0000269|PubMed:29249359, ECO:0000269|PubMed:30197295}. |
| Q9C0B5 | ZDHHC5 | S247 | ochoa | Palmitoyltransferase ZDHHC5 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 5) (DHHC-5) (Zinc finger protein 375) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates such as CTNND2, CD36, GSDMD, NLRP3, NOD1, NOD2, STAT3 and S1PR1 thus plays a role in various biological processes including cell adhesion, inflammation, fatty acid uptake, bacterial sensing or cardiac functions (PubMed:21820437, PubMed:29185452, PubMed:31402609, PubMed:31649195, PubMed:34293401, PubMed:38092000, PubMed:38530158, PubMed:38599239). Plays an important role in the regulation of synapse efficacy by mediating palmitoylation of delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) (PubMed:26334723). Under basal conditions, remains at the synaptic membrane through FYN-mediated phosphorylation that prevents association with endocytic proteins (PubMed:26334723). Neuronal activity enhances the internalization and trafficking of DHHC5 from spines to dendritic shafts where it palmitoylates delta-catenin/CTNND2 (PubMed:26334723). Regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2 (PubMed:31402609). Plays a role in innate immune response by mediating the palmitoylation of NOD1 and NOD2 and their proper recruitment to the bacterial entry site and phagosomes (PubMed:31649195, PubMed:34293401). Also participates in fatty acid uptake by palmitoylating CD36 and thereby targeting it to the plasma membrane (PubMed:32958780). Upon binding of fatty acids to CD36, gets phosphorylated by LYN leading to inactivation and subsequent CD36 caveolar endocytosis (PubMed:32958780). Controls oligodendrocyte development by catalyzing STAT3 palmitoylation (By similarity). Acts as a regulator of inflammatory response by mediating palmitoylation of NLRP3 and GSDMD (PubMed:38092000, PubMed:38530158, PubMed:38599239). Palmitoylates NLRP3 to promote inflammasome assembly and activation (PubMed:38092000). Activates pyroptosis by catalyzing palmitoylation of gasdermin-D (GSDMD), thereby promoting membrane translocation and pore formation of GSDMD (PubMed:38530158, PubMed:38599239). {ECO:0000250|UniProtKB:Q8VDZ4, ECO:0000269|PubMed:21820437, ECO:0000269|PubMed:26334723, ECO:0000269|PubMed:29185452, ECO:0000269|PubMed:31402609, ECO:0000269|PubMed:31649195, ECO:0000269|PubMed:32958780, ECO:0000269|PubMed:34293401, ECO:0000269|PubMed:38092000, ECO:0000269|PubMed:38530158, ECO:0000269|PubMed:38599239}. |
| Q9H089 | LSG1 | S57 | ochoa | Large subunit GTPase 1 homolog (hLsg1) (EC 3.6.5.-) | Functions as a GTPase (PubMed:16209721). May act by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm during the 60S ribosomal subunit maturation (PubMed:31148378). {ECO:0000269|PubMed:16209721, ECO:0000269|PubMed:31148378}. |
| Q9H0H5 | RACGAP1 | S280 | ochoa | Rac GTPase-activating protein 1 (Male germ cell RacGap) (MgcRacGAP) (Protein CYK4 homolog) (CYK4) (HsCYK-4) | Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis. Required for proper attachment of the midbody to the cell membrane during cytokinesis. Sequentially binds to ECT2 and RAB11FIP3 which regulates cleavage furrow ingression and abscission during cytokinesis (PubMed:18511905). Plays key roles in controlling cell growth and differentiation of hematopoietic cells through mechanisms other than regulating Rac GTPase activity (PubMed:10979956). Has a critical role in erythropoiesis (PubMed:34818416). Also involved in the regulation of growth-related processes in adipocytes and myoblasts. May be involved in regulating spermatogenesis and in the RACGAP1 pathway in neuronal proliferation. Shows strong GAP (GTPase activation) activity towards CDC42 and RAC1 and less towards RHOA. Essential for the early stages of embryogenesis. May play a role in regulating cortical activity through RHOA during cytokinesis. May participate in the regulation of sulfate transport in male germ cells. {ECO:0000269|PubMed:10979956, ECO:0000269|PubMed:11085985, ECO:0000269|PubMed:11278976, ECO:0000269|PubMed:11782313, ECO:0000269|PubMed:14729465, ECO:0000269|PubMed:15642749, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:16129829, ECO:0000269|PubMed:16236794, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:23235882, ECO:0000269|PubMed:9497316}. |
| Q9H3Z4 | DNAJC5 | S34 | psp | DnaJ homolog subfamily C member 5 (Ceroid-lipofuscinosis neuronal protein 4) (Cysteine string protein) (CSP) | Acts as a general chaperone in regulated exocytosis (By similarity). Acts as a co-chaperone for the SNARE protein SNAP-25 (By similarity). Involved in the calcium-mediated control of a late stage of exocytosis (By similarity). May have an important role in presynaptic function. May be involved in calcium-dependent neurotransmitter release at nerve endings (By similarity). {ECO:0000250|UniProtKB:P60904, ECO:0000250|UniProtKB:Q29455}. |
| Q9H9J4 | USP42 | S1133 | ochoa | Ubiquitin carboxyl-terminal hydrolase 42 (EC 3.4.19.12) (Deubiquitinating enzyme 42) (Ubiquitin thioesterase 42) (Ubiquitin-specific-processing protease 42) | Deubiquitinating enzyme which may play an important role during spermatogenesis. {ECO:0000250}. |
| Q9HB21 | PLEKHA1 | S166 | ochoa | Pleckstrin homology domain-containing family A member 1 (PH domain-containing family A member 1) (Tandem PH domain-containing protein 1) (TAPP-1) | Binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2), but not to other phosphoinositides. May recruit other proteins to the plasma membrane. {ECO:0000269|PubMed:11001876, ECO:0000269|PubMed:11513726, ECO:0000269|PubMed:14516276}. |
| Q9NPI6 | DCP1A | S451 | ochoa | mRNA-decapping enzyme 1A (EC 3.6.1.62) (Smad4-interacting transcriptional co-activator) (Transcription factor SMIF) | Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:12417715). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12417715). Contributes to the transactivation of target genes after stimulation by TGFB1 (PubMed:11836524). Essential for embryonic development (PubMed:33813271). {ECO:0000269|PubMed:11836524, ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:33813271}. |
| Q9NPI6 | DCP1A | S545 | ochoa | mRNA-decapping enzyme 1A (EC 3.6.1.62) (Smad4-interacting transcriptional co-activator) (Transcription factor SMIF) | Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:12417715). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12417715). Contributes to the transactivation of target genes after stimulation by TGFB1 (PubMed:11836524). Essential for embryonic development (PubMed:33813271). {ECO:0000269|PubMed:11836524, ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:33813271}. |
| Q9NQW6 | ANLN | S276 | 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}. |
| Q9NUQ3 | TXLNG | S58 | ochoa | 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}. |
| Q9P0V3 | SH3BP4 | S296 | ochoa | SH3 domain-binding protein 4 (EH-binding protein 10) (Transferrin receptor-trafficking protein) | May function in transferrin receptor internalization at the plasma membrane through a cargo-specific control of clathrin-mediated endocytosis. Alternatively, may act as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy. {ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:22575674}. |
| Q9P107 | GMIP | S19 | ochoa | GEM-interacting protein (GMIP) | Stimulates, in vitro and in vivo, the GTPase activity of RhoA. {ECO:0000269|PubMed:12093360}. |
| Q9P1A6 | DLGAP2 | S668 | ochoa | Disks large-associated protein 2 (DAP-2) (PSD-95/SAP90-binding protein 2) (SAP90/PSD-95-associated protein 2) (SAPAP2) | May play a role in the molecular organization of synapses and neuronal cell signaling. Could be an adapter protein linking ion channel to the subsynaptic cytoskeleton. May induce enrichment of PSD-95/SAP90 at the plasma membrane. |
| Q9P246 | STIM2 | S678 | ochoa | Stromal interaction molecule 2 | Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Functions as a highly sensitive Ca(2+) sensor in the endoplasmic reticulum which activates both store-operated and store-independent Ca(2+)-influx. Regulates basal cytosolic and endoplasmic reticulum Ca(2+) concentrations. Upon mild variations of the endoplasmic reticulum Ca(2+) concentration, translocates from the endoplasmic reticulum to the plasma membrane where it probably activates the Ca(2+) release-activated Ca(2+) (CRAC) channels ORAI1, ORAI2 and ORAI3. May inhibit STIM1-mediated Ca(2+) influx. {ECO:0000269|PubMed:16005298, ECO:0000269|PubMed:16860747, ECO:0000269|PubMed:17905723, ECO:0000269|PubMed:18160041, ECO:0000269|PubMed:21217057, ECO:0000269|PubMed:22464749, ECO:0000269|PubMed:23359669}. |
| Q9P2E9 | RRBP1 | S803 | ochoa | Ribosome-binding protein 1 (180 kDa ribosome receptor homolog) (RRp) (ES/130-related protein) (Ribosome receptor protein) | Acts as a ribosome receptor and mediates interaction between the ribosome and the endoplasmic reticulum membrane. {ECO:0000250}. |
| Q9P2P5 | HECW2 | S1023 | ochoa | E3 ubiquitin-protein ligase HECW2 (EC 2.3.2.26) (HECT, C2 and WW domain-containing protein 2) (HECT-type E3 ubiquitin transferase HECW2) (NEDD4-like E3 ubiquitin-protein ligase 2) | E3 ubiquitin-protein ligase that mediates ubiquitination of TP73. Acts to stabilize TP73 and enhance activation of transcription by TP73 (PubMed:12890487). Involved in the regulation of mitotic metaphase/anaphase transition (PubMed:24163370). {ECO:0000269|PubMed:12890487, ECO:0000269|PubMed:24163370}. |
| Q9UBH6 | XPR1 | S668 | ochoa | Solute carrier family 53 member 1 (Phosphate exporter SLC53A1) (Protein SYG1 homolog) (Xenotropic and polytropic murine leukemia virus receptor X3) (X-receptor) (Xenotropic and polytropic retrovirus receptor 1) | Inorganic ion transporter that mediates phosphate ion export across plasma membrane (PubMed:23791524, PubMed:25938945, PubMed:27080106, PubMed:31043717, PubMed:39169184, PubMed:39325866, PubMed:39747008, PubMed:39814721). Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling (PubMed:27080106). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), which are important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106, PubMed:39169184, PubMed:39325866). {ECO:0000269|PubMed:23791524, ECO:0000269|PubMed:25938945, ECO:0000269|PubMed:27080106, ECO:0000269|PubMed:31043717, ECO:0000269|PubMed:39169184, ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721}. |
| Q9UK76 | JPT1 | S71 | ochoa | Jupiter microtubule associated homolog 1 (Androgen-regulated protein 2) (Hematological and neurological expressed 1 protein) [Cleaved into: Jupiter microtubule associated homolog 1, N-terminally processed] | Modulates negatively AKT-mediated GSK3B signaling (PubMed:21323578, PubMed:22155408). Induces CTNNB1 'Ser-33' phosphorylation and degradation through the suppression of the inhibitory 'Ser-9' phosphorylation of GSK3B, which represses the function of the APC:CTNNB1:GSK3B complex and the interaction with CDH1/E-cadherin in adherent junctions (PubMed:25169422). Plays a role in the regulation of cell cycle and cell adhesion (PubMed:25169422, PubMed:25450365). Has an inhibitory role on AR-signaling pathway through the induction of receptor proteasomal degradation (PubMed:22155408). {ECO:0000269|PubMed:21323578, ECO:0000269|PubMed:22155408, ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:25450365}. |
| Q9UKK3 | PARP4 | S1227 | ochoa | Protein mono-ADP-ribosyltransferase PARP4 (EC 2.4.2.-) (193 kDa vault protein) (ADP-ribosyltransferase diphtheria toxin-like 4) (ARTD4) (PARP-related/IalphaI-related H5/proline-rich) (PH5P) (Poly [ADP-ribose] polymerase 4) (PARP-4) (Vault poly(ADP-ribose) polymerase) (VPARP) | Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. {ECO:0000269|PubMed:25043379}. |
| Q9UN79 | SOX13 | S452 | ochoa | Transcription factor SOX-13 (Islet cell antigen 12) (SRY (Sex determining region Y)-box 13) (Type 1 diabetes autoantigen ICA12) | Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3' (PubMed:10871192). Binds to the proximal promoter region of the myelin protein MPZ gene, and may thereby be involved in the differentiation of oligodendroglia in the developing spinal tube (By similarity). Binds to the gene promoter of MBP and acts as a transcriptional repressor (By similarity). Binds to and modifies the activity of TCF7/TCF1, thereby inhibiting transcription and modulates normal gamma-delta T-cell development and differentiation of IL17A expressing gamma-delta T-cells (By similarity). Regulates expression of BLK in the differentiation of IL17A expressing gamma-delta T-cells (By similarity). Promotes brown adipocyte differentiation (By similarity). Inhibitor of WNT signaling (PubMed:20028982). {ECO:0000250|UniProtKB:Q04891, ECO:0000269|PubMed:10871192, ECO:0000269|PubMed:20028982}. |
| Q9UPN4 | CEP131 | S499 | ochoa | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9Y286 | SIGLEC7 | S404 | ochoa | Sialic acid-binding Ig-like lectin 7 (Siglec-7) (Adhesion inhibitory receptor molecule 1) (AIRM-1) (CDw328) (D-siglec) (QA79 membrane protein) (p75) (CD antigen CD328) | Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- and alpha-2,6-linked sialic acid. Also binds disialogangliosides (disialogalactosyl globoside, disialyl lactotetraosylceramide and disialyl GalNAc lactotetraoslylceramide). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Mediates inhibition of natural killer cells cytotoxicity. May play a role in hemopoiesis. Inhibits differentiation of CD34+ cell precursors towards myelomonocytic cell lineage and proliferation of leukemic myeloid cells (in vitro). {ECO:0000269|PubMed:10611343}. |
| Q9Y297 | BTRC | S82 | psp | F-box/WD repeat-containing protein 1A (E3RSIkappaB) (Epididymis tissue protein Li 2a) (F-box and WD repeats protein beta-TrCP) (pIkappaBalpha-E3 receptor subunit) | Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11158290, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:22087322, PubMed:25503564, PubMed:25704143, PubMed:36608670, PubMed:9859996, PubMed:9990852). Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11158290, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:22087322, PubMed:25503564, PubMed:25704143, PubMed:36608670, PubMed:9859996, PubMed:9990852). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14603323, PubMed:14681206). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:9859996). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). The SCF(FBXW11) complex also regulates NF-kappa-B by mediating ubiquitination of phosphorylated NFKB1: specifically ubiquitinates the p105 form of NFKB1, leading to its degradation (PubMed:10835356, PubMed:11158290, PubMed:14673179). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25503564, PubMed:25704143). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity). Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3 (PubMed:16371461). Mediates ubiquitination of REST, thereby leading to its proteasomal degradation (PubMed:18354482, PubMed:21258371). SCF(BTRC) mediates the ubiquitination and subsequent proteasomal degradation of KLF4; thereby negatively regulating cell pluripotency maintenance and embryogenesis (By similarity). SCF(BTRC) acts as a regulator of mTORC1 signaling pathway by catalyzing ubiquitination and subsequent proteasomal degradation of phosphorylated DEPTOR, TFE3 and MITF (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:33110214, PubMed:36608670). SCF(BTRC) directs 'Lys-48'-linked ubiquitination of UBR2 in the T-cell receptor signaling pathway (PubMed:38225265). {ECO:0000250|UniProtKB:Q3ULA2, ECO:0000269|PubMed:10066435, ECO:0000269|PubMed:10497169, ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11158290, ECO:0000269|PubMed:11238952, ECO:0000269|PubMed:11359933, ECO:0000269|PubMed:11994270, ECO:0000269|PubMed:12077367, ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:12820959, ECO:0000269|PubMed:12902344, ECO:0000269|PubMed:14603323, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988407, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16371461, ECO:0000269|PubMed:18354482, ECO:0000269|PubMed:21258371, ECO:0000269|PubMed:22017875, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:22017877, ECO:0000269|PubMed:22087322, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:33110214, ECO:0000269|PubMed:38225265, ECO:0000269|PubMed:9859996, ECO:0000269|PubMed:9990852}. |
| Q9Y2I7 | PIKFYVE | S73 | ochoa | 1-phosphatidylinositol 3-phosphate 5-kinase (Phosphatidylinositol 3-phosphate 5-kinase) (EC 2.7.1.150) (FYVE finger-containing phosphoinositide kinase) (PIKfyve) (Phosphatidylinositol 3-phosphate 5-kinase type III) (PIPkin-III) (Type III PIP kinase) (Serine-protein kinase PIKFYVE) (EC 2.7.11.1) | Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:23086417). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:17556371). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:22621786). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:33098764). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (PubMed:30612035). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (By similarity). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (PubMed:30612035). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (By similarity). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, through association with SPAG9 and RABEPK (By similarity). Mediates EGFR trafficking to the nucleus (PubMed:17909029). {ECO:0000250|UniProtKB:Q9Z1T6, ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:22621786, ECO:0000269|PubMed:27623384, ECO:0000269|PubMed:28779020, ECO:0000269|PubMed:29584722, ECO:0000269|PubMed:30612035, ECO:0000269|PubMed:33098764, ECO:0000303|PubMed:23086417}.; FUNCTION: (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC) by endocytosis. {ECO:0000269|PubMed:32221306}. |
| Q9Y2X7 | GIT1 | S54 | 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}. |
| Q9Y6E2 | BZW2 | S206 | ochoa | eIF5-mimic protein 1 (Basic leucine zipper and W2 domain-containing protein 2) | Translation initiation regulator which represses non-AUG initiated translation and repeat-associated non-AUG (RAN) initiated translation by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (PubMed:21745818, PubMed:28981728, PubMed:29470543, PubMed:34260931). Increases the accuracy of translation initiation by impeding EIF5-dependent translation from non-AUG codons by competing with it for interaction with EIF2S2 within the 43S pre-initiation complex (PIC) in an EIF3C-binding dependent manner (PubMed:21745818, PubMed:28981728, PubMed:34260931). {ECO:0000269|PubMed:21745818, ECO:0000269|PubMed:28981728, ECO:0000269|PubMed:29470543, ECO:0000269|PubMed:34260931}. |
| P13489 | RNH1 | S290 | Sugiyama | Ribonuclease inhibitor (Placental ribonuclease inhibitor) (Placental RNase inhibitor) (Ribonuclease/angiogenin inhibitor 1) (RAI) | Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and angiogenin (ANG) (PubMed:12578357, PubMed:14515218, PubMed:3219362, PubMed:3243277, PubMed:3470787, PubMed:9050852). May play a role in redox homeostasis (PubMed:17292889). Required to inhibit the cytotoxic tRNA ribonuclease activity of ANG in the cytoplasm in absence of stress (PubMed:23843625, PubMed:32510170). Relocates to the nucleus in response to stress, relieving inhibition of ANG in the cytoplasm, and inhibiting the angiogenic activity of ANG in the nucleus (PubMed:23843625). {ECO:0000269|PubMed:12578357, ECO:0000269|PubMed:14515218, ECO:0000269|PubMed:17292889, ECO:0000269|PubMed:23843625, ECO:0000269|PubMed:3219362, ECO:0000269|PubMed:3243277, ECO:0000269|PubMed:32510170, ECO:0000269|PubMed:3470787, ECO:0000269|PubMed:9050852}. |
| P17987 | TCP1 | S35 | Sugiyama | T-complex protein 1 subunit alpha (TCP-1-alpha) (EC 3.6.1.-) (CCT-alpha) (Chaperonin containing T-complex polypeptide 1 subunit 1) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P08195 | SLC3A2 | S253 | 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}. |
| P29401 | TKT | S332 | Sugiyama | Transketolase (TK) (EC 2.2.1.1) | Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate. {ECO:0000269|PubMed:27259054}. |
| P07814 | EPRS1 | S1473 | Sugiyama | 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}. |
| P24534 | EEF1B2 | S164 | Sugiyama | 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}. |
| O15111 | CHUK | S356 | Sugiyama | Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK-1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}. |
| Q9P212 | PLCE1 | S1146 | Sugiyama | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1 (EC 3.1.4.11) (Pancreas-enriched phospholipase C) (Phosphoinositide phospholipase C-epsilon-1) (Phospholipase C-epsilon-1) (PLC-epsilon-1) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine-exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation. In podocytes, is involved in the regulation of lamellipodia formation. Acts downstream of AVIL to allow ARP2/3 complex assembly (PubMed:29058690). {ECO:0000269|PubMed:11022047, ECO:0000269|PubMed:11395506, ECO:0000269|PubMed:11715024, ECO:0000269|PubMed:11877431, ECO:0000269|PubMed:12721365, ECO:0000269|PubMed:16537651, ECO:0000269|PubMed:17086182, ECO:0000269|PubMed:29058690}. |
| Q9NTJ3 | SMC4 | S504 | Sugiyama | Structural maintenance of chromosomes protein 4 (SMC protein 4) (SMC-4) (Chromosome-associated polypeptide C) (hCAP-C) (XCAP-C homolog) | Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. {ECO:0000269|PubMed:11136719}. |
| O60563 | CCNT1 | S431 | Sugiyama | Cyclin-T1 (CycT1) (Cyclin-T) | Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II) (PubMed:16109376, PubMed:16109377, PubMed:30134174, PubMed:35393539). Required to activate the protein kinase activity of CDK9: acts by mediating formation of liquid-liquid phase separation (LLPS) that enhances binding of P-TEFb to the CTD of RNA Pol II (PubMed:29849146, PubMed:35393539). {ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:35393539}.; FUNCTION: (Microbial infection) In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes. {ECO:0000269|PubMed:10329125, ECO:0000269|PubMed:10329126}. |
| O15230 | LAMA5 | S1611 | 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}. |
| P39019 | RPS19 | S98 | Sugiyama | Small ribosomal subunit protein eS19 (40S ribosomal protein S19) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for pre-rRNA processing and maturation of 40S ribosomal subunits (PubMed:16990592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:16990592, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| Q9Y3F4 | STRAP | S153 | 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}. |
| Q15139 | PRKD1 | S68 | Sugiyama | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| O95071 | UBR5 | S2384 | 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}. |
| Q8N568 | DCLK2 | S129 | Sugiyama | Serine/threonine-protein kinase DCLK2 (EC 2.7.11.1) (CaMK-like CREB regulatory kinase 2) (CL2) (CLICK-II) (CLICK2) (Doublecortin domain-containing protein 3B) (Doublecortin-like and CAM kinase-like 2) (Doublecortin-like kinase 2) | Protein kinase with a significantly reduced C(a2+)/CAM affinity and dependence compared to other members of the CaMK family. May play a role in the down-regulation of CRE-dependent gene activation probably by phosphorylation of the CREB coactivator CRTC2/TORC2 and the resulting retention of TORC2 in the cytoplasm (By similarity). {ECO:0000250}. |
| O60749 | SNX2 | S354 | Sugiyama | Sorting nexin-2 (Transformation-related gene 9 protein) (TRG-9) | Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (PubMed:16179610). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:17101778). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Can sense membrane curvature and has in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Required for retrograde endosome-to-TGN transport of TGN38 (PubMed:20138391). Promotes KALRN- and RHOG-dependent but retromer-independent membrane remodeling such as lamellipodium formation; the function is dependent on GEF activity of KALRN (PubMed:20604901). {ECO:0000269|PubMed:16179610, ECO:0000269|PubMed:17101778, ECO:0000269|PubMed:20138391, ECO:0000269|PubMed:20604901, ECO:0000269|PubMed:23085988, ECO:0000303|PubMed:16179610}. |
| P16455 | MGMT | S22 | Sugiyama | Methylated-DNA--protein-cysteine methyltransferase (EC 2.1.1.63) (6-O-methylguanine-DNA methyltransferase) (MGMT) (O-6-methylguanine-DNA-alkyltransferase) | Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. |
| Q96IU4 | ABHD14B | S149 | Sugiyama | Putative protein-lysine deacylase ABHD14B (EC 2.3.1.-) (Alpha/beta hydrolase domain-containing protein 14B) (Abhydrolase domain-containing protein 14B) (CCG1-interacting factor B) | Acts as an atypical protein-lysine deacetylase in vitro (PubMed:31478652). Catalyzes the deacetylation of lysine residues using CoA as substrate, generating acetyl-CoA and the free amine of protein-lysine residues (PubMed:31478652). Additional experiments are however required to confirm the protein-lysine deacetylase activity in vivo (Probable). Has hydrolase activity towards various surrogate p-nitrophenyl (pNp) substrates, such as pNp-butyrate, pNp-acetate and pNp-octanoate in vitro, with a strong preference for pNp-acetate (PubMed:14672934, PubMed:31478652). May activate transcription (PubMed:14672934). {ECO:0000269|PubMed:14672934, ECO:0000269|PubMed:31478652, ECO:0000305}. |
| P61764 | STXBP1 | S469 | Sugiyama | Syntaxin-binding protein 1 (MUNC18-1) (N-Sec1) (Protein unc-18 homolog 1) (Unc18-1) (Protein unc-18 homolog A) (Unc-18A) (p67) | Participates in the regulation of synaptic vesicle docking and fusion through interaction with GTP-binding proteins (By similarity). Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. Involved in the release of neurotransmitters from neurons through interacting with SNARE complex component STX1A and mediating the assembly of the SNARE complex at synaptic membranes (By similarity). May play a role in determining the specificity of intracellular fusion reactions. {ECO:0000250|UniProtKB:O08599, ECO:0000250|UniProtKB:P61765}. |
| A0A0J9YVX5 | None | S175 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (PDZ protein interacting specifically with TC10) | None |
| A0A1W2PNV4 | None | S236 | ochoa | Actin-related protein 2/3 complex subunit 1A | None |
| A2RU67 | FAM234B | S33 | ochoa | Protein FAM234B | None |
| A6NC98 | CCDC88B | S1253 | ochoa | Coiled-coil domain-containing protein 88B (Brain leucine zipper domain-containing protein) (Gipie) (Hook-related protein 3) (HkRP3) | Acts as a positive regulator of T-cell maturation and inflammatory function. Required for several functions of T-cells, in both the CD4(+) and the CD8(+) compartments and this includes expression of cell surface markers of activation, proliferation, and cytokine production in response to specific or non-specific stimulation (By similarity). Enhances NK cell cytotoxicity by positively regulating polarization of microtubule-organizing center (MTOC) to cytotoxic synapse, lytic granule transport along microtubules, and dynein-mediated clustering to MTOC (PubMed:25762780). Interacts with HSPA5 and stabilizes the interaction between HSPA5 and ERN1, leading to suppression of ERN1-induced JNK activation and endoplasmic reticulum stress-induced apoptosis (PubMed:21289099). {ECO:0000250|UniProtKB:Q4QRL3, ECO:0000269|PubMed:21289099, ECO:0000269|PubMed:25762780}. |
| O00273 | DFFA | S254 | 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). |
| O14737 | PDCD5 | S42 | ochoa | Programmed cell death protein 5 (TF-1 cell apoptosis-related protein 19) (Protein TFAR19) | May function in the process of apoptosis. |
| O14828 | SCAMP3 | S32 | ochoa | Secretory carrier-associated membrane protein 3 (Secretory carrier membrane protein 3) | Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface. |
| O14920 | IKBKB | S692 | ochoa | 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}. |
| O15061 | SYNM | S1435 | ochoa | Synemin (Desmuslin) | Type-VI intermediate filament (IF) which plays an important cytoskeletal role within the muscle cell cytoskeleton. It forms heteromeric IFs with desmin and/or vimentin, and via its interaction with cytoskeletal proteins alpha-dystrobrevin, dystrophin, talin-1, utrophin and vinculin, is able to link these heteromeric IFs to adherens-type junctions, such as to the costameres, neuromuscular junctions, and myotendinous junctions within striated muscle cells. {ECO:0000269|PubMed:11353857, ECO:0000269|PubMed:16777071, ECO:0000269|PubMed:18028034}. |
| O15085 | ARHGEF11 | S592 | ochoa | Rho guanine nucleotide exchange factor 11 (PDZ-RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. Involved in neurotrophin-induced neurite outgrowth. {ECO:0000269|PubMed:21670212}. |
| O15258 | RER1 | S95 | ochoa | Protein RER1 | Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment. {ECO:0000250}. |
| O15439 | ABCC4 | S668 | 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}. |
| O43296 | ZNF264 | S155 | ochoa | Zinc finger protein 264 | May be involved in transcriptional regulation. |
| O43353 | RIPK2 | S485 | ochoa | Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. |
| O43474 | KLF4 | S313 | ochoa | Krueppel-like factor 4 (Epithelial zinc finger protein EZF) (Gut-enriched krueppel-like factor) | Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription. {ECO:0000269|PubMed:17308127, ECO:0000269|PubMed:20071344}. |
| O43561 | LAT | S38 | ochoa | Linker for activation of T-cells family member 1 (36 kDa phosphotyrosine adapter protein) (pp36) (p36-38) | Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development (PubMed:23514740, PubMed:25907557). Involved in FCGR3 (low affinity immunoglobulin gamma Fc region receptor III)-mediated signaling in natural killer cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. {ECO:0000269|PubMed:10072481, ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:25907557}. |
| O43613 | HCRTR1 | S262 | psp | Orexin/Hypocretin receptor type 1 (Hypocretin receptor type 1) (Orexin receptor type 1) (Ox-1-R) (Ox1-R) (Ox1R) | Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide (PubMed:26950369, PubMed:9491897). Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding (PubMed:26950369, PubMed:9491897). {ECO:0000269|PubMed:26950369, ECO:0000269|PubMed:9491897}. |
| O60343 | TBC1D4 | S550 | ochoa | TBC1 domain family member 4 (Akt substrate of 160 kDa) (AS160) | May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Isoform 2 promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake. {ECO:0000269|PubMed:15971998, ECO:0000269|PubMed:18771725, ECO:0000269|PubMed:22908308}. |
| O60503 | ADCY9 | S706 | ochoa | Adenylate cyclase type 9 (EC 4.6.1.1) (ATP pyrophosphate-lyase 9) (Adenylate cyclase type IX) (ACIX) (Adenylyl cyclase 9) (AC9) | Adenylyl cyclase that catalyzes the formation of the signaling molecule cAMP in response to activation of G protein-coupled receptors (PubMed:10987815, PubMed:12972952, PubMed:15879435, PubMed:9628827). Contributes to signaling cascades activated by CRH (corticotropin-releasing factor), corticosteroids and beta-adrenergic receptors (PubMed:9628827). {ECO:0000269|PubMed:10987815, ECO:0000269|PubMed:12972952, ECO:0000269|PubMed:15879435, ECO:0000269|PubMed:9628827}. |
| O60524 | NEMF | S833 | ochoa | Ribosome quality control complex subunit NEMF (Antigen NY-CO-1) (Nuclear export mediator factor) (Serologically defined colon cancer antigen 1) | Key component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes as well as their ubiquitin-mediated proteasomal degradation (PubMed:25578875, PubMed:32726578, PubMed:33406423, PubMed:33909987). Thereby, frees 60S subunit ribosomes from the stalled translation complex and prevents the accumulation of nascent polypeptide chains that are potentially toxic for the cell (PubMed:25578875, PubMed:33406423, PubMed:33909987). Within the RQC complex, NEMF specifically binds stalled 60S ribosomal subunits by recognizing an exposed, nascent chain-conjugated tRNA moiety and promotes the recruitment of LTN1 to stalled 60S subunits (PubMed:25578875). Following binding to stalled 60S ribosomal subunits, NEMF mediates CAT tailing by recruiting alanine-charged tRNA to the A-site and directing the elongation of stalled nascent chains independently of mRNA or 40S subunits, leading to non-templated C-terminal alanine extensions (CAT tails) (PubMed:33406423, PubMed:33909987). Mainly recruits alanine-charged tRNAs, but can also other amino acid-charged tRNAs (PubMed:33406423, PubMed:33909987). CAT tailing is required to promote ubiquitination of stalled nascent chains by different E3 ubiquitin-protein ligases (PubMed:33909987). In the canonical RQC pathway (RQC-L), CAT tailing facilitates LTN1-dependent ubiquitination by exposing lysine residues that would otherwise remain buried in the ribosomal exit tunnel (By similarity). In the alternative RQC pathway (RQC-C) CAT tailing creates an C-degron mainly composed of alanine that is recognized by the CRL2(KLHDC10) and RCHY1/PIRH2 E3 ligases, leading to ubiquitination and degradation of stalled nascent chains (PubMed:33909987). NEMF may also indirectly play a role in nuclear export (PubMed:16103875). {ECO:0000250|UniProtKB:Q12532, ECO:0000269|PubMed:16103875, ECO:0000269|PubMed:25578875, ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:33406423, ECO:0000269|PubMed:33909987}. |
| O60664 | PLIN3 | S175 | 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}. |
| O75113 | N4BP1 | S226 | ochoa | NEDD4-binding protein 1 (N4BP1) (EC 3.1.-.-) | Potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation. Acts as a key negative regulator of select cytokine and chemokine responses elicited by TRIF-independent Toll-like receptors (TLRs), thereby limiting inflammatory cytokine responses to minor insults. In response to more threatening pathogens, cleaved by CASP8 downstream of TLR3 or TLR4, leading to its inactivation, thereby allowing production of inflammatory cytokines (By similarity). Acts as a restriction factor against some viruses, such as HIV-1: restricts HIV-1 replication by binding to HIV-1 mRNAs and mediating their degradation via its ribonuclease activity (PubMed:31133753). Also acts as an inhibitor of the E3 ubiquitin-protein ligase ITCH: acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates (By similarity). {ECO:0000250|UniProtKB:Q6A037, ECO:0000269|PubMed:31133753}. |
| O75410 | TACC1 | S568 | ochoa | Transforming acidic coiled-coil-containing protein 1 (Gastric cancer antigen Ga55) (Taxin-1) | Involved in transcription regulation induced by nuclear receptors, including in T3 thyroid hormone and all-trans retinoic acid pathways (PubMed:20078863). Might promote the nuclear localization of the receptors (PubMed:20078863). Likely involved in the processes that promote cell division prior to the formation of differentiated tissues. {ECO:0000269|PubMed:20078863}. |
| O75478 | TADA2A | S361 | ochoa | Transcriptional adapter 2-alpha (Transcriptional adapter 2-like) (ADA2-like protein) | Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Required for the function of some acidic activation domains, which activate transcription from a distant site (By similarity). Binds double-stranded DNA. Binds dinucleosomes, probably at the linker region between neighboring nucleosomes. Plays a role in chromatin remodeling. May promote TP53/p53 'Lys-321' acetylation, leading to reduced TP53 stability and transcriptional activity (PubMed:22644376). May also promote XRCC6 acetylation thus facilitating cell apoptosis in response to DNA damage (PubMed:22644376). {ECO:0000250|UniProtKB:Q8CHV6, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:22644376}. |
| O75534 | CSDE1 | S514 | ochoa | Cold shock domain-containing protein E1 (N-ras upstream gene protein) (Protein UNR) | RNA-binding protein involved in translationally coupled mRNA turnover (PubMed:11051545, PubMed:15314026). 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 (PubMed:11051545, PubMed:15314026). Required for efficient formation of stress granules (PubMed:29395067). {ECO:0000269|PubMed:11051545, ECO:0000269|PubMed:15314026, ECO:0000269|PubMed:29395067}.; FUNCTION: (Microbial infection) Required for internal initiation of translation of human rhinovirus RNA. {ECO:0000269|PubMed:10049359}. |
| O94776 | MTA2 | S440 | ochoa | Metastasis-associated protein MTA2 (Metastasis-associated 1-like 1) (MTA1-L1 protein) (p53 target protein in deacetylase complex) | May function as a transcriptional coregulator (PubMed:16428440, PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). {ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}. |
| O94804 | STK10 | S516 | ochoa | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
| O95163 | ELP1 | S471 | ochoa | Elongator complex protein 1 (ELP1) (IkappaB kinase complex-associated protein) (IKK complex-associated protein) (p150) | Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (By similarity). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (PubMed:9751059). {ECO:0000250|UniProtKB:Q06706, ECO:0000250|UniProtKB:Q7TT37, ECO:0000269|PubMed:9751059, ECO:0000303|PubMed:29332244}. |
| O95235 | KIF20A | S44 | ochoa | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95677 | EYA4 | S29 | ochoa | Protein phosphatase EYA4 (EC 3.1.3.48) (Eyes absent homolog 4) | 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. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. May be involved in development of the eye (By similarity). {ECO:0000250|UniProtKB:Q99502}. |
| O95863 | SNAI1 | S82 | psp | Zinc finger protein SNAI1 (Protein snail homolog 1) (Protein sna) | Involved in induction of the epithelial to mesenchymal transition (EMT), formation and maintenance of embryonic mesoderm, growth arrest, survival and cell migration (PubMed:10655587, PubMed:15647282, PubMed:20389281, PubMed:20562920, PubMed:21952048, PubMed:25827072). Binds to 3 E-boxes of the E-cadherin/CDH1 gene promoter and to the promoters of CLDN7 and KRT8 and, in association with histone demethylase KDM1A which it recruits to the promoters, causes a decrease in dimethylated H3K4 levels and represses transcription (PubMed:10655587, PubMed:20389281, PubMed:20562920). The N-terminal SNAG domain competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (in vitro) (PubMed:20389281, PubMed:21300290, PubMed:23721412). During EMT, involved with LOXL2 in negatively regulating pericentromeric heterochromatin transcription (PubMed:16096638). SNAI1 recruits LOXL2 to pericentromeric regions to oxidize histone H3 and repress transcription which leads to release of heterochromatin component CBX5/HP1A, enabling chromatin reorganization and acquisition of mesenchymal traits (By similarity). Associates with EGR1 and SP1 to mediate tetradecanoyl phorbol acetate (TPA)-induced up-regulation of CDKN2B, possibly by binding to the CDKN2B promoter region 5'-TCACA-3 (PubMed:20121949). In addition, may also activate the CDKN2B promoter by itself (PubMed:20121949). {ECO:0000250|UniProtKB:Q02085, ECO:0000269|PubMed:10655587, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16096638, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:20389281, ECO:0000269|PubMed:20562920, ECO:0000269|PubMed:21300290, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:23721412, ECO:0000269|PubMed:25827072}. |
| O95866 | MPIG6B | S208 | ochoa | Megakaryocyte and platelet inhibitory receptor G6b (Protein G6b) | Inhibitory receptor that acts as a critical regulator of hematopoietic lineage differentiation, megakaryocyte function and platelet production (PubMed:12665801, PubMed:17311996, PubMed:27743390). Inhibits platelet aggregation and activation by agonists such as ADP and collagen-related peptide (PubMed:12665801). This regulation of megakaryocate function as well as platelet production ann activation is done through the inhibition (via the 2 ITIM motifs) of the receptors CLEC1B and GP6:FcRgamma signaling (PubMed:17311996). Appears to operate in a calcium-independent manner (PubMed:12665801). {ECO:0000269|PubMed:12665801, ECO:0000269|PubMed:17311996, ECO:0000269|PubMed:27743390}.; FUNCTION: Isoform B, displayed in this entry, is the only isoform to contain both a transmembrane region and 2 immunoreceptor tyrosine-based inhibitor motifs (ITIMs) and, thus, the only one which probably has a role of inhibitory receptor. Isoform A may be the activating counterpart of isoform B. {ECO:0000305|PubMed:11544253}. |
| O96017 | CHEK2 | S210 | psp | Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}. |
| P00338 | LDHA | S274 | ochoa | L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}. |
| P00519 | ABL1 | S59 | ochoa | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P02671 | FGA | S22 | psp | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P02766 | TTR | S72 | ochoa | Transthyretin (ATTR) (Prealbumin) (TBPA) | Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain. {ECO:0000269|PubMed:3714052}. |
