Motif 904 (n=1,382)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| B7U540 | KCNJ18 | S405 | ochoa | Inward rectifier potassium channel 18 (Inward rectifier K(+) channel Kir2.6) (Potassium channel, inwardly rectifying subfamily J member 18) | Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. {ECO:0000269|PubMed:20074522, ECO:0000269|PubMed:27008341}. |
| E9PAV3 | NACA | S1977 | ochoa | Nascent polypeptide-associated complex subunit alpha, muscle-specific form (Alpha-NAC, muscle-specific form) (skNAC) | Cardiac- and muscle-specific transcription factor. May act to regulate the expression of genes involved in the development of myotubes. Plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration. Involved in the organized assembly of thick and thin filaments of myofibril sarcomeres (By similarity). {ECO:0000250|UniProtKB:P70670}. |
| H7C4K7 | None | S56 | ochoa | Nucleoporin NUP188 | None |
| O00161 | SNAP23 | S110 | ochoa|psp | Synaptosomal-associated protein 23 (SNAP-23) (Vesicle-membrane fusion protein SNAP-23) | Essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion. |
| O00418 | EEF2K | S359 | 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}. |
| O00472 | ELL2 | S604 | ochoa | RNA polymerase II elongation factor ELL2 | Elongation factor 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. 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). Plays a role in immunoglobulin secretion in plasma cells: directs efficient alternative mRNA processing, influencing both proximal poly(A) site choice and exon skipping, as well as immunoglobulin heavy chain (IgH) alternative processing. Probably acts by regulating histone modifications accompanying transition from membrane-specific to secretory IgH mRNA expression. {ECO:0000269|PubMed:20159561, ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:22195968, ECO:0000269|PubMed:23251033}. |
| O00566 | MPHOSPH10 | S163 | ochoa | U3 small nucleolar ribonucleoprotein protein MPP10 (M phase phosphoprotein 10) | Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing (PubMed:12655004). 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:12655004, ECO:0000269|PubMed:34516797}. |
| O14495 | PLPP3 | S19 | ochoa | Phospholipid phosphatase 3 (EC 3.1.3.-) (EC 3.1.3.4) (Lipid phosphate phosphohydrolase 3) (PAP2-beta) (Phosphatidate phosphohydrolase type 2b) (Phosphatidic acid phosphatase 2b) (PAP-2b) (PAP2b) (Vascular endothelial growth factor and type I collagen-inducible protein) (VCIP) | Magnesium-independent phospholipid phosphatase of the plasma membrane that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, diacylglycerol pyrophosphate/DGPP, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P (PubMed:27694435, PubMed:9607309, PubMed:9705349). Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound (PubMed:9607309). Has both an extracellular and an intracellular phosphatase activity, allowing the hydrolysis and the cellular uptake of these bioactive lipid mediators from the milieu, regulating signal transduction in different cellular processes (PubMed:23591818, PubMed:27694435, PubMed:9607309). Through the dephosphorylation of extracellular sphingosine-1-phosphate and the regulation of its extra- and intracellular availability, plays a role in vascular homeostasis, regulating endothelial cell migration, adhesion, survival, proliferation and the production of pro-inflammatory cytokines (PubMed:27694435). By maintaining the appropriate levels of this lipid in the cerebellum, also ensure its proper development and function (By similarity). Through its intracellular lipid phosphatase activity may act in early compartments of the secretory pathway, regulating the formation of Golgi to endoplasmic reticulum retrograde transport carriers (PubMed:23591818). {ECO:0000250|UniProtKB:Q99JY8, ECO:0000269|PubMed:23591818, ECO:0000269|PubMed:27694435, ECO:0000269|PubMed:9607309, ECO:0000269|PubMed:9705349}.; FUNCTION: Independently of this phosphatase activity may also function in the Wnt signaling pathway and the stabilization of beta-catenin/CTNNB1, thereby regulating cell proliferation, migration and differentiation in angiogenesis or yet in tumor growth (PubMed:20123964, PubMed:21569306). Also plays a role in integrin-mediated cell-cell adhesion in angiogenesis (PubMed:12660161, PubMed:16099422). {ECO:0000269|PubMed:12660161, ECO:0000269|PubMed:16099422, ECO:0000269|PubMed:20123964, ECO:0000269|PubMed:21569306}. |
| O14745 | NHERF1 | S280 | 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}. |
| O14964 | HGS | S240 | ochoa | Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) (Protein pp110) | Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (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. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation. |
| 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}. |
| O15195 | VILL | S723 | ochoa | Villin-like protein | Possible tumor suppressor. |
| O15409 | FOXP2 | S591 | ochoa | Forkhead box protein P2 (CAG repeat protein 44) (Trinucleotide repeat-containing gene 10 protein) | Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. Involved in neural mechanisms mediating the development of speech and language. |
| O43166 | SIPA1L1 | S1734 | 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}. |
| O43252 | PAPSS1 | S102 | ochoa | 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}. |
| O43314 | PPIP5K2 | S1152 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}. |
| O43379 | WDR62 | S614 | ochoa | WD repeat-containing protein 62 | Required for cerebral cortical development. Plays a role in neuronal proliferation and migration (PubMed:20729831, PubMed:20890278). Plays a role in mother-centriole-dependent centriole duplication; the function also seems to involve CEP152, CDK5RAP2 and CEP63 through a stepwise assembled complex at the centrosome that recruits CDK2 required for centriole duplication (PubMed:26297806). {ECO:0000269|PubMed:20729831, ECO:0000269|PubMed:20890278, ECO:0000269|PubMed:26297806}. |
| O43491 | EPB41L2 | S598 | ochoa | Band 4.1-like protein 2 (Erythrocyte membrane protein band 4.1-like 2) (Generally expressed protein 4.1) (4.1G) | Required for dynein-dynactin complex and NUMA1 recruitment at the mitotic cell cortex during anaphase (PubMed:23870127). {ECO:0000269|PubMed:23870127}. |
| O43707 | ACTN4 | S621 | ochoa | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| O43765 | SGTA | S77 | 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}. |
| O60318 | MCM3AP | S1727 | 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}. |
| O75038 | PLCH2 | S605 | ochoa | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-eta-2) (Phosphoinositide phospholipase C-like 4) (PLC-L4) (Phospholipase C-like protein 4) (Phospholipase C-eta-2) (PLC-eta2) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes (PubMed:18361507). This phospholipase activity is very sensitive to calcium. May be important for formation and maintenance of the neuronal network in the postnatal brain (By similarity). {ECO:0000250|UniProtKB:A2AP18, ECO:0000269|PubMed:18361507}. |
| 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}. |
| O75604 | USP2 | S252 | ochoa | Ubiquitin carboxyl-terminal hydrolase 2 (EC 3.4.19.12) (41 kDa ubiquitin-specific protease) (Deubiquitinating enzyme 2) (Ubiquitin thioesterase 2) (Ubiquitin-specific-processing protease 2) | Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1 (PubMed:17290220, PubMed:19838211, PubMed:19917254). Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities (By similarity). Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity (PubMed:17290220, PubMed:19838211). Has no deubiquitinase activity against p53/TP53 (PubMed:17290220). Prevents MDM2-mediated degradation of MDM4 (PubMed:17290220). Plays a role in the G1/S cell-cycle progression in normal and cancer cells (PubMed:19917254). Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues (By similarity). Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability (By similarity). Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and BMAL1 (By similarity). Plays a role in the regulation of myogenic differentiation of embryonic muscle cells (By similarity). {ECO:0000250|UniProtKB:O88623, ECO:0000250|UniProtKB:Q5U349, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:19917254}.; FUNCTION: [Isoform 4]: Circadian clock output effector that regulates Ca(2+) absorption in the small intestine. Probably functions by regulating protein levels of the membrane scaffold protein NHERF4 in a rhythmic manner, and is therefore likely to control Ca(2+) membrane permeability mediated by the Ca(2+) channel TRPV6 in the intestine. {ECO:0000250|UniProtKB:O88623}. |
| O75643 | SNRNP200 | S932 | 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}. |
| O94898 | LRIG2 | S913 | ochoa | Leucine-rich repeats and immunoglobulin-like domains protein 2 (LIG-2) | None |