| P02775 | PPBP | S55 | ochoa | Platelet basic protein (PBP) (C-X-C motif chemokine 7) (Leukocyte-derived growth factor) (LDGF) (Macrophage-derived growth factor) (MDGF) (Small-inducible cytokine B7) [Cleaved into: Connective tissue-activating peptide III (CTAP-III) (LA-PF4) (Low-affinity platelet factor IV); TC-2; Connective tissue-activating peptide III(1-81) (CTAP-III(1-81)); Beta-thromboglobulin (Beta-TG); Neutrophil-activating peptide 2(74) (NAP-2(74)); Neutrophil-activating peptide 2(73) (NAP-2(73)); Neutrophil-activating peptide 2 (NAP-2); TC-1; Neutrophil-activating peptide 2(1-66) (NAP-2(1-66)); Neutrophil-activating peptide 2(1-63) (NAP-2(1-63))] | LA-PF4 stimulates DNA synthesis, mitosis, glycolysis, intracellular cAMP accumulation, prostaglandin E2 secretion, and synthesis of hyaluronic acid and sulfated glycosaminoglycan. It also stimulates the formation and secretion of plasminogen activator by human synovial cells. NAP-2 is a ligand for CXCR1 and CXCR2, and NAP-2, NAP-2(73), NAP-2(74), NAP-2(1-66), and most potent NAP-2(1-63) are chemoattractants and activators for neutrophils. TC-1 and TC-2 are antibacterial proteins, in vitro released from activated platelet alpha-granules. CTAP-III(1-81) is more potent than CTAP-III desensitize chemokine-induced neutrophil activation. {ECO:0000269|PubMed:10877842, ECO:0000269|PubMed:7890771, ECO:0000269|PubMed:8950790, ECO:0000269|PubMed:9794434}. |
| P02786 | TFRC | S34 | ochoa | 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}. |
| P02810 | PRH1; | S24 | psp | Salivary acidic proline-rich phosphoprotein 1/2 (Db-s) (PRP-1/PRP-2) (Parotid acidic protein) (Pa) (Parotid double-band protein) (Parotid isoelectric focusing variant protein) (PIF-S) (Parotid proline-rich protein 1/2) (Pr1/Pr2) (Protein C) [Cleaved into: Salivary acidic proline-rich phosphoprotein 1/2; Salivary acidic proline-rich phosphoprotein 3/4 (Db-F) (PIF-F) (PRP-3/PRP-4) (Protein A); Peptide P-C] | PRP's act as highly potent inhibitors of crystal growth of calcium phosphates. They provide a protective and reparative environment for dental enamel which is important for the integrity of the teeth. |
| P04637 | TP53 | S20 | 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}. |
| P05062 | ALDOB | S276 | ochoa | Fructose-bisphosphate aldolase B (EC 4.1.2.13) (Liver-type aldolase) | Catalyzes the aldol cleavage of fructose 1,6-biphosphate to form two triosephosphates dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in glycolysis as well as the reverse stereospecific aldol addition reaction in gluconeogenesis. In fructolysis, metabolizes fructose 1-phosphate derived from the phosphorylation of dietary fructose by fructokinase into dihydroxyacetone phosphate and D-glyceraldehyde (PubMed:10970798, PubMed:12205126, PubMed:20848650). Acts as an adapter independently of its enzymatic activity, exerts a tumor suppressor role by stabilizing the ternary complex with G6PD and TP53 to inhibit G6PD activity and keep oxidative pentose phosphate metabolism in check (PubMed:35122041). {ECO:0000269|PubMed:10970798, ECO:0000269|PubMed:12205126, ECO:0000269|PubMed:20848650, ECO:0000269|PubMed:35122041}. |
| P05412 | JUN | S73 | ochoa|psp | Transcription factor Jun (Activator protein 1) (AP1) (Proto-oncogene c-Jun) (Transcription factor AP-1 subunit Jun) (V-jun avian sarcoma virus 17 oncogene homolog) (p39) | Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:10995748, PubMed:22083952). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity (By similarity). Together with FOSB, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway (PubMed:12618758). Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation (PubMed:17210646). Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306). {ECO:0000250|UniProtKB:P05627, ECO:0000269|PubMed:10995748, ECO:0000269|PubMed:12618758, ECO:0000269|PubMed:17210646, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:24623306}.; FUNCTION: (Microbial infection) Upon Epstein-Barr virus (EBV) infection, binds to viral BZLF1 Z promoter and activates viral BZLF1 expression. {ECO:0000269|PubMed:31341047}. |
| P05976 | MYL1 | S73 | 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}. |
| P07339 | CTSD | S359 | ochoa | Cathepsin D (EC 3.4.23.5) [Cleaved into: Cathepsin D light chain; Cathepsin D heavy chain] | Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. {ECO:0000269|PubMed:27333034}. |
| P07384 | CAPN1 | S415 | ochoa | Calpain-1 catalytic subunit (EC 3.4.22.52) (Calcium-activated neutral proteinase 1) (CANP 1) (Calpain mu-type) (Calpain-1 large subunit) (Cell proliferation-inducing gene 30 protein) (Micromolar-calpain) (muCANP) | Calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction (PubMed:19617626, PubMed:21531719, PubMed:2400579). Proteolytically cleaves CTBP1 at 'Asn-375', 'Gly-387' and 'His-409' (PubMed:23707407). Cleaves and activates caspase-7 (CASP7) (PubMed:19617626). {ECO:0000269|PubMed:19617626, ECO:0000269|PubMed:21531719, ECO:0000269|PubMed:23707407, ECO:0000269|PubMed:2400579}. |
| P07737 | PFN1 | S58 | ochoa | Profilin-1 (Epididymis tissue protein Li 184a) (Profilin I) | Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}. |
| P07910 | HNRNPC | S260 | ochoa|psp | Heterogeneous nuclear ribonucleoproteins C1/C2 (hnRNP C1/C2) | Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). {ECO:0000269|PubMed:12509468, ECO:0000269|PubMed:16010978, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:7567451, ECO:0000269|PubMed:8264621}. |
| P08047 | SP1 | S641 | psp | Transcription factor Sp1 | Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21046154, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity). {ECO:0000250|UniProtKB:O89090, ECO:0000250|UniProtKB:Q01714, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21046154, ECO:0000269|PubMed:21798247}. |
| P08559 | PDHA1 | S314 | 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}. |
| P09936 | UCHL1 | S188 | psp | Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1) (EC 3.4.19.12) (Neuron cytoplasmic protein 9.5) (PGP 9.5) (PGP9.5) (Ubiquitin thioesterase L1) | Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis (PubMed:22212137, PubMed:23359680). Abrogates the ubiquitination of multiple proteins including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor protein cleaving enzyme 1/BACE1 (PubMed:22212137, PubMed:25615526). In addition, recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin to maintain a stable pool of monoubiquitin that is a key requirement for the ubiquitin-proteasome and the autophagy-lysosome pathways (PubMed:12408865, PubMed:8639624, PubMed:9774100). Regulates amyloid precursor protein/APP processing by promoting BACE1 degradation resulting in decreased amyloid beta production (PubMed:22212137). Plays a role in the immune response by regulating the ability of MHC I molecules to reach cross-presentation compartments competent for generating Ag-MHC I complexes (By similarity). Mediates the 'Lys-48'-linked deubiquitination of the transcriptional coactivator WWTR1/TAZ leading to its stabilization and inhibition of osteoclastogenesis (By similarity). Deubiquitinates and stabilizes epidermal growth factor receptor EGFR to prevent its degradation and to activate its downstream mediators (By similarity). Modulates oxidative activity in skeletal muscle by regulating key mitochondrial oxidative proteins (By similarity). Enhances the activity of hypoxia-inducible factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated ubiquitination and consequently inhibiting its degradation (PubMed:25615526). {ECO:0000250|UniProtKB:Q9R0P9, ECO:0000269|PubMed:12408865, ECO:0000269|PubMed:22212137, ECO:0000269|PubMed:23359680, ECO:0000269|PubMed:25615526, ECO:0000269|PubMed:8639624, ECO:0000269|PubMed:9774100}. |
| P10451 | SPP1 | S126 | psp | Osteopontin (Bone sialoprotein 1) (Nephropontin) (Secreted phosphoprotein 1) (SPP-1) (Urinary stone protein) (Uropontin) | Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. {ECO:0000250|UniProtKB:P31096}.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity. {ECO:0000250|UniProtKB:P10923}. |
| P13489 | RNH1 | S255 | ochoa | Ribonuclease inhibitor (Placental ribonuclease inhibitor) (Placental RNase inhibitor) (Ribonuclease/angiogenin inhibitor 1) (RAI) | Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and angiogenin (ANG) (PubMed:12578357, PubMed:14515218, PubMed:3219362, PubMed:3243277, PubMed:3470787, PubMed:9050852). May play a role in redox homeostasis (PubMed:17292889). Required to inhibit the cytotoxic tRNA ribonuclease activity of ANG in the cytoplasm in absence of stress (PubMed:23843625, PubMed:32510170). Relocates to the nucleus in response to stress, relieving inhibition of ANG in the cytoplasm, and inhibiting the angiogenic activity of ANG in the nucleus (PubMed:23843625). {ECO:0000269|PubMed:12578357, ECO:0000269|PubMed:14515218, ECO:0000269|PubMed:17292889, ECO:0000269|PubMed:23843625, ECO:0000269|PubMed:3219362, ECO:0000269|PubMed:3243277, ECO:0000269|PubMed:32510170, ECO:0000269|PubMed:3470787, ECO:0000269|PubMed:9050852}. |
| P13861 | PRKAR2A | S205 | ochoa | cAMP-dependent protein kinase type II-alpha regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P15884 | TCF4 | S528 | ochoa | Transcription factor 4 (TCF-4) (Class B basic helix-loop-helix protein 19) (bHLHb19) (Immunoglobulin transcription factor 2) (ITF-2) (SL3-3 enhancer factor 2) (SEF-2) | Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'. {ECO:0000250}. |
| P16070 | CD44 | S706 | ochoa|psp | CD44 antigen (CDw44) (Epican) (Extracellular matrix receptor III) (ECMR-III) (GP90 lymphocyte homing/adhesion receptor) (HUTCH-I) (Heparan sulfate proteoglycan) (Hermes antigen) (Hyaluronate receptor) (Phagocytic glycoprotein 1) (PGP-1) (Phagocytic glycoprotein I) (PGP-I) (CD antigen CD44) | Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment (PubMed:16541107, PubMed:19703720, PubMed:22726066). Participates thereby in a wide variety of cellular functions including the activation, recirculation and homing of T-lymphocytes, hematopoiesis, inflammation and response to bacterial infection (PubMed:7528188). Engages, through its ectodomain, extracellular matrix components such as hyaluronan/HA, collagen, growth factors, cytokines or proteases and serves as a platform for signal transduction by assembling, via its cytoplasmic domain, protein complexes containing receptor kinases and membrane proteases (PubMed:18757307, PubMed:23589287). Such effectors include PKN2, the RhoGTPases RAC1 and RHOA, Rho-kinases and phospholipase C that coordinate signaling pathways promoting calcium mobilization and actin-mediated cytoskeleton reorganization essential for cell migration and adhesion (PubMed:15123640). {ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:16541107, ECO:0000269|PubMed:18757307, ECO:0000269|PubMed:19703720, ECO:0000269|PubMed:22726066, ECO:0000269|PubMed:23589287, ECO:0000269|PubMed:7528188}. |
| P16144 | ITGB4 | S1111 | 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}. |
| P17535 | JUND | S100 | ochoa|psp | Transcription factor JunD (Transcription factor AP-1 subunit JunD) | Transcription factor binding AP-1 sites (PubMed:9989505). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription factor complex, thereby enhancing their DNA binding activity to an AP-1 consensus sequence 3'-TGA[GC]TCA-5' and enhancing their transcriptional activity (PubMed:28981703, PubMed:9989505). {ECO:0000269|PubMed:28981703, ECO:0000269|PubMed:9989505}. |
| P18146 | EGR1 | S104 | psp | Early growth response protein 1 (EGR-1) (AT225) (Nerve growth factor-induced protein A) (NGFI-A) (Transcription factor ETR103) (Transcription factor Zif268) (Zinc finger protein 225) (Zinc finger protein Krox-24) | Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, PubMed:25999311). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (By similarity). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (By similarity). {ECO:0000250|UniProtKB:P08046, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:25999311}. |
| P18206 | VCL | S117 | ochoa | Vinculin (Metavinculin) (MV) | Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion. {ECO:0000269|PubMed:20484056}. |
| P18583 | SON | S1490 | ochoa | Protein SON (Bax antagonist selected in saccharomyces 1) (BASS1) (Negative regulatory element-binding protein) (NRE-binding protein) (Protein DBP-5) (SON3) | RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-GA[GT]AN[CG][AG]CC-3'. May indirectly repress hepatitis B virus (HBV) core promoter activity and transcription of HBV genes and production of HBV virions. Essential for correct RNA splicing of multiple genes critical for brain development, neuronal migration and metabolism, including TUBG1, FLNA, PNKP, WDR62, PSMD3, PCK2, PFKL, IDH2, and ACY1 (PubMed:27545680). {ECO:0000269|PubMed:20581448, ECO:0000269|PubMed:21504830, ECO:0000269|PubMed:27545680}. |
| P20810 | CAST | S561 | ochoa | Calpastatin (Calpain inhibitor) (Sperm BS-17 component) | Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue. |
| P21731 | TBXA2R | S324 | psp | Thromboxane A2 receptor (TXA2-R) (Prostanoid TP receptor) | Receptor for thromboxane A2 (TXA2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of TXA2 to glomerular TP receptors causes intense vasoconstriction. Activates phospholipase C. {ECO:0000269|PubMed:8613548}.; FUNCTION: [Isoform 1]: Activates adenylyl cyclase. {ECO:0000269|PubMed:8613548}.; FUNCTION: [Isoform 2]: Inhibits adenylyl cyclase. {ECO:0000269|PubMed:8613548}. |
| P22314 | UBA1 | S820 | 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}. |
| P23258 | TUBG1 | S131 | psp | Tubulin gamma-1 chain (Gamma-1-tubulin) (Gamma-tubulin complex component 1) (GCP-1) | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:38609661, PubMed:39321809). Gamma-tubulin is a key component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation (PubMed:38305685, PubMed:38609661, PubMed:39321809). The gTuRC regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments, a critical step in centrosome duplication and spindle formation (PubMed:38305685, PubMed:38609661, PubMed:39321809). {ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}. |
| P24534 | EEF1B2 | S112 | 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}. |
| P25786 | PSMA1 | S230 | ochoa | Proteasome subunit alpha type-1 (30 kDa prosomal protein) (PROS-30) (Macropain subunit C2) (Multicatalytic endopeptidase complex subunit C2) (Proteasome component C2) (Proteasome nu chain) (Proteasome subunit alpha-6) (alpha-6) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P26196 | DDX6 | S462 | ochoa | Probable ATP-dependent RNA helicase DDX6 (EC 3.6.4.13) (ATP-dependent RNA helicase p54) (DEAD box protein 6) (Oncogene RCK) | Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions (PubMed:25995375, PubMed:27342281, PubMed:31422817). Plays a role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:27342281). In the process of mRNA degradation, plays a role in mRNA decapping (PubMed:16364915). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573). {ECO:0000269|PubMed:16364915, ECO:0000269|PubMed:25995375, ECO:0000269|PubMed:26098573, ECO:0000269|PubMed:27342281, ECO:0000269|PubMed:31422817}. |
| P26641 | EEF1G | S406 | ochoa | Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) | Probably plays a role in anchoring the complex to other cellular components. |
| P27348 | YWHAQ | S210 | 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}. |
| P27448 | MARK3 | S439 | ochoa | MAP/microtubule affinity-regulating kinase 3 (EC 2.7.11.1) (C-TAK1) (cTAK1) (Cdc25C-associated protein kinase 1) (ELKL motif kinase 2) (EMK-2) (Protein kinase STK10) (Ser/Thr protein kinase PAR-1) (Par-1a) (Serine/threonine-protein kinase p78) | Serine/threonine-protein kinase (PubMed:16822840, PubMed:16980613, PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216' (PubMed:12941695). Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol (PubMed:16822840). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). Phosphorylates PKP2 and KSR1 (PubMed:12941695). {ECO:0000269|PubMed:12941695, ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}. |
| P27815 | PDE4A | S830 | ochoa | 3',5'-cyclic-AMP phosphodiesterase 4A (EC 3.1.4.53) (DPDE2) (PDE46) (cAMP-specific phosphodiesterase 4A) | Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes. {ECO:0000269|PubMed:11566027, ECO:0000269|PubMed:2160582}.; FUNCTION: [Isoform 1]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 2]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:15738310}.; FUNCTION: [Isoform 3]: Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP. {ECO:0000269|PubMed:7888306}.; FUNCTION: [Isoform 4]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:9677330}.; FUNCTION: [Isoform 6]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:11306681, ECO:0000269|PubMed:15738310, ECO:0000269|PubMed:17727341}.; FUNCTION: [Isoform 7]: Efficiently hydrolyzes cAMP. {ECO:0000269|PubMed:18095939}. |
| P29692 | EEF1D | S106 | 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). |
| P30086 | PEBP1 | S60 | ochoa | 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}. |
| P30260 | CDC27 | S426 | ochoa|psp | Cell division cycle protein 27 homolog (Anaphase-promoting complex subunit 3) (APC3) (CDC27 homolog) (CDC27Hs) (H-NUC) | Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}. |
| P30793 | GCH1 | S60 | ochoa | GTP cyclohydrolase 1 (EC 3.5.4.16) (GTP cyclohydrolase I) (GTP-CH-I) | Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown. {ECO:0000269|PubMed:12176133, ECO:0000269|PubMed:16338639, ECO:0000269|PubMed:17057711, ECO:0000269|PubMed:8068008, ECO:0000269|PubMed:9445252}. |
| P31323 | PRKAR2B | S220 | ochoa | cAMP-dependent protein kinase type II-beta regulatory subunit | Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase. |
| P31946 | YWHAB | S212 | 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}. |
| P34932 | HSPA4 | S692 | ochoa | Heat shock 70 kDa protein 4 (HSP70RY) (Heat shock 70-related protein APG-2) (Heat shock protein family H member 2) | None |
| P38398 | BRCA1 | S425 | ochoa | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P40926 | MDH2 | S47 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P42858 | HTT | S118 | psp | Huntingtin (Huntington disease protein) (HD protein) [Cleaved into: Huntingtin, myristoylated N-terminal fragment] | [Huntingtin]: May play a role in microtubule-mediated transport or vesicle function.; FUNCTION: [Huntingtin, myristoylated N-terminal fragment]: Promotes the formation of autophagic vesicles. {ECO:0000269|PubMed:24459296}. |
| P46109 | CRKL | S112 | ochoa | Crk-like protein | May mediate the transduction of intracellular signals. |
| P46199 | MTIF2 | S426 | ochoa | Translation initiation factor IF-2, mitochondrial (IF-2(Mt)) (IF-2Mt) (IF2(mt)) | One of the essential components for the initiation of protein synthesis. Protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the 30S ribosomal subunits. Also involved in the hydrolysis of GTP during the formation of the 70S ribosomal complex. |
| P48444 | ARCN1 | S220 | ochoa | Coatomer subunit delta (Archain) (Delta-coat protein) (Delta-COP) | Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}. |
| P48730 | CSNK1D | S328 | ochoa | Casein kinase I isoform delta (CKI-delta) (CKId) (EC 2.7.11.1) (Tau-protein kinase CSNK1D) (EC 2.7.11.26) | Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (By similarity). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. {ECO:0000250|UniProtKB:Q9DC28, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:16027726, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:19043076, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:20407760, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:20696890, ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:21084295, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092}. |
| P49023 | PXN | S143 | ochoa | Paxillin | Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion. {ECO:0000269|PubMed:25015296}. |
| P49327 | FASN | S1028 | psp | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49756 | RBM25 | S516 | ochoa | RNA-binding protein 25 (Arg/Glu/Asp-rich protein of 120 kDa) (RED120) (Protein S164) (RNA-binding motif protein 25) (RNA-binding region-containing protein 7) | RNA-binding protein that acts as a regulator of alternative pre-mRNA splicing. Involved in apoptotic cell death through the regulation of the apoptotic factor BCL2L1 isoform expression. Modulates the ratio of proapoptotic BCL2L1 isoform S to antiapoptotic BCL2L1 isoform L mRNA expression. When overexpressed, stimulates proapoptotic BCL2L1 isoform S 5'-splice site (5'-ss) selection, whereas its depletion caused the accumulation of antiapoptotic BCL2L1 isoform L. Promotes BCL2L1 isoform S 5'-ss usage through the 5'-CGGGCA-3' RNA sequence. Its association with LUC7L3 promotes U1 snRNP binding to a weak 5' ss in a 5'-CGGGCA-3'-dependent manner. Binds to the exonic splicing enhancer 5'-CGGGCA-3' RNA sequence located within exon 2 of the BCL2L1 pre-mRNA. Also involved in the generation of an abnormal and truncated splice form of SCN5A in heart failure. {ECO:0000269|PubMed:18663000, ECO:0000269|PubMed:21859973}. |
| P49792 | RANBP2 | S2693 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P49815 | TSC2 | S1341 | ochoa | Tuberin (Tuberous sclerosis 2 protein) | Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:33436626, ECO:0000269|PubMed:35772404}. |
| P50851 | LRBA | S2065 | 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}. |
| P51523 | ZNF84 | S126 | ochoa | Zinc finger protein 84 (Zinc finger protein HPF2) | May be involved in transcriptional regulation. |
| P52209 | PGD | S37 | ochoa | 6-phosphogluconate dehydrogenase, decarboxylating (EC 1.1.1.44) | Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. {ECO:0000250}. |
| P52569 | SLC7A2 | S24 | ochoa | Cationic amino acid transporter 2 (CAT-2) (CAT2) (Low affinity cationic amino acid transporter 2) (Solute carrier family 7 member 2) | Functions as a permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine); the affinity for its substrates differs between isoforms created by alternative splicing (PubMed:28684763, PubMed:9174363). May play a role in classical or alternative activation of macrophages via its role in arginine transport (By similarity). {ECO:0000250|UniProtKB:P18581, ECO:0000269|PubMed:28684763, ECO:0000269|PubMed:9174363}.; FUNCTION: [Isoform 1]: Functions as a permease that mediates the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine). Shows a much higher affinity for L-arginine and L-homoarginine than isoform 2. {ECO:0000269|PubMed:28684763, ECO:0000269|PubMed:9174363}.; FUNCTION: [Isoform 2]: Functions as a low-affinity, high capacity permease involved in the transport of the cationic amino acids (L-arginine, L-lysine, L-ornithine and L-homoarginine). {ECO:0000269|PubMed:28684763, ECO:0000269|PubMed:9174363}. |
| P53004 | BLVRA | S21 | psp | Biliverdin reductase A (BVR A) (EC 1.3.1.24) (Biliverdin-IX alpha-reductase) | Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IXalpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor (PubMed:10858451, PubMed:7929092, PubMed:8424666, PubMed:8631357). Does not reduce bilirubin IXbeta (PubMed:10858451). Uses the reactants NADH or NADPH depending on the pH; NADH is used at the acidic pH range (6-6.9) and NADPH at the alkaline range (8.5-8.7) (PubMed:7929092, PubMed:8424666, PubMed:8631357). NADPH, however, is the probable reactant in biological systems (PubMed:7929092). {ECO:0000269|PubMed:10858451, ECO:0000269|PubMed:7929092, ECO:0000269|PubMed:8424666, ECO:0000269|PubMed:8631357}. |
| P53814 | SMTN | S729 | ochoa | Smoothelin | Structural protein of the cytoskeleton. |
| P54132 | BLM | S336 | ochoa | RecQ-like DNA helicase BLM (EC 5.6.2.4) (Bloom syndrome protein) (DNA 3'-5' helicase BLM) (DNA helicase, RecQ-like type 2) (RecQ2) (RecQ protein-like 3) | ATP-dependent DNA helicase that unwinds double-stranded (ds)DNA in a 3'-5' direction (PubMed:24816114, PubMed:25901030, PubMed:9388193, PubMed:9765292). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and Holliday junction DNA (PubMed:20639533, PubMed:24257077, PubMed:25901030). Unwinds G-quadruplex DNA; unwinding occurs in the 3'-5' direction and requires a 3' single-stranded end of at least 7 nucleotides (PubMed:18426915, PubMed:9765292). Helicase activity is higher on G-quadruplex substrates than on duplex DNA substrates (PubMed:9765292). Telomeres, immunoglobulin heavy chain switch regions and rDNA are notably G-rich; formation of G-quadruplex DNA would block DNA replication and transcription (PubMed:18426915, PubMed:9765292). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity). {ECO:0000250|UniProtKB:O88700, ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:18426915, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:34606619, ECO:0000269|PubMed:9388193, ECO:0000269|PubMed:9765292}.; FUNCTION: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration. {ECO:0000269|PubMed:32690953}. |
| P54278 | PMS2 | S588 | 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}. |
| P54886 | ALDH18A1 | S427 | ochoa | Delta-1-pyrroline-5-carboxylate synthase (P5CS) (Aldehyde dehydrogenase family 18 member A1) [Includes: Glutamate 5-kinase (GK) (EC 2.7.2.11) (Gamma-glutamyl kinase); Gamma-glutamyl phosphate reductase (GPR) (EC 1.2.1.41) (Glutamate-5-semialdehyde dehydrogenase) (Glutamyl-gamma-semialdehyde dehydrogenase)] | Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine. {ECO:0000269|PubMed:10037775, ECO:0000269|PubMed:11092761, ECO:0000269|PubMed:26297558, ECO:0000269|PubMed:26320891, ECO:0000269|PubMed:39506109}. |
| P55210 | CASP7 | S239 | psp | Caspase-7 (CASP-7) (EC 3.4.22.60) (Apoptotic protease Mch-3) (CMH-1) (ICE-like apoptotic protease 3) (ICE-LAP3) [Cleaved into: Caspase-7 subunit p20; Caspase-7 subunit p11] | Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (PubMed:11257230, PubMed:11257231, PubMed:11701129, PubMed:15314233, PubMed:16916640, PubMed:17646170, PubMed:18723680, PubMed:19581639, PubMed:8521391, PubMed:8567622, PubMed:8576161, PubMed:9070923). Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences (PubMed:12824163, PubMed:15314233, PubMed:17697120, PubMed:19581639, PubMed:20566630, PubMed:23650375, PubMed:23897474, PubMed:27032039). Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (By similarity). Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and YY1 (PubMed:10497198, PubMed:16123041, PubMed:16374543, PubMed:16916640, PubMed:18723680, PubMed:20566630, PubMed:21555521, PubMed:22184066, PubMed:22451931, PubMed:27889207, PubMed:28863261, PubMed:31586028, PubMed:34156061, PubMed:35338844, PubMed:35446120). Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins (PubMed:18723680). Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair (PubMed:21157428). Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores (By similarity). Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores (By similarity). Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1 (PubMed:22464733). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (By similarity). Cleaves and activates sterol regulatory element binding proteins (SREBPs) (PubMed:8643593). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9 (By similarity). In case of infection, catalyzes cleavage of Kaposi sarcoma-associated herpesvirus protein ORF57, thereby preventing expression of viral lytic genes (PubMed:20159985). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106). {ECO:0000250|UniProtKB:P97864, ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:16374543, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17646170, ECO:0000269|PubMed:17697120, ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:20159985, ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:21157428, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:22184066, ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23897474, ECO:0000269|PubMed:27032039, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:28863261, ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106, ECO:0000269|PubMed:8521391, ECO:0000269|PubMed:8567622, ECO:0000269|PubMed:8576161, ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9070923}.; FUNCTION: [Isoform Beta]: Lacks enzymatic activity. {ECO:0000269|PubMed:8521391}. |
| P55265 | ADAR | S629 | ochoa | Double-stranded RNA-specific adenosine deaminase (DRADA) (EC 3.5.4.37) (136 kDa double-stranded RNA-binding protein) (p136) (Interferon-inducible protein 4) (IFI-4) (K88DSRBP) | Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}. |
| P60880 | SNAP25 | S154 | ochoa | Synaptosomal-associated protein 25 (SNAP-25) (Super protein) (SUP) (Synaptosomal-associated 25 kDa protein) | t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells. {ECO:0000250|UniProtKB:P60881}. |
| P61981 | YWHAG | S215 | 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 | S213 | 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}. |
| P62280 | RPS11 | S67 | ochoa | Small ribosomal subunit protein uS17 (40S ribosomal protein S11) | Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P63104 | YWHAZ | S210 | 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}. |
| P98175 | RBM10 | S710 | ochoa | RNA-binding protein 10 (G patch domain-containing protein 9) (RNA-binding motif protein 10) (RNA-binding protein S1-1) (S1-1) | Binds to ssRNA containing the consensus sequence 5'-AGGUAA-3' (PubMed:21256132). May be involved in post-transcriptional processing, most probably in mRNA splicing (PubMed:18315527). Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000250|UniProtKB:P70501, ECO:0000269|PubMed:18315527, ECO:0000269|PubMed:21256132, ECO:0000269|PubMed:28431233}. |
| Q00325 | SLC25A3 | S297 | ochoa | Solute carrier family 25 member 3 (Phosphate carrier protein, mitochondrial) (Phosphate transport protein) (PTP) | Inorganic ion transporter that transports phosphate or copper ions across the mitochondrial inner membrane into the matrix compartment (By similarity) (PubMed:17273968, PubMed:29237729). Mediates proton-coupled symport of phosphate ions necessary for mitochondrial oxidative phosphorylation of ADP to ATP (By similarity) (PubMed:17273968). Transports copper ions probably in the form of anionic copper(I) complexes to maintain mitochondrial matrix copper pool and to supply copper for cytochrome C oxidase complex assembly (PubMed:29237729). May also play a role in regulation of the mitochondrial permeability transition pore (mPTP) (By similarity). {ECO:0000250|UniProtKB:P12234, ECO:0000250|UniProtKB:P16036, ECO:0000269|PubMed:17273968, ECO:0000269|PubMed:29237729}. |
| Q02880 | TOP2B | S1441 | ochoa | DNA topoisomerase 2-beta (EC 5.6.2.2) (DNA topoisomerase II, beta isozyme) | Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation. {ECO:0000269|PubMed:10684600, ECO:0000269|PubMed:31409799, ECO:0000269|PubMed:32128574}. |
| Q03001 | DST | S7464 | ochoa | Dystonin (230 kDa bullous pemphigoid antigen) (230/240 kDa bullous pemphigoid antigen) (Bullous pemphigoid antigen 1) (BPA) (Bullous pemphigoid antigen) (Dystonia musculorum protein) (Hemidesmosomal plaque protein) | Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin-containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two-dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: [Isoform 3]: Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity.; FUNCTION: [Isoform 6]: Required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.; FUNCTION: [Isoform 7]: Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. |
| Q04912 | MST1R | S1056 | ochoa | Macrophage-stimulating protein receptor (MSP receptor) (EC 2.7.10.1) (CDw136) (Protein-tyrosine kinase 8) (p185-Ron) (CD antigen CD136) [Cleaved into: Macrophage-stimulating protein receptor alpha chain; Macrophage-stimulating protein receptor beta chain] | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}. |
| Q05086 | UBE3A | S218 | ochoa | Ubiquitin-protein ligase E3A (EC 2.3.2.26) (E6AP ubiquitin-protein ligase) (HECT-type ubiquitin transferase E3A) (Human papillomavirus E6-associated protein) (Oncogenic protein-associated protein E6-AP) (Renal carcinoma antigen NY-REN-54) | E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates (PubMed:10373495, PubMed:16772533, PubMed:19204938, PubMed:19233847, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24273172, PubMed:24728990, PubMed:30020076). Several substrates have been identified including the BMAL1, ARC, LAMTOR1, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B (PubMed:10373495, PubMed:19204938, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24728990, PubMed:30020076). Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins (PubMed:19233847). Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component BMAL1, leading to its proteasomal degradation (PubMed:24728990). Acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation (PubMed:16772533). Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (By similarity). Required for synaptic remodeling in neurons by mediating ubiquitination and degradation of LAMTOR1, thereby limiting mTORC1 signaling and activity-dependent synaptic remodeling (By similarity). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533). {ECO:0000250|UniProtKB:O08759, ECO:0000269|PubMed:10373495, ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:19204938, ECO:0000269|PubMed:19233847, ECO:0000269|PubMed:19325566, ECO:0000269|PubMed:19591933, ECO:0000269|PubMed:22645313, ECO:0000269|PubMed:24273172, ECO:0000269|PubMed:24728990, ECO:0000269|PubMed:30020076}.; FUNCTION: (Microbial infection) Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses. {ECO:0000269|PubMed:8380895}. |
| Q05682 | CALD1 | S744 | psp | Caldesmon (CDM) | Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments). Stimulates actin binding of tropomyosin which increases the stabilization of actin filament structure. In muscle tissues, inhibits the actomyosin ATPase by binding to F-actin. This inhibition is attenuated by calcium-calmodulin and is potentiated by tropomyosin. Interacts with actin, myosin, two molecules of tropomyosin and with calmodulin. Also plays an essential role during cellular mitosis and receptor capping. Involved in Schwann cell migration during peripheral nerve regeneration (By similarity). {ECO:0000250, ECO:0000269|PubMed:8227296}. |
| Q08357 | SLC20A2 | S422 | ochoa | Sodium-dependent phosphate transporter 2 (Gibbon ape leukemia virus receptor 2) (GLVR-2) (Phosphate transporter 2) (PiT-2) (Pit2) (hPit2) (Solute carrier family 20 member 2) | Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:12205090, PubMed:15955065, PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, PubMed:30704756). Plays a critical role in the determination of bone quality and strength by providing phosphate for bone mineralization (By similarity). Required to maintain normal cerebrospinal fluid phosphate levels (By similarity). Mediates phosphate-induced calcification of vascular smooth muscle cells (VCMCs) and can functionally compensate for loss of SLC20A1 in VCMCs (By similarity). {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}.; FUNCTION: (Microbial infection) Functions as a retroviral receptor and confers human cells susceptibility to infection to amphotropic murine leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some feline leukemia virus subgroup B (FeLV-B) variants. {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. |
| Q09666 | AHNAK | S5386 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q09666 | AHNAK | S5577 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12802 | AKAP13 | S850 | ochoa | A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47) | Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:24993829, PubMed:25186459). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:21224381, PubMed:23716597). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:11579095, PubMed:9627117). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as a scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597, ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}. |
| Q12851 | MAP4K2 | S298 | ochoa | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
| Q12882 | DPYD | S436 | ochoa | Dihydropyrimidine dehydrogenase [NADP(+)] (DHPDHase) (DPD) (EC 1.3.1.2) (Dihydrothymine dehydrogenase) (Dihydrouracil dehydrogenase) | Involved in pyrimidine base degradation (PubMed:1512248). Catalyzes the reduction of uracil and thymine (PubMed:1512248). Also involved the degradation of the chemotherapeutic drug 5-fluorouracil (PubMed:1512248). {ECO:0000269|PubMed:1512248}. |
| Q12905 | ILF2 | S52 | ochoa | Interleukin enhancer-binding factor 2 (Nuclear factor of activated T-cells 45 kDa) | Chromatin-interacting protein that forms a stable heterodimer with interleukin enhancer-binding factor 3/ILF3 and plays a role in several biological processes including transcription, innate immunity or cell growth (PubMed:18458058, PubMed:31212927). Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. Together with ILF3, forms an RNA-binding complex that is required for mitotic progression and cytokinesis by regulating the expression of a cluster of mitotic genes. Mechanistically, competes with STAU1/STAU2-mediated mRNA decay (PubMed:32433969). Also plays a role in the inhibition of various viruses including Japanese encephalitis virus or enterovirus 71. {ECO:0000269|PubMed:10574923, ECO:0000269|PubMed:11739746, ECO:0000269|PubMed:18458058, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:31212927, ECO:0000269|PubMed:32433969, ECO:0000269|PubMed:9442054}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3. {ECO:0000269|PubMed:26891316}. |
| Q12929 | EPS8 | S787 | psp | Epidermal growth factor receptor kinase substrate 8 | Signaling adapter that controls various cellular protrusions by regulating actin cytoskeleton dynamics and architecture. Depending on its association with other signal transducers, can regulate different processes. Together with SOS1 and ABI1, forms a trimeric complex that participates in transduction of signals from Ras to Rac by activating the Rac-specific guanine nucleotide exchange factor (GEF) activity. Acts as a direct regulator of actin dynamics by binding actin filaments and has both barbed-end actin filament capping and actin bundling activities depending on the context. Displays barbed-end actin capping activity when associated with ABI1, thereby regulating actin-based motility process: capping activity is auto-inhibited and inhibition is relieved upon ABI1 interaction. Also shows actin bundling activity when associated with BAIAP2, enhancing BAIAP2-dependent membrane extensions and promoting filopodial protrusions. Involved in the regulation of processes such as axonal filopodia growth, stereocilia length, dendritic cell migration and cancer cell migration and invasion. Acts as a regulator of axonal filopodia formation in neurons: in the absence of neurotrophic factors, negatively regulates axonal filopodia formation via actin-capping activity. In contrast, it is phosphorylated in the presence of BDNF leading to inhibition of its actin-capping activity and stimulation of filopodia formation. Component of a complex with WHRN and MYO15A that localizes at stereocilia tips and is required for elongation of the stereocilia actin core. Indirectly involved in cell cycle progression; its degradation following ubiquitination being required during G2 phase to promote cell shape changes. {ECO:0000269|PubMed:15558031, ECO:0000269|PubMed:17115031}. |
| Q12965 | MYO1E | S991 | ochoa | Unconventional myosin-Ie (Myosin-Ic) (Unconventional myosin 1E) | Actin-based motor molecule with ATPase activity (PubMed:11940582, PubMed:36316095). Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. Binds to membranes containing anionic phospholipids via its tail domain. Involved in clathrin-mediated endocytosis and intracellular movement of clathrin-coated vesicles (PubMed:36316095). Required for normal morphology of the glomerular basement membrane, normal development of foot processes by kidney podocytes and normal kidney function. In dendritic cells, may control the movement of class II-containing cytoplasmic vesicles along the actin cytoskeleton by connecting them with the actin network via ARL14EP and ARL14. {ECO:0000269|PubMed:11940582, ECO:0000269|PubMed:17257598, ECO:0000269|PubMed:20860408, ECO:0000269|PubMed:36316095}. |
| Q13191 | CBLB | S886 | ochoa | E3 ubiquitin-protein ligase CBL-B (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene b) (RING finger protein 56) (RING-type E3 ubiquitin transferase CBL-B) (SH3-binding protein CBL-B) (Signal transduction protein CBL-B) | E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:Q3TTA7, ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}. |
| Q13426 | XRCC4 | S315 | ochoa | DNA repair protein XRCC4 (hXRCC4) (X-ray repair cross-complementing protein 4) [Cleaved into: Protein XRCC4, C-terminus (XRCC4/C)] | [DNA repair protein XRCC4]: DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:16412978, PubMed:17124166, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25742519, PubMed:25934149, PubMed:26100018, PubMed:26774286, PubMed:8548796). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014, PubMed:9242410). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831, PubMed:9242410). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785). {ECO:0000269|PubMed:10757784, ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:12517771, ECO:0000269|PubMed:15385968, ECO:0000269|PubMed:16412978, ECO:0000269|PubMed:17124166, ECO:0000269|PubMed:17290226, ECO:0000269|PubMed:19837014, ECO:0000269|PubMed:20852255, ECO:0000269|PubMed:21768349, ECO:0000269|PubMed:21775435, ECO:0000269|PubMed:21982441, ECO:0000269|PubMed:22228831, ECO:0000269|PubMed:22287571, ECO:0000269|PubMed:25597996, ECO:0000269|PubMed:25742519, ECO:0000269|PubMed:25934149, ECO:0000269|PubMed:26100018, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:27437582, ECO:0000269|PubMed:28453785, ECO:0000269|PubMed:28500754, ECO:0000269|PubMed:8548796, ECO:0000269|PubMed:9242410}.; FUNCTION: [Protein XRCC4, C-terminus]: Acts as an activator of the phospholipid scramblase activity of XKR4 (PubMed:33725486). This form, which is generated upon caspase-3 (CASP3) cleavage, translocates into the cytoplasm and interacts with XKR4, thereby promoting phosphatidylserine scramblase activity of XKR4 and leading to phosphatidylserine exposure on apoptotic cell surface (PubMed:33725486). {ECO:0000269|PubMed:33725486}. |
| Q13772 | NCOA4 | S554 | ochoa | Nuclear receptor coactivator 4 (NCoA-4) (Androgen receptor coactivator 70 kDa protein) (70 kDa AR-activator) (70 kDa androgen receptor coactivator) (Androgen receptor-associated protein of 70 kDa) (Ferritin cargo receptor NCOA4) (Ret-activating protein ELE1) | Cargo receptor for the autophagic turnover of the iron-binding ferritin complex, playing a central role in iron homeostasis (PubMed:25327288, PubMed:26436293). Acts as an adapter for delivery of ferritin to lysosomes and autophagic degradation of ferritin, a process named ferritinophagy (PubMed:25327288, PubMed:26436293). Targets the iron-binding ferritin complex to autolysosomes following starvation or iron depletion (PubMed:25327288). Ensures efficient erythropoiesis, possibly by regulating hemin-induced erythroid differentiation (PubMed:26436293). In some studies, has been shown to enhance the androgen receptor AR transcriptional activity as well as acting as ligand-independent coactivator of the peroxisome proliferator-activated receptor (PPAR) gamma (PubMed:10347167, PubMed:8643607). Another study shows only weak behavior as a coactivator for the androgen receptor and no alteration of the ligand responsiveness of the AR (PubMed:10517667). Binds to DNA replication origins, binding is not restricted to sites of active transcription and may likely be independent from the nuclear receptor transcriptional coactivator function (PubMed:24910095). May inhibit activation of DNA replication origins, possibly by obstructing DNA unwinding via interaction with the MCM2-7 complex (PubMed:24910095). {ECO:0000269|PubMed:10347167, ECO:0000269|PubMed:10517667, ECO:0000269|PubMed:24910095, ECO:0000269|PubMed:25327288, ECO:0000269|PubMed:26436293, ECO:0000269|PubMed:8643607}. |
| Q13950 | RUNX2 | S240 | ochoa | Runt-related transcription factor 2 (Acute myeloid leukemia 3 protein) (Core-binding factor subunit alpha-1) (CBF-alpha-1) (Oncogene AML-3) (Osteoblast-specific transcription factor 2) (OSF-2) (Polyomavirus enhancer-binding protein 2 alpha A subunit) (PEA2-alpha A) (PEBP2-alpha A) (SL3-3 enhancer factor 1 alpha A subunit) (SL3/AKV core-binding factor alpha A subunit) | Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28703881, PubMed:28738062). Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Inhibits KAT6B-dependent transcriptional activation. {ECO:0000250, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:28505335, ECO:0000269|PubMed:28703881, ECO:0000269|PubMed:28738062}. |
| Q14244 | MAP7 | S268 | ochoa | Ensconsin (Epithelial microtubule-associated protein of 115 kDa) (E-MAP-115) (Microtubule-associated protein 7) (MAP-7) | Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments. {ECO:0000269|PubMed:11719555, ECO:0000269|PubMed:8408219, ECO:0000269|PubMed:9989799}. |
| Q14257 | RCN2 | S146 | ochoa | Reticulocalbin-2 (Calcium-binding protein ERC-55) (E6-binding protein) (E6BP) | Not known. Binds calcium. |
| Q14315 | FLNC | S379 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14457 | BECN1 | S93 | psp | Beclin-1 (Coiled-coil myosin-like BCL2-interacting protein) (Protein GT197) [Cleaved into: Beclin-1-C 35 kDa; Beclin-1-C 37 kDa] | Plays a central role in autophagy (PubMed:18570871, PubMed:21358617, PubMed:23184933, PubMed:23974797, PubMed:25484083, PubMed:28445460, PubMed:37776275). Acts as a core subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis. Involved in regulation of degradative endocytic trafficking and required for the abscission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530, PubMed:20643123, PubMed:23974797, PubMed:26783301). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms. Involved in endocytosis (PubMed:25275521). May play a role in antiviral host defense. {ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20208530, ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:21358617, ECO:0000269|PubMed:23184933, ECO:0000269|PubMed:23974797, ECO:0000269|PubMed:25275521, ECO:0000269|PubMed:25484083, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:37776275, ECO:0000269|PubMed:9765397}.; FUNCTION: Beclin-1-C 35 kDa localized to mitochondria can promote apoptosis; it induces the mitochondrial translocation of BAX and the release of proapoptotic factors. {ECO:0000269|PubMed:21364619, ECO:0000269|PubMed:26263979}.; FUNCTION: (Microbial infection) Protects against infection by a neurovirulent strain of Sindbis virus. {ECO:0000269|PubMed:9765397}. |
| Q14562 | DHX8 | S385 | ochoa | ATP-dependent RNA helicase DHX8 (EC 3.6.4.13) (DEAH box protein 8) (RNA helicase HRH1) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). Facilitates nuclear export of spliced mRNA by releasing the RNA from the spliceosome (PubMed:8608946). {ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:8608946}. |
| Q14574 | DSC3 | S823 | ochoa | Desmocollin-3 (Cadherin family member 3) (Desmocollin-4) (HT-CP) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (By similarity). Required for cell-cell adhesion in the epidermis, as a result required for the maintenance of the dermal cohesion and the dermal barrier function (PubMed:19717567). Required for cell-cell adhesion of epithelial cell layers surrounding the telogen hair club, as a result plays an important role in telogen hair shaft anchorage (By similarity). Essential for successful completion of embryo compaction and embryo development (By similarity). {ECO:0000250|UniProtKB:P55850, ECO:0000269|PubMed:19717567}. |
| Q14814 | MEF2D | S275 | psp | 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}. |
| Q14CB8 | ARHGAP19 | S386 | ochoa | Rho GTPase-activating protein 19 (Rho-type GTPase-activating protein 19) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}. |
| Q15043 | SLC39A14 | S309 | ochoa | Metal cation symporter ZIP14 (LIV-1 subfamily of ZIP zinc transporter 4) (LZT-Hs4) (Solute carrier family 39 member 14) (Zrt- and Irt-like protein 14) (ZIP-14) | Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15642354, PubMed:27231142, PubMed:29621230). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (By similarity). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (By similarity). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (By similarity). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (By similarity). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (PubMed:31699897). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (By similarity). Also functions in the extracellular uptake of free iron. May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages (PubMed:23052185). {ECO:0000250|UniProtKB:Q75N73, ECO:0000269|PubMed:15642354, ECO:0000269|PubMed:20682781, ECO:0000269|PubMed:23052185, ECO:0000269|PubMed:27231142, ECO:0000269|PubMed:27703010, ECO:0000269|PubMed:29621230, ECO:0000269|PubMed:31028174, ECO:0000269|PubMed:31699897}. |
| Q15149 | PLEC | S3853 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15291 | RBBP5 | S497 | ochoa | Retinoblastoma-binding protein 5 (RBBP-5) (Retinoblastoma-binding protein RBQ-3) | In embryonic stem (ES) cells, plays a crucial role in the differentiation potential, particularly along the neural lineage, regulating gene induction and H3 'Lys-4' methylation at key developmental loci, including that mediated by retinoic acid (By similarity). Does not affect ES cell self-renewal (By similarity). Component or associated component of some histone methyltransferase complexes which regulates transcription through recruitment of those complexes to gene promoters (PubMed:19131338). As part of the MLL1/MLL complex, involved in mono-, di- and trimethylation at 'Lys-4' of histone H3 (PubMed:19556245). Histone H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation (PubMed:19556245). In association with ASH2L and WDR5, stimulates the histone methyltransferase activities of KMT2A, KMT2B, KMT2C, KMT2D, SETD1A and SETD1B (PubMed:21220120, PubMed:22266653). {ECO:0000250|UniProtKB:Q8BX09, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22266653}. |
| Q15418 | RPS6KA1 | S687 | 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}. |
| Q15544 | TAF11 | S60 | ochoa | Transcription initiation factor TFIID subunit 11 (TFIID subunit p30-beta) (Transcription initiation factor TFIID 28 kDa subunit) (TAF(II)28) (TAFII-28) (TAFII28) | The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473). TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). TAF11, together with TAF13 and TBP, play key roles during promoter binding by the TFIID and TFIIA transcription factor complexes (PubMed:33795473). {ECO:0000269|PubMed:33795473}. |
| Q15691 | MAPRE1 | S140 | ochoa | Microtubule-associated protein RP/EB family member 1 (APC-binding protein EB1) (End-binding protein 1) (EB1) | Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton (PubMed:12388762, PubMed:16109370, PubMed:19632184, PubMed:21646404, PubMed:23001180, PubMed:28726242, PubMed:28814570, PubMed:34608293). Recruits other +TIP proteins to microtubules by binding to a conserved Ser-X-Leu-Pro (SXLP) motif in their polypeptide chains (PubMed:19632184, PubMed:36592928). Promotes cytoplasmic microtubule nucleation and elongation (PubMed:12388762, PubMed:16109370, PubMed:19632184, PubMed:21646404, PubMed:28726242, PubMed:28814570). Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation (PubMed:12388762, PubMed:34608293). Assists chromosome alignment in metaphase by recruiting the SKA complex to the spindle and stabilizing its interactions with microtubule bundles (K-fibers) (PubMed:27225956, PubMed:36592928). Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:28814570). Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules (PubMed:28814570). Acts as a regulator of autophagosome transport via interaction with CAMSAP2 (PubMed:28726242). Functions downstream of Rho GTPases and DIAPH1 in stable microtubule formation (By similarity). May play a role in cell migration (By similarity). {ECO:0000250|UniProtKB:Q61166, ECO:0000269|PubMed:12388762, ECO:0000269|PubMed:16109370, ECO:0000269|PubMed:19632184, ECO:0000269|PubMed:21646404, ECO:0000269|PubMed:23001180, ECO:0000269|PubMed:27225956, ECO:0000269|PubMed:28726242, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:36592928}. |
| Q15911 | ZFHX3 | S519 | 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}. |
| Q16643 | DBN1 | S134 | ochoa | Drebrin (Developmentally-regulated brain protein) | Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (PubMed:20215400). Required for actin polymerization at immunological synapses (IS) and for the recruitment of the chemokine receptor CXCR4 to IS (PubMed:20215400). Plays a role in dendritic spine morphogenesis and organization, including the localization of the dopamine receptor DRD1 to the dendritic spines (By similarity). Involved in memory-related synaptic plasticity in the hippocampus (By similarity). {ECO:0000250|UniProtKB:Q9QXS6, ECO:0000269|PubMed:20215400}. |
| Q16665 | HIF1A | S551 | psp | Hypoxia-inducible factor 1-alpha (HIF-1-alpha) (HIF1-alpha) (ARNT-interacting protein) (Basic-helix-loop-helix-PAS protein MOP1) (Class E basic helix-loop-helix protein 78) (bHLHe78) (Member of PAS protein 1) (PAS domain-containing protein 8) | Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:16543236, PubMed:9887100). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}. |
| Q5FWF5 | ESCO1 | S412 | ochoa | N-acetyltransferase ESCO1 (EC 2.3.1.-) (CTF7 homolog 1) (Establishment factor-like protein 1) (EFO1) (EFO1p) (hEFO1) (Establishment of cohesion 1 homolog 1) (ECO1 homolog 1) (ESO1 homolog 1) | Acetyltransferase required for the establishment of sister chromatid cohesion (PubMed:15958495, PubMed:18614053). Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3 (PubMed:18614053). {ECO:0000269|PubMed:14576321, ECO:0000269|PubMed:15958495, ECO:0000269|PubMed:18614053, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:27112597, ECO:0000269|PubMed:27803161}. |
| Q5JSZ5 | PRRC2B | S1399 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5SW79 | CEP170 | S886 | 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}. |
| Q5T5X7 | BEND3 | S54 | ochoa | BEN domain-containing protein 3 | Transcriptional repressor which associates with the NoRC (nucleolar remodeling complex) complex and plays a key role in repressing rDNA transcription. The sumoylated form modulates the stability of the NoRC complex component BAZ2A/TIP5 by controlling its USP21-mediated deubiquitination (PubMed:21914818, PubMed:26100909). Binds to unmethylated major satellite DNA and is involved in the recruitment of the Polycomb repressive complex 2 (PRC2) to major satellites (By similarity). Stimulates the ERCC6L translocase and ATPase activities (PubMed:28977671). {ECO:0000250|UniProtKB:Q6PAL0, ECO:0000269|PubMed:21914818, ECO:0000269|PubMed:26100909, ECO:0000269|PubMed:28977671}. |
| Q5TBA9 | FRY | S2420 | ochoa | Protein furry homolog | Plays a crucial role in the structural integrity of mitotic centrosomes and in the maintenance of spindle bipolarity by promoting PLK1 activity at the spindle poles in early mitosis. May function as a scaffold promoting the interaction between AURKA and PLK1, thereby enhancing AURKA-mediated PLK1 phosphorylation. {ECO:0000269|PubMed:22753416}. |
| Q5TH69 | ARFGEF3 | S597 | ochoa | Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (ARFGEF family member 3) | Participates in the regulation of systemic glucose homeostasis, where it negatively regulates insulin granule biogenesis in pancreatic islet beta cells (By similarity). Also regulates glucagon granule production in pancreatic alpha cells (By similarity). Inhibits nuclear translocation of the transcriptional coregulator PHB2 and may enhance estrogen receptor alpha (ESR1) transcriptional activity in breast cancer cells (PubMed:19496786). {ECO:0000250|UniProtKB:Q3UGY8, ECO:0000269|PubMed:19496786}. |
| Q5UIP0 | RIF1 | S1843 | 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 | S1653 | 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}. |
| Q5VTT5 | MYOM3 | S240 | 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}. |
| Q5VU43 | PDE4DIP | S736 | ochoa | Myomegalin (Cardiomyopathy-associated protein 2) (Phosphodiesterase 4D-interacting protein) | Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes (By similarity). {ECO:0000250|UniProtKB:Q9WUJ3}.; FUNCTION: [Isoform 13]: Participates in microtubule dynamics, promoting microtubule assembly. Depending upon the cell context, may act at the level of the Golgi apparatus or that of the centrosome (PubMed:25217626, PubMed:27666745, PubMed:28814570, PubMed:29162697). In complex with AKAP9, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement (PubMed:27666745, PubMed:28814570). In complex with AKAP9, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension from the centrosome to the cell periphery, a crucial process for directed cell migration, mitotic spindle orientation and cell-cycle progression (PubMed:29162697). {ECO:0000269|PubMed:25217626, ECO:0000269|PubMed:27666745, ECO:0000269|PubMed:28814570, ECO:0000269|PubMed:29162697}. |
| Q5VUB5 | FAM171A1 | S460 | ochoa | Protein FAM171A1 (Astroprincin) (APCN) | Involved in the regulation of the cytoskeletal dynamics, plays a role in actin stress fiber formation. {ECO:0000269|PubMed:30312582}. |
| Q5VWJ9 | SNX30 | S48 | ochoa | Sorting nexin-30 | Involved in the regulation of endocytosis and in several stages of intracellular trafficking (PubMed:32513819). Together with SNX4, involved in autophagosome assembly (PubMed:32513819). {ECO:0000269|PubMed:32513819}. |
| Q5W0Q7 | USPL1 | S208 | ochoa | SUMO-specific isopeptidase USPL1 (EC 3.4.22.-) (Ubiquitin-specific peptidase-like protein 1) (USP-like 1) | SUMO-specific isopeptidase involved in protein desumoylation. Specifically binds SUMO proteins with a higher affinity for SUMO2 and SUMO3 which it cleaves more efficiently. Also able to process full-length SUMO proteins to their mature forms (PubMed:22878415). Plays a key role in RNA polymerase-II-mediated snRNA transcription in the Cajal bodies (PubMed:24413172). Is a component of complexes that can bind to U snRNA genes (PubMed:24413172). {ECO:0000269|PubMed:22878415, ECO:0000269|PubMed:24413172}. |
| Q68E01 | INTS3 | S578 | ochoa | Integrator complex subunit 3 (Int3) (SOSS complex subunit A) (Sensor of single-strand DNA complex subunit A) (SOSS-A) (Sensor of ssDNA subunit A) | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:38570683). The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA (PubMed:38570683). The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs) (PubMed:16239144). Within the integrator complex, INTS3 is involved in the post-termination step: INTS3 binds INTS7 in the open conformation of integrator complex and prevents the rebinding of Pol II to the integrator after termination cycle (PubMed:38570683). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex (PubMed:23904267). {ECO:0000269|PubMed:16239144, ECO:0000269|PubMed:23904267, ECO:0000269|PubMed:38570683}.; FUNCTION: Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. The SOSS complex is required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. In the SOSS complex, it is required for the assembly of the complex and for stabilization of the complex at DNA damage sites. {ECO:0000269|PubMed:19605351, ECO:0000269|PubMed:19683501}. |
| Q6BDS2 | BLTP3A | S1106 | ochoa | Bridge-like lipid transfer protein family member 3A (ICBP90-binding protein 1) (UHRF1-binding protein 1) (Ubiquitin-like containing PHD and RING finger domains 1-binding protein 1) | Tube-forming lipid transport protein which probably mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). May be involved in the retrograde traffic of vesicle clusters in the endocytic pathway to the Golgi complex (PubMed:35499567). {ECO:0000269|PubMed:35499567}. |
| Q6IQ55 | TTBK2 | S1101 | 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}. |
| Q6P0N0 | MIS18BP1 | S192 | ochoa | Mis18-binding protein 1 (Kinetochore-associated protein KNL-2 homolog) (HsKNL-2) (P243) | Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. {ECO:0000269|PubMed:17199038, ECO:0000269|PubMed:17339379}. |
| Q6PCD5 | RFWD3 | S63 | psp | E3 ubiquitin-protein ligase RFWD3 (EC 2.3.2.27) (RING finger and WD repeat domain-containing protein 3) (RING finger protein 201) | E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658, PubMed:33321094). Plays a key role in RPA-mediated DNA damage signaling and repair (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658, PubMed:28691929). Acts by mediating ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and RAD51 at stalled replication forks, leading to remove them from DNA damage sites and promote homologous recombination (PubMed:26474068, PubMed:28575657, PubMed:28575658). Also mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint (PubMed:20173098). May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:20173098). In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53 (PubMed:20173098). Required to translesion DNA synthesis across DNA-protein cross-link adducts by catalyzing ubiquitination of proteins on single-stranded DNA (ssDNA) (PubMed:33321094). {ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:21558276, ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:28691929, ECO:0000269|PubMed:33321094}. |
| Q6R327 | RICTOR | S1388 | ochoa | Rapamycin-insensitive companion of mTOR (AVO3 homolog) (hAVO3) | Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output (PubMed:15268862, PubMed:15718470, PubMed:19720745, PubMed:19995915, PubMed:21343617, PubMed:33158864, PubMed:35904232, PubMed:35926713). In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1 (PubMed:19720745, PubMed:19935711, PubMed:19995915). In contrast to mTORC1, mTORC2 is nutrient-insensitive (PubMed:15467718, PubMed:21343617). Within the mTORC2 complex, RICTOR probably acts as a molecular adapter (PubMed:21343617, PubMed:33158864, PubMed:35926713). RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2 (PubMed:33158864). mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation (PubMed:15718470, PubMed:19720745, PubMed:19935711, PubMed:35926713). mTORC2 catalyzes the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657' (By similarity). The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1 (By similarity). mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors (PubMed:15467718). mTORC2 promotes the serum-induced formation of stress-fibers or F-actin (PubMed:15467718). {ECO:0000250|UniProtKB:Q6QI06, ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:33158864, ECO:0000269|PubMed:35904232, ECO:0000269|PubMed:35926713}. |
| Q6STE5 | SMARCD3 | S247 | psp | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 (60 kDa BRG-1/Brm-associated factor subunit C) (BRG1-associated factor 60C) (BAF60C) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Stimulates nuclear receptor mediated transcription. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:Q6P9Z1, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:8804307, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q6ZNJ1 | NBEAL2 | S1836 | ochoa | Neurobeachin-like protein 2 | Probably involved in thrombopoiesis. Plays a role in the development or secretion of alpha-granules, that contain several growth factors important for platelet biogenesis. {ECO:0000269|PubMed:21765411, ECO:0000269|PubMed:21765412}. |
| Q7Z2Z1 | TICRR | S1771 | ochoa | Treslin (TopBP1-interacting checkpoint and replication regulator) (TopBP1-interacting, replication-stimulating protein) | Regulator of DNA replication and S/M and G2/M checkpoints. Regulates the triggering of DNA replication initiation via its interaction with TOPBP1 by participating in CDK2-mediated loading of CDC45L onto replication origins. Required for the transition from pre-replication complex (pre-RC) to pre-initiation complex (pre-IC). Required to prevent mitotic entry after treatment with ionizing radiation. {ECO:0000269|PubMed:20116089}. |
| Q7Z412 | PEX26 | S224 | ochoa | Peroxisome assembly protein 26 (Peroxin-26) | Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes (PubMed:12717447, PubMed:12851857, PubMed:16257970, PubMed:16763195, PubMed:16854980, PubMed:21362118). PEX26 is therefore required for the formation of the PEX1-PEX6 AAA ATPase complex, a complex that mediates the extraction of the PEX5 receptor from peroxisomal membrane (PubMed:12717447, PubMed:12851857, PubMed:16257970, PubMed:16763195, PubMed:16854980, PubMed:21362118). {ECO:0000269|PubMed:12717447, ECO:0000269|PubMed:12851857, ECO:0000269|PubMed:16257970, ECO:0000269|PubMed:16763195, ECO:0000269|PubMed:16854980, ECO:0000269|PubMed:21362118}. |
| Q7Z4V5 | HDGFL2 | S149 | ochoa | Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) | Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}. |
| Q7Z4W1 | DCXR | S38 | ochoa | L-xylulose reductase (XR) (EC 1.1.1.10) (Carbonyl reductase II) (Dicarbonyl/L-xylulose reductase) (Kidney dicarbonyl reductase) (kiDCR) (Short chain dehydrogenase/reductase family 20C member 1) (Sperm surface protein P34H) | Catalyzes the NADPH-dependent reduction of several pentoses, tetroses, trioses, alpha-dicarbonyl compounds and L-xylulose. Participates in the uronate cycle of glucose metabolism. May play a role in the water absorption and cellular osmoregulation in the proximal renal tubules by producing xylitol, an osmolyte, thereby preventing osmolytic stress from occurring in the renal tubules. |
| Q86TV6 | TTC7B | S625 | ochoa | Tetratricopeptide repeat protein 7B (TPR repeat protein 7B) (Tetratricopeptide repeat protein 7-like-1) (TPR repeat protein 7-like-1) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (PubMed:26571211). {ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:26571211}. |
| Q86U86 | PBRM1 | S32 | 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}. |
| Q86UX7 | FERMT3 | S328 | ochoa | Fermitin family homolog 3 (Kindlin-3) (MIG2-like protein) (Unc-112-related protein 2) | Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells (PubMed:19234460). Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs) (By similarity). {ECO:0000250|UniProtKB:Q8K1B8, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463, ECO:0000269|PubMed:26359933}.; FUNCTION: Isoform 2 may act as a repressor of NF-kappa-B and apoptosis. {ECO:0000269|PubMed:19064721, ECO:0000269|PubMed:19234460, ECO:0000269|PubMed:19234463}. |
| Q86V48 | LUZP1 | S724 | 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}. |
| Q86V48 | LUZP1 | S772 | 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}. |
| Q86VF7 | NRAP | S1487 | ochoa | Nebulin-related-anchoring protein (N-RAP) | May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix. {ECO:0000250|UniProtKB:Q80XB4}. |
| Q86WV6 | STING1 | S241 | ochoa | Stimulator of interferon genes protein (hSTING) (Endoplasmic reticulum interferon stimulator) (ERIS) (Mediator of IRF3 activation) (hMITA) (Transmembrane protein 173) | Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23747010, PubMed:23910378, PubMed:27801882, PubMed:29973723, PubMed:30842659, PubMed:35045565, PubMed:35388221, PubMed:36808561, PubMed:37832545, PubMed:25704810, PubMed:39255680). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:23747010, PubMed:23910378, PubMed:26229117, PubMed:30842659, PubMed:35388221, PubMed:37379839). Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state (PubMed:22394562, PubMed:25636800, PubMed:29973723, PubMed:30842653, PubMed:35045565, PubMed:35388221). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:23747010, PubMed:23910378, PubMed:26300263). The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation (PubMed:26150511). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (PubMed:30842662). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (PubMed:30842662). Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation (PubMed:37535724). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (PubMed:18724357). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity). {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000269|PubMed:18724357, ECO:0000269|PubMed:18818105, ECO:0000269|PubMed:19433799, ECO:0000269|PubMed:19776740, ECO:0000269|PubMed:21947006, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:23258412, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23747010, ECO:0000269|PubMed:23910378, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:26150511, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29973723, ECO:0000269|PubMed:30568238, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:30842659, ECO:0000269|PubMed:30842662, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35388221, ECO:0000269|PubMed:36808561, ECO:0000269|PubMed:37379839, ECO:0000269|PubMed:37535724, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:39255680}.; FUNCTION: (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230). {ECO:0000269|PubMed:26405230}. |
| Q8IU60 | DCP2 | S375 | ochoa | m7GpppN-mRNA hydrolase (EC 3.6.1.62) (Nucleoside diphosphate-linked moiety X motif 20) (Nudix motif 20) (mRNA-decapping enzyme 2) (hDpc) | Decapping metalloenzyme that catalyzes the cleavage of the cap structure on mRNAs (PubMed:12218187, PubMed:12417715, PubMed:12923261, PubMed:21070968, PubMed:28002401, PubMed:31875550). Removes the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (PubMed:12486012, PubMed:12923261, PubMed:21070968, PubMed:28002401, PubMed:31875550). Necessary for the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay (PubMed:14527413). Plays a role in replication-dependent histone mRNA degradation (PubMed:18172165). Has higher activity towards mRNAs that lack a poly(A) tail (PubMed:21070968). Has no activity towards a cap structure lacking an RNA moiety (PubMed:21070968). The presence of a N(6)-methyladenosine methylation at the second transcribed position of mRNAs (N(6),2'-O-dimethyladenosine cap; m6A(m)) provides resistance to DCP2-mediated decapping (PubMed:28002401). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573). {ECO:0000269|PubMed:12218187, ECO:0000269|PubMed:12417715, ECO:0000269|PubMed:12486012, ECO:0000269|PubMed:12923261, ECO:0000269|PubMed:14527413, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:21070968, ECO:0000269|PubMed:26098573, ECO:0000269|PubMed:28002401}. |
| Q8IVF2 | AHNAK2 | S5349 | ochoa | Protein AHNAK2 | None |
| Q8IVL1 | NAV2 | S2365 | ochoa | Neuron navigator 2 (EC 3.6.4.12) (Helicase APC down-regulated 1) (Pore membrane and/or filament-interacting-like protein 2) (Retinoic acid inducible in neuroblastoma 1) (Steerin-2) (Unc-53 homolog 2) (unc53H2) | Possesses 3' to 5' helicase activity and exonuclease activity. Involved in neuronal development, specifically in the development of different sensory organs. {ECO:0000269|PubMed:12214280, ECO:0000269|PubMed:15158073}. |
| Q8IW41 | MAPKAPK5 | S354 | ochoa|psp | MAP kinase-activated protein kinase 5 (MAPK-activated protein kinase 5) (MAPKAP kinase 5) (MAPKAP-K5) (MAPKAPK-5) (MK-5) (MK5) (EC 2.7.11.1) (p38-regulated/activated protein kinase) (PRAK) | Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}. |
| Q8IWU2 | LMTK2 | S525 | ochoa | Serine/threonine-protein kinase LMTK2 (EC 2.7.11.1) (Apoptosis-associated tyrosine kinase 2) (Brain-enriched kinase) (hBREK) (CDK5/p35-regulated kinase) (CPRK) (Kinase/phosphatase/inhibitor 2) (Lemur tyrosine kinase 2) (Serine/threonine-protein kinase KPI-2) | Phosphorylates PPP1C, phosphorylase b and CFTR. |
| Q8IX03 | WWC1 | S978 | psp | 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}. |
| Q8IXJ9 | ASXL1 | S470 | ochoa | Polycomb group protein ASXL1 (Additional sex combs-like protein 1) | Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG) (PubMed:16606617). Acts as a coactivator of RARA and RXRA through association with NCOA1 (PubMed:16606617). Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity (By similarity). Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:20436459, PubMed:30664650, PubMed:36180891). Acts as a sensor of N(6)-methyladenine methylation on DNA (6mA): recognizes and binds 6mA DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing (PubMed:30982744). The PR-DUB complex is an epigenetic regulator of gene expression and acts as a transcriptional coactivator, affecting genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:30664650, PubMed:36180891). ASXL1, ASXL2 and ASXL3 function redundantly in the PR-DUB complex (By similarity) (PubMed:30664650). The ASXL proteins are essential for chromatin recruitment and transcriptional activation of associated genes (By similarity). ASXL1 and ASXL2 are important for BAP1 protein stability (PubMed:30664650). Together with BAP1, negatively regulates epithelial-mesenchymal transition (EMT) of trophoblast stem cells during placental development by regulating genes involved in epithelial cell integrity, cell adhesion and cytoskeletal organization (PubMed:34170818). {ECO:0000250|UniProtKB:P59598, ECO:0000269|PubMed:16606617, ECO:0000269|PubMed:20436459, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:30982744, ECO:0000269|PubMed:34170818, ECO:0000269|PubMed:36180891}. |
| Q8IY92 | SLX4 | S884 | ochoa | Structure-specific endonuclease subunit SLX4 (BTB/POZ domain-containing protein 12) | Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks. {ECO:0000269|PubMed:19595721, ECO:0000269|PubMed:19595722, ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:19596236}. |
| Q8IYF3 | TEX11 | S178 | ochoa | Testis-expressed protein 11 (Protein ZIP4 homolog) (ZIP4H) | Regulator of crossing-over during meiosis. Involved in initiation and/or maintenance of chromosome synapsis and formation of crossovers. {ECO:0000250|UniProtKB:Q14AT2}. |
| Q8IZT6 | ASPM | S244 | ochoa | Abnormal spindle-like microcephaly-associated protein (Abnormal spindle protein homolog) (Asp homolog) | Involved in mitotic spindle regulation and coordination of mitotic processes. The function in regulating microtubule dynamics at spindle poles including spindle orientation, astral microtubule density and poleward microtubule flux seems to depend on the association with the katanin complex formed by KATNA1 and KATNB1. Enhances the microtubule lattice severing activity of KATNA1 by recruiting the katanin complex to microtubules. Can block microtubule minus-end growth and reversely this function can be enhanced by the katanin complex (PubMed:28436967). May have a preferential role in regulating neurogenesis. {ECO:0000269|PubMed:12355089, ECO:0000269|PubMed:15972725, ECO:0000269|PubMed:28436967}. |
| Q8N1F7 | NUP93 | S72 | ochoa | Nuclear pore complex protein Nup93 (93 kDa nucleoporin) (Nucleoporin Nup93) | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor nucleoporins, but not NUP153 and TPR, to the NPC. During renal development, regulates podocyte migration and proliferation through SMAD4 signaling (PubMed:26878725). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:15703211, ECO:0000269|PubMed:26878725, ECO:0000269|PubMed:9348540}. |
| Q8N1W1 | ARHGEF28 | S758 | ochoa | Rho guanine nucleotide exchange factor 28 (190 kDa guanine nucleotide exchange factor) (p190-RhoGEF) (p190RhoGEF) (Rho guanine nucleotide exchange factor) | Functions as a RHOA-specific guanine nucleotide exchange factor regulating signaling pathways downstream of integrins and growth factor receptors. Functions in axonal branching, synapse formation and dendritic morphogenesis. Also functions in focal adhesion formation, cell motility and B-lymphocytes activation. May regulate NEFL expression and aggregation and play a role in apoptosis (By similarity). {ECO:0000250}. |
| Q8N302 | AGGF1 | S184 | ochoa | Angiogenic factor with G patch and FHA domains 1 (Angiogenic factor VG5Q) (hVG5Q) (G patch domain-containing protein 7) (Vasculogenesis gene on 5q protein) | Promotes angiogenesis and the proliferation of endothelial cells. Able to bind to endothelial cells and promote cell proliferation, suggesting that it may act in an autocrine fashion. {ECO:0000269|PubMed:14961121}. |
| Q8N4S0 | CCDC82 | S154 | ochoa | Coiled-coil domain-containing protein 82 | None |
| Q8N6H7 | ARFGAP2 | S338 | ochoa | ADP-ribosylation factor GTPase-activating protein 2 (ARF GAP 2) (GTPase-activating protein ZNF289) (Zinc finger protein 289) | GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Implicated in coatomer-mediated protein transport between the Golgi complex and the endoplasmic reticulum. Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. {ECO:0000269|PubMed:17760859}. |
| Q8NC51 | SERBP1 | S25 | ochoa | SERPINE1 mRNA-binding protein 1 (PAI1 RNA-binding protein 1) (PAI-RBP1) (Plasminogen activator inhibitor 1 RNA-binding protein) | Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:36691768). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (By similarity). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay (PubMed:11001948). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). {ECO:0000250|UniProtKB:Q9CY58, ECO:0000269|PubMed:11001948, ECO:0000269|PubMed:28695742, ECO:0000269|PubMed:36691768}. |
| Q8NEV8 | EXPH5 | S873 | ochoa | Exophilin-5 (Synaptotagmin-like protein homolog lacking C2 domains b) (SlaC2-b) (Slp homolog lacking C2 domains b) | May act as Rab effector protein and play a role in vesicle trafficking. |
| Q8NEZ4 | KMT2C | S1387 | ochoa | Histone-lysine N-methyltransferase 2C (Lysine N-methyltransferase 2C) (EC 2.1.1.364) (Homologous to ALR protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 3) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:22266653, PubMed:24081332, PubMed:25561738). Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements (PubMed:24081332). {ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q8NFA2 | NOXO1 | S162 | ochoa | NADPH oxidase organizer 1 (NADPH oxidase regulatory protein) (Nox organizer 1) (Nox-organizing protein 1) (SH3 and PX domain-containing protein 5) | Constitutively potentiates the superoxide-generating activity of NOX1 and NOX3 and is required for the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity. Isoform 3 is more potent than isoform 1 in activating NOX3. Together with NOXA1, may also substitute to NCF1/p47phox and NCF2/p67phox in supporting the phagocyte NOX2/gp91phox superoxide-generating activity. {ECO:0000269|PubMed:12657628, ECO:0000269|PubMed:14617635, ECO:0000269|PubMed:15326186, ECO:0000269|PubMed:15824103, ECO:0000269|PubMed:15949904, ECO:0000269|PubMed:16329988, ECO:0000269|PubMed:17126813, ECO:0000269|PubMed:19755710}. |
| Q8NFP9 | NBEA | S1219 | ochoa | Neurobeachin (Lysosomal-trafficking regulator 2) (Protein BCL8B) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity). {ECO:0000250}. |
| Q8NHS3 | MFSD8 | S20 | ochoa | Major facilitator superfamily domain-containing protein 8 (Ceroid-lipofuscinosis neuronal protein 7) | Outward-rectifying chloride channel involved in endolysosomal chloride homeostasis, membrane fusion and function. Conducts chloride currents up to hundreds of picoamperes. Regulates lysosomal calcium content by reducing the lysosomal membrane potential, thereby activating TRPML1 channel and further release of lysosomal calcium ions. Regulates the pH in endolysosomal compartments and may contribute to progressive acidification from endosome to lysosome. Permeable to other halides such as iodide and fluoride ions. {ECO:0000269|PubMed:34910516}. |
| Q8NHV4 | NEDD1 | S377 | psp | Protein NEDD1 (Neural precursor cell expressed developmentally down-regulated protein 1) (NEDD-1) | Required for mitosis progression. Promotes the nucleation of microtubules from the spindle. {ECO:0000269|PubMed:19029337, ECO:0000269|PubMed:19509060}. |
| Q8TCN5 | ZNF507 | S74 | ochoa | Zinc finger protein 507 | May be involved in transcriptional regulation. |
| Q8TCN5 | ZNF507 | S494 | ochoa | Zinc finger protein 507 | May be involved in transcriptional regulation. |
| Q8TER5 | ARHGEF40 | S866 | ochoa | Rho guanine nucleotide exchange factor 40 (Protein SOLO) | May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}. |
| Q8TEW0 | PARD3 | S174 | 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}. |
| Q8TF76 | HASPIN | S211 | psp | Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) | Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}. |
| Q8WTT2 | NOC3L | S108 | ochoa | Nucleolar complex protein 3 homolog (NOC3 protein homolog) (Factor for adipocyte differentiation 24) (NOC3-like protein) (Nucleolar complex-associated protein 3-like protein) | May be required for adipogenesis. {ECO:0000250}. |
| Q8WVM8 | SCFD1 | S252 | ochoa | Sec1 family domain-containing protein 1 (SLY1 homolog) (Sly1p) (Syntaxin-binding protein 1-like 2) | Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. Involved in vesicular transport between the endoplasmic reticulum and the Golgi (By similarity). {ECO:0000250}. |
| Q8WWQ0 | PHIP | S1274 | ochoa | PH-interacting protein (PHIP) (DDB1- and CUL4-associated factor 14) (IRS-1 PH domain-binding protein) (WD repeat-containing protein 11) | Probable regulator of the insulin and insulin-like growth factor signaling pathways. Stimulates cell proliferation through regulation of cyclin transcription and has an anti-apoptotic activity through AKT1 phosphorylation and activation. Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:12242307, ECO:0000269|PubMed:21834987}. |
| Q8WYK0 | ACOT12 | S161 | ochoa | Acetyl-coenzyme A thioesterase (EC 3.1.2.1) (Acyl-CoA thioester hydrolase 12) (Acyl-coenzyme A thioesterase 12) (Acyl-CoA thioesterase 12) (Cytoplasmic acetyl-CoA hydrolase 1) (CACH-1) (hCACH-1) (START domain-containing protein 15) (StARD15) | Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16951743). Preferentially hydrolyzes acetyl-CoA (PubMed:16951743). {ECO:0000269|PubMed:16951743}. |
| Q8WZ82 | OVCA2 | S161 | ochoa | Esterase OVCA2 (EC 3.1.1.1) (OVCA2 serine hydrolase domain-containing protein) (Ovarian cancer-associated gene 2 protein) | Exhibits ester hydrolase activity with a strong preference for long-chain alkyl ester substrates and high selectivity against a variety of short, branched, and substituted esters. Is able to hydrolyze ester bonds within a wide range of p-nitrophenyl derivatives (C2-C14) in vitro, with a strong preference toward substrates of >8 carbons. {ECO:0000269|PubMed:32182256}. |