| O94913 | PCF11 | S728 | ochoa | Pre-mRNA cleavage complex 2 protein Pcf11 (Pre-mRNA cleavage complex II protein Pcf11) | Component of pre-mRNA cleavage complex II, which promotes transcription termination by RNA polymerase II. {ECO:0000269|PubMed:11060040, ECO:0000269|PubMed:29196535}. |
| O95155 | UBE4B | S803 | 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}. |
| O95197 | RTN3 | S575 | ochoa | Reticulon-3 (Homolog of ASY protein) (HAP) (Neuroendocrine-specific protein-like 2) (NSP-like protein 2) (Neuroendocrine-specific protein-like II) (NSP-like protein II) (NSPLII) | May be involved in membrane trafficking in the early secretory pathway. Inhibits BACE1 activity and amyloid precursor protein processing. May induce caspase-8 cascade and apoptosis. May favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress. Induces the formation of endoplasmic reticulum tubules (PubMed:25612671). Also acts as an inflammation-resolving regulator by interacting with both TRIM25 and RIGI, subsequently impairing RIGI 'Lys-63'-linked polyubiquitination leading to IRF3 and NF-kappa-B inhibition. {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16054885, ECO:0000269|PubMed:17031492, ECO:0000269|PubMed:17191123, ECO:0000269|PubMed:25612671}.; FUNCTION: (Microbial infection) Plays a positive role in viral replication and pathogenesis of enteroviruses. {ECO:0000269|PubMed:17182608}. |
| O95249 | GOSR1 | S41 | ochoa | Golgi SNAP receptor complex member 1 (28 kDa Golgi SNARE protein) (28 kDa cis-Golgi SNARE p28) (GOS-28) | Involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. It belongs to a super-family of proteins called t-SNAREs or soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor. May play a protective role against hydrogen peroxide induced cytotoxicity under glutathione depleted conditions in neuronal cells by regulating the intracellular ROS levels via inhibition of p38 MAPK (MAPK11, MAPK12, MAPK13 and MAPK14). Participates in docking and fusion stage of ER to cis-Golgi transport. Plays an important physiological role in VLDL-transport vesicle-Golgi fusion and thus in VLDL delivery to the hepatic cis-Golgi. {ECO:0000269|PubMed:15215310, ECO:0000269|PubMed:21860593}. |
| O95340 | PAPSS2 | S92 | ochoa | Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPS synthase 2) (PAPSS 2) (Sulfurylase kinase 2) (SK 2) (SK2) [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, the activated sulfate donor used by sulfotransferases (PubMed:11773860, PubMed:19474428, PubMed:23824674, PubMed:25594860). In mammals, PAPS is the sole source of sulfate while APS appears to only be an intermediate in the sulfate-activation pathway (PubMed:11773860, PubMed:19474428, PubMed:23824674, PubMed:25594860). Plays indirectly an important role in skeletogenesis during postnatal growth (PubMed:9771708). {ECO:0000269|PubMed:11773860, ECO:0000269|PubMed:19474428, ECO:0000269|PubMed:23824674, ECO:0000269|PubMed:25594860, ECO:0000269|PubMed:9771708}. |
| O95402 | MED26 | S535 | 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. |
| O95487 | SEC24B | S556 | ochoa | Protein transport protein Sec24B (SEC24-related protein B) | Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex (PubMed:17499046, PubMed:18843296, PubMed:20427317). Plays a central role in cargo selection within the COPII complex and together with SEC24A may have a different specificity compared to SEC24C and SEC24D. May package preferentially cargos with cytoplasmic DxE or LxxLE motifs and may also recognize conformational epitopes (PubMed:17499046, PubMed:18843296). {ECO:0000269|PubMed:17499046, ECO:0000269|PubMed:18843296, ECO:0000269|PubMed:20427317}. |
| O95602 | POLR1A | S1695 | ochoa | DNA-directed RNA polymerase I subunit RPA1 (RNA polymerase I subunit A1) (EC 2.7.7.6) (A190) (DNA-directed RNA polymerase I largest subunit) (DNA-directed RNA polymerase I subunit A) (RNA polymerase I 194 kDa subunit) (RPA194) | Catalytic core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates. Transcribes 47S pre-rRNAs from multicopy rRNA gene clusters, giving rise to 5.8S, 18S and 28S ribosomal RNAs (PubMed:11250903, PubMed:11283244, PubMed:16858408, PubMed:34671025, PubMed:34887565, PubMed:36271492). Pol I-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol I pre-initiation complex (PIC) is recruited by the selectivity factor 1 (SL1/TIF-IB) complex bound to the core promoter that precedes an rDNA repeat unit. The PIC assembly bends the promoter favoring the formation of the transcription bubble and promoter escape. 