| Q92599 | SEPTIN8 | S163 | psp | Septin-8 | Filament-forming cytoskeletal GTPase (By similarity). May play a role in platelet secretion (PubMed:15116257). Seems to participate in the process of SNARE complex formation in synaptic vesicles (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:B0BNF1, ECO:0000269|PubMed:15116257}.; FUNCTION: [Isoform 4]: Stabilizes BACE1 protein levels and promotes the sorting and accumulation of BACE1 to the recycling or endosomal compartments, modulating the beta-amyloidogenic processing of APP. {ECO:0000269|PubMed:27084579}. |
| Q92608 | DOCK2 | S1202 | ochoa | Dedicator of cytokinesis protein 2 | Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2. {ECO:0000269|PubMed:21613211}. |
| Q92616 | GCN1 | S1491 | ochoa | Stalled ribosome sensor GCN1 (GCN1 eIF-2-alpha kinase activator homolog) (GCN1-like protein 1) (General control of amino-acid synthesis 1-like protein 1) (Translational activator GCN1) (HsGCN1) | Ribosome collision sensor that plays a key role in the RNF14-RNF25 translation quality control pathway, a pathway that takes place when a ribosome has stalled during translation, and which promotes ubiquitination and degradation of translation factors on stalled ribosomes (PubMed:32610081, PubMed:36638793, PubMed:37651229, PubMed:37951215, PubMed:37951216). Directly binds to the ribosome and acts as a sentinel for colliding ribosomes: activated following ribosome stalling and promotes recruitment of RNF14, which directly ubiquitinates EEF1A1/eEF1A, leading to its degradation (PubMed:36638793, PubMed:37951215, PubMed:37951216). In addition to EEF1A1/eEF1A, the RNF14-RNF25 translation quality control pathway mediates degradation of ETF1/eRF1 and ubiquitination of ribosomal protein (PubMed:36638793, PubMed:37651229). GCN1 also acts as a positive activator of the integrated stress response (ISR) by mediating activation of EIF2AK4/GCN2 in response to amino acid starvation (By similarity). Interaction with EIF2AK4/GCN2 on translating ribosomes stimulates EIF2AK4/GCN2 kinase activity, leading to phosphorylation of eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) (By similarity). EIF2S1/eIF-2-alpha phosphorylation converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (By similarity). {ECO:0000250|UniProtKB:E9PVA8, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:36638793, ECO:0000269|PubMed:37651229, ECO:0000269|PubMed:37951215, ECO:0000269|PubMed:37951216}. |
| Q92747 | ARPC1A | S236 | ochoa | Actin-related protein 2/3 complex subunit 1A (SOP2-like protein) | Probably functions as a component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. {ECO:0000305|PubMed:8978670}. |
| Q92785 | DPF2 | S113 | 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}. |
| Q92797 | SYMPK | S547 | ochoa | Symplekin | Scaffold protein that functions as a component of a multimolecular complex involved in histone mRNA 3'-end processing. Specific component of the tight junction (TJ) plaque, but might not be an exclusively junctional component. May have a house-keeping rule. Is involved in pre-mRNA polyadenylation. Enhances SSU72 phosphatase activity. {ECO:0000269|PubMed:16230528, ECO:0000269|PubMed:20861839}. |
| Q92989 | CLP1 | S344 | ochoa | Polyribonucleotide 5'-hydroxyl-kinase Clp1 (EC 2.7.1.78) (Polyadenylation factor Clp1) (Polynucleotide kinase Clp1) (Pre-mRNA cleavage complex II protein Clp1) | Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double-stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Plays a key role in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex: phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA (PubMed:24766809, PubMed:24766810). Its role in tRNA splicing and maturation is required for cerebellar development (PubMed:24766809, PubMed:24766810). Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by DICER1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing. {ECO:0000269|PubMed:17495927, ECO:0000269|PubMed:18648070, ECO:0000269|PubMed:24766809, ECO:0000269|PubMed:24766810}. |
| Q96AV8 | E2F7 | S261 | ochoa | Transcription factor E2F7 (E2F-7) | Atypical E2F transcription factor that participates in various processes such as angiogenesis, polyploidization of specialized cells and DNA damage response. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1. Acts as a regulator of S-phase by recognizing and binding the E2-related site 5'-TTCCCGCC-3' and mediating repression of G1/S-regulated genes. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Also involved in DNA damage response: up-regulated by p53/TP53 following genotoxic stress and acts as a downstream effector of p53/TP53-dependent repression by mediating repression of indirect p53/TP53 target genes involved in DNA replication. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. Acts as a negative regulator of keratinocyte differentiation. {ECO:0000269|PubMed:14633988, ECO:0000269|PubMed:15133492, ECO:0000269|PubMed:18202719, ECO:0000269|PubMed:19223542, ECO:0000269|PubMed:21248772, ECO:0000269|PubMed:22802528, ECO:0000269|PubMed:22802529, ECO:0000269|PubMed:22903062}. |
| Q96BY6 | DOCK10 | S302 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96BY6 | DOCK10 | S1261 | ochoa | Dedicator of cytokinesis protein 10 (Zizimin-3) | Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression. {ECO:0000250|UniProtKB:Q8BZN6}. |
| Q96BY6 | DOCK10 | S1413 | 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}. |
| Q96CC6 | RHBDF1 | S128 | ochoa | Inactive rhomboid protein 1 (iRhom1) (Epidermal growth factor receptor-related protein) (Rhomboid 5 homolog 1) (Rhomboid family member 1) (p100hRho) | Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own. {ECO:0000269|PubMed:15965977, ECO:0000269|PubMed:18524845, ECO:0000269|PubMed:18832597, ECO:0000269|PubMed:21439629}. |
| Q96DY7 | MTBP | S796 | ochoa | Mdm2-binding protein (hMTBP) | Inhibits cell migration in vitro and suppresses the invasive behavior of tumor cells (By similarity). May play a role in MDM2-dependent p53/TP53 homeostasis in unstressed cells. Inhibits autoubiquitination of MDM2, thereby enhancing MDM2 stability. This promotes MDM2-mediated ubiquitination of p53/TP53 and its subsequent degradation. {ECO:0000250, ECO:0000269|PubMed:15632057}. |
| Q96HC4 | PDLIM5 | S214 | ochoa | PDZ and LIM domain protein 5 (Enigma homolog) (Enigma-like PDZ and LIM domains protein) | May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation. {ECO:0000250|UniProtKB:Q62920}. |
| Q96NT1 | NAP1L5 | S76 | ochoa | Nucleosome assembly protein 1-like 5 (Down-regulated in liver malignancy) | None |
| Q96RG2 | PASK | S939 | 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}. |
| Q96RL1 | UIMC1 | S668 | ochoa | BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) | Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}. |
| Q96S59 | RANBP9 | S603 | psp | Ran-binding protein 9 (RanBP9) (BPM-L) (BPM90) (Ran-binding protein M) (RanBPM) (RanBP7) | May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways (Probable). Acts as a mediator of cell spreading and actin cytoskeleton rearrangement (PubMed:18710924). Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1 (PubMed:29911972). May be involved in signaling of ITGB2/LFA-1 and other integrins (PubMed:14722085). Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway (PubMed:12147692). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation (PubMed:12361945, PubMed:18222118). Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity (PubMed:15558019). Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA. {ECO:0000269|PubMed:12147692, ECO:0000269|PubMed:12361945, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14722085, ECO:0000269|PubMed:15381419, ECO:0000269|PubMed:15558019, ECO:0000269|PubMed:18222118, ECO:0000269|PubMed:18710924, ECO:0000269|PubMed:29911972, ECO:0000305}. |
| Q99569 | PKP4 | S127 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99569 | PKP4 | S457 | ochoa | Plakophilin-4 (p0071) | Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques. {ECO:0000269|PubMed:17115030}. |
| Q99590 | SCAF11 | S413 | ochoa | Protein SCAF11 (CTD-associated SR protein 11) (Renal carcinoma antigen NY-REN-40) (SC35-interacting protein 1) (SR-related and CTD-associated factor 11) (SRSF2-interacting protein) (Serine/arginine-rich splicing factor 2-interacting protein) (Splicing factor, arginine/serine-rich 2-interacting protein) (Splicing regulatory protein 129) (SRrp129) | Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly. {ECO:0000269|PubMed:9447963}. |
| Q99959 | PKP2 | S172 | 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}. |
| Q99959 | PKP2 | S183 | 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}. |
| Q99959 | PKP2 | S313 | 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}. |
| Q9BQP7 | MGME1 | S71 | ochoa | Mitochondrial genome maintenance exonuclease 1 (EC 3.1.-.-) | Metal-dependent single-stranded DNA (ssDNA) exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity but is also capable of endonuclease activity on linear substrates. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair, possibly via the processing of displaced DNA containing Okazaki fragments during RNA-primed DNA synthesis on the lagging strand or via processing of DNA flaps during long-patch base excision repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells. {ECO:0000255|HAMAP-Rule:MF_03030, ECO:0000269|PubMed:23313956, ECO:0000269|PubMed:23358826}. |
| Q9BV36 | MLPH | S569 | 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}. |
| Q9BXL6 | CARD14 | S787 | ochoa | Caspase recruitment domain-containing protein 14 (CARD-containing MAGUK protein 2) (Carma 2) | Acts as a scaffolding protein that can activate the inflammatory transcription factor NF-kappa-B and p38/JNK MAP kinase signaling pathways. Forms a signaling complex with BCL10 and MALT1, and activates MALT1 proteolytic activity and inflammatory gene expression. MALT1 is indispensable for CARD14-induced activation of NF-kappa-B and p38/JNK MAP kinases (PubMed:11278692, PubMed:21302310, PubMed:27071417, PubMed:27113748). May play a role in signaling mediated by TRAF2, TRAF3 and TRAF6 and protects cells against apoptosis. {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:21302310, ECO:0000269|PubMed:27071417, ECO:0000269|PubMed:27113748}.; FUNCTION: [Isoform 3]: Not able to activate the inflammatory transcription factor NF-kappa-B and may function as a dominant negative regulator (PubMed:21302310, PubMed:26358359). {ECO:0000269|PubMed:21302310, ECO:0000269|PubMed:26358359}. |
| Q9BXL7 | CARD11 | S893 | psp | Caspase recruitment domain-containing protein 11 (CARD-containing MAGUK protein 1) (Carma 1) | Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement (PubMed:11278692, PubMed:11356195, PubMed:12356734). Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11356195). Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway (PubMed:28628108). {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28628108}. |
| Q9BYD6 | MRPL1 | S298 | ochoa | Large ribosomal subunit protein uL1m (39S ribosomal protein L1, mitochondrial) (L1mt) (MRP-L1) | None |
| Q9BYW2 | SETD2 | S1849 | ochoa | Histone-lysine N-methyltransferase SETD2 (EC 2.1.1.359) (HIF-1) (Huntingtin yeast partner B) (Huntingtin-interacting protein 1) (HIP-1) (Huntingtin-interacting protein B) (Lysine N-methyltransferase 3A) (Protein-lysine N-methyltransferase SETD2) (EC 2.1.1.-) (SET domain-containing protein 2) (hSET2) (p231HBP) | Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565, PubMed:28753426). Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling (PubMed:27518565). Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription (PubMed:28753426). {ECO:0000250|UniProtKB:E9Q5F9, ECO:0000269|PubMed:16118227, ECO:0000269|PubMed:19141475, ECO:0000269|PubMed:21526191, ECO:0000269|PubMed:21792193, ECO:0000269|PubMed:23043551, ECO:0000269|PubMed:23325844, ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:24509477, ECO:0000269|PubMed:24843002, ECO:0000269|PubMed:27317772, ECO:0000269|PubMed:27474439, ECO:0000269|PubMed:27518565, ECO:0000269|PubMed:28753426}.; FUNCTION: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. {ECO:0000269|PubMed:11461154}. |
| Q9BZC7 | ABCA2 | S1322 | ochoa | ATP-binding cassette sub-family A member 2 (EC 7.6.2.-) (ATP-binding cassette transporter 2) (ATP-binding cassette 2) | Probable lipid transporter that modulates cholesterol sequestration in the late endosome/lysosome by regulating the intracellular sphingolipid metabolism, in turn participates in cholesterol homeostasis (Probable) (PubMed:15238223, PubMed:21810484, PubMed:24201375). May alter the transbilayer distribution of ceramide in the intraluminal membrane lipid bilayer, favoring its retention in the outer leaflet that results in increased acid ceramidase activity in the late endosome/lysosome, facilitating ceramide deacylation to sphingosine leading to the sequestration of free cholesterol in lysosomes (PubMed:24201375). In addition regulates amyloid-beta production either by activating a signaling pathway that regulates amyloid precursor protein transcription through the modulation of sphingolipid metabolism or through its role in gamma-secretase processing of APP (PubMed:22086926, PubMed:26510981). May play a role in myelin formation (By similarity). {ECO:0000250|UniProtKB:P41234, ECO:0000269|PubMed:15238223, ECO:0000269|PubMed:21810484, ECO:0000269|PubMed:22086926, ECO:0000269|PubMed:24201375, ECO:0000269|PubMed:26510981, ECO:0000305|PubMed:15999530}. |
| Q9C0I1 | MTMR12 | S699 | ochoa | Myotubularin-related protein 12 (Inactive phosphatidylinositol 3-phosphatase 12) (Phosphatidylinositol 3 phosphate 3-phosphatase adapter subunit) (3-PAP) (3-phosphatase adapter protein) | Acts as an adapter for the myotubularin-related phosphatases (PubMed:11504939, PubMed:12847286, PubMed:23818870). Regulates phosphatase MTM1 protein stability and possibly its intracellular location (PubMed:23818870). By stabilizing MTM1 protein levels, required for skeletal muscle maintenance but not for myogenesis (By similarity). {ECO:0000250|UniProtKB:Q80TA6, ECO:0000269|PubMed:11504939, ECO:0000269|PubMed:12847286, ECO:0000269|PubMed:23818870}. |
| Q9GZY8 | MFF | S105 | ochoa | Mitochondrial fission factor | Plays a role in mitochondrial and peroxisomal fission (PubMed:18353969, PubMed:23530241, PubMed:24196833). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface (PubMed:23530241). May be involved in regulation of synaptic vesicle membrane dynamics by recruitment of DNM1L to clathrin-containing vesicles (By similarity). {ECO:0000250|UniProtKB:Q4KM98, ECO:0000269|PubMed:18353969, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:24196833}. |
| Q9GZZ9 | UBA5 | S358 | ochoa | Ubiquitin-like modifier-activating enzyme 5 (Ubiquitin-activating enzyme 5) (ThiFP1) (UFM1-activating enzyme) (Ubiquitin-activating enzyme E1 domain-containing protein 1) | E1-like enzyme which specifically catalyzes the first step in ufmylation (PubMed:15071506, PubMed:18442052, PubMed:20368332, PubMed:25219498, PubMed:26929408, PubMed:27545674, PubMed:27545681, PubMed:27653677, PubMed:30412706, PubMed:30626644, PubMed:34588452). Activates UFM1 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 UFM1-E1 thioester and free AMP (PubMed:20368332, PubMed:26929408, PubMed:27653677, PubMed:30412706). Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (PubMed:27653677). Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding (PubMed:29295865). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism (PubMed:27653677, PubMed:34588452). Ufmylation plays a key role in various processes, such as ribosome recycling, response to DNA damage, interferon response or reticulophagy (also called ER-phagy) (PubMed:30412706, PubMed:32160526, PubMed:35394863). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (By similarity). {ECO:0000250|UniProtKB:Q8VE47, ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:18442052, ECO:0000269|PubMed:20368332, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:26929408, ECO:0000269|PubMed:27545674, ECO:0000269|PubMed:27545681, ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:29295865, ECO:0000269|PubMed:30412706, ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:34588452, ECO:0000269|PubMed:35394863}. |
| Q9H3K6 | BOLA2 | S32 | ochoa | BolA-like protein 2 | Acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (PubMed:26613676, PubMed:27519415). Acts together with the monothiol glutaredoxin GLRX3 (PubMed:26613676, PubMed:27519415). {ECO:0000269|PubMed:26613676, ECO:0000269|PubMed:27519415}. |
| Q9HAU0 | PLEKHA5 | S478 | ochoa | Pleckstrin homology domain-containing family A member 5 (PH domain-containing family A member 5) (Phosphoinositol 3-phosphate-binding protein 2) (PEPP-2) | None |
| Q9HBI1 | PARVB | S254 | ochoa | Beta-parvin (Affixin) | Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6. Is involved in the reorganization of the actin cytoskeleton and formation of lamellipodia. Plays a role in cell adhesion, cell spreading, establishment or maintenance of cell polarity, and cell migration. {ECO:0000269|PubMed:11402068, ECO:0000269|PubMed:15005707, ECO:0000269|PubMed:15159419, ECO:0000269|PubMed:15284246, ECO:0000269|PubMed:18325335}. |
| Q9HC77 | CPAP | S595 | psp | Centrosomal P4.1-associated protein (Centromere protein J) (CENP-J) (Centrosome assembly and centriole elongation protein) (LAG-3-associated protein) (LYST-interacting protein 1) | Plays an important role in cell division and centrosome function by participating in centriole duplication (PubMed:17681131, PubMed:20531387). Inhibits microtubule nucleation from the centrosome. Involved in the regulation of slow processive growth of centriolar microtubules. Acts as a microtubule plus-end tracking protein that stabilizes centriolar microtubules and inhibits microtubule polymerization and extension from the distal ends of centrioles (PubMed:15047868, PubMed:27219064, PubMed:27306797). Required for centriole elongation and for STIL-mediated centriole amplification (PubMed:22020124). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865). May be involved in the control of centriolar-microtubule growth by acting as a regulator of tubulin release (PubMed:27306797). {ECO:0000269|PubMed:15047868, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:20531387, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27185865, ECO:0000269|PubMed:27219064, ECO:0000305|PubMed:27306797}. |
| Q9HCS5 | EPB41L4A | S464 | ochoa | Band 4.1-like protein 4A (Erythrocyte membrane protein band 4.1-like 4A) (Protein NBL4) | None |
| Q9HCU4 | CELSR2 | S2678 | ochoa | Cadherin EGF LAG seven-pass G-type receptor 2 (Cadherin family member 10) (Epidermal growth factor-like protein 2) (EGF-like protein 2) (Flamingo homolog 3) (Multiple epidermal growth factor-like domains protein 3) (Multiple EGF-like domains protein 3) | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| Q9HD20 | ATP13A1 | S945 | ochoa | Endoplasmic reticulum transmembrane helix translocase (EC 7.4.2.-) (Endoplasmic reticulum P5A-ATPase) | Endoplasmic reticulum translocase required to remove mitochondrial transmembrane proteins mistargeted to the endoplasmic reticulum (PubMed:32973005, PubMed:36264797). Acts as a dislocase that mediates the ATP-dependent extraction of mislocalized mitochondrial transmembrane proteins from the endoplasmic reticulum membrane (PubMed:32973005). Specifically binds mitochondrial tail-anchored transmembrane proteins: has an atypically large substrate-binding pocket that recognizes and binds moderately hydrophobic transmembranes with short hydrophilic lumenal domains (PubMed:32973005). {ECO:0000269|PubMed:32973005, ECO:0000269|PubMed:36264797}. |
| Q9HD26 | GOPC | S412 | ochoa | Golgi-associated PDZ and coiled-coil motif-containing protein (CFTR-associated ligand) (Fused in glioblastoma) (PDZ protein interacting specifically with TC10) (PIST) | Plays a role in intracellular protein trafficking and degradation (PubMed:11707463, PubMed:14570915, PubMed:15358775). May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels (By similarity). May also regulate the intracellular trafficking of the ADR1B receptor (PubMed:15358775). May play a role in autophagy (By similarity). Together with MARCHF2 mediates the ubiquitination and lysosomal degradation of CFTR (PubMed:23818989). Overexpression results in CFTR intracellular retention and lysosomaldegradation in the lysosomes (PubMed:11707463, PubMed:14570915). {ECO:0000250|UniProtKB:Q8BH60, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:14570915, ECO:0000269|PubMed:15358775, ECO:0000269|PubMed:23818989}. |
| Q9NP66 | HMG20A | S20 | ochoa | High mobility group protein 20A (HMG box-containing protein 20A) (HMG domain-containing protein 1) (HMG domain-containing protein HMGX1) | Plays a role in neuronal differentiation as chromatin-associated protein. Acts as inhibitor of HMG20B. Overcomes the repressive effects of the neuronal silencer REST and induces the activation of neuronal-specific genes. Involved in the recruitment of the histone methyltransferase KMT2A/MLL1 and consequent increased methylation of histone H3 lysine 4 (By similarity). {ECO:0000250}. |
| Q9NPI1 | BRD7 | S42 | ochoa | Bromodomain-containing protein 7 (75 kDa bromodomain protein) (Protein CELTIX-1) | Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR (By similarity). Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase. {ECO:0000250, ECO:0000269|PubMed:16265664, ECO:0000269|PubMed:16475162, ECO:0000269|PubMed:20215511, ECO:0000269|PubMed:20228809, ECO:0000269|PubMed:20660729}. |
| Q9NQW6 | ANLN | S664 | ochoa | Anillin | Required for cytokinesis (PubMed:16040610). Essential for the structural integrity of the cleavage furrow and for completion of cleavage furrow ingression. Plays a role in bleb assembly during metaphase and anaphase of mitosis (PubMed:23870127). May play a significant role in podocyte cell migration (PubMed:24676636). {ECO:0000269|PubMed:10931866, ECO:0000269|PubMed:12479805, ECO:0000269|PubMed:15496454, ECO:0000269|PubMed:16040610, ECO:0000269|PubMed:16357138, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:24676636}. |
| Q9NW97 | TMEM51 | S192 | ochoa | Transmembrane protein 51 | None |
| Q9NWV8 | BABAM1 | S57 | ochoa | BRISC and BRCA1-A complex member 1 (Mediator of RAP80 interactions and targeting subunit of 40 kDa) (New component of the BRCA1-A complex) | Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). {ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749}. |
| Q9NY33 | DPP3 | S272 | ochoa | Dipeptidyl peptidase 3 (EC 3.4.14.4) (Dipeptidyl aminopeptidase III) (Dipeptidyl arylamidase III) (Dipeptidyl peptidase III) (DPP III) (Enkephalinase B) | Cleaves and degrades bioactive peptides, including angiotensin, Leu-enkephalin and Met-enkephalin (PubMed:1515063, PubMed:3233187). Also cleaves Arg-Arg-beta-naphthylamide (in vitro) (PubMed:11209758, PubMed:3233187, PubMed:9425109). {ECO:0000269|PubMed:11209758, ECO:0000269|PubMed:1515063, ECO:0000269|PubMed:3233187, ECO:0000269|PubMed:9425109}. |
| Q9NYD6 | HOXC10 | S152 | ochoa | Homeobox protein Hox-C10 (Homeobox protein Hox-3I) | Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. |
| Q9NYF8 | BCLAF1 | S559 | ochoa | Bcl-2-associated transcription factor 1 (Btf) (BCLAF1 and THRAP3 family member 1) | Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:18794151}. |
| Q9NZI5 | GRHL1 | S35 | ochoa | Grainyhead-like protein 1 homolog (Mammalian grainyhead) (NH32) (Transcription factor CP2-like 2) (Transcription factor LBP-32) | Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, nor functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity). May play a role in regulating glucose homeostasis and insulin signaling. {ECO:0000250|UniProtKB:Q921D9, ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:18288204, ECO:0000269|PubMed:29309642, ECO:0000269|PubMed:35013237}.; FUNCTION: [Isoform 1]: Functions as a transcription activator. {ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:29309642}.; FUNCTION: [Isoform 2]: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed. {ECO:0000269|PubMed:12175488}. |
| Q9P260 | RELCH | S341 | ochoa | RAB11-binding protein RELCH (LisH domain and HEAT repeat-containing protein KIAA1468) (RAB11 binding and LisH domain, coiled-coil and HEAT repeat-containing) (RAB11-binding protein containing LisH, coiled-coil, and HEAT repeats) | Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP (PubMed:29514919). Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes (PubMed:29514919). {ECO:0000269|PubMed:29514919}. |
| Q9UBN7 | HDAC6 | S146 | psp | Protein deacetylase HDAC6 (EC 3.5.1.-) (E3 ubiquitin-protein ligase HDAC6) (EC 2.3.2.-) (Tubulin-lysine deacetylase HDAC6) (EC 3.5.1.-) | Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:38534334, PubMed:39567688). Plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin (PubMed:12024216, PubMed:20308065, PubMed:26246421). Required for cilia disassembly via deacetylation of alpha-tubulin (PubMed:17604723, PubMed:26246421). Alpha-tubulin deacetylation results in destabilization of dynamic microtubules (By similarity). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Deacetylates SQSTM1 (PubMed:31857589). Deacetylates peroxiredoxins PRDX1 and PRDX2, decreasing their reducing activity (PubMed:18606987). Deacetylates antiviral protein RIGI in the presence of viral mRNAs which is required for viral RNA detection by RIGI (By similarity). Sequentially deacetylates and polyubiquitinates DNA mismatch repair protein MSH2 which leads to MSH2 degradation, reducing cellular sensitivity to DNA-damaging agents and decreasing cellular DNA mismatch repair activities (PubMed:24882211). Deacetylates DNA mismatch repair protein MLH1 which prevents recruitment of the MutL alpha complex (formed by the MLH1-PMS2 heterodimer) to the MutS alpha complex (formed by the MSH2-MSH6 heterodimer), leading to tolerance of DNA damage (PubMed:30770470). Deacetylates RHOT1/MIRO1 which blocks mitochondrial transport and mediates axon growth inhibition (By similarity). Deacetylates transcription factor SP1 which leads to increased expression of ENG, positively regulating angiogenesis (PubMed:38534334). Deacetylates KHDRBS1/SAM68 which regulates alternative splicing by inhibiting the inclusion of CD44 alternate exons (PubMed:26080397). Acts as a valine sensor by binding to valine through the primate-specific SE14 repeat region (PubMed:39567688). In valine deprivation conditions, translocates from the cytoplasm to the nucleus where it deacetylates TET2 which promotes TET2-dependent DNA demethylation, leading to DNA damage (PubMed:39567688). Promotes odontoblast differentiation following IPO7-mediated nuclear import and subsequent repression of RUNX2 expression (By similarity). In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome (PubMed:17846173). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and targets them to the aggresome, facilitating their clearance by autophagy (PubMed:17846173). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532). {ECO:0000250|UniProtKB:D3ZVD8, ECO:0000250|UniProtKB:Q9Z2V5, ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:18606987, ECO:0000269|PubMed:20308065, ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:24882211, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:26246421, ECO:0000269|PubMed:30538141, ECO:0000269|PubMed:30770470, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:38534334, ECO:0000269|PubMed:39567688}.; FUNCTION: (Microbial infection) Deacetylates the SARS-CoV-2 N protein which promotes association of the viral N protein with human G3BP1, leading to disruption of cellular stress granule formation and facilitating viral replication. {ECO:0000269|PubMed:39135075}. |
| Q9UFC0 | LRWD1 | S267 | ochoa | Leucine-rich repeat and WD repeat-containing protein 1 (Centromere protein 33) (CENP-33) (Origin recognition complex-associated protein) (ORC-associated protein) (ORCA) | Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability. {ECO:0000269|PubMed:20850016, ECO:0000269|PubMed:20932478, ECO:0000269|PubMed:21029866, ECO:0000269|PubMed:22427655, ECO:0000269|PubMed:22645314}. |
| Q9UHB6 | LIMA1 | S228 | ochoa | LIM domain and actin-binding protein 1 (Epithelial protein lost in neoplasm) | Actin-binding protein involved in actin cytoskeleton regulation and dynamics. Increases the number and size of actin stress fibers and inhibits membrane ruffling. Inhibits actin filament depolymerization. Bundles actin filaments, delays filament nucleation and reduces formation of branched filaments (PubMed:12566430, PubMed:33999101). Acts as a negative regulator of primary cilium formation (PubMed:32496561). Plays a role in cholesterol homeostasis. Influences plasma cholesterol levels through regulation of intestinal cholesterol absorption. May act as a scaffold protein by regulating NPC1L1 transportation, an essential protein for cholesterol absorption, to the plasma membrane by recruiting MYO5B to NPC1L1, and thus facilitates cholesterol uptake (By similarity). {ECO:0000250|UniProtKB:Q9ERG0, ECO:0000269|PubMed:12566430, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:33999101}. |
| Q9UHY8 | FEZ2 | S195 | ochoa | Fasciculation and elongation protein zeta-2 (Zygin II) (Zygin-2) | Involved in axonal outgrowth and fasciculation. {ECO:0000250}. |
| Q9UJM3 | ERRFI1 | S374 | ochoa | ERBB receptor feedback inhibitor 1 (Mitogen-inducible gene 6 protein) (MIG-6) | Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity). {ECO:0000250}. |
| Q9UKA4 | AKAP11 | S239 | ochoa | A-kinase anchor protein 11 (AKAP-11) (A-kinase anchor protein 220 kDa) (AKAP 220) (hAKAP220) (Protein kinase A-anchoring protein 11) (PRKA11) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them. |
| Q9UKA4 | AKAP11 | S613 | ochoa | A-kinase anchor protein 11 (AKAP-11) (A-kinase anchor protein 220 kDa) (AKAP 220) (hAKAP220) (Protein kinase A-anchoring protein 11) (PRKA11) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them. |
| Q9UKV3 | ACIN1 | S525 | 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}. |
| Q9ULE6 | PALD1 | S483 | ochoa | Paladin | None |
| Q9ULH7 | MRTFB | S409 | ochoa | Myocardin-related transcription factor B (MRTF-B) (MKL/myocardin-like protein 2) (Megakaryoblastic leukemia 2) | Acts as a transcriptional coactivator of serum response factor (SRF). Required for skeletal myogenic differentiation. {ECO:0000269|PubMed:14565952}. |
| Q9ULK5 | VANGL2 | S82 | ochoa | Vang-like protein 2 (Loop-tail protein 1 homolog) (Strabismus 1) (Van Gogh-like protein 2) | Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate. Plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea. Required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process. Required for cell surface localization of FZD3 and FZD6 in the inner ear (By similarity). {ECO:0000250|UniProtKB:Q91ZD4}. |
| Q9ULL8 | SHROOM4 | S411 | ochoa | Protein Shroom4 (Second homolog of apical protein) | Probable regulator of cytoskeletal architecture that plays an important role in development. May regulate cellular and cytoskeletal architecture by modulating the spatial distribution of myosin II (By similarity). {ECO:0000250, ECO:0000269|PubMed:16684770}. |
| Q9UN70 | PCDHGC3 | S766 | 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. |
| Q9UNS1 | TIMELESS | S105 | ochoa | Protein timeless homolog (hTIM) | Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication, DNA repair and in the regulation of the circadian clock (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:23418588, PubMed:26344098, PubMed:31138685, PubMed:32705708, PubMed:35585232, PubMed:9856465). Required to stabilize replication forks during DNA replication by forming a complex with TIPIN: this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress (PubMed:17141802, PubMed:17296725, PubMed:23359676, PubMed:35585232). During DNA replication, inhibits the CMG complex ATPase activity and activates DNA polymerases catalytic activities, coupling DNA unwinding and DNA synthesis (PubMed:23359676). TIMELESS promotes TIPIN nuclear localization (PubMed:17141802, PubMed:17296725). Plays a role in maintaining processive DNA replication past genomic guanine-rich DNA sequences that form G-quadruplex (G4) structures, possibly together with DDX1 (PubMed:32705708). Involved in cell survival after DNA damage or replication stress by promoting DNA repair (PubMed:17141802, PubMed:17296725, PubMed:26344098, PubMed:30356214). In response to double-strand breaks (DSBs), accumulates at DNA damage sites and promotes homologous recombination repair via its interaction with PARP1 (PubMed:26344098, PubMed:30356214, PubMed:31138685). May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light (PubMed:15798197). Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock (PubMed:23418588, PubMed:31138685). Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus (PubMed:31138685, PubMed:9856465). May play a role as destabilizer of the PER2-CRY2 complex (PubMed:31138685). May also play an important role in epithelial cell morphogenesis and formation of branching tubules (By similarity). {ECO:0000250|UniProtKB:Q9R1X4, ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:17141802, ECO:0000269|PubMed:17296725, ECO:0000269|PubMed:23359676, ECO:0000269|PubMed:23418588, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31138685, ECO:0000269|PubMed:32705708, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9856465}. |
| Q9UPS6 | SETD1B | S1275 | ochoa | Histone-lysine N-methyltransferase SETD1B (EC 2.1.1.364) (Lysine N-methyltransferase 2G) (SET domain-containing protein 1B) (hSET1B) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism (PubMed:17355966, PubMed:25561738). Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17355966, PubMed:25561738). Plays an essential role in regulating the transcriptional programming of multipotent hematopoietic progenitor cells and lymphoid lineage specification during hematopoiesis (By similarity). {ECO:0000250|UniProtKB:Q8CFT2, ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:25561738}. |
| Q9UQ26 | RIMS2 | S403 | ochoa | Regulating synaptic membrane exocytosis protein 2 (Rab-3-interacting molecule 2) (RIM 2) (Rab-3-interacting protein 3) | Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}. |
| Q9UQ35 | SRRM2 | S2456 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9Y247 | FAM50B | S121 | ochoa | Protein FAM50B (Protein XAP-5-like) | None |
| Q9Y2F5 | ICE1 | S546 | ochoa | Little elongation complex subunit 1 (Interactor of little elongator complex ELL subunit 1) | Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically acts as a scaffold protein that promotes the LEC complex formation and recruitment and RNA polymerase II occupancy at snRNA genes in subnuclear bodies (PubMed:23932780). {ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23932780}. |
| Q9Y2K1 | ZBTB1 | S355 | ochoa | Zinc finger and BTB domain-containing protein 1 | Acts as a transcriptional repressor (PubMed:20797634). Represses cAMP-responsive element (CRE)-mediated transcriptional activation (PubMed:21706167). In addition, has a role in translesion DNA synthesis. Requires for UV-inducible RAD18 loading, PCNA monoubiquitination, POLH recruitment to replication factories and efficient translesion DNA synthesis (PubMed:24657165). Plays a key role in the transcriptional regulation of T lymphocyte development (By similarity). {ECO:0000250|UniProtKB:Q91VL9, ECO:0000269|PubMed:20797634, ECO:0000269|PubMed:21706167, ECO:0000269|PubMed:24657165}. |
| Q9Y2X9 | ZNF281 | S638 | ochoa|psp | 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}. |
| Q9Y446 | PKP3 | S180 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y446 | PKP3 | S196 | ochoa | Plakophilin-3 | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:24124604). Required for the localization of DSG2, DSP and PKP2 to mature desmosome junctions (PubMed:20859650). May also play a role in the maintenance of DSG3 protein abundance in keratinocytes (By similarity). Required for the formation of DSP-containing desmosome precursors in the cytoplasm during desmosome assembly (PubMed:25208567). Also regulates the accumulation of CDH1 to mature desmosome junctions, via cAMP-dependent signaling and its interaction with activated RAP1A (PubMed:25208567). Positively regulates the stabilization of PKP2 mRNA and therefore protein abundance, via its interaction with FXR1, may also regulate the protein abundance of DSP via the same mechanism (PubMed:25225333). May also regulate the protein abundance of the desmosome component PKP1 (By similarity). Required for the organization of desmosome junctions at intercellular borders between basal keratinocytes of the epidermis, as a result plays a role in maintenance of the dermal barrier and regulation of the dermal inflammatory response (By similarity). Required during epidermal keratinocyte differentiation for cell adherence at tricellular cell-cell contacts, via regulation of the timely formation of adherens junctions and desmosomes in a calcium-dependent manner, and may also play a role in the organization of the intracellular actin fiber belt (By similarity). Acts as a negative regulator of the inflammatory response in hematopoietic cells of the skin and intestine, via modulation of proinflammatory cytokine production (By similarity). Important for epithelial barrier maintenance in the intestine to reduce intestinal permeability, thereby plays a role in protection from intestinal-derived endotoxemia (By similarity). Required for the development of hair follicles, via a role in the regulation of inner root sheaf length, correct alignment and anterior-posterior polarity of hair follicles (By similarity). Promotes proliferation and cell-cycle G1/S phase transition of keratinocytes (By similarity). Promotes E2F1-driven transcription of G1/S phase promoting genes by acting to release E2F1 from its inhibitory interaction with RB1, via sequestering RB1 and CDKN1A to the cytoplasm and thereby increasing CDK4- and CDK6-driven phosphorylation of RB1 (By similarity). May act as a scaffold protein to facilitate MAPK phosphorylation of RPS6KA protein family members and subsequently promote downstream EGFR signaling (By similarity). May play a role in the positive regulation of transcription of Wnt-mediated TCF-responsive target genes (PubMed:34058472). {ECO:0000250|UniProtKB:Q9QY23, ECO:0000269|PubMed:20859650, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:25208567, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:34058472}. |
| Q9Y4F1 | FARP1 | S894 | ochoa | FERM, ARHGEF and pleckstrin domain-containing protein 1 (Chondrocyte-derived ezrin-like protein) (FERM, RhoGEF and pleckstrin domain-containing protein 1) (Pleckstrin homology domain-containing family C member 2) (PH domain-containing family C member 2) | Functions as a guanine nucleotide exchange factor for RAC1. May play a role in semaphorin signaling. Plays a role in the assembly and disassembly of dendritic filopodia, the formation of dendritic spines, regulation of dendrite length and ultimately the formation of synapses (By similarity). {ECO:0000250}. |
| Q9Y4F5 | CEP170B | S1196 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q15648 | MED1 | S935 | Sugiyama | Mediator of RNA polymerase II transcription subunit 1 (Activator-recruited cofactor 205 kDa component) (ARC205) (Mediator complex subunit 1) (Peroxisome proliferator-activated receptor-binding protein) (PBP) (PPAR-binding protein) (Thyroid hormone receptor-associated protein complex 220 kDa component) (Trap220) (Thyroid receptor-interacting protein 2) (TR-interacting protein 2) (TRIP-2) (Vitamin D receptor-interacting protein complex component DRIP205) (p53 regulatory protein RB18A) | Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (PubMed:10406464, PubMed:11867769, PubMed:12037571, PubMed:12218053, PubMed:12556447, PubMed:14636573, PubMed:15340084, PubMed:15471764, PubMed:15989967, PubMed:16574658, PubMed:9653119). Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). {ECO:0000269|PubMed:10406464, ECO:0000269|PubMed:11867769, ECO:0000269|PubMed:12037571, ECO:0000269|PubMed:12218053, ECO:0000269|PubMed:12556447, ECO:0000269|PubMed:14636573, ECO:0000269|PubMed:15340084, ECO:0000269|PubMed:15471764, ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16574658, ECO:0000269|PubMed:24245781, ECO:0000269|PubMed:9653119}. |
| Q96GA3 | LTV1 | S34 | Sugiyama | Protein LTV1 homolog | Essential for ribosome biogenesis. {ECO:0000250|UniProtKB:Q5U3J8}. |
| Q9BTT0 | ANP32E | S48 | Sugiyama | Acidic leucine-rich nuclear phosphoprotein 32 family member E (LANP-like protein) (LANP-L) | Histone chaperone that specifically mediates the genome-wide removal of histone H2A.Z/H2AZ1 from the nucleosome: removes H2A.Z/H2AZ1 from its normal sites of deposition, especially from enhancer and insulator regions. Not involved in deposition of H2A.Z/H2AZ1 in the nucleosome. May stabilize the evicted H2A.Z/H2AZ1-H2B dimer, thus shifting the equilibrium towards dissociation and the off-chromatin state (PubMed:24463511). Inhibits activity of protein phosphatase 2A (PP2A). Does not inhibit protein phosphatase 1. May play a role in cerebellar development and synaptogenesis. {ECO:0000269|PubMed:24463511}. |