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. Highly processive, assembles in structures referred to as 'Miller trees' where many elongating Pol I complexes queue and transcribe the same rDNA coding regions. At terminator sequences downstream of the rDNA gene, PTRF interacts with Pol I and halts Pol I transcription leading to the release of the RNA transcript and polymerase from the DNA (PubMed:11250903, PubMed:11283244, PubMed:16858408, PubMed:34671025, PubMed:34887565, PubMed:36271492). Forms Pol I active center together with the second largest subunit POLR1B/RPA2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR1A/RPA1 contributing a Mg(2+)-coordinating DxDGD motif, and POLR1B/RPA2 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 the 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. Has proofreading activity: Pauses and backtracks to allow the cleavage of a missincorporated nucleotide via POLR1H/RPA12. High Pol I processivity is associated with decreased transcription fidelity (By similarity) (PubMed:11250903, PubMed:11283244, PubMed:16858408, PubMed:34671025, PubMed:34887565, PubMed:36271492). {ECO:0000250|UniProtKB:P10964, ECO:0000269|PubMed:11250903, ECO:0000269|PubMed:11283244, ECO:0000269|PubMed:16858408, ECO:0000269|PubMed:34671025, ECO:0000269|PubMed:34887565, ECO:0000269|PubMed:36271492}. |
| O95644 | NFATC1 | S903 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 1 (NF-ATc1) (NFATc1) (NFAT transcription complex cytosolic component) (NF-ATc) (NFATc) | Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (By similarity). {ECO:0000250|UniProtKB:O88942, ECO:0000269|PubMed:10358178}. |
| O95671 | ASMTL | S421 | ochoa | Probable bifunctional dTTP/UTP pyrophosphatase/methyltransferase protein [Includes: dTTP/UTP pyrophosphatase (dTTPase/UTPase) (EC 3.6.1.9) (Nucleoside triphosphate pyrophosphatase) (Nucleotide pyrophosphatase) (Nucleotide PPase); N-acetylserotonin O-methyltransferase-like protein (ASMTL) (EC 2.1.1.-)] | Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP. Can also hydrolyze CTP and the modified nucleotides pseudo-UTP, 5-methyl-UTP (m(5)UTP) and 5-methyl-CTP (m(5)CTP). Has weak activity with dCTP, 8-oxo-GTP and N(4)-methyl-dCTP (PubMed:24210219). May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids (PubMed:24210219). In addition, the presence of the putative catalytic domain of S-adenosyl-L-methionine binding in the C-terminal region argues for a methyltransferase activity (Probable). {ECO:0000269|PubMed:24210219, ECO:0000305}. |
| O95833 | CLIC3 | S49 | ochoa | Chloride intracellular channel protein 3 (Glutaredoxin-like oxidoreductase CLIC3) (EC 1.8.-.-) | In the soluble state, catalyzes glutaredoxin-like thiol disulfide exchange reactions with reduced glutathione as electron donor (PubMed:28198360, PubMed:37759794). Reduced in a glutathione-dependent way and secreted into the extracellular matrix where it activates TGM2 and promotes blood vessel growth during tissue remodeling as occurs in tumorigenesis. Can reduce specific cysteines in TGM2 and regulate cofactor binding (PubMed:28198360). Can insert into membranes and form outwardly rectifying chloride ion channels. May participate in cellular growth control. {ECO:0000269|PubMed:28198360, ECO:0000269|PubMed:32066374, ECO:0000269|PubMed:37759794, ECO:0000269|PubMed:9880541}. |
| O96019 | ACTL6A | S86 | ochoa|psp | Actin-like protein 6A (53 kDa BRG1-associated factor A) (Actin-related protein Baf53a) (ArpNbeta) (BRG1-associated factor 53A) (BAF53A) (INO80 complex subunit K) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Required for maximal ATPase activity of SMARCA4/BRG1/BAF190A and for association of the SMARCA4/BRG1/BAF190A containing remodeling complex BAF with chromatin/nuclear matrix. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Putative core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. {ECO:0000250|UniProtKB:Q9Z2N8, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:29374058, ECO:0000303|PubMed:15196461, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| O96028 | NSD2 | S121 | ochoa | Histone-lysine N-methyltransferase NSD2 (EC 2.1.1.357) (Multiple myeloma SET domain-containing protein) (MMSET) (Nuclear SET domain-containing protein 2) (Protein trithorax-5) (Wolf-Hirschhorn syndrome candidate 1 protein) | Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:19808676, PubMed:22099308, PubMed:27571355, PubMed:29728617, PubMed:33941880). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:22099308). Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (PubMed:22099308). However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells (By similarity). By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes (PubMed:16115125, PubMed:22099308, PubMed:29728617). In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation (By similarity). During heart development, associates with transcription factor NKX2-5 to repress transcription of NKX2-5 target genes (By similarity). Plays an essential role in adipogenesis, by regulating expression of genes involved in pre-adipocyte differentiation (PubMed:29728617). During T-cell receptor (TCR) and CD28-mediated T-cell activation, promotes the transcription of transcription factor BCL6 which is required for follicular helper T (Tfh) cell differentiation (By similarity). During B-cell development, required for the generation of the B1 lineage (By similarity). During B2 cell activation, may contribute to the control of isotype class switch recombination (CRS), splenic germinal center formation, and the humoral immune response (By similarity). Plays a role in class switch recombination of the immunoglobulin heavy chain (IgH) locus during B-cell activation (By similarity). By regulating the methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 recruitment to the IgH switch region and promotes the transcription of IgA (By similarity). {ECO:0000250|UniProtKB:Q8BVE8, ECO:0000269|PubMed:16115125, ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308, ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617, ECO:0000269|PubMed:33941880}.; FUNCTION: [Isoform 1]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). {ECO:0000269|PubMed:22099308}.; FUNCTION: [Isoform 4]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:22099308). Methylation of histone H3 at 'Lys-27' is controversial (PubMed:18172012, PubMed:22099308). Mono-, di- or tri-methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2 and H3K27me3) (PubMed:18172012). Does not methylate histone H3 at 'Lys-27' (PubMed:22099308). May act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment (PubMed:11152655, PubMed:18172012). {ECO:0000269|PubMed:11152655, ECO:0000269|PubMed:18172012, ECO:0000269|PubMed:22099308}. |
| P09327 | VIL1 | S219 | ochoa | Villin-1 | Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination. {ECO:0000269|PubMed:11500485, ECO:0000269|PubMed:14594952, ECO:0000269|PubMed:15084600, ECO:0000269|PubMed:15272027, ECO:0000269|PubMed:15342783, ECO:0000269|PubMed:16921170, ECO:0000269|PubMed:17182858, ECO:0000269|PubMed:17229814, ECO:0000269|PubMed:17606613, ECO:0000269|PubMed:18054784, ECO:0000269|PubMed:18198174, ECO:0000269|PubMed:19808673, ECO:0000269|PubMed:3087992}. |
| P10244 | MYBL2 | S393 | ochoa|psp | Myb-related protein B (B-Myb) (Myb-like protein 2) | Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene. {ECO:0000269|PubMed:10770937}. |
| 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}. |
| P14923 | JUP | S182 | 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}. |
| P15336 | ATF2 | S136 | ochoa | Cyclic AMP-dependent transcription factor ATF-2 (cAMP-dependent transcription factor ATF-2) (Activating transcription factor 2) (Cyclic AMP-responsive element-binding protein 2) (CREB-2) (cAMP-responsive element-binding protein 2) (HB16) (cAMP response element-binding protein CRE-BP1) | Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3'). In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form (mediated by ATM) plays a role in the DNA damage response and is involved in the ionizing radiation (IR)-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci (IRIF). Exhibits histone acetyltransferase (HAT) activity which specifically acetylates histones H2B and H4 in vitro (PubMed:10821277). In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. {ECO:0000269|PubMed:10821277, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:22304920}. |
| P15622 | ZNF250 | S134 | ochoa | Zinc finger protein 250 (Zinc finger protein 647) | May be involved in transcriptional regulation. |
| 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}. |
| P18858 | LIG1 | S819 | ochoa | 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}. |