| Q8NFD5 | ARID1B | S1744 | Sugiyama | AT-rich interactive domain-containing protein 1B (ARID domain-containing protein 1B) (BRG1-associated factor 250b) (BAF250B) (BRG1-binding protein hELD/OSA1) (Osa homolog 2) (hOsa2) (p250R) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Binds DNA non-specifically (PubMed:14982958, PubMed:15170388). {ECO:0000250|UniProtKB:E9Q4N7, ECO:0000269|PubMed:14982958, ECO:0000269|PubMed:15170388, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| Q99615 | DNAJC7 | S94 | 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}. |
| Q9HB07 | MYG1 | S196 | Sugiyama | MYG1 exonuclease (EC 3.1.-.-) | 3'-5' RNA exonuclease which cleaves in situ on specific transcripts in both nucleus and mitochondrion. Involved in regulating spatially segregated organellar RNA processing, acts as a coordinator of nucleo-mitochondrial crosstalk (PubMed:31081026). In nucleolus, processes pre-ribosomal RNA involved in ribosome assembly and alters cytoplasmic translation. In mitochondrial matrix, processes 3'-termini of the mito-ribosomal and messenger RNAs and controls translation of mitochondrial proteins (Probable). {ECO:0000269|PubMed:31081026, ECO:0000305|PubMed:31081026}. |
| Q04917 | YWHAH | S215 | 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}. |
| Q9NY33 | DPP3 | S194 | Sugiyama | Dipeptidyl peptidase 3 (EC 3.4.14.4) (Dipeptidyl aminopeptidase III) (Dipeptidyl arylamidase III) (Dipeptidyl peptidase III) (DPP III) (Enkephalinase B) | Cleaves and degrades bioactive peptides, including angiotensin, Leu-enkephalin and Met-enkephalin (PubMed:1515063, PubMed:3233187). Also cleaves Arg-Arg-beta-naphthylamide (in vitro) (PubMed:11209758, PubMed:3233187, PubMed:9425109). {ECO:0000269|PubMed:11209758, ECO:0000269|PubMed:1515063, ECO:0000269|PubMed:3233187, ECO:0000269|PubMed:9425109}. |
| P31947 | SFN | S212 | 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}. |
| Q99614 | TTC1 | S187 | Sugiyama | Tetratricopeptide repeat protein 1 (TPR repeat protein 1) | None |
| P11717 | IGF2R | S1378 | Sugiyama | Cation-independent mannose-6-phosphate receptor (CI Man-6-P receptor) (CI-MPR) (M6PR) (300 kDa mannose 6-phosphate receptor) (MPR 300) (Insulin-like growth factor 2 receptor) (Insulin-like growth factor II receptor) (IGF-II receptor) (M6P/IGF2 receptor) (M6P/IGF2R) (CD antigen CD222) | Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes (PubMed:18817523, PubMed:2963003). Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate receptors in the Golgi apparatus and the resulting receptor-ligand complex is transported to an acidic prelysosomal compartment where the low pH mediates the dissociation of the complex (PubMed:18817523, PubMed:2963003). The receptor is then recycled back to the Golgi for another round of trafficking through its binding to the retromer (PubMed:18817523). This receptor also binds IGF2 (PubMed:18046459). Acts as a positive regulator of T-cell coactivation by binding DPP4 (PubMed:10900005). {ECO:0000269|PubMed:10900005, ECO:0000269|PubMed:18046459, ECO:0000269|PubMed:18817523, ECO:0000269|PubMed:2963003}. |
| Q96S66 | CLCC1 | S65 | Sugiyama | Chloride channel CLIC-like protein 1 (ER anion channel 1) (ERAC1) (Mid-1-related chloride channel protein) | Anion-selective channel with Ca(2+)-dependent and voltage-independent gating. Permeable to small monovalent anions with selectivity for bromide > chloride > nitrate > fluoride (By similarity). Operates in the endoplasmic reticulum (ER) membrane where it mediates chloride efflux to compensate for the loss of positive charges from the ER lumen upon Ca(2+) release. Contributes to the maintenance of ER Ca(2+) pools and activation of unfolded protein response to prevent accumulation of misfolded proteins in the ER lumen. Particularly involved in ER homeostasis mechanisms underlying motor neurons and retinal photoreceptors survival (By similarity) (PubMed:25698737, PubMed:30157172, PubMed:37142673). {ECO:0000250|UniProtKB:Q99LI2, ECO:0000269|PubMed:25698737, ECO:0000269|PubMed:30157172, ECO:0000269|PubMed:37142673}. |
| Q9BX68 | HINT2 | S63 | Sugiyama | Adenosine 5'-monophosphoramidase HINT2 (EC 3.9.1.-) (HINT-3) (HIT-17kDa) (Histidine triad nucleotide-binding protein 2, mitochondrial) (HINT-2) (PKCI-1-related HIT protein) | Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:16762638, PubMed:31990367). Hydrolyzes adenosine 5'-O-p-nitrophenylphosphoramidate (AMP-pNA) (PubMed:16762638). Hydrolyzes fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:31990367). May be involved in steroid biosynthesis (PubMed:18653718). May play a role in apoptosis (PubMed:16762638). {ECO:0000269|PubMed:16762638, ECO:0000269|PubMed:18653718, ECO:0000269|PubMed:31990367}. |
| O95273 | CCNDBP1 | S313 | GPS6 | Cyclin-D1-binding protein 1 (Grap2 and cyclin-D-interacting protein) (Human homolog of Maid) | May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription. {ECO:0000269|PubMed:10801854}. |
| O14965 | AURKA | S283 | SIGNOR | Aurora kinase A (EC 2.7.11.1) (Aurora 2) (Aurora/IPL1-related kinase 1) (ARK-1) (Aurora-related kinase 1) (Breast tumor-amplified kinase) (Ipl1- and aurora-related kinase 1) (Serine/threonine-protein kinase 15) (Serine/threonine-protein kinase 6) (Serine/threonine-protein kinase Ayk1) (Serine/threonine-protein kinase aurora-A) | Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735). {ECO:0000250|UniProtKB:A0A8I3S724, ECO:0000269|PubMed:11039908, ECO:0000269|PubMed:11551964, ECO:0000269|PubMed:12390251, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:14523000, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15128871, ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:15987997, ECO:0000269|PubMed:17125279, ECO:0000269|PubMed:17360485, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19668197, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:27192185, ECO:0000269|PubMed:27335426, ECO:0000269|PubMed:28218735}. |
| P51957 | NEK4 | S772 | Sugiyama | Serine/threonine-protein kinase Nek4 (EC 2.7.11.1) (Never in mitosis A-related kinase 4) (NimA-related protein kinase 4) (Serine/threonine-protein kinase 2) (Serine/threonine-protein kinase NRK2) | Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}. |
| P33981 | TTK | S333 | SIGNOR|PSP | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P30101 | PDIA3 | S343 | 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}. |
| Q15349 | RPS6KA2 | S684 | Sugiyama | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
| Q15759 | MAPK11 | S40 | Sugiyama | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q16288 | NTRK3 | S706 | Sugiyama | NT-3 growth factor receptor (EC 2.7.10.1) (GP145-TrkC) (Trk-C) (Neurotrophic tyrosine kinase receptor type 3) (TrkC tyrosine kinase) | Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. {ECO:0000269|PubMed:25196463}. |
| Q6PHR2 | ULK3 | S300 | GPS6|SIGNOR|EPSD|PSP | Serine/threonine-protein kinase ULK3 (EC 2.7.11.1) (Unc-51-like kinase 3) | Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy. {ECO:0000269|PubMed:19279323, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:20643644}. |
| P18858 | LIG1 | S388 | Sugiyama | DNA ligase 1 (EC 6.5.1.1) (DNA ligase I) (Polydeoxyribonucleotide synthase [ATP] 1) | DNA ligase that seals nicks in double-stranded during DNA repair (PubMed:30395541). Also involved in DNA replication and DNA recombination. {ECO:0000269|PubMed:30395541}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-1640170 | Cell Cycle | 1.110223e-16 | 15.955 |
| R-HSA-69278 | Cell Cycle, Mitotic | 1.110223e-16 | 15.955 |
| R-HSA-68886 | M Phase | 1.356693e-13 | 12.868 |
| R-HSA-69620 | Cell Cycle Checkpoints | 1.252853e-11 | 10.902 |
| R-HSA-68877 | Mitotic Prometaphase | 1.864364e-11 | 10.729 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 1.774344e-09 | 8.751 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 4.744329e-09 | 8.324 |
| R-HSA-69275 | G2/M Transition | 7.141777e-09 | 8.146 |
| R-HSA-8953897 | Cellular responses to stimuli | 2.709459e-08 | 7.567 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 5.418907e-08 | 7.266 |
| R-HSA-2262752 | Cellular responses to stress | 6.892157e-08 | 7.162 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 1.094026e-07 | 6.961 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 1.517483e-07 | 6.819 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 1.517483e-07 | 6.819 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 2.587289e-07 | 6.587 |
| R-HSA-199991 | Membrane Trafficking | 2.786016e-07 | 6.555 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 6.950132e-07 | 6.158 |
| R-HSA-380287 | Centrosome maturation | 1.129385e-06 | 5.947 |
| R-HSA-2467813 | Separation of Sister Chromatids | 1.487958e-06 | 5.827 |
| R-HSA-69481 | G2/M Checkpoints | 1.704805e-06 | 5.768 |
| R-HSA-68882 | Mitotic Anaphase | 1.643112e-06 | 5.784 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 1.869636e-06 | 5.728 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 2.850224e-06 | 5.545 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 3.466648e-06 | 5.460 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 4.973894e-06 | 5.303 |
| R-HSA-68875 | Mitotic Prophase | 5.639257e-06 | 5.249 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 9.184782e-06 | 5.037 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 1.032314e-05 | 4.986 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 1.596893e-05 | 4.797 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.721745e-05 | 4.764 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 1.914644e-05 | 4.718 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 2.211633e-05 | 4.655 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 2.376675e-05 | 4.624 |
| R-HSA-422475 | Axon guidance | 2.304379e-05 | 4.637 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 3.103264e-05 | 4.508 |
| R-HSA-9700206 | Signaling by ALK in cancer | 3.103264e-05 | 4.508 |
| R-HSA-9675108 | Nervous system development | 3.367492e-05 | 4.473 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 3.946526e-05 | 4.404 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 4.276247e-05 | 4.369 |
| R-HSA-5357801 | Programmed Cell Death | 4.727849e-05 | 4.325 |
| R-HSA-983189 | Kinesins | 5.140569e-05 | 4.289 |
| R-HSA-5617833 | Cilium Assembly | 5.257164e-05 | 4.279 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 6.034916e-05 | 4.219 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 5.996727e-05 | 4.222 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 6.491615e-05 | 4.188 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 7.001039e-05 | 4.155 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 7.322309e-05 | 4.135 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 7.529279e-05 | 4.123 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 8.769610e-05 | 4.057 |
| R-HSA-109581 | Apoptosis | 8.972050e-05 | 4.047 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 1.008335e-04 | 3.996 |
| R-HSA-5693538 | Homology Directed Repair | 1.016007e-04 | 3.993 |
| R-HSA-75153 | Apoptotic execution phase | 1.354604e-04 | 3.868 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 1.432699e-04 | 3.844 |
| R-HSA-3371556 | Cellular response to heat stress | 1.543015e-04 | 3.812 |
| R-HSA-450294 | MAP kinase activation | 1.678175e-04 | 3.775 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 1.697828e-04 | 3.770 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 1.766385e-04 | 3.753 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 1.766385e-04 | 3.753 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 1.777624e-04 | 3.750 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 1.908302e-04 | 3.719 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 2.080853e-04 | 3.682 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 2.093430e-04 | 3.679 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 2.012103e-04 | 3.696 |
| R-HSA-9646399 | Aggrephagy | 2.171391e-04 | 3.663 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 2.171391e-04 | 3.663 |
| R-HSA-69242 | S Phase | 2.416604e-04 | 3.617 |
| R-HSA-438064 | Post NMDA receptor activation events | 2.444083e-04 | 3.612 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 2.473446e-04 | 3.607 |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment | 2.556186e-04 | 3.592 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 2.752817e-04 | 3.560 |
| R-HSA-72649 | Translation initiation complex formation | 2.796805e-04 | 3.553 |
| R-HSA-9663891 | Selective autophagy | 2.862440e-04 | 3.543 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 2.999770e-04 | 3.523 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 3.110247e-04 | 3.507 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 3.110247e-04 | 3.507 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 3.362268e-04 | 3.473 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 3.362268e-04 | 3.473 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 3.756950e-04 | 3.425 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 4.125744e-04 | 3.384 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 4.063282e-04 | 3.391 |
| R-HSA-2559583 | Cellular Senescence | 3.964254e-04 | 3.402 |
| R-HSA-5653656 | Vesicle-mediated transport | 4.045736e-04 | 3.393 |
| R-HSA-8953854 | Metabolism of RNA | 4.089633e-04 | 3.388 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 4.911723e-04 | 3.309 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 4.911723e-04 | 3.309 |
| R-HSA-437239 | Recycling pathway of L1 | 4.656600e-04 | 3.332 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 4.909045e-04 | 3.309 |
| R-HSA-5633007 | Regulation of TP53 Activity | 4.924290e-04 | 3.308 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 5.083217e-04 | 3.294 |
| R-HSA-162582 | Signal Transduction | 5.176331e-04 | 3.286 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 5.238327e-04 | 3.281 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 5.327954e-04 | 3.273 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 5.813808e-04 | 3.236 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 5.813808e-04 | 3.236 |
| R-HSA-9612973 | Autophagy | 5.933057e-04 | 3.227 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 6.036863e-04 | 3.219 |
| R-HSA-156902 | Peptide chain elongation | 6.321435e-04 | 3.199 |
| R-HSA-198753 | ERK/MAPK targets | 7.827089e-04 | 3.106 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 8.052807e-04 | 3.094 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 7.629643e-04 | 3.117 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 7.600378e-04 | 3.119 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 7.600378e-04 | 3.119 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 7.600378e-04 | 3.119 |
| R-HSA-448424 | Interleukin-17 signaling | 8.399471e-04 | 3.076 |
| R-HSA-9948299 | Ribosome-associated quality control | 9.062377e-04 | 3.043 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 9.468619e-04 | 3.024 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 1.020363e-03 | 2.991 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 1.029623e-03 | 2.987 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 1.051927e-03 | 2.978 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 1.063340e-03 | 2.973 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 1.063340e-03 | 2.973 |
| R-HSA-177929 | Signaling by EGFR | 1.029623e-03 | 2.987 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 1.055828e-03 | 2.976 |
| R-HSA-168255 | Influenza Infection | 1.138373e-03 | 2.944 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 1.152253e-03 | 2.938 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 1.153869e-03 | 2.938 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 1.200585e-03 | 2.921 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 1.226526e-03 | 2.911 |
| R-HSA-180746 | Nuclear import of Rev protein | 1.281765e-03 | 2.892 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 1.281765e-03 | 2.892 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 1.282210e-03 | 2.892 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 1.282210e-03 | 2.892 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 1.342697e-03 | 2.872 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 1.364191e-03 | 2.865 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 | 1.486577e-03 | 2.828 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 1.465657e-03 | 2.834 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 1.465657e-03 | 2.834 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 1.488541e-03 | 2.827 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 1.427713e-03 | 2.845 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 1.505731e-03 | 2.822 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 1.532238e-03 | 2.815 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 1.505395e-03 | 2.822 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 1.426137e-03 | 2.846 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 1.568360e-03 | 2.805 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 1.596953e-03 | 2.797 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 1.596953e-03 | 2.797 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 1.684239e-03 | 2.774 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 1.720037e-03 | 2.764 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 1.726148e-03 | 2.763 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 1.836180e-03 | 2.736 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 1.838905e-03 | 2.735 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 2.058064e-03 | 2.687 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 2.058064e-03 | 2.687 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 2.016961e-03 | 2.695 |
| R-HSA-6807004 | Negative regulation of MET activity | 1.993853e-03 | 2.700 |
| R-HSA-162587 | HIV Life Cycle | 2.125822e-03 | 2.672 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 2.267108e-03 | 2.645 |
| R-HSA-1632852 | Macroautophagy | 2.270209e-03 | 2.644 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 2.300293e-03 | 2.638 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 2.300293e-03 | 2.638 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 2.379077e-03 | 2.624 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 2.659225e-03 | 2.575 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 2.422274e-03 | 2.616 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 2.503451e-03 | 2.601 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 2.636311e-03 | 2.579 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 2.486299e-03 | 2.604 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 2.659225e-03 | 2.575 |
| R-HSA-373760 | L1CAM interactions | 2.518574e-03 | 2.599 |
| R-HSA-9909396 | Circadian clock | 2.692409e-03 | 2.570 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 2.844932e-03 | 2.546 |
| R-HSA-2132295 | MHC class II antigen presentation | 2.874477e-03 | 2.541 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 2.906348e-03 | 2.537 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 2.951063e-03 | 2.530 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 3.469265e-03 | 2.460 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 3.469265e-03 | 2.460 |
| R-HSA-114452 | Activation of BH3-only proteins | 3.320747e-03 | 2.479 |
| R-HSA-376176 | Signaling by ROBO receptors | 3.205314e-03 | 2.494 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 3.490495e-03 | 2.457 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 3.490495e-03 | 2.457 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 3.490495e-03 | 2.457 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 3.570934e-03 | 2.447 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 3.585179e-03 | 2.445 |
| R-HSA-444257 | RSK activation | 3.585179e-03 | 2.445 |
| R-HSA-9825895 | Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... | 3.585179e-03 | 2.445 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 3.715723e-03 | 2.430 |
| R-HSA-5610787 | Hedgehog 'off' state | 3.866916e-03 | 2.413 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 3.890145e-03 | 2.410 |
| R-HSA-194441 | Metabolism of non-coding RNA | 3.890145e-03 | 2.410 |
| R-HSA-191859 | snRNP Assembly | 3.890145e-03 | 2.410 |
| R-HSA-193639 | p75NTR signals via NF-kB | 4.004934e-03 | 2.397 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 4.004934e-03 | 2.397 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 4.008276e-03 | 2.397 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 4.024528e-03 | 2.395 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 4.354658e-03 | 2.361 |
| R-HSA-182971 | EGFR downregulation | 4.109187e-03 | 2.386 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 4.081648e-03 | 2.389 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 4.354658e-03 | 2.361 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 4.187995e-03 | 2.378 |
| R-HSA-187687 | Signalling to ERKs | 4.250104e-03 | 2.372 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 4.511053e-03 | 2.346 |
| R-HSA-74160 | Gene expression (Transcription) | 4.601735e-03 | 2.337 |
| R-HSA-2408557 | Selenocysteine synthesis | 4.327710e-03 | 2.364 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 4.644510e-03 | 2.333 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 4.293026e-03 | 2.367 |
| R-HSA-73894 | DNA Repair | 4.687011e-03 | 2.329 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 4.708437e-03 | 2.327 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 4.708437e-03 | 2.327 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 4.938286e-03 | 2.306 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 4.953902e-03 | 2.305 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 5.239374e-03 | 2.281 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 5.398914e-03 | 2.268 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 5.423326e-03 | 2.266 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 5.480247e-03 | 2.261 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 5.570625e-03 | 2.254 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 5.640978e-03 | 2.249 |
| R-HSA-5693606 | DNA Double Strand Break Response | 5.649759e-03 | 2.248 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 5.746798e-03 | 2.241 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 5.994526e-03 | 2.222 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 6.030211e-03 | 2.220 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 6.034929e-03 | 2.219 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 6.134244e-03 | 2.212 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 6.167971e-03 | 2.210 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 6.370215e-03 | 2.196 |
| R-HSA-5602636 | IKBKB deficiency causes SCID | 7.456582e-03 | 2.127 |
| R-HSA-5603027 | IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... | 7.456582e-03 | 2.127 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 7.062724e-03 | 2.151 |
| R-HSA-9615710 | Late endosomal microautophagy | 7.300046e-03 | 2.137 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 6.453272e-03 | 2.190 |
| R-HSA-69206 | G1/S Transition | 6.921752e-03 | 2.160 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 7.356293e-03 | 2.133 |
| R-HSA-9711097 | Cellular response to starvation | 6.757577e-03 | 2.170 |
| R-HSA-70171 | Glycolysis | 7.252488e-03 | 2.140 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 7.627564e-03 | 2.118 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 7.717647e-03 | 2.113 |
| R-HSA-9664873 | Pexophagy | 7.870520e-03 | 2.104 |
| R-HSA-72764 | Eukaryotic Translation Termination | 7.898389e-03 | 2.102 |
| R-HSA-73887 | Death Receptor Signaling | 8.050271e-03 | 2.094 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 8.101480e-03 | 2.091 |
| R-HSA-166520 | Signaling by NTRKs | 8.132625e-03 | 2.090 |
| R-HSA-69895 | Transcriptional activation of cell cycle inhibitor p21 | 8.408470e-03 | 2.075 |
| R-HSA-69560 | Transcriptional activation of p53 responsive genes | 8.408470e-03 | 2.075 |
| R-HSA-68962 | Activation of the pre-replicative complex | 8.876072e-03 | 2.052 |
| R-HSA-9008059 | Interleukin-37 signaling | 8.876072e-03 | 2.052 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 9.437115e-03 | 2.025 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 9.437115e-03 | 2.025 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 9.437115e-03 | 2.025 |
| R-HSA-69236 | G1 Phase | 9.871050e-03 | 2.006 |
| R-HSA-69231 | Cyclin D associated events in G1 | 9.871050e-03 | 2.006 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 1.016907e-02 | 1.993 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.038970e-02 | 1.983 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 1.056692e-02 | 1.976 |
| R-HSA-525793 | Myogenesis | 1.060434e-02 | 1.975 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 1.070295e-02 | 1.970 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 1.070295e-02 | 1.970 |
| R-HSA-4411364 | Binding of TCF/LEF:CTNNB1 to target gene promoters | 1.076936e-02 | 1.968 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 1.076936e-02 | 1.968 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 1.102608e-02 | 1.958 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 1.102608e-02 | 1.958 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 1.102608e-02 | 1.958 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 1.183079e-02 | 1.927 |
| R-HSA-3928664 | Ephrin signaling | 1.183079e-02 | 1.927 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 1.183079e-02 | 1.927 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 1.280476e-02 | 1.893 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 1.147448e-02 | 1.940 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 1.147448e-02 | 1.940 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.327383e-02 | 1.877 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.327383e-02 | 1.877 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.327383e-02 | 1.877 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.327383e-02 | 1.877 |
| R-HSA-69190 | DNA strand elongation | 1.280476e-02 | 1.893 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 1.203147e-02 | 1.920 |
| R-HSA-6784531 | tRNA processing in the nucleus | 1.240518e-02 | 1.906 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 1.327383e-02 | 1.877 |
| R-HSA-194138 | Signaling by VEGF | 1.190004e-02 | 1.924 |
| R-HSA-162906 | HIV Infection | 1.224307e-02 | 1.912 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 1.280476e-02 | 1.893 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 1.197872e-02 | 1.922 |
| R-HSA-9675135 | Diseases of DNA repair | 1.327383e-02 | 1.877 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 1.203147e-02 | 1.920 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 1.352290e-02 | 1.869 |
| R-HSA-171007 | p38MAPK events | 1.352290e-02 | 1.869 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 1.352290e-02 | 1.869 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 1.352290e-02 | 1.869 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 1.352290e-02 | 1.869 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 1.357500e-02 | 1.867 |
| R-HSA-6806834 | Signaling by MET | 1.379765e-02 | 1.860 |
| R-HSA-9833482 | PKR-mediated signaling | 1.379765e-02 | 1.860 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.401589e-02 | 1.853 |
| R-HSA-9706377 | FLT3 signaling by CBL mutants | 1.408114e-02 | 1.851 |
| R-HSA-449147 | Signaling by Interleukins | 1.426014e-02 | 1.846 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 1.467957e-02 | 1.833 |
| R-HSA-110320 | Translesion Synthesis by POLH | 1.488690e-02 | 1.827 |
| R-HSA-113510 | E2F mediated regulation of DNA replication | 1.488690e-02 | 1.827 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 1.488690e-02 | 1.827 |
| R-HSA-209560 | NF-kB is activated and signals survival | 1.498502e-02 | 1.824 |
| R-HSA-113501 | Inhibition of replication initiation of damaged DNA by RB1/E2F1 | 1.498502e-02 | 1.824 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 1.498502e-02 | 1.824 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 1.520573e-02 | 1.818 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 1.520573e-02 | 1.818 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 1.562289e-02 | 1.806 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 1.562289e-02 | 1.806 |
| R-HSA-69239 | Synthesis of DNA | 1.584195e-02 | 1.800 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 1.584535e-02 | 1.800 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 1.624186e-02 | 1.789 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 1.637176e-02 | 1.786 |
| R-HSA-913531 | Interferon Signaling | 1.651381e-02 | 1.782 |
| R-HSA-162909 | Host Interactions of HIV factors | 1.686175e-02 | 1.773 |
| R-HSA-192823 | Viral mRNA Translation | 1.740250e-02 | 1.759 |
| R-HSA-163358 | PKA-mediated phosphorylation of key metabolic factors | 2.172528e-02 | 1.663 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 2.175177e-02 | 1.663 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 2.175177e-02 | 1.663 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 1.847860e-02 | 1.733 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 1.847860e-02 | 1.733 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 1.847860e-02 | 1.733 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 1.847860e-02 | 1.733 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 1.876217e-02 | 1.727 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 1.851339e-02 | 1.733 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 2.192540e-02 | 1.659 |
| R-HSA-5696400 | Dual Incision in GG-NER | 2.100135e-02 | 1.678 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 1.996564e-02 | 1.700 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 1.788538e-02 | 1.748 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 1.990609e-02 | 1.701 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 2.099171e-02 | 1.678 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 1.793001e-02 | 1.746 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 2.172528e-02 | 1.663 |
| R-HSA-5205647 | Mitophagy | 2.100135e-02 | 1.678 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 2.172528e-02 | 1.663 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 1.990609e-02 | 1.701 |
| R-HSA-180024 | DARPP-32 events | 1.851339e-02 | 1.733 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 2.041745e-02 | 1.690 |
| R-HSA-168898 | Toll-like Receptor Cascades | 2.046003e-02 | 1.689 |
| R-HSA-9860276 | SLC15A4:TASL-dependent IRF5 activation | 2.172528e-02 | 1.663 |
| R-HSA-446652 | Interleukin-1 family signaling | 1.807705e-02 | 1.743 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 1.904924e-02 | 1.720 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 1.854495e-02 | 1.732 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 2.094705e-02 | 1.679 |
| R-HSA-69186 | Lagging Strand Synthesis | 2.265080e-02 | 1.645 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 2.265080e-02 | 1.645 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 2.350593e-02 | 1.629 |
| R-HSA-75893 | TNF signaling | 2.367483e-02 | 1.626 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 2.444291e-02 | 1.612 |
| R-HSA-72312 | rRNA processing | 2.448581e-02 | 1.611 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 2.454011e-02 | 1.610 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 2.521407e-02 | 1.598 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 2.565501e-02 | 1.591 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 2.572714e-02 | 1.590 |
| R-HSA-73857 | RNA Polymerase II Transcription | 2.590585e-02 | 1.587 |
| R-HSA-70326 | Glucose metabolism | 2.604513e-02 | 1.584 |
| R-HSA-5689901 | Metalloprotease DUBs | 2.684286e-02 | 1.571 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 2.684286e-02 | 1.571 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 2.707576e-02 | 1.567 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 2.723812e-02 | 1.565 |
| R-HSA-9617828 | FOXO-mediated transcription of cell cycle genes | 2.744542e-02 | 1.562 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 2.770205e-02 | 1.557 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 2.790198e-02 | 1.554 |
| R-HSA-8941326 | RUNX2 regulates bone development | 2.827698e-02 | 1.549 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 2.827698e-02 | 1.549 |
| R-HSA-9682385 | FLT3 signaling in disease | 2.827698e-02 | 1.549 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 2.829113e-02 | 1.548 |
| R-HSA-9672393 | Defective F8 binding to von Willebrand factor | 2.863055e-02 | 1.543 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 2.869567e-02 | 1.542 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 2.881502e-02 | 1.540 |
| R-HSA-164843 | 2-LTR circle formation | 2.926047e-02 | 1.534 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 2.926047e-02 | 1.534 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 2.926047e-02 | 1.534 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 2.926047e-02 | 1.534 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 3.002505e-02 | 1.523 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 3.018001e-02 | 1.520 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 3.018001e-02 | 1.520 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 3.018001e-02 | 1.520 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 3.018001e-02 | 1.520 |
| R-HSA-1500931 | Cell-Cell communication | 3.021288e-02 | 1.520 |
| R-HSA-2682334 | EPH-Ephrin signaling | 3.035054e-02 | 1.518 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 3.063166e-02 | 1.514 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 3.063166e-02 | 1.514 |
| R-HSA-9842640 | Signaling by LTK in cancer | 3.148955e-02 | 1.502 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 3.168858e-02 | 1.499 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 3.217887e-02 | 1.492 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 3.259259e-02 | 1.487 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 3.290068e-02 | 1.483 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 3.337238e-02 | 1.477 |
| R-HSA-163615 | PKA activation | 3.337238e-02 | 1.477 |
| R-HSA-156711 | Polo-like kinase mediated events | 3.337238e-02 | 1.477 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 3.337238e-02 | 1.477 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 3.360190e-02 | 1.474 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 3.360190e-02 | 1.474 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 3.421042e-02 | 1.466 |
| R-HSA-111996 | Ca-dependent events | 3.432828e-02 | 1.464 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 3.487164e-02 | 1.458 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 3.487164e-02 | 1.458 |
| R-HSA-9614085 | FOXO-mediated transcription | 3.549846e-02 | 1.450 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 3.711007e-02 | 1.431 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 3.711007e-02 | 1.431 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 3.711007e-02 | 1.431 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 3.999420e-02 | 1.398 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 3.999420e-02 | 1.398 |
| R-HSA-9711123 | Cellular response to chemical stress | 4.005273e-02 | 1.397 |
| R-HSA-912631 | Regulation of signaling by CBL | 4.036291e-02 | 1.394 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 4.036291e-02 | 1.394 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 4.045721e-02 | 1.393 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 4.045721e-02 | 1.393 |
| R-HSA-110312 | Translesion synthesis by REV1 | 4.045721e-02 | 1.393 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 4.045721e-02 | 1.393 |
| R-HSA-2514853 | Condensation of Prometaphase Chromosomes | 4.870191e-02 | 1.312 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 4.870191e-02 | 1.312 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 4.870191e-02 | 1.312 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 4.953306e-02 | 1.305 |
| R-HSA-5656121 | Translesion synthesis by POLI | 4.953306e-02 | 1.305 |
| R-HSA-176412 | Phosphorylation of the APC/C | 4.953306e-02 | 1.305 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 4.953306e-02 | 1.305 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 4.824312e-02 | 1.317 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 5.354327e-02 | 1.271 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 4.524621e-02 | 1.344 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 4.830306e-02 | 1.316 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 5.402325e-02 | 1.267 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 5.354327e-02 | 1.271 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 5.354327e-02 | 1.271 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 4.541782e-02 | 1.343 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 4.313263e-02 | 1.365 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 4.541782e-02 | 1.343 |
| R-HSA-169893 | Prolonged ERK activation events | 4.953306e-02 | 1.305 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 4.977805e-02 | 1.303 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 4.953306e-02 | 1.305 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 4.870191e-02 | 1.312 |
| R-HSA-162592 | Integration of provirus | 4.870191e-02 | 1.312 |
| R-HSA-4839726 | Chromatin organization | 4.242212e-02 | 1.372 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 4.345333e-02 | 1.362 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 5.292662e-02 | 1.276 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 5.402325e-02 | 1.267 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 4.592341e-02 | 1.338 |
| R-HSA-8863678 | Neurodegenerative Diseases | 4.592341e-02 | 1.338 |
| R-HSA-212436 | Generic Transcription Pathway | 4.463687e-02 | 1.350 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 4.977507e-02 | 1.303 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 5.045346e-02 | 1.297 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 4.524621e-02 | 1.344 |
| R-HSA-8948747 | Regulation of PTEN localization | 4.345333e-02 | 1.362 |
| R-HSA-373753 | Nephrin family interactions | 4.824312e-02 | 1.317 |
| R-HSA-2559585 | Oncogene Induced Senescence | 5.237053e-02 | 1.281 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 5.402325e-02 | 1.267 |
| R-HSA-9607240 | FLT3 Signaling | 5.402325e-02 | 1.267 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 4.870191e-02 | 1.312 |
| R-HSA-9679506 | SARS-CoV Infections | 4.850134e-02 | 1.314 |
| R-HSA-204005 | COPII-mediated vesicle transport | 5.453019e-02 | 1.263 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 5.453019e-02 | 1.263 |
| R-HSA-3247509 | Chromatin modifying enzymes | 5.471552e-02 | 1.262 |
| R-HSA-202403 | TCR signaling | 5.480932e-02 | 1.261 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 5.703785e-02 | 1.244 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 5.703785e-02 | 1.244 |
| R-HSA-111931 | PKA-mediated phosphorylation of CREB | 5.703785e-02 | 1.244 |
| R-HSA-167044 | Signalling to RAS | 5.703785e-02 | 1.244 |
| R-HSA-5358351 | Signaling by Hedgehog | 5.721829e-02 | 1.242 |
| R-HSA-446107 | Type I hemidesmosome assembly | 5.763167e-02 | 1.239 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 5.763167e-02 | 1.239 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 5.763167e-02 | 1.239 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 5.763167e-02 | 1.239 |
| R-HSA-9603505 | NTRK3 as a dependence receptor | 5.920142e-02 | 1.228 |
| R-HSA-9636667 | Manipulation of host energy metabolism | 5.920142e-02 | 1.228 |
| R-HSA-352238 | Breakdown of the nuclear lamina | 5.920142e-02 | 1.228 |
| R-HSA-3371511 | HSF1 activation | 5.930182e-02 | 1.227 |
| R-HSA-111933 | Calmodulin induced events | 5.930182e-02 | 1.227 |
| R-HSA-111997 | CaM pathway | 5.930182e-02 | 1.227 |
| R-HSA-2408522 | Selenoamino acid metabolism | 5.953119e-02 | 1.225 |
| R-HSA-5655862 | Translesion synthesis by POLK | 5.976380e-02 | 1.224 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 5.976380e-02 | 1.224 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 5.976380e-02 | 1.224 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 5.976380e-02 | 1.224 |
| R-HSA-9675151 | Disorders of Developmental Biology | 5.976380e-02 | 1.224 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 6.060162e-02 | 1.218 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 6.060162e-02 | 1.218 |
| R-HSA-2691230 | Signaling by NOTCH1 HD Domain Mutants in Cancer | 6.070809e-02 | 1.217 |