| P21333 | FLNA | S2510 | 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}. |
| P23497 | SP100 | S31 | 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}. |
| P28562 | DUSP1 | S296 | 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 | S615 | ochoa|psp | Retinoblastoma-like protein 1 (107 kDa retinoblastoma-associated protein) (p107) (pRb1) | Key regulator of entry into cell division (PubMed:17671431). Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation (By similarity). Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression (By similarity). Controls histone H4 'Lys-20' trimethylation (By similarity). Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters (By similarity). Potent inhibitor of E2F-mediated trans-activation (PubMed:8319904). May act as a tumor suppressor (PubMed:8319904). {ECO:0000250|UniProtKB:Q64701, ECO:0000269|PubMed:17671431, ECO:0000269|PubMed:8319904}. |
| P28749 | RBL1 | S1041 | 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}. |
| 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}. |
| P30411 | BDKRB2 | S366 | psp | B2 bradykinin receptor (B2R) (BK-2 receptor) | Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:1314587, ECO:0000269|PubMed:1329734}. |
| P31327 | CPS1 | S1079 | 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. |
| P36404 | ARL2 | S45 | ochoa | ADP-ribosylation factor-like protein 2 | Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). GTP-binding protein that does not act as an allosteric activator of the cholera toxin catalytic subunit. Regulates formation of new microtubules and centrosome integrity. Prevents the TBCD-induced microtubule destruction. Participates in association with TBCD, in the disassembly of the apical junction complexes. Antagonizes the effect of TBCD on epithelial cell detachment and tight and adherens junctions disassembly. Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. Component of a regulated secretory pathway involved in Ca(2+)-dependent release of acetylcholine. Required for normal progress through the cell cycle (PubMed:10831612, PubMed:16525022, PubMed:18234692, PubMed:18588884, PubMed:20740604). Also regulates mitochondrial integrity and function (PubMed:30945270). {ECO:0000269|PubMed:10831612, ECO:0000269|PubMed:16525022, ECO:0000269|PubMed:18234692, ECO:0000269|PubMed:18588884, ECO:0000269|PubMed:20740604, ECO:0000269|PubMed:30945270}. |
| P37198 | NUP62 | S468 | ochoa | Nuclear pore glycoprotein p62 (62 kDa nucleoporin) (Nucleoporin Nup62) | Essential component of the nuclear pore complex (PubMed:1915414). The N-terminal is probably involved in nucleocytoplasmic transport (PubMed:1915414). The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex (PubMed:1915414, PubMed:24107630). Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation (PubMed:24107630). It might be involved in protein recruitment to the centrosome after nuclear breakdown (PubMed:24107630). {ECO:0000269|PubMed:1915414, ECO:0000269|PubMed:24107630}. |
| P38398 | BRCA1 | S956 | 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}. |
| P42684 | ABL2 | S72 | 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}. |
| P46939 | UTRN | S3304 | ochoa | Utrophin (Dystrophin-related protein 1) (DRP-1) | May play a role in anchoring the cytoskeleton to the plasma membrane. {ECO:0000250}. |
| P46940 | IQGAP1 | S330 | ochoa | Ras GTPase-activating-like protein IQGAP1 (p195) | Plays a crucial role in regulating the dynamics and assembly of the actin cytoskeleton. Recruited to the cell cortex by interaction with ILK which allows it to cooperate with its effector DIAPH1 to locally stabilize microtubules and allow stable insertion of caveolae into the plasma membrane (By similarity). Binds to activated CDC42 but does not stimulate its GTPase activity. Associates with calmodulin. May promote neurite outgrowth (PubMed:15695813). May play a possible role in cell cycle regulation by contributing to cell cycle progression after DNA replication arrest (PubMed:20883816). {ECO:0000250|UniProtKB:Q9JKF1, ECO:0000269|PubMed:15695813, ECO:0000269|PubMed:20883816}. |
| P49116 | NR2C2 | S68 | 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 | S1221 | ochoa | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P49327 | FASN | S1411 | 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}. |