| R-HSA-2691232 | Constitutive Signaling by NOTCH1 HD Domain Mutants | 6.070809e-02 | 1.217 |
| R-HSA-69091 | Polymerase switching | 6.070809e-02 | 1.217 |
| R-HSA-69109 | Leading Strand Synthesis | 6.070809e-02 | 1.217 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 6.070809e-02 | 1.217 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 6.070809e-02 | 1.217 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 6.070809e-02 | 1.217 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 6.070809e-02 | 1.217 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 6.070809e-02 | 1.217 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 6.070809e-02 | 1.217 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 6.070809e-02 | 1.217 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 6.070809e-02 | 1.217 |
| R-HSA-6811440 | Retrograde transport at the Trans-Golgi-Network | 6.120803e-02 | 1.213 |
| R-HSA-2122948 | Activated NOTCH1 Transmits Signal to the Nucleus | 6.192774e-02 | 1.208 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 6.192774e-02 | 1.208 |
| R-HSA-446728 | Cell junction organization | 6.325103e-02 | 1.199 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 6.401605e-02 | 1.194 |
| R-HSA-8941284 | RUNX2 regulates chondrocyte maturation | 6.495376e-02 | 1.187 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 6.495379e-02 | 1.187 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 6.495379e-02 | 1.187 |
| R-HSA-1538133 | G0 and Early G1 | 6.500527e-02 | 1.187 |
| R-HSA-202424 | Downstream TCR signaling | 6.574498e-02 | 1.182 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 6.676303e-02 | 1.175 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 6.676303e-02 | 1.175 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 6.744115e-02 | 1.171 |
| R-HSA-69306 | DNA Replication | 6.762091e-02 | 1.170 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 6.789758e-02 | 1.168 |
| R-HSA-6804754 | Regulation of TP53 Expression | 9.681835e-02 | 1.014 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 9.681835e-02 | 1.014 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 9.681835e-02 | 1.014 |
| R-HSA-9672391 | Defective F8 cleavage by thrombin | 9.681835e-02 | 1.014 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 9.681835e-02 | 1.014 |
| R-HSA-9758919 | Epithelial-Mesenchymal Transition (EMT) during gastrulation | 8.838723e-02 | 1.054 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 8.838723e-02 | 1.054 |
| R-HSA-176417 | Phosphorylation of Emi1 | 8.838723e-02 | 1.054 |
| R-HSA-448706 | Interleukin-1 processing | 7.398240e-02 | 1.131 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 9.241450e-02 | 1.034 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 7.424199e-02 | 1.129 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 7.424199e-02 | 1.129 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 8.927531e-02 | 1.049 |
| R-HSA-69166 | Removal of the Flap Intermediate | 8.927531e-02 | 1.049 |
| R-HSA-9027284 | Erythropoietin activates RAS | 1.057573e-01 | 0.976 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 1.057573e-01 | 0.976 |
| R-HSA-164378 | PKA activation in glucagon signalling | 8.371749e-02 | 1.077 |
| R-HSA-350054 | Notch-HLH transcription pathway | 7.742555e-02 | 1.111 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 8.103169e-02 | 1.091 |
| R-HSA-9006335 | Signaling by Erythropoietin | 9.175649e-02 | 1.037 |
| R-HSA-390522 | Striated Muscle Contraction | 8.288588e-02 | 1.082 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 8.288588e-02 | 1.082 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 7.435525e-02 | 1.129 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 9.928236e-02 | 1.003 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 9.928236e-02 | 1.003 |
| R-HSA-1980143 | Signaling by NOTCH1 | 8.964047e-02 | 1.047 |
| R-HSA-73893 | DNA Damage Bypass | 7.504570e-02 | 1.125 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 1.032566e-01 | 0.986 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 7.504570e-02 | 1.125 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 9.283178e-02 | 1.032 |
| R-HSA-180786 | Extension of Telomeres | 1.055174e-01 | 0.977 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 9.073602e-02 | 1.042 |
| R-HSA-5654736 | Signaling by FGFR1 | 8.151063e-02 | 1.089 |
| R-HSA-4086400 | PCP/CE pathway | 1.039577e-01 | 0.983 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 8.927531e-02 | 1.049 |
| R-HSA-170968 | Frs2-mediated activation | 7.424199e-02 | 1.129 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 7.938043e-02 | 1.100 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 1.057573e-01 | 0.976 |
| R-HSA-5683057 | MAPK family signaling cascades | 1.054058e-01 | 0.977 |
| R-HSA-9764561 | Regulation of CDH1 Function | 8.908854e-02 | 1.050 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 7.063870e-02 | 1.151 |
| R-HSA-9708296 | tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis | 9.681835e-02 | 1.014 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 7.424199e-02 | 1.129 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 7.424199e-02 | 1.129 |
| R-HSA-982772 | Growth hormone receptor signaling | 8.902328e-02 | 1.050 |
| R-HSA-68949 | Orc1 removal from chromatin | 9.928236e-02 | 1.003 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 7.742555e-02 | 1.111 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling | 1.057573e-01 | 0.976 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 7.172341e-02 | 1.144 |
| R-HSA-72766 | Translation | 9.905990e-02 | 1.004 |
| R-HSA-9766229 | Degradation of CDH1 | 7.504570e-02 | 1.125 |
| R-HSA-111885 | Opioid Signalling | 8.210577e-02 | 1.086 |
| R-HSA-442720 | CREB1 phosphorylation through the activation of Adenylate Cyclase | 7.424199e-02 | 1.129 |
| R-HSA-112040 | G-protein mediated events | 7.207278e-02 | 1.142 |
| R-HSA-9012852 | Signaling by NOTCH3 | 7.435525e-02 | 1.129 |
| R-HSA-1433559 | Regulation of KIT signaling | 8.927531e-02 | 1.049 |
| R-HSA-196780 | Biotin transport and metabolism | 1.057573e-01 | 0.976 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 8.927531e-02 | 1.049 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 1.057573e-01 | 0.976 |
| R-HSA-157858 | Gap junction trafficking and regulation | 7.504570e-02 | 1.125 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 9.741880e-02 | 1.011 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 7.398240e-02 | 1.131 |
| R-HSA-112043 | PLC beta mediated events | 7.333402e-02 | 1.135 |
| R-HSA-5654743 | Signaling by FGFR4 | 7.528066e-02 | 1.123 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 8.191406e-02 | 1.087 |
| R-HSA-190828 | Gap junction trafficking | 8.339411e-02 | 1.079 |
| R-HSA-5654741 | Signaling by FGFR3 | 9.202783e-02 | 1.036 |
| R-HSA-2028269 | Signaling by Hippo | 7.115992e-02 | 1.148 |
| R-HSA-446343 | Localization of the PINCH-ILK-PARVIN complex to focal adhesions | 9.681835e-02 | 1.014 |
| R-HSA-427652 | Sodium-coupled phosphate cotransporters | 8.838723e-02 | 1.054 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 9.241450e-02 | 1.034 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 1.057573e-01 | 0.976 |
| R-HSA-844456 | The NLRP3 inflammasome | 9.741880e-02 | 1.011 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 7.333402e-02 | 1.135 |
| R-HSA-1489509 | DAG and IP3 signaling | 9.202783e-02 | 1.036 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 1.026421e-01 | 0.989 |
| R-HSA-190861 | Gap junction assembly | 9.283178e-02 | 1.032 |
| R-HSA-9762293 | Regulation of CDH11 gene transcription | 7.398240e-02 | 1.131 |
| R-HSA-5218859 | Regulated Necrosis | 7.843022e-02 | 1.106 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 9.504175e-02 | 1.022 |
| R-HSA-111458 | Formation of apoptosome | 9.241450e-02 | 1.034 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 8.388478e-02 | 1.076 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 9.283178e-02 | 1.032 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 8.371749e-02 | 1.077 |
| R-HSA-9694493 | Maturation of protein E | 8.838723e-02 | 1.054 |
| R-HSA-9683683 | Maturation of protein E | 8.838723e-02 | 1.054 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 8.838723e-02 | 1.054 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 1.026091e-01 | 0.989 |
| R-HSA-193648 | NRAGE signals death through JNK | 8.151063e-02 | 1.089 |
| R-HSA-1500620 | Meiosis | 1.077638e-01 | 0.968 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 1.082955e-01 | 0.965 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 1.082955e-01 | 0.965 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 1.108536e-01 | 0.955 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 1.108536e-01 | 0.955 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1.116140e-01 | 0.952 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 1.122331e-01 | 0.950 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 1.127969e-01 | 0.948 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 1.127969e-01 | 0.948 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 1.127969e-01 | 0.948 |
| R-HSA-9635465 | Suppression of apoptosis | 1.127969e-01 | 0.948 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 1.127969e-01 | 0.948 |
| R-HSA-4839744 | Signaling by APC mutants | 1.127969e-01 | 0.948 |
| R-HSA-9683701 | Translation of Structural Proteins | 1.130601e-01 | 0.947 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 1.143668e-01 | 0.942 |
| R-HSA-114604 | GPVI-mediated activation cascade | 1.147175e-01 | 0.940 |
| R-HSA-199920 | CREB phosphorylation | 1.148097e-01 | 0.940 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 1.149724e-01 | 0.939 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 1.149724e-01 | 0.939 |
| R-HSA-389356 | Co-stimulation by CD28 | 1.210379e-01 | 0.917 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 1.216729e-01 | 0.915 |
| R-HSA-9672387 | Defective F8 accelerates dissociation of the A2 domain | 1.222685e-01 | 0.913 |
| R-HSA-9661070 | Defective translocation of RB1 mutants to the nucleus | 1.222685e-01 | 0.913 |
| R-HSA-9672397 | Defective F8 secretion | 1.222685e-01 | 0.913 |
| R-HSA-9723907 | Loss of Function of TP53 in Cancer | 1.222685e-01 | 0.913 |
| R-HSA-9723905 | Loss of function of TP53 in cancer due to loss of tetramerization ability | 1.222685e-01 | 0.913 |
| R-HSA-9672395 | Defective F8 binding to the cell membrane | 1.222685e-01 | 0.913 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 1.236172e-01 | 0.908 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 1.236172e-01 | 0.908 |
| R-HSA-9634600 | Regulation of glycolysis by fructose 2,6-bisphosphate metabolism | 1.236172e-01 | 0.908 |
| R-HSA-9708530 | Regulation of BACH1 activity | 1.236172e-01 | 0.908 |
| R-HSA-9706369 | Negative regulation of FLT3 | 1.236172e-01 | 0.908 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 1.236357e-01 | 0.908 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 1.258546e-01 | 0.900 |
| R-HSA-4641258 | Degradation of DVL | 1.266375e-01 | 0.897 |
| R-HSA-6807070 | PTEN Regulation | 1.270860e-01 | 0.896 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 1.281225e-01 | 0.892 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 1.292771e-01 | 0.888 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 1.292771e-01 | 0.888 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 1.349674e-01 | 0.870 |
| R-HSA-202670 | ERKs are inactivated | 1.349674e-01 | 0.870 |
| R-HSA-5693548 | Sensing of DNA Double Strand Breaks | 1.349674e-01 | 0.870 |
| R-HSA-4839735 | Signaling by AXIN mutants | 1.349674e-01 | 0.870 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 1.349674e-01 | 0.870 |
| R-HSA-1839120 | Signaling by FGFR1 amplification mutants | 1.393029e-01 | 0.856 |
| R-HSA-9960519 | CASP4-mediated substrate cleavage | 1.393029e-01 | 0.856 |
| R-HSA-9960525 | CASP5-mediated substrate cleavage | 1.393029e-01 | 0.856 |
| R-HSA-9673766 | Signaling by cytosolic PDGFRA and PDGFRB fusion proteins | 1.393029e-01 | 0.856 |
| R-HSA-5368598 | Negative regulation of TCF-dependent signaling by DVL-interacting proteins | 1.393029e-01 | 0.856 |
| R-HSA-9944971 | Loss of Function of KMT2D in Kabuki Syndrome | 1.393029e-01 | 0.856 |
| R-HSA-9944997 | Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome | 1.393029e-01 | 0.856 |
| R-HSA-9854907 | Regulation of MITF-M dependent genes involved in metabolism | 1.393029e-01 | 0.856 |
| R-HSA-1483249 | Inositol phosphate metabolism | 1.407286e-01 | 0.852 |
| R-HSA-9020591 | Interleukin-12 signaling | 1.420923e-01 | 0.847 |
| R-HSA-9930044 | Nuclear RNA decay | 1.422573e-01 | 0.847 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 1.422573e-01 | 0.847 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 1.422573e-01 | 0.847 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 1.422573e-01 | 0.847 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 1.427676e-01 | 0.845 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 1.434104e-01 | 0.843 |
| R-HSA-373755 | Semaphorin interactions | 1.434104e-01 | 0.843 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 1.437839e-01 | 0.842 |
| R-HSA-8951430 | RUNX3 regulates WNT signaling | 1.437839e-01 | 0.842 |
| R-HSA-163767 | PP2A-mediated dephosphorylation of key metabolic factors | 1.437839e-01 | 0.842 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 1.437839e-01 | 0.842 |
| R-HSA-8849473 | PTK6 Expression | 1.437839e-01 | 0.842 |
| R-HSA-3371599 | Defective HLCS causes multiple carboxylase deficiency | 1.437839e-01 | 0.842 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 1.437839e-01 | 0.842 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1.444250e-01 | 0.840 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 1.444250e-01 | 0.840 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.444250e-01 | 0.840 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 1.444250e-01 | 0.840 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 1.450199e-01 | 0.839 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 1.450199e-01 | 0.839 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 1.477007e-01 | 0.831 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 1.478715e-01 | 0.830 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 1.523515e-01 | 0.817 |
| R-HSA-69541 | Stabilization of p53 | 1.523515e-01 | 0.817 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 1.523515e-01 | 0.817 |
| R-HSA-201556 | Signaling by ALK | 1.523515e-01 | 0.817 |
| R-HSA-9020702 | Interleukin-1 signaling | 1.530591e-01 | 0.815 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 1.530869e-01 | 0.815 |
| R-HSA-211000 | Gene Silencing by RNA | 1.548647e-01 | 0.810 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 1.566801e-01 | 0.805 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 1.587403e-01 | 0.799 |
| R-HSA-4641265 | Repression of WNT target genes | 1.587403e-01 | 0.799 |
| R-HSA-9005895 | Pervasive developmental disorders | 1.587403e-01 | 0.799 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 1.587403e-01 | 0.799 |
| R-HSA-9697154 | Disorders of Nervous System Development | 1.587403e-01 | 0.799 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 1.603293e-01 | 0.795 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 1.603293e-01 | 0.795 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 1.603293e-01 | 0.795 |
| R-HSA-5620971 | Pyroptosis | 1.603748e-01 | 0.795 |
| R-HSA-416482 | G alpha (12/13) signalling events | 1.615001e-01 | 0.792 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 1.617533e-01 | 0.791 |
| R-HSA-9948011 | CASP5 inflammasome assembly | 2.295936e-01 | 0.639 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 2.295936e-01 | 0.639 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 2.295936e-01 | 0.639 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 2.295936e-01 | 0.639 |
| R-HSA-5657655 | MGMT-mediated DNA damage reversal | 2.295936e-01 | 0.639 |
| R-HSA-9763198 | Impaired BRCA2 binding to SEM1 (DSS1) | 2.295936e-01 | 0.639 |
| R-HSA-9699150 | Defective DNA double strand break response due to BARD1 loss of function | 2.295936e-01 | 0.639 |
| R-HSA-5657560 | Hereditary fructose intolerance | 2.295936e-01 | 0.639 |
| R-HSA-5632987 | Defective Mismatch Repair Associated With PMS2 | 2.295936e-01 | 0.639 |
| R-HSA-5545483 | Defective Mismatch Repair Associated With MLH1 | 2.295936e-01 | 0.639 |
| R-HSA-9709275 | Impaired BRCA2 translocation to the nucleus | 2.295936e-01 | 0.639 |
| R-HSA-3642279 | TGFBR2 MSI Frameshift Mutants in Cancer | 2.295936e-01 | 0.639 |
| R-HSA-5602566 | TICAM1 deficiency - HSE | 2.295936e-01 | 0.639 |
| R-HSA-5579031 | Defective ACTH causes obesity and POMCD | 2.295936e-01 | 0.639 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 2.295936e-01 | 0.639 |
| R-HSA-9663199 | Defective DNA double strand break response due to BRCA1 loss of function | 2.295936e-01 | 0.639 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 2.295936e-01 | 0.639 |
| R-HSA-8941333 | RUNX2 regulates genes involved in differentiation of myeloid cells | 1.849037e-01 | 0.733 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 1.849037e-01 | 0.733 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 1.849037e-01 | 0.733 |
| R-HSA-176034 | Interactions of Tat with host cellular proteins | 3.238010e-01 | 0.490 |
| R-HSA-5687583 | Defective SLC34A2 causes PALM | 3.238010e-01 | 0.490 |
| R-HSA-5619109 | Defective SLC6A2 causes orthostatic intolerance (OI) | 3.238010e-01 | 0.490 |
| R-HSA-5339700 | Signaling by TCF7L2 mutants | 3.238010e-01 | 0.490 |
| R-HSA-5619111 | Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1) | 3.238010e-01 | 0.490 |
| R-HSA-9845622 | Defective VWF binding to collagen type I | 3.238010e-01 | 0.490 |
| R-HSA-5619045 | Defective SLC34A2 causes pulmonary alveolar microlithiasis (PALM) | 3.238010e-01 | 0.490 |
| R-HSA-5602571 | TRAF3 deficiency - HSE | 3.238010e-01 | 0.490 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 2.322244e-01 | 0.634 |
| R-HSA-111463 | SMAC (DIABLO) binds to IAPs | 2.322244e-01 | 0.634 |
| R-HSA-111464 | SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | 2.322244e-01 | 0.634 |
| R-HSA-68911 | G2 Phase | 2.322244e-01 | 0.634 |
| R-HSA-9673768 | Signaling by membrane-tethered fusions of PDGFRA or PDGFRB | 2.322244e-01 | 0.634 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 2.322244e-01 | 0.634 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 2.322244e-01 | 0.634 |
| R-HSA-9012546 | Interleukin-18 signaling | 1.748563e-01 | 0.757 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 2.075769e-01 | 0.683 |
| R-HSA-9700645 | ALK mutants bind TKIs | 2.075769e-01 | 0.683 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 2.801634e-01 | 0.553 |
| R-HSA-68689 | CDC6 association with the ORC:origin complex | 2.801634e-01 | 0.553 |
| R-HSA-9652817 | Signaling by MAPK mutants | 2.801634e-01 | 0.553 |
| R-HSA-9022537 | Loss of MECP2 binding ability to the NCoR/SMRT complex | 2.801634e-01 | 0.553 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 2.415137e-01 | 0.617 |
| R-HSA-68952 | DNA replication initiation | 2.415137e-01 | 0.617 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 1.631070e-01 | 0.788 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 1.631070e-01 | 0.788 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 2.376232e-01 | 0.624 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 1.770791e-01 | 0.752 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 1.770791e-01 | 0.752 |
| R-HSA-429947 | Deadenylation of mRNA | 2.011645e-01 | 0.696 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 2.011645e-01 | 0.696 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 2.300945e-01 | 0.638 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 2.300945e-01 | 0.638 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 2.657326e-01 | 0.576 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 1.874697e-01 | 0.727 |
| R-HSA-77595 | Processing of Intronless Pre-mRNAs | 2.944019e-01 | 0.531 |
| R-HSA-186763 | Downstream signal transduction | 2.125374e-01 | 0.673 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 1.734678e-01 | 0.761 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 1.734678e-01 | 0.761 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 2.784655e-01 | 0.555 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 2.205861e-01 | 0.656 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 2.638081e-01 | 0.579 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 2.638081e-01 | 0.579 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 3.234340e-01 | 0.490 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 3.234340e-01 | 0.490 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 1.923111e-01 | 0.716 |
| R-HSA-167287 | HIV elongation arrest and recovery | 2.857294e-01 | 0.544 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 2.857294e-01 | 0.544 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 2.426301e-01 | 0.615 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 2.195518e-01 | 0.658 |
| R-HSA-5673000 | RAF activation | 2.899550e-01 | 0.538 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 2.899550e-01 | 0.538 |
| R-HSA-6782135 | Dual incision in TC-NER | 2.482470e-01 | 0.605 |
| R-HSA-72187 | mRNA 3'-end processing | 2.616025e-01 | 0.582 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 2.775681e-01 | 0.557 |
| R-HSA-1221632 | Meiotic synapsis | 2.775681e-01 | 0.557 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 2.781887e-01 | 0.556 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 2.781887e-01 | 0.556 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 2.781887e-01 | 0.556 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 2.781887e-01 | 0.556 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 2.781887e-01 | 0.556 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 2.513793e-01 | 0.600 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 2.935574e-01 | 0.532 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 2.918869e-01 | 0.535 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 3.179246e-01 | 0.498 |
| R-HSA-1989781 | PPARA activates gene expression | 2.599906e-01 | 0.585 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 2.937093e-01 | 0.532 |
| R-HSA-6798695 | Neutrophil degranulation | 2.117888e-01 | 0.674 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 2.924728e-01 | 0.534 |
| R-HSA-389948 | Co-inhibition by PD-1 | 2.826166e-01 | 0.549 |
| R-HSA-1234174 | Cellular response to hypoxia | 2.497829e-01 | 0.602 |
| R-HSA-73886 | Chromosome Maintenance | 1.738857e-01 | 0.760 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 3.202062e-01 | 0.495 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 2.638081e-01 | 0.579 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 1.628765e-01 | 0.788 |
| R-HSA-111469 | SMAC, XIAP-regulated apoptotic response | 2.801634e-01 | 0.553 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 1.839145e-01 | 0.735 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 2.423473e-01 | 0.616 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 1.621719e-01 | 0.790 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 1.906516e-01 | 0.720 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 2.638081e-01 | 0.579 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 1.760620e-01 | 0.754 |
| R-HSA-1170546 | Prolactin receptor signaling | 2.102800e-01 | 0.677 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 2.592472e-01 | 0.586 |
| R-HSA-5688426 | Deubiquitination | 3.206654e-01 | 0.494 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 2.764244e-01 | 0.558 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 2.021813e-01 | 0.694 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 2.102800e-01 | 0.677 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 2.923235e-01 | 0.534 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 3.102846e-01 | 0.508 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 2.753578e-01 | 0.560 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 2.959660e-01 | 0.529 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 2.473775e-01 | 0.607 |
| R-HSA-111448 | Activation of NOXA and translocation to mitochondria | 1.849037e-01 | 0.733 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 2.075769e-01 | 0.683 |
| R-HSA-9762292 | Regulation of CDH11 function | 2.415137e-01 | 0.617 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 2.102800e-01 | 0.677 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 2.102800e-01 | 0.677 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 2.657326e-01 | 0.576 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 1.717633e-01 | 0.765 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 2.638081e-01 | 0.579 |
| R-HSA-9007101 | Rab regulation of trafficking | 2.698830e-01 | 0.569 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 1.685708e-01 | 0.773 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 1.717633e-01 | 0.765 |
| R-HSA-9664420 | Killing mechanisms | 2.657326e-01 | 0.576 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 2.657326e-01 | 0.576 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 1.804134e-01 | 0.744 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 1.952558e-01 | 0.709 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 1.849037e-01 | 0.733 |
| R-HSA-166208 | mTORC1-mediated signalling | 1.628765e-01 | 0.788 |
| R-HSA-174430 | Telomere C-strand synthesis initiation | 2.376232e-01 | 0.624 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 2.944019e-01 | 0.531 |
| R-HSA-162588 | Budding and maturation of HIV virion | 2.125374e-01 | 0.673 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 2.037586e-01 | 0.691 |
| R-HSA-392518 | Signal amplification | 2.899550e-01 | 0.538 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 1.804134e-01 | 0.744 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 2.205861e-01 | 0.656 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 2.738254e-01 | 0.563 |
| R-HSA-5260271 | Diseases of Immune System | 2.738254e-01 | 0.563 |
| R-HSA-186797 | Signaling by PDGF | 3.091529e-01 | 0.510 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 3.234340e-01 | 0.490 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 2.630757e-01 | 0.580 |
| R-HSA-6811438 | Intra-Golgi traffic | 3.111113e-01 | 0.507 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 2.928791e-01 | 0.533 |
| R-HSA-205025 | NADE modulates death signalling | 1.849037e-01 | 0.733 |
| R-HSA-190704 | Oligomerization of connexins into connexons | 3.238010e-01 | 0.490 |
| R-HSA-2025928 | Calcineurin activates NFAT | 2.075769e-01 | 0.683 |
| R-HSA-5689877 | Josephin domain DUBs | 2.415137e-01 | 0.617 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 1.631070e-01 | 0.788 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 3.114530e-01 | 0.507 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 2.944019e-01 | 0.531 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 2.944019e-01 | 0.531 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 3.234340e-01 | 0.490 |
| R-HSA-4641263 | Regulation of FZD by ubiquitination | 3.234340e-01 | 0.490 |
| R-HSA-1433557 | Signaling by SCF-KIT | 2.264002e-01 | 0.645 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 2.738254e-01 | 0.563 |
| R-HSA-5620924 | Intraflagellar transport | 3.110148e-01 | 0.507 |
| R-HSA-1280218 | Adaptive Immune System | 2.570716e-01 | 0.590 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 2.699488e-01 | 0.569 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 2.762113e-01 | 0.559 |
| R-HSA-4791275 | Signaling by WNT in cancer | 2.311743e-01 | 0.636 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 2.264002e-01 | 0.645 |
| R-HSA-1227986 | Signaling by ERBB2 | 2.781887e-01 | 0.556 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 2.899550e-01 | 0.538 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 2.918519e-01 | 0.535 |
| R-HSA-190236 | Signaling by FGFR | 2.624049e-01 | 0.581 |
| R-HSA-5654738 | Signaling by FGFR2 | 1.822158e-01 | 0.739 |
| R-HSA-1266695 | Interleukin-7 signaling | 2.214366e-01 | 0.655 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 2.556690e-01 | 0.592 |
| R-HSA-74749 | Signal attenuation | 2.415137e-01 | 0.617 |
| R-HSA-163685 | Integration of energy metabolism | 2.750171e-01 | 0.561 |
| R-HSA-73942 | DNA Damage Reversal | 2.376232e-01 | 0.624 |
| R-HSA-114608 | Platelet degranulation | 1.745976e-01 | 0.758 |
| R-HSA-111471 | Apoptotic factor-mediated response | 1.845226e-01 | 0.734 |
| R-HSA-8939211 | ESR-mediated signaling | 2.945501e-01 | 0.531 |
| R-HSA-9006936 | Signaling by TGFB family members | 2.406287e-01 | 0.619 |
| R-HSA-77042 | Formation of editosomes by ADAR proteins | 2.295936e-01 | 0.639 |
| R-HSA-190827 | Transport of connexins along the secretory pathway | 3.238010e-01 | 0.490 |
| R-HSA-9818025 | NFE2L2 regulating TCA cycle genes | 2.322244e-01 | 0.634 |
| R-HSA-3785653 | Myoclonic epilepsy of Lafora | 1.748563e-01 | 0.757 |
| R-HSA-3323169 | Defects in biotin (Btn) metabolism | 2.075769e-01 | 0.683 |
| R-HSA-2465910 | MASTL Facilitates Mitotic Progression | 2.075769e-01 | 0.683 |
| R-HSA-176974 | Unwinding of DNA | 2.075769e-01 | 0.683 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 2.801634e-01 | 0.553 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 1.770791e-01 | 0.752 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 2.539951e-01 | 0.595 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 2.205861e-01 | 0.656 |
| R-HSA-418990 | Adherens junctions interactions | 2.067841e-01 | 0.684 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 2.379058e-01 | 0.624 |
| R-HSA-9707616 | Heme signaling | 2.092500e-01 | 0.679 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 2.638081e-01 | 0.579 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 2.503332e-01 | 0.601 |
| R-HSA-109582 | Hemostasis | 2.237651e-01 | 0.650 |
| R-HSA-432142 | Platelet sensitization by LDL | 1.845226e-01 | 0.734 |
| R-HSA-1592230 | Mitochondrial biogenesis | 2.698830e-01 | 0.569 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 2.102800e-01 | 0.677 |
| R-HSA-392517 | Rap1 signalling | 2.068939e-01 | 0.684 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 2.807036e-01 | 0.552 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 2.698050e-01 | 0.569 |
| R-HSA-1266738 | Developmental Biology | 1.776878e-01 | 0.750 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 1.930412e-01 | 0.714 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 2.762625e-01 | 0.559 |
| R-HSA-622312 | Inflammasomes | 2.857294e-01 | 0.544 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 2.899550e-01 | 0.538 |
| R-HSA-9683686 | Maturation of spike protein | 2.415137e-01 | 0.617 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 1.667112e-01 | 0.778 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 2.224385e-01 | 0.653 |
| R-HSA-8848021 | Signaling by PTK6 | 2.224385e-01 | 0.653 |
| R-HSA-9683610 | Maturation of nucleoprotein | 1.839145e-01 | 0.735 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 3.234340e-01 | 0.490 |
| R-HSA-210990 | PECAM1 interactions | 2.762625e-01 | 0.559 |
| R-HSA-9694631 | Maturation of nucleoprotein | 2.068939e-01 | 0.684 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 2.264002e-01 | 0.645 |
| R-HSA-175474 | Assembly Of The HIV Virion | 2.784655e-01 | 0.555 |
| R-HSA-9694635 | Translation of Structural Proteins | 3.203602e-01 | 0.494 |
| R-HSA-3134963 | DEx/H-box helicases activate type I IFN and inflammatory cytokines production | 2.322244e-01 | 0.634 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 2.762625e-01 | 0.559 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 3.033768e-01 | 0.518 |
| R-HSA-9637628 | Modulation by Mtb of host immune system | 1.748563e-01 | 0.757 |
| R-HSA-447115 | Interleukin-12 family signaling | 1.949421e-01 | 0.710 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 3.080211e-01 | 0.511 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 3.249456e-01 | 0.488 |
| R-HSA-9662001 | Defective factor VIII causes hemophilia A | 3.278625e-01 | 0.484 |
| R-HSA-113507 | E2F-enabled inhibition of pre-replication complex formation | 3.278625e-01 | 0.484 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 3.278625e-01 | 0.484 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 3.278625e-01 | 0.484 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 3.278625e-01 | 0.484 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 3.278625e-01 | 0.484 |
| R-HSA-164944 | Nef and signal transduction | 3.278625e-01 | 0.484 |
| R-HSA-912526 | Interleukin receptor SHC signaling | 3.286028e-01 | 0.483 |
| R-HSA-165159 | MTOR signalling | 3.301365e-01 | 0.481 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 3.305944e-01 | 0.481 |
| R-HSA-8853659 | RET signaling | 3.308711e-01 | 0.480 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 3.317951e-01 | 0.479 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 3.378877e-01 | 0.471 |
| R-HSA-936837 | Ion transport by P-type ATPases | 3.409057e-01 | 0.467 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 3.419602e-01 | 0.466 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 3.467046e-01 | 0.460 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 3.467522e-01 | 0.460 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 3.467522e-01 | 0.460 |
| R-HSA-8866427 | VLDLR internalisation and degradation | 3.467522e-01 | 0.460 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 3.467522e-01 | 0.460 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 3.467522e-01 | 0.460 |
| R-HSA-73943 | Reversal of alkylation damage by DNA dioxygenases | 3.467522e-01 | 0.460 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 3.467522e-01 | 0.460 |
| R-HSA-421270 | Cell-cell junction organization | 3.483497e-01 | 0.458 |
| R-HSA-8854214 | TBC/RABGAPs | 3.493469e-01 | 0.457 |
| R-HSA-4641257 | Degradation of AXIN | 3.516483e-01 | 0.454 |
| R-HSA-5358508 | Mismatch Repair | 3.526428e-01 | 0.453 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 3.526428e-01 | 0.453 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 3.526428e-01 | 0.453 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 3.531679e-01 | 0.452 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 3.533620e-01 | 0.452 |
| R-HSA-5694530 | Cargo concentration in the ER | 3.533620e-01 | 0.452 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 3.540217e-01 | 0.451 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 3.540217e-01 | 0.451 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 3.540217e-01 | 0.451 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 3.540217e-01 | 0.451 |
| R-HSA-391251 | Protein folding | 3.557754e-01 | 0.449 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 3.641899e-01 | 0.439 |
| R-HSA-3214858 | RMTs methylate histone arginines | 3.686909e-01 | 0.433 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 3.686909e-01 | 0.433 |
| R-HSA-8875878 | MET promotes cell motility | 3.725513e-01 | 0.429 |
| R-HSA-167590 | Nef Mediated CD4 Down-regulation | 3.746639e-01 | 0.426 |
| R-HSA-112412 | SOS-mediated signalling | 3.746639e-01 | 0.426 |
| R-HSA-72731 | Recycling of eIF2:GDP | 3.746639e-01 | 0.426 |
| R-HSA-114516 | Disinhibition of SNARE formation | 3.746639e-01 | 0.426 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 3.746639e-01 | 0.426 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 3.746639e-01 | 0.426 |
| R-HSA-9022707 | MECP2 regulates transcription factors | 3.746639e-01 | 0.426 |
| R-HSA-110357 | Displacement of DNA glycosylase by APEX1 | 3.746639e-01 | 0.426 |
| R-HSA-5576890 | Phase 3 - rapid repolarisation | 3.746639e-01 | 0.426 |
| R-HSA-8949275 | RUNX3 Regulates Immune Response and Cell Migration | 3.746639e-01 | 0.426 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 3.795175e-01 | 0.421 |
| R-HSA-3214842 | HDMs demethylate histones | 3.795175e-01 | 0.421 |
| R-HSA-157118 | Signaling by NOTCH | 3.814909e-01 | 0.419 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 3.818659e-01 | 0.418 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 3.818659e-01 | 0.418 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 3.829433e-01 | 0.417 |
| R-HSA-6794361 | Neurexins and neuroligins | 3.829433e-01 | 0.417 |
| R-HSA-983712 | Ion channel transport | 3.841014e-01 | 0.416 |
| R-HSA-1236394 | Signaling by ERBB4 | 3.841222e-01 | 0.416 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 3.935173e-01 | 0.405 |
| R-HSA-72172 | mRNA Splicing | 3.942089e-01 | 0.404 |
| R-HSA-8873719 | RAB geranylgeranylation | 3.951572e-01 | 0.403 |
| R-HSA-354192 | Integrin signaling | 3.991456e-01 | 0.399 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 3.991456e-01 | 0.399 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 3.991456e-01 | 0.399 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 3.991525e-01 | 0.399 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 4.064933e-01 | 0.391 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 4.064933e-01 | 0.391 |
| R-HSA-9034013 | NTF3 activates NTRK3 signaling | 4.064933e-01 | 0.391 |
| R-HSA-8854521 | Interaction between PHLDA1 and AURKA | 4.064933e-01 | 0.391 |
| R-HSA-9918449 | Defective visual phototransduction due to STRA6 loss of function | 4.064933e-01 | 0.391 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 4.064933e-01 | 0.391 |
| R-HSA-9674519 | Defective F8 sulfation at Y1699 | 4.064933e-01 | 0.391 |
| R-HSA-9672383 | Defective factor IX causes thrombophilia | 4.064933e-01 | 0.391 |
| R-HSA-5619089 | Defective SLC6A5 causes hyperekplexia 3 (HKPX3) | 4.064933e-01 | 0.391 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 4.064933e-01 | 0.391 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 4.064933e-01 | 0.391 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 4.064933e-01 | 0.391 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 4.064933e-01 | 0.391 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 4.064933e-01 | 0.391 |
| R-HSA-9753510 | Signaling by RAS GAP mutants | 4.064933e-01 | 0.391 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 4.064933e-01 | 0.391 |
| R-HSA-9845621 | Defective VWF cleavage by ADAMTS13 variant | 4.064933e-01 | 0.391 |
| R-HSA-68881 | Mitotic Metaphase/Anaphase Transition | 4.064933e-01 | 0.391 |
| R-HSA-9845619 | Enhanced cleavage of VWF variant by ADAMTS13 | 4.064933e-01 | 0.391 |
| R-HSA-9673202 | Defective F9 variant does not activate FX | 4.064933e-01 | 0.391 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 4.064933e-01 | 0.391 |
| R-HSA-5662853 | Essential pentosuria | 4.064933e-01 | 0.391 |
| R-HSA-9672396 | Defective cofactor function of FVIIIa variant | 4.064933e-01 | 0.391 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 4.064933e-01 | 0.391 |
| R-HSA-75064 | mRNA Editing: A to I Conversion | 4.064933e-01 | 0.391 |
| R-HSA-8985801 | Regulation of cortical dendrite branching | 4.064933e-01 | 0.391 |
| R-HSA-75102 | C6 deamination of adenosine | 4.064933e-01 | 0.391 |
| R-HSA-844615 | The AIM2 inflammasome | 4.064933e-01 | 0.391 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 4.109128e-01 | 0.386 |
| R-HSA-445144 | Signal transduction by L1 | 4.109128e-01 | 0.386 |
| R-HSA-1181150 | Signaling by NODAL | 4.109128e-01 | 0.386 |
| R-HSA-167169 | HIV Transcription Elongation | 4.144853e-01 | 0.382 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 4.144853e-01 | 0.382 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 4.144853e-01 | 0.382 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 4.144853e-01 | 0.382 |
| R-HSA-3371568 | Attenuation phase | 4.144853e-01 | 0.382 |
| R-HSA-202433 | Generation of second messenger molecules | 4.144853e-01 | 0.382 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 4.144853e-01 | 0.382 |
| R-HSA-9686114 | Non-canonical inflammasome activation | 4.165386e-01 | 0.380 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 4.165386e-01 | 0.380 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 4.165386e-01 | 0.380 |
| R-HSA-9856872 | Malate-aspartate shuttle | 4.165386e-01 | 0.380 |
| R-HSA-435354 | Zinc transporters | 4.165386e-01 | 0.380 |
| R-HSA-8963896 | HDL assembly | 4.165386e-01 | 0.380 |
| R-HSA-111995 | phospho-PLA2 pathway | 4.200742e-01 | 0.377 |
| R-HSA-196025 | Formation of annular gap junctions | 4.200742e-01 | 0.377 |
| R-HSA-9927354 | Co-stimulation by ICOS | 4.200742e-01 | 0.377 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 4.220029e-01 | 0.375 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 4.220029e-01 | 0.375 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 4.220029e-01 | 0.375 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 4.237780e-01 | 0.373 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 4.270263e-01 | 0.370 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 4.270263e-01 | 0.370 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 4.303073e-01 | 0.366 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 4.303073e-01 | 0.366 |
| R-HSA-201451 | Signaling by BMP | 4.303073e-01 | 0.366 |
| R-HSA-264876 | Insulin processing | 4.303073e-01 | 0.366 |
| R-HSA-3214815 | HDACs deacetylate histones | 4.376138e-01 | 0.359 |
| R-HSA-157579 | Telomere Maintenance | 4.385305e-01 | 0.358 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 4.396718e-01 | 0.357 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 4.396718e-01 | 0.357 |
| R-HSA-2979096 | NOTCH2 Activation and Transmission of Signal to the Nucleus | 4.396718e-01 | 0.357 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 4.408693e-01 | 0.356 |
| R-HSA-1980145 | Signaling by NOTCH2 | 4.447382e-01 | 0.352 |
| R-HSA-9634597 | GPER1 signaling | 4.464137e-01 | 0.350 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 4.505522e-01 | 0.346 |
| R-HSA-8876725 | Protein methylation | 4.505522e-01 | 0.346 |
| R-HSA-416700 | Other semaphorin interactions | 4.505522e-01 | 0.346 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 4.561971e-01 | 0.341 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 4.561971e-01 | 0.341 |
| R-HSA-170984 | ARMS-mediated activation | 4.637339e-01 | 0.334 |
| R-HSA-190873 | Gap junction degradation | 4.637339e-01 | 0.334 |
| R-HSA-201688 | WNT mediated activation of DVL | 4.637339e-01 | 0.334 |
| R-HSA-442380 | Zinc influx into cells by the SLC39 gene family | 4.637339e-01 | 0.334 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 4.637339e-01 | 0.334 |
| R-HSA-9768777 | Regulation of NPAS4 gene transcription | 4.637339e-01 | 0.334 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 4.637339e-01 | 0.334 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 4.637339e-01 | 0.334 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 4.637339e-01 | 0.334 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 4.637339e-01 | 0.334 |
| R-HSA-169911 | Regulation of Apoptosis | 4.672833e-01 | 0.330 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 4.680039e-01 | 0.330 |
| R-HSA-9824446 | Viral Infection Pathways | 4.685339e-01 | 0.329 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 4.685622e-01 | 0.329 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 4.749877e-01 | 0.323 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 4.768332e-01 | 0.322 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 4.768332e-01 | 0.322 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 4.768332e-01 | 0.322 |
| R-HSA-75157 | FasL/ CD95L signaling | 4.790773e-01 | 0.320 |
| R-HSA-9034793 | Activated NTRK3 signals through PLCG1 | 4.790773e-01 | 0.320 |
| R-HSA-8853336 | Signaling by plasma membrane FGFR1 fusions | 4.790773e-01 | 0.320 |
| R-HSA-9909438 | 3-Methylcrotonyl-CoA carboxylase deficiency | 4.790773e-01 | 0.320 |
| R-HSA-5679001 | Defective ABCC2 causes DJS | 4.790773e-01 | 0.320 |
| R-HSA-5579006 | Defective GSS causes GSS deficiency | 4.790773e-01 | 0.320 |
| R-HSA-5660862 | Defective SLC7A7 causes lysinuric protein intolerance (LPI) | 4.790773e-01 | 0.320 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 4.790773e-01 | 0.320 |
| R-HSA-3249367 | STAT6-mediated induction of chemokines | 4.790773e-01 | 0.320 |
| R-HSA-111446 | Activation of BIM and translocation to mitochondria | 4.790773e-01 | 0.320 |
| R-HSA-8875513 | MET interacts with TNS proteins | 4.790773e-01 | 0.320 |
| R-HSA-417973 | Adenosine P1 receptors | 4.790773e-01 | 0.320 |
| R-HSA-844623 | The IPAF inflammasome | 4.790773e-01 | 0.320 |
| R-HSA-427589 | Type II Na+/Pi cotransporters | 4.790773e-01 | 0.320 |
| R-HSA-9022538 | Loss of MECP2 binding ability to 5mC-DNA | 4.790773e-01 | 0.320 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 4.790773e-01 | 0.320 |
| R-HSA-390650 | Histamine receptors | 4.790773e-01 | 0.320 |
| R-HSA-418360 | Platelet calcium homeostasis | 4.801842e-01 | 0.319 |
| R-HSA-399955 | SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 4.837242e-01 | 0.315 |
| R-HSA-9603798 | Class I peroxisomal membrane protein import | 4.837242e-01 | 0.315 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 4.837242e-01 | 0.315 |
| R-HSA-4086398 | Ca2+ pathway | 4.872425e-01 | 0.312 |
| R-HSA-9837999 | Mitochondrial protein degradation | 4.887706e-01 | 0.311 |
| R-HSA-69205 | G1/S-Specific Transcription | 4.895747e-01 | 0.310 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 4.895747e-01 | 0.310 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 4.917418e-01 | 0.308 |
| R-HSA-6803529 | FGFR2 alternative splicing | 4.957961e-01 | 0.305 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 4.957961e-01 | 0.305 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 4.957961e-01 | 0.305 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 4.957961e-01 | 0.305 |
| R-HSA-9669938 | Signaling by KIT in disease | 4.957961e-01 | 0.305 |
| R-HSA-9645723 | Diseases of programmed cell death | 4.981514e-01 | 0.303 |
| R-HSA-2672351 | Stimuli-sensing channels | 4.983594e-01 | 0.302 |
| R-HSA-9013694 | Signaling by NOTCH4 | 5.032924e-01 | 0.298 |
| R-HSA-3371571 | HSF1-dependent transactivation | 5.037900e-01 | 0.298 |
| R-HSA-912446 | Meiotic recombination | 5.037900e-01 | 0.298 |
| R-HSA-2424491 | DAP12 signaling | 5.045689e-01 | 0.297 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 5.053921e-01 | 0.296 |
| R-HSA-198203 | PI3K/AKT activation | 5.053921e-01 | 0.296 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 5.053921e-01 | 0.296 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 5.053921e-01 | 0.296 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 5.053921e-01 | 0.296 |
| R-HSA-426048 | Arachidonate production from DAG | 5.053921e-01 | 0.296 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 5.053921e-01 | 0.296 |
| R-HSA-9761174 | Formation of intermediate mesoderm | 5.053921e-01 | 0.296 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 5.073936e-01 | 0.295 |
| R-HSA-9033241 | Peroxisomal protein import | 5.095011e-01 | 0.293 |
| R-HSA-1236974 | ER-Phagosome pathway | 5.128081e-01 | 0.290 |
| R-HSA-909733 | Interferon alpha/beta signaling | 5.154525e-01 | 0.288 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 5.159051e-01 | 0.287 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 5.159051e-01 | 0.287 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 5.159051e-01 | 0.287 |
| R-HSA-9907900 | Proteasome assembly | 5.174213e-01 | 0.286 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 5.191367e-01 | 0.285 |
| R-HSA-917937 | Iron uptake and transport | 5.192074e-01 | 0.285 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 5.225228e-01 | 0.282 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 5.229506e-01 | 0.282 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 5.229506e-01 | 0.282 |
| R-HSA-3000170 | Syndecan interactions | 5.229506e-01 | 0.282 |
| R-HSA-73884 | Base Excision Repair | 5.273487e-01 | 0.278 |
| R-HSA-5689880 | Ub-specific processing proteases | 5.301808e-01 | 0.276 |
| R-HSA-5689603 | UCH proteinases | 5.349654e-01 | 0.272 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 5.372859e-01 | 0.270 |
| R-HSA-774815 | Nucleosome assembly | 5.372859e-01 | 0.270 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 5.372859e-01 | 0.270 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 5.372859e-01 | 0.270 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 5.372859e-01 | 0.270 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 5.410003e-01 | 0.267 |
| R-HSA-445355 | Smooth Muscle Contraction | 5.410003e-01 | 0.267 |
| R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death | 5.427883e-01 | 0.265 |
| R-HSA-165181 | Inhibition of TSC complex formation by PKB | 5.427883e-01 | 0.265 |
| R-HSA-8952158 | RUNX3 regulates BCL2L11 (BIM) transcription | 5.427883e-01 | 0.265 |
| R-HSA-2644607 | Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling | 5.427883e-01 | 0.265 |
| R-HSA-5083630 | Defective LFNG causes SCDO3 | 5.427883e-01 | 0.265 |
| R-HSA-2644605 | FBXW7 Mutants and NOTCH1 in Cancer | 5.427883e-01 | 0.265 |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... | 5.427883e-01 | 0.265 |
| R-HSA-191650 | Regulation of gap junction activity | 5.427883e-01 | 0.265 |
| R-HSA-5626978 | TNFR1-mediated ceramide production | 5.427883e-01 | 0.265 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 5.427883e-01 | 0.265 |
| R-HSA-397014 | Muscle contraction | 5.433929e-01 | 0.265 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 5.444090e-01 | 0.264 |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 5.448855e-01 | 0.264 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS | 5.448855e-01 | 0.264 |
| R-HSA-9020558 | Interleukin-2 signaling | 5.448855e-01 | 0.264 |
| R-HSA-9832991 | Formation of the posterior neural plate | 5.448855e-01 | 0.264 |
| R-HSA-8963888 | Chylomicron assembly | 5.448855e-01 | 0.264 |
| R-HSA-75205 | Dissolution of Fibrin Clot | 5.448855e-01 | 0.264 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 5.469758e-01 | 0.262 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 5.469758e-01 | 0.262 |
| R-HSA-3229121 | Glycogen storage diseases | 5.469758e-01 | 0.262 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 5.493839e-01 | 0.260 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 5.493839e-01 | 0.260 |
| R-HSA-381070 | IRE1alpha activates chaperones | 5.560148e-01 | 0.255 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 5.568120e-01 | 0.254 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 5.568120e-01 | 0.254 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 5.615027e-01 | 0.251 |
| R-HSA-73864 | RNA Polymerase I Transcription | 5.659280e-01 | 0.247 |
| R-HSA-216083 | Integrin cell surface interactions | 5.659280e-01 | 0.247 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 5.701088e-01 | 0.244 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 5.746935e-01 | 0.241 |
| R-HSA-3000157 | Laminin interactions | 5.750262e-01 | 0.240 |
| R-HSA-1482801 | Acyl chain remodelling of PS | 5.750262e-01 | 0.240 |
| R-HSA-9620244 | Long-term potentiation | 5.750262e-01 | 0.240 |
| R-HSA-9839394 | TGFBR3 expression | 5.750262e-01 | 0.240 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 5.751170e-01 | 0.240 |
| R-HSA-451927 | Interleukin-2 family signaling | 5.751170e-01 | 0.240 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 5.768448e-01 | 0.239 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 5.768448e-01 | 0.239 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 5.768448e-01 | 0.239 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 5.768448e-01 | 0.239 |
| R-HSA-180292 | GAB1 signalosome | 5.768448e-01 | 0.239 |
| R-HSA-5632684 | Hedgehog 'on' state | 5.796781e-01 | 0.237 |
| R-HSA-1234158 | Regulation of gene expression by Hypoxia-inducible Factor | 5.821204e-01 | 0.235 |
| R-HSA-1839122 | Signaling by activated point mutants of FGFR1 | 5.821204e-01 | 0.235 |
| R-HSA-5358493 | Synthesis of diphthamide-EEF2 | 5.821204e-01 | 0.235 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 5.821204e-01 | 0.235 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 5.821204e-01 | 0.235 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 5.825485e-01 | 0.235 |
| R-HSA-5578775 | Ion homeostasis | 5.945990e-01 | 0.226 |
| R-HSA-9031628 | NGF-stimulated transcription | 5.947139e-01 | 0.226 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 5.953711e-01 | 0.225 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 5.960468e-01 | 0.225 |
| R-HSA-70268 | Pyruvate metabolism | 5.968389e-01 | 0.224 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 5.968795e-01 | 0.224 |
| R-HSA-74713 | IRS activation | 5.987104e-01 | 0.223 |
| R-HSA-190374 | FGFR1c and Klotho ligand binding and activation | 5.987104e-01 | 0.223 |
| R-HSA-9022535 | Loss of phosphorylation of MECP2 at T308 | 5.987104e-01 | 0.223 |
| R-HSA-9846298 | Defective binding of VWF variant to GPIb:IX:V | 5.987104e-01 | 0.223 |
| R-HSA-9845620 | Enhanced binding of GP1BA variant to VWF multimer:collagen | 5.987104e-01 | 0.223 |
| R-HSA-8939247 | RUNX1 regulates transcription of genes involved in interleukin signaling | 5.987104e-01 | 0.223 |
| R-HSA-8939245 | RUNX1 regulates transcription of genes involved in BCR signaling | 5.987104e-01 | 0.223 |
| R-HSA-8866376 | Reelin signalling pathway | 5.987104e-01 | 0.223 |
| R-HSA-429593 | Inositol transporters | 5.987104e-01 | 0.223 |
| R-HSA-9927353 | Co-inhibition by BTLA | 5.987104e-01 | 0.223 |
| R-HSA-447038 | NrCAM interactions | 5.987104e-01 | 0.223 |
| R-HSA-5250971 | Toxicity of botulinum toxin type C (botC) | 5.987104e-01 | 0.223 |
| R-HSA-8849468 | PTK6 Regulates Proteins Involved in RNA Processing | 5.987104e-01 | 0.223 |
| R-HSA-435368 | Zinc efflux and compartmentalization by the SLC30 family | 5.987104e-01 | 0.223 |
| R-HSA-168316 | Assembly of Viral Components at the Budding Site | 5.987104e-01 | 0.223 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 5.998209e-01 | 0.222 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 6.008313e-01 | 0.221 |
| R-HSA-168256 | Immune System | 6.053236e-01 | 0.218 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 6.054447e-01 | 0.218 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 6.054447e-01 | 0.218 |
| R-HSA-9679191 | Potential therapeutics for SARS | 6.065150e-01 | 0.217 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 6.130315e-01 | 0.213 |
| R-HSA-2197563 | NOTCH2 intracellular domain regulates transcription | 6.170586e-01 | 0.210 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 6.170586e-01 | 0.210 |
| R-HSA-9931530 | Phosphorylation and nuclear translocation of the CRY:PER:kinase complex | 6.170586e-01 | 0.210 |
| R-HSA-8851805 | MET activates RAS signaling | 6.170586e-01 | 0.210 |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation | 6.170586e-01 | 0.210 |
| R-HSA-8983711 | OAS antiviral response | 6.170586e-01 | 0.210 |
| R-HSA-9842663 | Signaling by LTK | 6.170586e-01 | 0.210 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 6.184011e-01 | 0.209 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 6.184011e-01 | 0.209 |
| R-HSA-8949613 | Cristae formation | 6.237234e-01 | 0.205 |
| R-HSA-112315 | Transmission across Chemical Synapses | 6.238307e-01 | 0.205 |
| R-HSA-8951664 | Neddylation | 6.258077e-01 | 0.204 |
| R-HSA-163210 | Formation of ATP by chemiosmotic coupling | 6.327303e-01 | 0.199 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 6.327303e-01 | 0.199 |
| R-HSA-3322077 | Glycogen synthesis | 6.327303e-01 | 0.199 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 6.376374e-01 | 0.195 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 6.392794e-01 | 0.194 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 6.392794e-01 | 0.194 |
| R-HSA-8852135 | Protein ubiquitination | 6.406231e-01 | 0.193 |
| R-HSA-171319 | Telomere Extension By Telomerase | 6.467003e-01 | 0.189 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 6.467003e-01 | 0.189 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 6.467003e-01 | 0.189 |
| R-HSA-77387 | Insulin receptor recycling | 6.467003e-01 | 0.189 |
| R-HSA-2660826 | Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 6.477954e-01 | 0.189 |
| R-HSA-9823587 | Defects of platelet adhesion to exposed collagen | 6.477954e-01 | 0.189 |
| R-HSA-2660825 | Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 6.477954e-01 | 0.189 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 6.477954e-01 | 0.189 |
| R-HSA-5340588 | Signaling by RNF43 mutants | 6.477954e-01 | 0.189 |
| R-HSA-8852405 | Signaling by MST1 | 6.477954e-01 | 0.189 |
| R-HSA-111457 | Release of apoptotic factors from the mitochondria | 6.477954e-01 | 0.189 |
| R-HSA-187024 | NGF-independant TRKA activation | 6.477954e-01 | 0.189 |
| R-HSA-111459 | Activation of caspases through apoptosome-mediated cleavage | 6.477954e-01 | 0.189 |
| R-HSA-389397 | Orexin and neuropeptides FF and QRFP bind to their respective receptors | 6.477954e-01 | 0.189 |
| R-HSA-444821 | Relaxin receptors | 6.477954e-01 | 0.189 |
| R-HSA-5660668 | CLEC7A/inflammasome pathway | 6.477954e-01 | 0.189 |
| R-HSA-5250992 | Toxicity of botulinum toxin type E (botE) | 6.477954e-01 | 0.189 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 6.480226e-01 | 0.188 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 6.482806e-01 | 0.188 |
| R-HSA-9861559 | PDH complex synthesizes acetyl-CoA from PYR | 6.497047e-01 | 0.187 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 6.497047e-01 | 0.187 |
| R-HSA-9796292 | Formation of axial mesoderm | 6.497047e-01 | 0.187 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 6.497047e-01 | 0.187 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 6.528805e-01 | 0.185 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 6.550884e-01 | 0.184 |
| R-HSA-167172 | Transcription of the HIV genome | 6.576111e-01 | 0.182 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 6.576111e-01 | 0.182 |
| R-HSA-210991 | Basigin interactions | 6.586750e-01 | 0.181 |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane | 6.586750e-01 | 0.181 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 6.586750e-01 | 0.181 |
| R-HSA-9636383 | Prevention of phagosomal-lysosomal fusion | 6.586750e-01 | 0.181 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 6.593330e-01 | 0.181 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 6.608847e-01 | 0.180 |
| R-HSA-379724 | tRNA Aminoacylation | 6.608847e-01 | 0.180 |
| R-HSA-5696398 | Nucleotide Excision Repair | 6.617760e-01 | 0.179 |
| R-HSA-422356 | Regulation of insulin secretion | 6.630630e-01 | 0.178 |
| R-HSA-9658195 | Leishmania infection | 6.637227e-01 | 0.178 |
| R-HSA-9824443 | Parasitic Infection Pathways | 6.637227e-01 | 0.178 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 6.651745e-01 | 0.177 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 6.687281e-01 | 0.175 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 6.692203e-01 | 0.174 |
| R-HSA-195721 | Signaling by WNT | 6.722063e-01 | 0.172 |
| R-HSA-9609690 | HCMV Early Events | 6.767291e-01 | 0.170 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 6.799467e-01 | 0.168 |
| R-HSA-1855191 | Synthesis of IPs in the nucleus | 6.800967e-01 | 0.167 |
| R-HSA-77348 | Beta oxidation of octanoyl-CoA to hexanoyl-CoA | 6.800967e-01 | 0.167 |
| R-HSA-77350 | Beta oxidation of hexanoyl-CoA to butanoyl-CoA | 6.800967e-01 | 0.167 |
| R-HSA-77310 | Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA | 6.800967e-01 | 0.167 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 6.800967e-01 | 0.167 |
| R-HSA-391160 | Signal regulatory protein family interactions | 6.800967e-01 | 0.167 |
| R-HSA-1482798 | Acyl chain remodeling of CL | 6.800967e-01 | 0.167 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 6.815618e-01 | 0.166 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 6.830712e-01 | 0.166 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 6.832686e-01 | 0.165 |
| R-HSA-76066 | RNA Polymerase III Transcription Initiation From Type 2 Promoter | 6.832686e-01 | 0.165 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 6.832686e-01 | 0.165 |
| R-HSA-382556 | ABC-family proteins mediated transport | 6.874730e-01 | 0.163 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 6.882923e-01 | 0.162 |
| R-HSA-9824272 | Somitogenesis | 6.882923e-01 | 0.162 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 6.897927e-01 | 0.161 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 6.897927e-01 | 0.161 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 6.897927e-01 | 0.161 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 6.897927e-01 | 0.161 |
| R-HSA-8964026 | Chylomicron clearance | 6.908790e-01 | 0.161 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 6.908790e-01 | 0.161 |
| R-HSA-8951671 | RUNX3 regulates YAP1-mediated transcription | 6.908790e-01 | 0.161 |
| R-HSA-177539 | Autointegration results in viral DNA circles | 6.908790e-01 | 0.161 |
| R-HSA-69478 | G2/M DNA replication checkpoint | 6.908790e-01 | 0.161 |
| R-HSA-3595174 | Defective CHST14 causes EDS, musculocontractural type | 6.908790e-01 | 0.161 |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants | 6.908790e-01 | 0.161 |
| R-HSA-3595172 | Defective CHST3 causes SEDCJD | 6.908790e-01 | 0.161 |
| R-HSA-5619070 | Defective SLC16A1 causes symptomatic deficiency in lactate transport (SDLT) | 6.908790e-01 | 0.161 |
| R-HSA-426486 | Small interfering RNA (siRNA) biogenesis | 6.908790e-01 | 0.161 |
| R-HSA-175567 | Integration of viral DNA into host genomic DNA | 6.908790e-01 | 0.161 |
| R-HSA-2161517 | Abacavir transmembrane transport | 6.908790e-01 | 0.161 |
| R-HSA-8866423 | VLDL assembly | 6.908790e-01 | 0.161 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 6.914902e-01 | 0.160 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 7.019592e-01 | 0.154 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 7.037040e-01 | 0.153 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 7.050774e-01 | 0.152 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 7.050774e-01 | 0.152 |
| R-HSA-9839373 | Signaling by TGFBR3 | 7.050774e-01 | 0.152 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 7.065150e-01 | 0.151 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 7.065150e-01 | 0.151 |
| R-HSA-76061 | RNA Polymerase III Transcription Initiation From Type 1 Promoter | 7.065150e-01 | 0.151 |
| R-HSA-170670 | Adenylate cyclase inhibitory pathway | 7.082976e-01 | 0.150 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 7.082976e-01 | 0.150 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 7.082976e-01 | 0.150 |
| R-HSA-9823739 | Formation of the anterior neural plate | 7.082976e-01 | 0.150 |
| R-HSA-1502540 | Signaling by Activin | 7.082976e-01 | 0.150 |
| R-HSA-399719 | Trafficking of AMPA receptors | 7.098882e-01 | 0.149 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 7.098882e-01 | 0.149 |
| R-HSA-1474165 | Reproduction | 7.121038e-01 | 0.147 |
| R-HSA-418597 | G alpha (z) signalling events | 7.127751e-01 | 0.147 |
| R-HSA-9648002 | RAS processing | 7.151767e-01 | 0.146 |
| R-HSA-9843745 | Adipogenesis | 7.220381e-01 | 0.141 |
| R-HSA-977225 | Amyloid fiber formation | 7.222389e-01 | 0.141 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 7.284296e-01 | 0.138 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 7.284296e-01 | 0.138 |
| R-HSA-2562578 | TRIF-mediated programmed cell death | 7.286945e-01 | 0.137 |
| R-HSA-1912399 | Pre-NOTCH Processing in the Endoplasmic Reticulum | 7.286945e-01 | 0.137 |
| R-HSA-3595177 | Defective CHSY1 causes TPBS | 7.286945e-01 | 0.137 |
| R-HSA-111367 | SLBP independent Processing of Histone Pre-mRNAs | 7.286945e-01 | 0.137 |
| R-HSA-9632974 | NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis | 7.286945e-01 | 0.137 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 7.286945e-01 | 0.137 |
| R-HSA-163754 | Insulin effects increased synthesis of Xylulose-5-Phosphate | 7.286945e-01 | 0.137 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 7.286945e-01 | 0.137 |
| R-HSA-8964041 | LDL remodeling | 7.286945e-01 | 0.137 |
| R-HSA-187015 | Activation of TRKA receptors | 7.286945e-01 | 0.137 |
| R-HSA-426117 | Cation-coupled Chloride cotransporters | 7.286945e-01 | 0.137 |
| R-HSA-418886 | Netrin mediated repulsion signals | 7.286945e-01 | 0.137 |
| R-HSA-72306 | tRNA processing | 7.317156e-01 | 0.136 |
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand | 7.343885e-01 | 0.134 |
| R-HSA-70350 | Fructose catabolism | 7.343885e-01 | 0.134 |
| R-HSA-70263 | Gluconeogenesis | 7.367729e-01 | 0.133 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 7.471833e-01 | 0.127 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 7.471833e-01 | 0.127 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 7.486160e-01 | 0.126 |
| R-HSA-9694548 | Maturation of spike protein | 7.486160e-01 | 0.126 |
| R-HSA-428930 | Thromboxane signalling through TP receptor | 7.490377e-01 | 0.125 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 7.490377e-01 | 0.125 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 7.490377e-01 | 0.125 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 7.526318e-01 | 0.123 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 7.526318e-01 | 0.123 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 7.526972e-01 | 0.123 |
| R-HSA-9758941 | Gastrulation | 7.544582e-01 | 0.122 |
| R-HSA-9651496 | Defects of contact activation system (CAS) and kallikrein/kinin system (KKS) | 7.584635e-01 | 0.120 |
| R-HSA-77346 | Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA | 7.584635e-01 | 0.120 |
| R-HSA-5576893 | Phase 2 - plateau phase | 7.584635e-01 | 0.120 |
| R-HSA-1483148 | Synthesis of PG | 7.584635e-01 | 0.120 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 7.584635e-01 | 0.120 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 7.585360e-01 | 0.120 |
| R-HSA-112126 | ALKBH3 mediated reversal of alkylation damage | 7.618859e-01 | 0.118 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 7.618859e-01 | 0.118 |
| R-HSA-190370 | FGFR1b ligand binding and activation | 7.618859e-01 | 0.118 |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K | 7.618859e-01 | 0.118 |
| R-HSA-8875656 | MET receptor recycling | 7.618859e-01 | 0.118 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 7.618859e-01 | 0.118 |
| R-HSA-164940 | Nef mediated downregulation of MHC class I complex cell surface expression | 7.618859e-01 | 0.118 |
| R-HSA-77588 | SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs | 7.618859e-01 | 0.118 |
| R-HSA-8985947 | Interleukin-9 signaling | 7.618859e-01 | 0.118 |
| R-HSA-3371378 | Regulation by c-FLIP | 7.618859e-01 | 0.118 |
| R-HSA-1169092 | Activation of RAS in B cells | 7.618859e-01 | 0.118 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 7.618859e-01 | 0.118 |
| R-HSA-69416 | Dimerization of procaspase-8 | 7.618859e-01 | 0.118 |
| R-HSA-425986 | Sodium/Proton exchangers | 7.618859e-01 | 0.118 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 7.618859e-01 | 0.118 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 7.618859e-01 | 0.118 |
| R-HSA-1462054 | Alpha-defensins | 7.618859e-01 | 0.118 |
| R-HSA-9020933 | Interleukin-23 signaling | 7.618859e-01 | 0.118 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 7.645302e-01 | 0.117 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 7.683726e-01 | 0.114 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 7.683726e-01 | 0.114 |
| R-HSA-9830364 | Formation of the nephric duct | 7.683726e-01 | 0.114 |
| R-HSA-186712 | Regulation of beta-cell development | 7.688187e-01 | 0.114 |
| R-HSA-3214847 | HATs acetylate histones | 7.688910e-01 | 0.114 |
| R-HSA-74752 | Signaling by Insulin receptor | 7.741733e-01 | 0.111 |
| R-HSA-5654219 | Phospholipase C-mediated cascade: FGFR1 | 7.806254e-01 | 0.108 |
| R-HSA-1660517 | Synthesis of PIPs at the late endosome membrane | 7.806254e-01 | 0.108 |
| R-HSA-139853 | Elevation of cytosolic Ca2+ levels | 7.806254e-01 | 0.108 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 7.806254e-01 | 0.108 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 7.806947e-01 | 0.108 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 7.836433e-01 | 0.106 |
| R-HSA-112316 | Neuronal System | 7.853379e-01 | 0.105 |
| R-HSA-8874081 | MET activates PTK2 signaling | 7.864737e-01 | 0.104 |
| R-HSA-70635 | Urea cycle | 7.864737e-01 | 0.104 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 7.864737e-01 | 0.104 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 7.864737e-01 | 0.104 |
| R-HSA-3295583 | TRP channels | 7.864737e-01 | 0.104 |
| R-HSA-9637687 | Suppression of phagosomal maturation | 7.864737e-01 | 0.104 |
| R-HSA-9613354 | Lipophagy | 7.910184e-01 | 0.102 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 7.910184e-01 | 0.102 |
| R-HSA-5218900 | CASP8 activity is inhibited | 7.910184e-01 | 0.102 |
| R-HSA-9020958 | Interleukin-21 signaling | 7.910184e-01 | 0.102 |
| R-HSA-428543 | Inactivation of CDC42 and RAC1 | 7.910184e-01 | 0.102 |
| R-HSA-75072 | mRNA Editing | 7.910184e-01 | 0.102 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 7.910184e-01 | 0.102 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 7.910184e-01 | 0.102 |
| R-HSA-5250968 | Toxicity of botulinum toxin type A (botA) | 7.910184e-01 | 0.102 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 7.910184e-01 | 0.102 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 7.910184e-01 | 0.102 |
| R-HSA-193692 | Regulated proteolysis of p75NTR | 7.910184e-01 | 0.102 |
| R-HSA-418889 | Caspase activation via Dependence Receptors in the absence of ligand | 7.910184e-01 | 0.102 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 7.926811e-01 | 0.101 |
| R-HSA-445717 | Aquaporin-mediated transport | 7.936530e-01 | 0.100 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 7.960785e-01 | 0.099 |
| R-HSA-917977 | Transferrin endocytosis and recycling | 7.960785e-01 | 0.099 |
| R-HSA-381042 | PERK regulates gene expression | 7.960785e-01 | 0.099 |
| R-HSA-9659379 | Sensory processing of sound | 7.980014e-01 | 0.098 |
| R-HSA-1483255 | PI Metabolism | 7.980892e-01 | 0.098 |
| R-HSA-2564830 | Cytosolic iron-sulfur cluster assembly | 8.009817e-01 | 0.096 |
| R-HSA-190242 | FGFR1 ligand binding and activation | 8.009817e-01 | 0.096 |
| R-HSA-8849932 | Synaptic adhesion-like molecules | 8.009817e-01 | 0.096 |
| R-HSA-210993 | Tie2 Signaling | 8.009817e-01 | 0.096 |
| R-HSA-9831926 | Nephron development | 8.009817e-01 | 0.096 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 8.033854e-01 | 0.095 |
| R-HSA-901032 | ER Quality Control Compartment (ERQC) | 8.033854e-01 | 0.095 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 8.033854e-01 | 0.095 |
| R-HSA-2172127 | DAP12 interactions | 8.065606e-01 | 0.093 |
| R-HSA-373752 | Netrin-1 signaling | 8.065606e-01 | 0.093 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 8.094480e-01 | 0.092 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 8.094480e-01 | 0.092 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 8.094480e-01 | 0.092 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 8.105801e-01 | 0.091 |
| R-HSA-74158 | RNA Polymerase III Transcription | 8.105801e-01 | 0.091 |
| R-HSA-163560 | Triglyceride catabolism | 8.105801e-01 | 0.091 |
| R-HSA-173107 | Binding and entry of HIV virion | 8.165881e-01 | 0.088 |
| R-HSA-9948001 | CASP4 inflammasome assembly | 8.165881e-01 | 0.088 |
| R-HSA-451308 | Activation of Ca-permeable Kainate Receptor | 8.165881e-01 | 0.088 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 8.165881e-01 | 0.088 |
| R-HSA-5221030 | TET1,2,3 and TDG demethylate DNA | 8.165881e-01 | 0.088 |
| R-HSA-140342 | Apoptosis induced DNA fragmentation | 8.165881e-01 | 0.088 |
| R-HSA-5140745 | WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 8.165881e-01 | 0.088 |
| R-HSA-6803544 | Ion influx/efflux at host-pathogen interface | 8.165881e-01 | 0.088 |
| R-HSA-9022702 | MECP2 regulates transcription of neuronal ligands | 8.165881e-01 | 0.088 |
| R-HSA-9668250 | Defective factor IX causes hemophilia B | 8.165881e-01 | 0.088 |
| R-HSA-209952 | Peptide hormone biosynthesis | 8.165881e-01 | 0.088 |
| R-HSA-6799990 | Metal sequestration by antimicrobial proteins | 8.165881e-01 | 0.088 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 8.165881e-01 | 0.088 |
| R-HSA-9020956 | Interleukin-27 signaling | 8.165881e-01 | 0.088 |
| R-HSA-2586552 | Signaling by Leptin | 8.165881e-01 | 0.088 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 8.169399e-01 | 0.088 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 8.191560e-01 | 0.087 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 8.196425e-01 | 0.086 |
| R-HSA-9671793 | Diseases of hemostasis | 8.196425e-01 | 0.086 |
| R-HSA-9834899 | Specification of the neural plate border | 8.196425e-01 | 0.086 |
| R-HSA-9913635 | Strand-asynchronous mitochondrial DNA replication | 8.196425e-01 | 0.086 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 8.196425e-01 | 0.086 |
| R-HSA-449836 | Other interleukin signaling | 8.196425e-01 | 0.086 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 8.245191e-01 | 0.084 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 8.245191e-01 | 0.084 |
| R-HSA-74751 | Insulin receptor signalling cascade | 8.270415e-01 | 0.082 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 8.270836e-01 | 0.082 |
| R-HSA-72086 | mRNA Capping | 8.338360e-01 | 0.079 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 8.338360e-01 | 0.079 |
| R-HSA-1226099 | Signaling by FGFR in disease | 8.365799e-01 | 0.077 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 8.367178e-01 | 0.077 |
| R-HSA-9629569 | Protein hydroxylation | 8.367178e-01 | 0.077 |
| R-HSA-140875 | Common Pathway of Fibrin Clot Formation | 8.367178e-01 | 0.077 |
| R-HSA-9823730 | Formation of definitive endoderm | 8.367178e-01 | 0.077 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 8.370497e-01 | 0.077 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 8.370497e-01 | 0.077 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 8.389999e-01 | 0.076 |
| R-HSA-112308 | Presynaptic depolarization and calcium channel opening | 8.390306e-01 | 0.076 |
| R-HSA-451306 | Ionotropic activity of kainate receptors | 8.390306e-01 | 0.076 |
| R-HSA-192814 | vRNA Synthesis | 8.390306e-01 | 0.076 |
| R-HSA-192905 | vRNP Assembly | 8.390306e-01 | 0.076 |
| R-HSA-9706019 | RHOBTB3 ATPase cycle | 8.390306e-01 | 0.076 |
| R-HSA-71032 | Propionyl-CoA catabolism | 8.390306e-01 | 0.076 |
| R-HSA-1483248 | Synthesis of PIPs at the ER membrane | 8.390306e-01 | 0.076 |
| R-HSA-5682910 | LGI-ADAM interactions | 8.390306e-01 | 0.076 |
| R-HSA-391908 | Prostanoid ligand receptors | 8.390306e-01 | 0.076 |
| R-HSA-76046 | RNA Polymerase III Transcription Initiation | 8.474779e-01 | 0.072 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 8.474779e-01 | 0.072 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 8.474779e-01 | 0.072 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 8.490791e-01 | 0.071 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 8.490791e-01 | 0.071 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 8.523163e-01 | 0.069 |
| R-HSA-140837 | Intrinsic Pathway of Fibrin Clot Formation | 8.523163e-01 | 0.069 |
| R-HSA-422085 | Synthesis, secretion, and deacylation of Ghrelin | 8.523163e-01 | 0.069 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 8.540349e-01 | 0.069 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 8.587281e-01 | 0.066 |
| R-HSA-2022923 | DS-GAG biosynthesis | 8.587281e-01 | 0.066 |
| R-HSA-433692 | Proton-coupled monocarboxylate transport | 8.587281e-01 | 0.066 |
| R-HSA-428540 | Activation of RAC1 | 8.587281e-01 | 0.066 |
| R-HSA-2214320 | Anchoring fibril formation | 8.587281e-01 | 0.066 |
| R-HSA-1250342 | PI3K events in ERBB4 signaling | 8.587281e-01 | 0.066 |
| R-HSA-9623433 | NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis | 8.587281e-01 | 0.066 |
| R-HSA-180689 | APOBEC3G mediated resistance to HIV-1 infection | 8.587281e-01 | 0.066 |
| R-HSA-9026519 | Activated NTRK2 signals through RAS | 8.587281e-01 | 0.066 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 8.601347e-01 | 0.065 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 8.603481e-01 | 0.065 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 8.603481e-01 | 0.065 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 8.603481e-01 | 0.065 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 8.603481e-01 | 0.065 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 8.603481e-01 | 0.065 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 8.665435e-01 | 0.062 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 8.665435e-01 | 0.062 |
| R-HSA-174403 | Glutathione synthesis and recycling | 8.665435e-01 | 0.062 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 8.679443e-01 | 0.062 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 8.690403e-01 | 0.061 |
| R-HSA-5619084 | ABC transporter disorders | 8.708482e-01 | 0.060 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 8.708899e-01 | 0.060 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 8.718599e-01 | 0.060 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 8.718599e-01 | 0.060 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 8.730604e-01 | 0.059 |
| R-HSA-9609646 | HCMV Infection | 8.751028e-01 | 0.058 |
| R-HSA-3656237 | Defective EXT2 causes exostoses 2 | 8.760163e-01 | 0.057 |
| R-HSA-3656253 | Defective EXT1 causes exostoses 1, TRPS2 and CHDS | 8.760163e-01 | 0.057 |
| R-HSA-8983432 | Interleukin-15 signaling | 8.760163e-01 | 0.057 |
| R-HSA-77285 | Beta oxidation of myristoyl-CoA to lauroyl-CoA | 8.760163e-01 | 0.057 |
| R-HSA-77305 | Beta oxidation of palmitoyl-CoA to myristoyl-CoA | 8.760163e-01 | 0.057 |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft | 8.760163e-01 | 0.057 |
| R-HSA-70688 | Proline catabolism | 8.760163e-01 | 0.057 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 8.760163e-01 | 0.057 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 8.760163e-01 | 0.057 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 8.760163e-01 | 0.057 |
| R-HSA-877312 | Regulation of IFNG signaling | 8.760163e-01 | 0.057 |
| R-HSA-418890 | Role of second messengers in netrin-1 signaling | 8.760163e-01 | 0.057 |
| R-HSA-2428933 | SHC-related events triggered by IGF1R | 8.760163e-01 | 0.057 |
| R-HSA-1247673 | Erythrocytes take up oxygen and release carbon dioxide | 8.760163e-01 | 0.057 |
| R-HSA-5687613 | Diseases associated with surfactant metabolism | 8.760163e-01 | 0.057 |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 | 8.760163e-01 | 0.057 |
| R-HSA-8984722 | Interleukin-35 Signalling | 8.760163e-01 | 0.057 |
| R-HSA-5619102 | SLC transporter disorders | 8.782309e-01 | 0.056 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 8.795014e-01 | 0.056 |
| R-HSA-8964038 | LDL clearance | 8.795014e-01 | 0.056 |
| R-HSA-5652084 | Fructose metabolism | 8.795014e-01 | 0.056 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 8.807383e-01 | 0.055 |
| R-HSA-167161 | HIV Transcription Initiation | 8.807383e-01 | 0.055 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 8.807383e-01 | 0.055 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 8.807383e-01 | 0.055 |
| R-HSA-877300 | Interferon gamma signaling | 8.818925e-01 | 0.055 |
| R-HSA-9733709 | Cardiogenesis | 8.827066e-01 | 0.054 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 8.856439e-01 | 0.053 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 8.883931e-01 | 0.051 |
| R-HSA-3000178 | ECM proteoglycans | 8.883931e-01 | 0.051 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 8.903226e-01 | 0.050 |
| R-HSA-170660 | Adenylate cyclase activating pathway | 8.911897e-01 | 0.050 |
| R-HSA-9956593 | Microbial factors inhibit CASP4 activity | 8.911897e-01 | 0.050 |
| R-HSA-190373 | FGFR1c ligand binding and activation | 8.911897e-01 | 0.050 |
| R-HSA-8949664 | Processing of SMDT1 | 8.911897e-01 | 0.050 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 8.911897e-01 | 0.050 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 8.911897e-01 | 0.050 |
| R-HSA-8877330 | RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) | 8.911897e-01 | 0.050 |
| R-HSA-1059683 | Interleukin-6 signaling | 8.911897e-01 | 0.050 |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome | 8.911897e-01 | 0.050 |
| R-HSA-8854691 | Interleukin-20 family signaling | 8.912875e-01 | 0.050 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 8.927269e-01 | 0.049 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 8.984900e-01 | 0.046 |
| R-HSA-9710421 | Defective pyroptosis | 8.984900e-01 | 0.046 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 8.994296e-01 | 0.046 |
| R-HSA-418346 | Platelet homeostasis | 9.000694e-01 | 0.046 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 9.019718e-01 | 0.045 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 9.019946e-01 | 0.045 |
| R-HSA-5669034 | TNFs bind their physiological receptors | 9.019946e-01 | 0.045 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 9.045069e-01 | 0.044 |
| R-HSA-418457 | cGMP effects | 9.045069e-01 | 0.044 |
| R-HSA-9018681 | Biosynthesis of protectins | 9.045069e-01 | 0.044 |
| R-HSA-1483115 | Hydrolysis of LPC | 9.045069e-01 | 0.044 |
| R-HSA-5578768 | Physiological factors | 9.045069e-01 | 0.044 |
| R-HSA-9023661 | Biosynthesis of E-series 18(R)-resolvins | 9.045069e-01 | 0.044 |
| R-HSA-9793528 | Ciprofloxacin ADME | 9.045069e-01 | 0.044 |
| R-HSA-9679514 | SARS-CoV-1 Genome Replication and Transcription | 9.045069e-01 | 0.044 |
| R-HSA-5683826 | Surfactant metabolism | 9.064600e-01 | 0.043 |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism | 9.104910e-01 | 0.041 |
| R-HSA-1660516 | Synthesis of PIPs at the early endosome membrane | 9.117101e-01 | 0.040 |
| R-HSA-420029 | Tight junction interactions | 9.117101e-01 | 0.040 |
| R-HSA-2160916 | Hyaluronan degradation | 9.117101e-01 | 0.040 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 9.117101e-01 | 0.040 |
| R-HSA-9610379 | HCMV Late Events | 9.135965e-01 | 0.039 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 9.138699e-01 | 0.039 |