| P49736 | MCM2 | S381 | ochoa | DNA replication licensing factor MCM2 (EC 3.6.4.12) (Minichromosome maintenance protein 2 homolog) (Nuclear protein BM28) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (PubMed:8175912). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (PubMed:26196677). {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:8175912}. |
| P49802 | RGS7 | S241 | ochoa | Regulator of G-protein signaling 7 (RGS7) | GTPase activator component of the RGS7-GNB5 complex that regulates G protein-coupled receptor signaling cascades (PubMed:10521509, PubMed:10862767, PubMed:31189666). The RGS7-GNB5 complex acts as an inhibitor signal transduction by promoting the GTPase activity of G protein alpha subunits, such as GNAO1, thereby driving them into their inactive GDP-bound form (PubMed:10521509, PubMed:10862767). May play a role in synaptic vesicle exocytosis (Probable) (PubMed:12659861). Glycine-dependent regulation of the RGS7-GNB5 complex by GPR158 affects mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (By similarity). Modulates the activity of potassium channels that are activated by GNAO1 in response to muscarinic acetylcholine receptor M2/CHRM2 signaling (PubMed:15897264). {ECO:0000250|UniProtKB:O54829, ECO:0000269|PubMed:10521509, ECO:0000269|PubMed:10862767, ECO:0000269|PubMed:15897264, ECO:0000269|PubMed:31189666, ECO:0000305|PubMed:12659861}. |
| P51946 | CCNH | S132 | ochoa | Cyclin-H (MO15-associated protein) (p34) (p37) | Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:7533895}. |
| P51956 | NEK3 | S355 | ochoa | Serine/threonine-protein kinase Nek3 (EC 2.7.11.1) (HSPK 36) (Never in mitosis A-related kinase 3) (NimA-related protein kinase 3) | Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2. {ECO:0000269|PubMed:15618286, ECO:0000269|PubMed:17297458}. |
| P53992 | SEC24C | S862 | ochoa | Protein transport protein Sec24C (SEC24-related protein C) | Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex (PubMed:10214955, PubMed:17499046, PubMed:18843296, PubMed:20427317). Plays a central role in cargo selection within the COPII complex and together with SEC24D may have a different specificity compared to SEC24A and SEC24B (PubMed:17499046, PubMed:18843296, PubMed:20427317). May more specifically package GPI-anchored proteins through the cargo receptor TMED10 (PubMed:20427317). May also be specific for IxM motif-containing cargos like the SNAREs GOSR2 and STX5 (PubMed:18843296). {ECO:0000269|PubMed:10214955, ECO:0000269|PubMed:17499046, ECO:0000269|PubMed:18843296, ECO:0000269|PubMed:20427317}. |
| 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}. |
| P54278 | PMS2 | S403 | 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}. |
| P54750 | PDE1A | S487 | ochoa | Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A (Cam-PDE 1A) (EC 3.1.4.17) (61 kDa Cam-PDE) (hCam-1) | Calcium/calmodulin-dependent cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cGMP and cAMP, which are key regulators of many important physiological processes. Has a higher efficiency with cGMP compared to cAMP. {ECO:0000269|PubMed:8557689}. |
| P54821 | PRRX1 | S67 | ochoa | Paired mesoderm homeobox protein 1 (Homeobox protein PHOX1) (Paired-related homeobox protein 1) (PRX-1) | Master transcription factor of stromal fibroblasts for myofibroblastic lineage progression. Orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-beta signaling by remodeling a super-enhancer landscape. Through this function, plays an essential role in wound healing process (PubMed:35589735). Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer (By similarity). May play a role in homeostasis and regeneration of bone, white adipose tissue and derm (By similarity). {ECO:0000250|UniProtKB:P63013, ECO:0000269|PubMed:35589735}.; FUNCTION: [Isoform 1]: Transcriptional activator, when transfected in fibroblastic or myoblastic cell lines. This activity may be masked by the C-terminal OAR domain. {ECO:0000250|UniProtKB:P63013}.; FUNCTION: [Isoform 2]: Transcriptional repressor, when transfected in fibroblastic or myoblastic cell lines. {ECO:0000250|UniProtKB:P63013}. |
| P54829 | PTPN5 | S268 | psp | Tyrosine-protein phosphatase non-receptor type 5 (EC 3.1.3.48) (Neural-specific protein-tyrosine phosphatase) (Striatum-enriched protein-tyrosine phosphatase) (STEP) | May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors. {ECO:0000269|PubMed:21777200}. |