| R-HSA-418885 | DCC mediated attractive signaling | 9.161950e-01 | 0.038 |
| R-HSA-174362 | Transport and metabolism of PAPS | 9.161950e-01 | 0.038 |
| R-HSA-2142712 | Synthesis of 12-eicosatetraenoic acid derivatives | 9.161950e-01 | 0.038 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 9.161950e-01 | 0.038 |
| R-HSA-77352 | Beta oxidation of butanoyl-CoA to acetyl-CoA | 9.161950e-01 | 0.038 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 9.170690e-01 | 0.038 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 9.175622e-01 | 0.037 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 9.179400e-01 | 0.037 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 9.183321e-01 | 0.037 |
| R-HSA-9845576 | Glycosphingolipid transport | 9.183321e-01 | 0.037 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 9.205163e-01 | 0.036 |
| R-HSA-9845614 | Sphingolipid catabolism | 9.205163e-01 | 0.036 |
| R-HSA-9638630 | Attachment of bacteria to epithelial cells | 9.205163e-01 | 0.036 |
| R-HSA-196807 | Nicotinate metabolism | 9.246222e-01 | 0.034 |
| R-HSA-112399 | IRS-mediated signalling | 9.250026e-01 | 0.034 |
| R-HSA-1296072 | Voltage gated Potassium channels | 9.255411e-01 | 0.034 |
| R-HSA-110331 | Cleavage of the damaged purine | 9.255411e-01 | 0.034 |
| R-HSA-196757 | Metabolism of folate and pterines | 9.255411e-01 | 0.034 |
| R-HSA-8948216 | Collagen chain trimerization | 9.255411e-01 | 0.034 |
| R-HSA-168275 | Entry of Influenza Virion into Host Cell via Endocytosis | 9.264530e-01 | 0.033 |
| R-HSA-5635838 | Activation of SMO | 9.264530e-01 | 0.033 |
| R-HSA-434316 | Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion | 9.264530e-01 | 0.033 |
| R-HSA-9754706 | Atorvastatin ADME | 9.264530e-01 | 0.033 |
| R-HSA-168268 | Virus Assembly and Release | 9.264530e-01 | 0.033 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 9.271510e-01 | 0.033 |
| R-HSA-171306 | Packaging Of Telomere Ends | 9.284902e-01 | 0.032 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 9.284902e-01 | 0.032 |
| R-HSA-193807 | Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 9.284902e-01 | 0.032 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 9.284902e-01 | 0.032 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 9.306378e-01 | 0.031 |
| R-HSA-5663205 | Infectious disease | 9.307404e-01 | 0.031 |
| R-HSA-73927 | Depurination | 9.321619e-01 | 0.031 |
| R-HSA-9609507 | Protein localization | 9.324927e-01 | 0.030 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 9.328913e-01 | 0.030 |
| R-HSA-425410 | Metal ion SLC transporters | 9.330519e-01 | 0.030 |
| R-HSA-4420332 | Defective B3GALT6 causes EDSP2 and SEMDJL1 | 9.354560e-01 | 0.029 |
| R-HSA-3560783 | Defective B4GALT7 causes EDS, progeroid type | 9.354560e-01 | 0.029 |
| R-HSA-964975 | Vitamin B6 activation to pyridoxal phosphate | 9.354560e-01 | 0.029 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 9.354560e-01 | 0.029 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 9.354560e-01 | 0.029 |
| R-HSA-9927020 | Heme assimilation | 9.354560e-01 | 0.029 |
| R-HSA-77288 | mitochondrial fatty acid beta-oxidation of unsaturated fatty acids | 9.354560e-01 | 0.029 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 9.354560e-01 | 0.029 |
| R-HSA-1566977 | Fibronectin matrix formation | 9.354560e-01 | 0.029 |
| R-HSA-5661270 | Formation of xylulose-5-phosphate | 9.354560e-01 | 0.029 |
| R-HSA-196783 | Coenzyme A biosynthesis | 9.354560e-01 | 0.029 |
| R-HSA-6787450 | tRNA modification in the mitochondrion | 9.354560e-01 | 0.029 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 9.354560e-01 | 0.029 |
| R-HSA-451326 | Activation of kainate receptors upon glutamate binding | 9.357036e-01 | 0.029 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 9.357036e-01 | 0.029 |
| R-HSA-8979227 | Triglyceride metabolism | 9.358919e-01 | 0.029 |
| R-HSA-71336 | Pentose phosphate pathway | 9.382363e-01 | 0.028 |
| R-HSA-168249 | Innate Immune System | 9.401097e-01 | 0.027 |
| R-HSA-5334118 | DNA methylation | 9.422231e-01 | 0.026 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 9.422231e-01 | 0.026 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 9.422231e-01 | 0.026 |
| R-HSA-3560801 | Defective B3GAT3 causes JDSSDHD | 9.433573e-01 | 0.025 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 9.433573e-01 | 0.025 |
| R-HSA-2408550 | Metabolism of ingested H2SeO4 and H2SeO3 into H2Se | 9.433573e-01 | 0.025 |
| R-HSA-2142770 | Synthesis of 15-eicosatetraenoic acid derivatives | 9.433573e-01 | 0.025 |
| R-HSA-9020265 | Biosynthesis of aspirin-triggered D-series resolvins | 9.433573e-01 | 0.025 |
| R-HSA-1614517 | Sulfide oxidation to sulfate | 9.433573e-01 | 0.025 |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome | 9.433573e-01 | 0.025 |
| R-HSA-109704 | PI3K Cascade | 9.435965e-01 | 0.025 |
| R-HSA-8982491 | Glycogen metabolism | 9.438040e-01 | 0.025 |
| R-HSA-5576891 | Cardiac conduction | 9.445079e-01 | 0.025 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 9.453414e-01 | 0.024 |
| R-HSA-6809371 | Formation of the cornified envelope | 9.457665e-01 | 0.024 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 9.465462e-01 | 0.024 |
| R-HSA-9664417 | Leishmania phagocytosis | 9.465462e-01 | 0.024 |
| R-HSA-9664407 | Parasite infection | 9.465462e-01 | 0.024 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 9.481105e-01 | 0.023 |
| R-HSA-112311 | Neurotransmitter clearance | 9.481105e-01 | 0.023 |
| R-HSA-73817 | Purine ribonucleoside monophosphate biosynthesis | 9.489024e-01 | 0.023 |
| R-HSA-1268020 | Mitochondrial protein import | 9.495772e-01 | 0.022 |
| R-HSA-418217 | G beta:gamma signalling through PLC beta | 9.502918e-01 | 0.022 |
| R-HSA-500657 | Presynaptic function of Kainate receptors | 9.502918e-01 | 0.022 |
| R-HSA-73980 | RNA Polymerase III Transcription Termination | 9.502918e-01 | 0.022 |
| R-HSA-196791 | Vitamin D (calciferol) metabolism | 9.502918e-01 | 0.022 |
| R-HSA-428643 | Organic anion transport by SLC5/17/25 transporters | 9.502918e-01 | 0.022 |
| R-HSA-418038 | Nucleotide-like (purinergic) receptors | 9.502918e-01 | 0.022 |
| R-HSA-9679504 | Translation of Replicase and Assembly of the Replication Transcription Complex | 9.502918e-01 | 0.022 |
| R-HSA-2980736 | Peptide hormone metabolism | 9.534095e-01 | 0.021 |
| R-HSA-2129379 | Molecules associated with elastic fibres | 9.534227e-01 | 0.021 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 9.535670e-01 | 0.021 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 9.563777e-01 | 0.019 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 9.563777e-01 | 0.019 |
| R-HSA-8964058 | HDL remodeling | 9.563777e-01 | 0.019 |
| R-HSA-429958 | mRNA decay by 3' to 5' exoribonuclease | 9.563777e-01 | 0.019 |
| R-HSA-1237044 | Erythrocytes take up carbon dioxide and release oxygen | 9.563777e-01 | 0.019 |
| R-HSA-2142688 | Synthesis of 5-eicosatetraenoic acids | 9.563777e-01 | 0.019 |
| R-HSA-1480926 | O2/CO2 exchange in erythrocytes | 9.563777e-01 | 0.019 |
| R-HSA-1237112 | Methionine salvage pathway | 9.563777e-01 | 0.019 |
| R-HSA-9694682 | SARS-CoV-2 Genome Replication and Transcription | 9.563777e-01 | 0.019 |
| R-HSA-2428924 | IGF1R signaling cascade | 9.571664e-01 | 0.019 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 9.578310e-01 | 0.019 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 9.578310e-01 | 0.019 |
| R-HSA-73928 | Depyrimidination | 9.578310e-01 | 0.019 |
| R-HSA-418555 | G alpha (s) signalling events | 9.595469e-01 | 0.018 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 9.602672e-01 | 0.018 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 9.605556e-01 | 0.017 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 9.617188e-01 | 0.017 |
| R-HSA-9609523 | Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 9.617188e-01 | 0.017 |
| R-HSA-1482922 | Acyl chain remodelling of PI | 9.617188e-01 | 0.017 |
| R-HSA-71288 | Creatine metabolism | 9.617188e-01 | 0.017 |
| R-HSA-77111 | Synthesis of Ketone Bodies | 9.617188e-01 | 0.017 |
| R-HSA-391903 | Eicosanoid ligand-binding receptors | 9.617188e-01 | 0.017 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 9.625279e-01 | 0.017 |
| R-HSA-397795 | G-protein beta:gamma signalling | 9.625279e-01 | 0.017 |
| R-HSA-159418 | Recycling of bile acids and salts | 9.625279e-01 | 0.017 |
| R-HSA-9753281 | Paracetamol ADME | 9.636532e-01 | 0.016 |
| R-HSA-9833110 | RSV-host interactions | 9.654319e-01 | 0.015 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 9.664062e-01 | 0.015 |
| R-HSA-392170 | ADP signalling through P2Y purinoceptor 12 | 9.664062e-01 | 0.015 |
| R-HSA-202040 | G-protein activation | 9.664062e-01 | 0.015 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 9.664062e-01 | 0.015 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 9.664062e-01 | 0.015 |
| R-HSA-9018896 | Biosynthesis of E-series 18(S)-resolvins | 9.664062e-01 | 0.015 |
| R-HSA-196836 | Vitamin C (ascorbate) metabolism | 9.664062e-01 | 0.015 |
| R-HSA-1482925 | Acyl chain remodelling of PG | 9.664062e-01 | 0.015 |
| R-HSA-1482788 | Acyl chain remodelling of PC | 9.664134e-01 | 0.015 |
| R-HSA-5223345 | Miscellaneous transport and binding events | 9.664134e-01 | 0.015 |
| R-HSA-189483 | Heme degradation | 9.664134e-01 | 0.015 |
| R-HSA-8964539 | Glutamate and glutamine metabolism | 9.664134e-01 | 0.015 |
| R-HSA-9830369 | Kidney development | 9.666069e-01 | 0.015 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 9.667694e-01 | 0.015 |
| R-HSA-1971475 | Glycosaminoglycan-protein linkage region biosynthesis | 9.699095e-01 | 0.013 |
| R-HSA-2142845 | Hyaluronan metabolism | 9.699095e-01 | 0.013 |
| R-HSA-2022870 | CS-GAG biosynthesis | 9.705199e-01 | 0.013 |
| R-HSA-193048 | Androgen biosynthesis | 9.705199e-01 | 0.013 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 9.705199e-01 | 0.013 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 9.705199e-01 | 0.013 |
| R-HSA-194002 | Glucocorticoid biosynthesis | 9.705199e-01 | 0.013 |
| R-HSA-2022377 | Metabolism of Angiotensinogen to Angiotensins | 9.705199e-01 | 0.013 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 9.714749e-01 | 0.013 |
| R-HSA-1482839 | Acyl chain remodelling of PE | 9.730532e-01 | 0.012 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 9.730532e-01 | 0.012 |
| R-HSA-112310 | Neurotransmitter release cycle | 9.730632e-01 | 0.012 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 9.740930e-01 | 0.011 |
| R-HSA-76071 | RNA Polymerase III Transcription Initiation From Type 3 Promoter | 9.741300e-01 | 0.011 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 9.741300e-01 | 0.011 |
| R-HSA-9018676 | Biosynthesis of D-series resolvins | 9.741300e-01 | 0.011 |
| R-HSA-975578 | Reactions specific to the complex N-glycan synthesis pathway | 9.741300e-01 | 0.011 |
| R-HSA-9857377 | Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autopha... | 9.741300e-01 | 0.011 |
| R-HSA-168799 | Neurotoxicity of clostridium toxins | 9.741300e-01 | 0.011 |
| R-HSA-9694676 | Translation of Replicase and Assembly of the Replication Transcription Complex | 9.741300e-01 | 0.011 |
| R-HSA-1483191 | Synthesis of PC | 9.741647e-01 | 0.011 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 9.746868e-01 | 0.011 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 9.758785e-01 | 0.011 |
| R-HSA-9734767 | Developmental Cell Lineages | 9.759583e-01 | 0.011 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 9.772983e-01 | 0.010 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 9.772983e-01 | 0.010 |
| R-HSA-400451 | Free fatty acids regulate insulin secretion | 9.772983e-01 | 0.010 |
| R-HSA-1369062 | ABC transporters in lipid homeostasis | 9.772983e-01 | 0.010 |
| R-HSA-200425 | Carnitine shuttle | 9.772983e-01 | 0.010 |
| R-HSA-74182 | Ketone body metabolism | 9.772983e-01 | 0.010 |
| R-HSA-1855167 | Synthesis of pyrophosphates in the cytosol | 9.772983e-01 | 0.010 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 9.784162e-01 | 0.009 |
| R-HSA-549127 | SLC-mediated transport of organic cations | 9.784162e-01 | 0.009 |
| R-HSA-419037 | NCAM1 interactions | 9.784162e-01 | 0.009 |
| R-HSA-1442490 | Collagen degradation | 9.789410e-01 | 0.009 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 9.799179e-01 | 0.009 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 9.799924e-01 | 0.009 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 9.800787e-01 | 0.009 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 9.800787e-01 | 0.009 |
| R-HSA-6783589 | Interleukin-6 family signaling | 9.800787e-01 | 0.009 |
| R-HSA-392499 | Metabolism of proteins | 9.802812e-01 | 0.009 |
| R-HSA-6785470 | tRNA processing in the mitochondrion | 9.806943e-01 | 0.008 |
| R-HSA-1566948 | Elastic fibre formation | 9.806943e-01 | 0.008 |
| R-HSA-9931953 | Biofilm formation | 9.806943e-01 | 0.008 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 9.808061e-01 | 0.008 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 9.808615e-01 | 0.008 |
| R-HSA-2162123 | Synthesis of Prostaglandins (PG) and Thromboxanes (TX) | 9.808615e-01 | 0.008 |
| R-HSA-1474290 | Collagen formation | 9.817277e-01 | 0.008 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 9.825187e-01 | 0.008 |
| R-HSA-2453864 | Retinoid cycle disease events | 9.825187e-01 | 0.008 |
| R-HSA-9675143 | Diseases of the neuronal system | 9.825187e-01 | 0.008 |
| R-HSA-2474795 | Diseases associated with visual transduction | 9.825187e-01 | 0.008 |
| R-HSA-2514856 | The phototransduction cascade | 9.826990e-01 | 0.008 |
| R-HSA-381771 | Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) | 9.827383e-01 | 0.008 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 9.827383e-01 | 0.008 |
| R-HSA-379726 | Mitochondrial tRNA aminoacylation | 9.845714e-01 | 0.007 |
| R-HSA-400042 | Adrenaline,noradrenaline inhibits insulin secretion | 9.846599e-01 | 0.007 |
| R-HSA-1855183 | Synthesis of IP2, IP, and Ins in the cytosol | 9.846599e-01 | 0.007 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 9.846599e-01 | 0.007 |
| R-HSA-2046105 | Linoleic acid (LA) metabolism | 9.846599e-01 | 0.007 |
| R-HSA-2161522 | Abacavir ADME | 9.846599e-01 | 0.007 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 9.846599e-01 | 0.007 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.846797e-01 | 0.007 |
| R-HSA-8956320 | Nucleotide biosynthesis | 9.858802e-01 | 0.006 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 9.865390e-01 | 0.006 |
| R-HSA-75109 | Triglyceride biosynthesis | 9.865390e-01 | 0.006 |
| R-HSA-1483213 | Synthesis of PE | 9.865390e-01 | 0.006 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 9.868157e-01 | 0.006 |
| R-HSA-597592 | Post-translational protein modification | 9.868518e-01 | 0.006 |
| R-HSA-189451 | Heme biosynthesis | 9.876867e-01 | 0.005 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 9.878323e-01 | 0.005 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 9.880105e-01 | 0.005 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 9.881881e-01 | 0.005 |
| R-HSA-9638334 | Iron assimilation using enterobactin | 9.881881e-01 | 0.005 |
| R-HSA-73614 | Pyrimidine salvage | 9.881881e-01 | 0.005 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.882079e-01 | 0.005 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.882079e-01 | 0.005 |
| R-HSA-991365 | Activation of GABAB receptors | 9.890052e-01 | 0.005 |
| R-HSA-977444 | GABA B receptor activation | 9.890052e-01 | 0.005 |
| R-HSA-400508 | Incretin synthesis, secretion, and inactivation | 9.890052e-01 | 0.005 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 9.891017e-01 | 0.005 |
| R-HSA-1643685 | Disease | 9.891372e-01 | 0.005 |
| R-HSA-209968 | Thyroxine biosynthesis | 9.896351e-01 | 0.005 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 9.896351e-01 | 0.005 |
| R-HSA-9018679 | Biosynthesis of EPA-derived SPMs | 9.896351e-01 | 0.005 |
| R-HSA-73621 | Pyrimidine catabolism | 9.901856e-01 | 0.004 |
| R-HSA-1483166 | Synthesis of PA | 9.906414e-01 | 0.004 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 9.911680e-01 | 0.004 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 9.913160e-01 | 0.004 |
| R-HSA-189445 | Metabolism of porphyrins | 9.918346e-01 | 0.004 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 9.920194e-01 | 0.003 |
| R-HSA-8963693 | Aspartate and asparagine metabolism | 9.920194e-01 | 0.003 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 9.920620e-01 | 0.003 |
| R-HSA-3560782 | Diseases associated with glycosaminoglycan metabolism | 9.921867e-01 | 0.003 |
| R-HSA-77286 | mitochondrial fatty acid beta-oxidation of saturated fatty acids | 9.921867e-01 | 0.003 |
| R-HSA-9937080 | Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 9.929973e-01 | 0.003 |
| R-HSA-156590 | Glutathione conjugation | 9.931526e-01 | 0.003 |
| R-HSA-351202 | Metabolism of polyamines | 9.931526e-01 | 0.003 |
| R-HSA-211976 | Endogenous sterols | 9.938342e-01 | 0.003 |
| R-HSA-5083635 | Defective B3GALTL causes PpS | 9.938554e-01 | 0.003 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 9.943181e-01 | 0.002 |
| R-HSA-8963899 | Plasma lipoprotein remodeling | 9.944615e-01 | 0.002 |
| R-HSA-2024101 | CS/DS degradation | 9.946084e-01 | 0.002 |
| R-HSA-416476 | G alpha (q) signalling events | 9.948947e-01 | 0.002 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 9.952691e-01 | 0.002 |
| R-HSA-203615 | eNOS activation | 9.952691e-01 | 0.002 |
| R-HSA-5686938 | Regulation of TLR by endogenous ligand | 9.952691e-01 | 0.002 |
| R-HSA-9748787 | Azathioprine ADME | 9.956025e-01 | 0.002 |
| R-HSA-193775 | Synthesis of bile acids and bile salts via 24-hydroxycholesterol | 9.958490e-01 | 0.002 |
| R-HSA-6783783 | Interleukin-10 signaling | 9.958915e-01 | 0.002 |
| R-HSA-2022928 | HS-GAG biosynthesis | 9.963577e-01 | 0.002 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 9.963577e-01 | 0.002 |
| R-HSA-5173214 | O-glycosylation of TSR domain-containing proteins | 9.968042e-01 | 0.001 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 9.968042e-01 | 0.001 |
| R-HSA-71064 | Lysine catabolism | 9.968042e-01 | 0.001 |
| R-HSA-1474244 | Extracellular matrix organization | 9.969879e-01 | 0.001 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 9.971959e-01 | 0.001 |
| R-HSA-74217 | Purine salvage | 9.971959e-01 | 0.001 |
| R-HSA-2046106 | alpha-linolenic acid (ALA) metabolism | 9.971959e-01 | 0.001 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 9.976343e-01 | 0.001 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 9.977441e-01 | 0.001 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 9.977441e-01 | 0.001 |
| R-HSA-9854311 | Maturation of TCA enzymes and regulation of TCA cycle | 9.978413e-01 | 0.001 |
| R-HSA-8868766 | rRNA processing in the mitochondrion | 9.978413e-01 | 0.001 |
| R-HSA-975576 | N-glycan antennae elongation in the medial/trans-Golgi | 9.978413e-01 | 0.001 |
| R-HSA-71240 | Tryptophan catabolism | 9.978413e-01 | 0.001 |
| R-HSA-8978934 | Metabolism of cofactors | 9.978763e-01 | 0.001 |
| R-HSA-975634 | Retinoid metabolism and transport | 9.978763e-01 | 0.001 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 9.980765e-01 | 0.001 |
| R-HSA-5423646 | Aflatoxin activation and detoxification | 9.981060e-01 | 0.001 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 9.982682e-01 | 0.001 |
| R-HSA-9749641 | Aspirin ADME | 9.982899e-01 | 0.001 |
| R-HSA-71403 | Citric acid cycle (TCA cycle) | 9.986243e-01 | 0.001 |
| R-HSA-977443 | GABA receptor activation | 9.986309e-01 | 0.001 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 9.986309e-01 | 0.001 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 9.986309e-01 | 0.001 |
| R-HSA-1461973 | Defensins | 9.987208e-01 | 0.001 |
| R-HSA-8956321 | Nucleotide salvage | 9.987830e-01 | 0.001 |
| R-HSA-375280 | Amine ligand-binding receptors | 9.988776e-01 | 0.000 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 9.988776e-01 | 0.000 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.990017e-01 | 0.000 |
| R-HSA-2453902 | The canonical retinoid cycle in rods (twilight vision) | 9.990153e-01 | 0.000 |
| R-HSA-1614558 | Degradation of cysteine and homocysteine | 9.990153e-01 | 0.000 |
| R-HSA-6799198 | Complex I biogenesis | 9.990389e-01 | 0.000 |
| R-HSA-2046104 | alpha-linolenic (omega3) and linoleic (omega6) acid metabolism | 9.992420e-01 | 0.000 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 9.992880e-01 | 0.000 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 9.994018e-01 | 0.000 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 9.994105e-01 | 0.000 |
| R-HSA-389661 | Glyoxylate metabolism and glycine degradation | 9.994166e-01 | 0.000 |
| R-HSA-380108 | Chemokine receptors bind chemokines | 9.994166e-01 | 0.000 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 9.995093e-01 | 0.000 |
| R-HSA-9864848 | Complex IV assembly | 9.995509e-01 | 0.000 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 9.995509e-01 | 0.000 |
| R-HSA-156584 | Cytosolic sulfonation of small molecules | 9.995509e-01 | 0.000 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.995856e-01 | 0.000 |
| R-HSA-5368286 | Mitochondrial translation initiation | 9.996130e-01 | 0.000 |
| R-HSA-1483257 | Phospholipid metabolism | 9.996154e-01 | 0.000 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 9.996286e-01 | 0.000 |
| R-HSA-9638482 | Metal ion assimilation from the host | 9.996286e-01 | 0.000 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.996518e-01 | 0.000 |
| R-HSA-1793185 | Chondroitin sulfate/dermatan sulfate metabolism | 9.997340e-01 | 0.000 |
| R-HSA-1222556 | ROS and RNS production in phagocytes | 9.997406e-01 | 0.000 |
| R-HSA-209776 | Metabolism of amine-derived hormones | 9.997666e-01 | 0.000 |
| R-HSA-5621480 | Dectin-2 family | 9.997953e-01 | 0.000 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.998010e-01 | 0.000 |
| R-HSA-9955298 | SLC-mediated transport of organic anions | 9.998396e-01 | 0.000 |
| R-HSA-1638091 | Heparan sulfate/heparin (HS-GAG) metabolism | 9.998424e-01 | 0.000 |
| R-HSA-4085001 | Sialic acid metabolism | 9.998424e-01 | 0.000 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.998503e-01 | 0.000 |
| R-HSA-5419276 | Mitochondrial translation termination | 9.998927e-01 | 0.000 |
| R-HSA-8957322 | Metabolism of steroids | 9.998934e-01 | 0.000 |
| R-HSA-2168880 | Scavenging of heme from plasma | 9.998942e-01 | 0.000 |
| R-HSA-5389840 | Mitochondrial translation elongation | 9.999055e-01 | 0.000 |
| R-HSA-1296071 | Potassium Channels | 9.999055e-01 | 0.000 |
| R-HSA-6803157 | Antimicrobial peptides | 9.999136e-01 | 0.000 |
| R-HSA-6805567 | Keratinization | 9.999174e-01 | 0.000 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 9.999181e-01 | 0.000 |
| R-HSA-211981 | Xenobiotics | 9.999181e-01 | 0.000 |
| R-HSA-196071 | Metabolism of steroid hormones | 9.999447e-01 | 0.000 |
| R-HSA-1614635 | Sulfur amino acid metabolism | 9.999460e-01 | 0.000 |
| R-HSA-9937383 | Mitochondrial ribosome-associated quality control | 9.999576e-01 | 0.000 |
| R-HSA-9840310 | Glycosphingolipid catabolism | 9.999627e-01 | 0.000 |
| R-HSA-373080 | Class B/2 (Secretin family receptors) | 9.999668e-01 | 0.000 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 9.999686e-01 | 0.000 |
| R-HSA-418594 | G alpha (i) signalling events | 9.999755e-01 | 0.000 |
| R-HSA-425397 | Transport of vitamins, nucleosides, and related molecules | 9.999779e-01 | 0.000 |
| R-HSA-2187338 | Visual phototransduction | 9.999792e-01 | 0.000 |
| R-HSA-2029481 | FCGR activation | 9.999796e-01 | 0.000 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.999864e-01 | 0.000 |
| R-HSA-5368287 | Mitochondrial translation | 9.999866e-01 | 0.000 |
| R-HSA-191273 | Cholesterol biosynthesis | 9.999869e-01 | 0.000 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.999872e-01 | 0.000 |
| R-HSA-388396 | GPCR downstream signalling | 9.999874e-01 | 0.000 |
| R-HSA-2142753 | Arachidonate metabolism | 9.999876e-01 | 0.000 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 9.999885e-01 | 0.000 |
| R-HSA-5579029 | Metabolic disorders of biological oxidation enzymes | 9.999885e-01 | 0.000 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 9.999912e-01 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 9.999924e-01 | 0.000 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 9.999925e-01 | 0.000 |
| R-HSA-611105 | Respiratory electron transport | 9.999967e-01 | 0.000 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 9.999983e-01 | 0.000 |
| R-HSA-8956319 | Nucleotide catabolism | 9.999987e-01 | 0.000 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 9.999992e-01 | 0.000 |
| R-HSA-9717207 | Sensory perception of sweet, bitter, and umami (glutamate) taste | 9.999997e-01 | 0.000 |
| R-HSA-372790 | Signaling by GPCR | 9.999998e-01 | 0.000 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 9.999999e-01 | 0.000 |
| R-HSA-9717189 | Sensory perception of taste | 9.999999e-01 | 0.000 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 9.999999e-01 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.999999e-01 | 0.000 |
| R-HSA-375276 | Peptide ligand-binding receptors | 9.999999e-01 | 0.000 |
| R-HSA-9748784 | Drug ADME | 1.000000e+00 | 0.000 |
| R-HSA-5173105 | O-linked glycosylation | 1.000000e+00 | 0.000 |
| R-HSA-1660662 | Glycosphingolipid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-977606 | Regulation of Complement cascade | 1.000000e+00 | 0.000 |
| R-HSA-428157 | Sphingolipid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-3781865 | Diseases of glycosylation | 1.000000e+00 | 0.000 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 1.000000e+00 | 0.000 |
| R-HSA-9640148 | Infection with Enterobacteria | 1.000000e+00 | 0.000 |
| R-HSA-15869 | Metabolism of nucleotides | 1.000000e+00 | 0.000 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 1.000000e+00 | 0.000 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 1.000000e+00 | 0.000 |
| R-HSA-166658 | Complement cascade | 1.000000e+00 | 0.000 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 1.000000e+00 | 0.000 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 1.000000e+00 | 0.000 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 1.000000e+00 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 1.000000e+00 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 1.000000e+00 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | -0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | -0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | -0.000 |
| R-HSA-211859 | Biological oxidations | 1.000000e+00 | -0.000 |
| R-HSA-500792 | GPCR ligand binding | 1.000000e+00 | -0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
CLK3 |
0.915 | 0.449 | 1 | 0.927 |
COT |
0.913 | 0.145 | 2 | 0.913 |
NLK |
0.906 | 0.385 | 1 | 0.927 |
KIS |
0.901 | 0.386 | 1 | 0.870 |
ERK5 |
0.900 | 0.258 | 1 | 0.888 |
CDC7 |
0.900 | 0.006 | 1 | 0.836 |
SRPK1 |
0.899 | 0.277 | -3 | 0.794 |
PIM3 |
0.899 | 0.106 | -3 | 0.875 |
MOS |
0.899 | 0.082 | 1 | 0.875 |
CDKL1 |
0.898 | 0.168 | -3 | 0.847 |
PRPK |
0.898 | -0.110 | -1 | 0.895 |
MTOR |
0.897 | 0.016 | 1 | 0.827 |
CAMK1B |
0.897 | 0.085 | -3 | 0.903 |
HIPK4 |
0.896 | 0.271 | 1 | 0.897 |
NDR2 |
0.895 | 0.054 | -3 | 0.876 |
DSTYK |
0.895 | 0.002 | 2 | 0.928 |
CDKL5 |
0.894 | 0.179 | -3 | 0.838 |
PRKD1 |
0.894 | 0.139 | -3 | 0.859 |
CDK8 |
0.894 | 0.375 | 1 | 0.847 |
ATR |
0.893 | 0.031 | 1 | 0.844 |
RAF1 |
0.893 | -0.125 | 1 | 0.818 |
PKN3 |
0.892 | 0.067 | -3 | 0.869 |
CAMK2G |
0.892 | -0.028 | 2 | 0.862 |
RSK2 |
0.892 | 0.129 | -3 | 0.814 |
ICK |
0.892 | 0.240 | -3 | 0.879 |
DYRK2 |
0.892 | 0.400 | 1 | 0.870 |
PIM1 |
0.891 | 0.168 | -3 | 0.823 |
BMPR2 |
0.891 | -0.126 | -2 | 0.931 |
PRKD2 |
0.891 | 0.146 | -3 | 0.808 |
IKKB |
0.890 | -0.147 | -2 | 0.786 |
GCN2 |
0.890 | -0.217 | 2 | 0.829 |
PDHK4 |
0.890 | -0.295 | 1 | 0.848 |
SRPK2 |
0.890 | 0.231 | -3 | 0.718 |
JNK2 |
0.889 | 0.471 | 1 | 0.811 |
CDK19 |
0.889 | 0.377 | 1 | 0.818 |
SKMLCK |
0.889 | 0.102 | -2 | 0.911 |
NUAK2 |
0.889 | 0.070 | -3 | 0.880 |
TBK1 |
0.889 | -0.144 | 1 | 0.716 |
WNK1 |
0.889 | 0.031 | -2 | 0.918 |
CDK18 |
0.889 | 0.431 | 1 | 0.802 |
CAMLCK |
0.888 | 0.079 | -2 | 0.910 |
NIK |
0.888 | 0.016 | -3 | 0.917 |
CDK7 |
0.888 | 0.359 | 1 | 0.857 |
P90RSK |
0.888 | 0.087 | -3 | 0.818 |
NDR1 |
0.887 | 0.027 | -3 | 0.873 |
CDK5 |
0.887 | 0.411 | 1 | 0.869 |
ULK2 |
0.887 | -0.206 | 2 | 0.812 |
CDK1 |
0.887 | 0.415 | 1 | 0.819 |
MST4 |
0.887 | 0.049 | 2 | 0.885 |
CLK4 |
0.886 | 0.292 | -3 | 0.810 |
JNK3 |
0.886 | 0.434 | 1 | 0.841 |
CLK1 |
0.886 | 0.316 | -3 | 0.788 |
NEK6 |
0.886 | -0.048 | -2 | 0.906 |
PKCD |
0.886 | 0.105 | 2 | 0.829 |
RIPK3 |
0.886 | -0.064 | 3 | 0.817 |
DAPK2 |
0.886 | 0.052 | -3 | 0.906 |
P38A |
0.886 | 0.417 | 1 | 0.871 |
TGFBR2 |
0.885 | -0.031 | -2 | 0.850 |
IKKE |
0.885 | -0.168 | 1 | 0.711 |
PKN2 |
0.885 | 0.044 | -3 | 0.876 |
CDK13 |
0.884 | 0.366 | 1 | 0.836 |
CLK2 |
0.884 | 0.368 | -3 | 0.791 |
PDHK1 |
0.884 | -0.281 | 1 | 0.832 |
RSK3 |
0.884 | 0.064 | -3 | 0.809 |
P38B |
0.883 | 0.432 | 1 | 0.824 |
CAMK2D |
0.883 | 0.010 | -3 | 0.876 |
NEK7 |
0.883 | -0.163 | -3 | 0.876 |
MAPKAPK3 |
0.883 | 0.040 | -3 | 0.813 |
FAM20C |
0.883 | 0.168 | 2 | 0.692 |
SRPK3 |
0.883 | 0.187 | -3 | 0.767 |
LATS2 |
0.883 | 0.020 | -5 | 0.784 |
MARK4 |
0.882 | -0.024 | 4 | 0.844 |
MLK1 |
0.882 | -0.117 | 2 | 0.850 |
P70S6KB |
0.882 | 0.063 | -3 | 0.837 |
HIPK2 |
0.882 | 0.415 | 1 | 0.807 |
CDK17 |
0.882 | 0.411 | 1 | 0.759 |
AMPKA1 |
0.882 | 0.017 | -3 | 0.889 |
HIPK1 |
0.882 | 0.393 | 1 | 0.878 |
MAPKAPK2 |
0.882 | 0.093 | -3 | 0.769 |
P38G |
0.881 | 0.428 | 1 | 0.753 |
ERK1 |
0.881 | 0.400 | 1 | 0.816 |
TSSK2 |
0.881 | 0.059 | -5 | 0.895 |
CHAK2 |
0.881 | -0.047 | -1 | 0.882 |
CAMK2B |
0.880 | 0.100 | 2 | 0.841 |
GRK1 |
0.880 | 0.033 | -2 | 0.805 |
GRK5 |
0.880 | -0.208 | -3 | 0.889 |
ATM |
0.880 | 0.040 | 1 | 0.786 |
GRK6 |
0.880 | -0.048 | 1 | 0.815 |
PKACG |
0.879 | 0.053 | -2 | 0.809 |
HUNK |
0.879 | -0.167 | 2 | 0.833 |
TSSK1 |
0.879 | 0.066 | -3 | 0.905 |
CDK3 |
0.878 | 0.404 | 1 | 0.776 |
AURC |
0.878 | 0.115 | -2 | 0.727 |
CDK14 |
0.878 | 0.420 | 1 | 0.832 |
BMPR1B |
0.878 | 0.128 | 1 | 0.771 |
DYRK4 |
0.878 | 0.413 | 1 | 0.821 |
IKKA |
0.878 | -0.077 | -2 | 0.773 |
CDK12 |
0.877 | 0.365 | 1 | 0.815 |
LATS1 |
0.877 | 0.116 | -3 | 0.890 |
WNK3 |
0.877 | -0.248 | 1 | 0.799 |
CDK16 |
0.877 | 0.438 | 1 | 0.774 |
ERK2 |
0.877 | 0.365 | 1 | 0.842 |
PRKD3 |
0.877 | 0.091 | -3 | 0.784 |
DYRK1A |
0.876 | 0.325 | 1 | 0.891 |
AMPKA2 |
0.876 | 0.024 | -3 | 0.858 |
CDK2 |
0.876 | 0.282 | 1 | 0.866 |
BCKDK |
0.876 | -0.212 | -1 | 0.840 |
ULK1 |
0.876 | -0.248 | -3 | 0.854 |
NEK9 |
0.876 | -0.174 | 2 | 0.863 |
CAMK2A |
0.875 | 0.074 | 2 | 0.852 |
CDK9 |
0.875 | 0.335 | 1 | 0.840 |
ALK4 |
0.875 | 0.017 | -2 | 0.878 |
TGFBR1 |
0.875 | 0.066 | -2 | 0.850 |
ANKRD3 |
0.875 | -0.161 | 1 | 0.837 |
PKR |
0.874 | 0.023 | 1 | 0.830 |
CAMK4 |
0.874 | -0.052 | -3 | 0.857 |
RSK4 |
0.874 | 0.112 | -3 | 0.783 |
NIM1 |
0.874 | -0.072 | 3 | 0.832 |
MASTL |
0.874 | -0.339 | -2 | 0.858 |
HIPK3 |
0.874 | 0.344 | 1 | 0.868 |
P38D |
0.874 | 0.433 | 1 | 0.778 |
MNK2 |
0.873 | 0.051 | -2 | 0.858 |
MSK2 |
0.873 | 0.023 | -3 | 0.783 |
IRE1 |
0.873 | -0.092 | 1 | 0.779 |
DLK |
0.873 | -0.237 | 1 | 0.807 |
MLK2 |
0.873 | -0.163 | 2 | 0.847 |
NUAK1 |
0.873 | 0.005 | -3 | 0.831 |
MLK3 |
0.872 | -0.029 | 2 | 0.784 |
PAK1 |
0.872 | 0.015 | -2 | 0.844 |
DYRK1B |
0.872 | 0.368 | 1 | 0.836 |
CDK10 |
0.872 | 0.407 | 1 | 0.823 |
PKCB |
0.871 | 0.046 | 2 | 0.779 |
RIPK1 |
0.871 | -0.229 | 1 | 0.789 |
PKACB |
0.871 | 0.132 | -2 | 0.746 |
PKCA |
0.871 | 0.054 | 2 | 0.770 |
DNAPK |
0.871 | 0.080 | 1 | 0.733 |
MELK |
0.871 | -0.013 | -3 | 0.842 |
IRE2 |
0.871 | -0.043 | 2 | 0.780 |
PLK1 |
0.870 | -0.079 | -2 | 0.866 |
DYRK3 |
0.870 | 0.322 | 1 | 0.873 |
PKCG |
0.870 | 0.017 | 2 | 0.778 |
MSK1 |
0.870 | 0.083 | -3 | 0.788 |
PAK3 |
0.870 | -0.038 | -2 | 0.844 |
MYLK4 |
0.870 | 0.058 | -2 | 0.833 |
AURB |
0.870 | 0.080 | -2 | 0.725 |
PRP4 |
0.870 | 0.232 | -3 | 0.803 |
ALK2 |
0.869 | 0.078 | -2 | 0.856 |
GRK4 |
0.869 | -0.205 | -2 | 0.852 |
MNK1 |
0.869 | 0.055 | -2 | 0.868 |
QSK |
0.869 | -0.003 | 4 | 0.821 |
PIM2 |
0.868 | 0.107 | -3 | 0.789 |
AKT2 |
0.868 | 0.110 | -3 | 0.731 |
PRKX |
0.868 | 0.165 | -3 | 0.718 |
VRK2 |
0.868 | -0.175 | 1 | 0.879 |
CHK1 |
0.867 | 0.019 | -3 | 0.862 |
QIK |
0.867 | -0.101 | -3 | 0.870 |
PAK6 |
0.867 | 0.068 | -2 | 0.770 |
ACVR2A |
0.867 | 0.010 | -2 | 0.841 |
ACVR2B |
0.867 | 0.022 | -2 | 0.851 |
SGK3 |
0.867 | 0.084 | -3 | 0.803 |
PKG2 |
0.867 | 0.080 | -2 | 0.748 |
SMG1 |
0.867 | -0.029 | 1 | 0.798 |
MEK1 |
0.867 | -0.214 | 2 | 0.864 |
SIK |
0.867 | -0.003 | -3 | 0.799 |
TTBK2 |
0.866 | -0.270 | 2 | 0.728 |
PHKG1 |
0.866 | -0.058 | -3 | 0.860 |
GRK7 |
0.866 | 0.026 | 1 | 0.764 |
PKCH |
0.866 | -0.006 | 2 | 0.761 |
PKCZ |
0.865 | -0.024 | 2 | 0.811 |
NEK2 |
0.865 | -0.119 | 2 | 0.836 |
YSK4 |
0.865 | -0.172 | 1 | 0.747 |
MLK4 |
0.864 | -0.099 | 2 | 0.758 |
PLK3 |
0.863 | -0.076 | 2 | 0.809 |
PAK2 |
0.863 | -0.051 | -2 | 0.828 |
CAMK1G |
0.863 | 0.008 | -3 | 0.802 |
AURA |
0.862 | 0.054 | -2 | 0.693 |
MARK3 |
0.862 | -0.021 | 4 | 0.779 |
MARK2 |
0.861 | -0.041 | 4 | 0.742 |
BMPR1A |
0.861 | 0.097 | 1 | 0.754 |
BRSK1 |
0.861 | -0.066 | -3 | 0.830 |
CHAK1 |
0.861 | -0.182 | 2 | 0.785 |
JNK1 |
0.861 | 0.357 | 1 | 0.802 |
SMMLCK |
0.860 | 0.044 | -3 | 0.859 |
BRAF |
0.859 | -0.104 | -4 | 0.865 |
DCAMKL1 |
0.859 | 0.003 | -3 | 0.822 |
PINK1 |
0.859 | -0.079 | 1 | 0.876 |
CDK6 |
0.859 | 0.368 | 1 | 0.818 |
TLK2 |
0.859 | -0.150 | 1 | 0.787 |
MAK |
0.859 | 0.344 | -2 | 0.793 |
DRAK1 |
0.858 | -0.121 | 1 | 0.729 |
MAPKAPK5 |
0.858 | -0.105 | -3 | 0.758 |
HRI |
0.858 | -0.190 | -2 | 0.899 |
BRSK2 |
0.858 | -0.128 | -3 | 0.851 |
CDK4 |
0.858 | 0.371 | 1 | 0.806 |
ERK7 |
0.857 | 0.155 | 2 | 0.578 |
PERK |
0.857 | -0.177 | -2 | 0.880 |
AKT1 |
0.857 | 0.099 | -3 | 0.747 |
PKACA |
0.857 | 0.104 | -2 | 0.697 |
WNK4 |
0.856 | -0.127 | -2 | 0.907 |
MARK1 |
0.856 | -0.072 | 4 | 0.803 |
MEKK1 |
0.856 | -0.189 | 1 | 0.795 |
NEK5 |
0.856 | -0.112 | 1 | 0.812 |
MST3 |
0.856 | -0.014 | 2 | 0.867 |
MPSK1 |
0.855 | 0.057 | 1 | 0.797 |
IRAK4 |
0.855 | -0.110 | 1 | 0.779 |
MEKK3 |
0.855 | -0.216 | 1 | 0.778 |
PLK4 |
0.854 | -0.170 | 2 | 0.646 |
MEKK2 |
0.854 | -0.143 | 2 | 0.831 |
MEK5 |
0.854 | -0.315 | 2 | 0.849 |
SNRK |
0.854 | -0.243 | 2 | 0.700 |
PKCT |
0.854 | -0.004 | 2 | 0.768 |
PASK |
0.854 | 0.006 | -3 | 0.889 |
DCAMKL2 |
0.854 | -0.030 | -3 | 0.847 |
ZAK |
0.854 | -0.201 | 1 | 0.757 |
SSTK |
0.854 | -0.009 | 4 | 0.808 |
CAMK1D |
0.853 | 0.053 | -3 | 0.725 |
PHKG2 |
0.853 | -0.041 | -3 | 0.836 |
GRK2 |
0.853 | -0.133 | -2 | 0.739 |
GAK |
0.853 | 0.059 | 1 | 0.843 |
MOK |
0.853 | 0.297 | 1 | 0.867 |
GSK3A |
0.852 | 0.074 | 4 | 0.444 |
P70S6K |
0.852 | -0.000 | -3 | 0.750 |
TAO3 |
0.852 | -0.068 | 1 | 0.783 |
DAPK3 |
0.851 | 0.074 | -3 | 0.838 |
TLK1 |
0.850 | -0.179 | -2 | 0.869 |
PKCI |
0.850 | -0.003 | 2 | 0.778 |
GSK3B |
0.848 | -0.029 | 4 | 0.431 |
PKCE |
0.848 | 0.066 | 2 | 0.762 |
CK1E |
0.848 | -0.068 | -3 | 0.566 |
TAO2 |
0.847 | -0.089 | 2 | 0.882 |
NEK8 |
0.846 | -0.191 | 2 | 0.846 |
CAMKK1 |
0.845 | -0.212 | -2 | 0.808 |
EEF2K |
0.844 | -0.021 | 3 | 0.876 |
PDK1 |
0.844 | -0.112 | 1 | 0.792 |
PAK5 |
0.844 | -0.010 | -2 | 0.705 |
PKN1 |
0.844 | 0.018 | -3 | 0.765 |
SGK1 |
0.844 | 0.103 | -3 | 0.651 |
NEK11 |
0.844 | -0.235 | 1 | 0.775 |
LKB1 |
0.844 | -0.121 | -3 | 0.867 |
AKT3 |
0.844 | 0.098 | -3 | 0.666 |
GCK |
0.843 | -0.052 | 1 | 0.777 |
DAPK1 |
0.843 | 0.041 | -3 | 0.821 |
TNIK |
0.843 | 0.005 | 3 | 0.901 |
MRCKB |
0.843 | 0.089 | -3 | 0.779 |
CK2A2 |
0.843 | 0.043 | 1 | 0.691 |
IRAK1 |
0.842 | -0.311 | -1 | 0.793 |
CHK2 |
0.842 | 0.038 | -3 | 0.675 |
NEK4 |
0.842 | -0.150 | 1 | 0.769 |
CAMK1A |
0.842 | 0.060 | -3 | 0.694 |
TTBK1 |
0.841 | -0.254 | 2 | 0.646 |
MRCKA |
0.841 | 0.073 | -3 | 0.795 |
CAMKK2 |
0.841 | -0.204 | -2 | 0.807 |
MST2 |
0.841 | -0.134 | 1 | 0.784 |
CK1D |
0.841 | -0.056 | -3 | 0.513 |
ROCK2 |
0.841 | 0.094 | -3 | 0.826 |
HGK |
0.841 | -0.069 | 3 | 0.902 |
PAK4 |
0.841 | 0.000 | -2 | 0.712 |
SBK |
0.841 | 0.113 | -3 | 0.609 |
BUB1 |
0.840 | 0.118 | -5 | 0.853 |
MINK |
0.840 | -0.089 | 1 | 0.765 |
TAK1 |
0.840 | -0.130 | 1 | 0.802 |
LRRK2 |
0.839 | -0.153 | 2 | 0.873 |
NEK1 |
0.839 | -0.097 | 1 | 0.778 |
MEKK6 |
0.839 | -0.156 | 1 | 0.777 |
MAP3K15 |
0.838 | -0.161 | 1 | 0.748 |
DMPK1 |
0.838 | 0.144 | -3 | 0.799 |
PLK2 |
0.837 | -0.029 | -3 | 0.833 |
HPK1 |
0.837 | -0.063 | 1 | 0.760 |
CK1A2 |
0.837 | -0.071 | -3 | 0.513 |
GRK3 |
0.837 | -0.134 | -2 | 0.688 |
CK1G1 |
0.837 | -0.128 | -3 | 0.562 |
LOK |
0.836 | -0.086 | -2 | 0.826 |
KHS1 |
0.835 | -0.013 | 1 | 0.761 |
VRK1 |
0.835 | -0.214 | 2 | 0.862 |
KHS2 |
0.835 | 0.026 | 1 | 0.773 |
PDHK3_TYR |
0.834 | 0.252 | 4 | 0.916 |
MST1 |
0.833 | -0.148 | 1 | 0.766 |
PBK |
0.832 | -0.013 | 1 | 0.777 |
CK2A1 |
0.832 | 0.009 | 1 | 0.666 |
SLK |
0.830 | -0.126 | -2 | 0.760 |
YSK1 |
0.830 | -0.122 | 2 | 0.837 |
TTK |
0.829 | 0.004 | -2 | 0.872 |
ROCK1 |
0.827 | 0.070 | -3 | 0.792 |
MEK2 |
0.827 | -0.335 | 2 | 0.827 |
BIKE |
0.827 | 0.065 | 1 | 0.735 |
RIPK2 |
0.827 | -0.334 | 1 | 0.715 |
STK33 |
0.827 | -0.233 | 2 | 0.641 |
CRIK |
0.826 | 0.082 | -3 | 0.746 |
PKG1 |
0.825 | 0.015 | -2 | 0.668 |
TESK1_TYR |
0.824 | -0.027 | 3 | 0.922 |
PDHK4_TYR |
0.824 | 0.074 | 2 | 0.911 |
NEK3 |
0.823 | -0.206 | 1 | 0.746 |
MAP2K4_TYR |
0.822 | -0.064 | -1 | 0.912 |
HASPIN |
0.822 | -0.023 | -1 | 0.713 |
MAP2K6_TYR |
0.822 | -0.003 | -1 | 0.913 |
PKMYT1_TYR |
0.822 | -0.035 | 3 | 0.899 |
OSR1 |
0.820 | -0.130 | 2 | 0.823 |
BMPR2_TYR |
0.820 | 0.001 | -1 | 0.902 |
MAP2K7_TYR |
0.820 | -0.218 | 2 | 0.887 |
LIMK2_TYR |
0.819 | 0.038 | -3 | 0.923 |
MYO3B |
0.819 | -0.068 | 2 | 0.848 |
PDHK1_TYR |
0.818 | -0.068 | -1 | 0.923 |
EPHA6 |
0.818 | 0.056 | -1 | 0.895 |
ALPHAK3 |
0.817 | -0.074 | -1 | 0.806 |
PINK1_TYR |
0.817 | -0.194 | 1 | 0.833 |
ASK1 |
0.815 | -0.214 | 1 | 0.735 |
MYO3A |
0.815 | -0.107 | 1 | 0.764 |
EPHB4 |
0.814 | 0.007 | -1 | 0.878 |
RET |
0.814 | -0.116 | 1 | 0.794 |
AAK1 |
0.813 | 0.116 | 1 | 0.645 |
TAO1 |
0.813 | -0.146 | 1 | 0.709 |
MST1R |
0.811 | -0.125 | 3 | 0.872 |
TYK2 |
0.811 | -0.179 | 1 | 0.790 |
LIMK1_TYR |
0.810 | -0.195 | 2 | 0.879 |
TYRO3 |
0.810 | -0.126 | 3 | 0.857 |
ROS1 |
0.810 | -0.106 | 3 | 0.834 |
YES1 |
0.809 | -0.018 | -1 | 0.885 |
JAK2 |
0.809 | -0.140 | 1 | 0.792 |
CSF1R |
0.809 | -0.086 | 3 | 0.855 |
TXK |
0.809 | 0.064 | 1 | 0.803 |
YANK3 |
0.809 | -0.119 | 2 | 0.427 |
ABL2 |
0.808 | -0.030 | -1 | 0.849 |
DDR1 |
0.807 | -0.162 | 4 | 0.825 |
EPHA4 |
0.806 | -0.015 | 2 | 0.811 |
FER |
0.806 | -0.124 | 1 | 0.850 |
TNK2 |
0.805 | -0.031 | 3 | 0.827 |
LCK |
0.805 | 0.036 | -1 | 0.870 |
BLK |
0.805 | 0.081 | -1 | 0.873 |
INSRR |
0.804 | -0.085 | 3 | 0.813 |
HCK |
0.804 | -0.047 | -1 | 0.870 |
FGR |
0.804 | -0.131 | 1 | 0.825 |
SRMS |
0.804 | -0.050 | 1 | 0.820 |
JAK3 |
0.804 | -0.137 | 1 | 0.771 |
EPHB1 |
0.803 | -0.061 | 1 | 0.817 |
ABL1 |
0.803 | -0.075 | -1 | 0.844 |
FGFR2 |
0.802 | -0.115 | 3 | 0.857 |
EPHB3 |
0.802 | -0.054 | -1 | 0.864 |
ITK |
0.802 | -0.065 | -1 | 0.844 |
EPHB2 |
0.801 | -0.033 | -1 | 0.858 |
TEK |
0.800 | -0.104 | 3 | 0.800 |
KDR |
0.800 | -0.101 | 3 | 0.826 |
TNNI3K_TYR |
0.799 | -0.051 | 1 | 0.810 |
KIT |
0.799 | -0.144 | 3 | 0.858 |
PDGFRB |
0.799 | -0.199 | 3 | 0.868 |
JAK1 |
0.799 | -0.071 | 1 | 0.729 |
STLK3 |
0.799 | -0.309 | 1 | 0.723 |
TNK1 |
0.799 | -0.111 | 3 | 0.833 |
FLT3 |
0.798 | -0.169 | 3 | 0.853 |
AXL |
0.798 | -0.124 | 3 | 0.843 |
MERTK |
0.798 | -0.083 | 3 | 0.834 |
FGFR1 |
0.797 | -0.156 | 3 | 0.833 |
TEC |
0.797 | -0.065 | -1 | 0.788 |
BMX |
0.796 | -0.057 | -1 | 0.765 |
NEK10_TYR |
0.796 | -0.172 | 1 | 0.667 |
FYN |
0.795 | 0.019 | -1 | 0.845 |
EPHA7 |
0.795 | -0.050 | 2 | 0.812 |
CK1A |
0.794 | -0.133 | -3 | 0.419 |
BTK |
0.793 | -0.206 | -1 | 0.815 |
DDR2 |
0.793 | -0.000 | 3 | 0.809 |
MET |
0.792 | -0.153 | 3 | 0.847 |
WEE1_TYR |
0.792 | -0.128 | -1 | 0.789 |
LTK |
0.792 | -0.145 | 3 | 0.807 |
ALK |
0.792 | -0.172 | 3 | 0.787 |
PDGFRA |
0.791 | -0.281 | 3 | 0.864 |
EPHA3 |
0.791 | -0.135 | 2 | 0.783 |
EPHA1 |
0.791 | -0.109 | 3 | 0.832 |
FGFR3 |
0.790 | -0.146 | 3 | 0.832 |
LYN |
0.790 | -0.078 | 3 | 0.781 |
FRK |
0.789 | -0.109 | -1 | 0.880 |
FLT1 |
0.789 | -0.159 | -1 | 0.862 |
NTRK1 |
0.789 | -0.243 | -1 | 0.852 |
EPHA5 |
0.788 | -0.053 | 2 | 0.799 |
PTK2B |
0.787 | -0.078 | -1 | 0.820 |
ERBB2 |
0.787 | -0.225 | 1 | 0.746 |
PTK6 |
0.786 | -0.296 | -1 | 0.772 |
FLT4 |
0.785 | -0.225 | 3 | 0.814 |
INSR |
0.785 | -0.211 | 3 | 0.790 |
NTRK2 |
0.784 | -0.267 | 3 | 0.820 |
EPHA8 |
0.783 | -0.092 | -1 | 0.843 |
SRC |
0.783 | -0.096 | -1 | 0.844 |
NTRK3 |
0.782 | -0.201 | -1 | 0.804 |
MATK |
0.782 | -0.170 | -1 | 0.771 |
EGFR |
0.780 | -0.117 | 1 | 0.656 |
PTK2 |
0.780 | -0.011 | -1 | 0.815 |
CSK |
0.778 | -0.202 | 2 | 0.810 |
FGFR4 |
0.776 | -0.144 | -1 | 0.804 |
CK1G3 |
0.776 | -0.125 | -3 | 0.370 |
EPHA2 |
0.774 | -0.089 | -1 | 0.808 |
SYK |
0.774 | -0.052 | -1 | 0.802 |
YANK2 |
0.772 | -0.168 | 2 | 0.446 |
IGF1R |
0.769 | -0.202 | 3 | 0.729 |
MUSK |
0.769 | -0.216 | 1 | 0.645 |
ERBB4 |
0.767 | -0.103 | 1 | 0.673 |
FES |
0.756 | -0.210 | -1 | 0.742 |
CK1G2 |
0.753 | -0.141 | -3 | 0.472 |
ZAP70 |
0.748 | -0.116 | -1 | 0.724 |