| P55084 | HADHB | S67 | ochoa | Trifunctional enzyme subunit beta, mitochondrial (TP-beta) [Includes: 3-ketoacyl-CoA thiolase (EC 2.3.1.155) (EC 2.3.1.16) (Acetyl-CoA acyltransferase) (Beta-ketothiolase)] | Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway (PubMed:29915090, PubMed:30850536, PubMed:8135828). The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the trifunctional enzyme subunit beta/HADHB described here bears the 3-ketoacyl-CoA thiolase activity (PubMed:29915090, PubMed:30850536, PubMed:8135828). {ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}. |
| P55265 | ADAR | S491 | 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}. |
| P57737 | CORO7 | S614 | ochoa | Coronin-7 (Crn7) (70 kDa WD repeat tumor rejection antigen homolog) | F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via 'Lys-33'-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network, where it promotes actin polymerization, thereby facilitating post-Golgi trafficking. May play a role in the maintenance of the Golgi apparatus morphology. {ECO:0000269|PubMed:16905771, ECO:0000269|PubMed:24768539}. |
| P61978 | HNRNPK | S116 | ochoa|psp | Heterogeneous nuclear ribonucleoprotein K (hnRNP K) (Transformation up-regulated nuclear protein) (TUNP) | One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPL and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33174841}. |
| P78559 | MAP1A | S2664 | ochoa | Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Cleaved into: MAP1A heavy chain; MAP1 light chain LC2] | Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements. |
| Q01518 | CAP1 | S34 | ochoa | Adenylyl cyclase-associated protein 1 (CAP 1) | Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. |
| Q01959 | SLC6A3 | S53 | psp | Sodium-dependent dopamine transporter (DA transporter) (DAT) (Solute carrier family 6 member 3) | Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:39112701, PubMed:39112703, PubMed:39112705, PubMed:8302271). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity). {ECO:0000250|UniProtKB:P23977, ECO:0000250|UniProtKB:Q61327, ECO:0000269|PubMed:10375632, ECO:0000269|PubMed:11093780, ECO:0000269|PubMed:1406597, ECO:0000269|PubMed:15505207, ECO:0000269|PubMed:19478460, ECO:0000269|PubMed:39112701, ECO:0000269|PubMed:39112703, ECO:0000269|PubMed:39112705, ECO:0000269|PubMed:8302271}. |
| 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}. |
| Q03989 | ARID5A | S256 | ochoa | AT-rich interactive domain-containing protein 5A (ARID domain-containing protein 5A) (Modulator recognition factor 1) (MRF-1) | DNA-binding protein that may regulate transcription and act as a repressor by binding to AT-rich stretches in the promoter region of target genes (PubMed:8649988). May positively regulate chondrocyte-specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention (By similarity). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (PubMed:15941852). As an RNA-binding protein, involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as STAT3 and TBX21 (By similarity). Also stabilizes IL6 mRNA (PubMed:32209697). Binds to stem loop structures located in the 3'UTRs of IL6, STAT3 and TBX21 mRNAs; at least for STAT3 prevents binding of ZC3H12A to the mRNA stem loop structure thus inhibiting its degradation activity. Contributes to elevated IL6 levels possibly implicated in autoimmunity processes. IL6-dependent stabilization of STAT3 mRNA may promote differentiation of naive CD4+ T-cells into T-helper Th17 cells. In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling. Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (By similarity). Stabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR; thereby competing with the mRNA-destabilizing functions of RC3H1 and endoribonuclease ZC3H12A (By similarity). {ECO:0000250|UniProtKB:Q3U108, ECO:0000269|PubMed:15941852, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:8649988}. |
| Q05639 | EEF1A2 | S358 | 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}. |
| Q05655 | PRKCD | S503 | 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}. |
| Q06265 | EXOSC9 | S65 | ochoa | Exosome complex component RRP45 (Autoantigen PM/Scl 1) (Exosome component 9) (P75 polymyositis-scleroderma overlap syndrome-associated autoantigen) (Polymyositis/scleroderma autoantigen 1) (Polymyositis/scleroderma autoantigen 75 kDa) (PM/Scl-75) | Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC9 binds to ARE-containing RNAs. {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:16455498, ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563}. |
| Q06587 | RING1 | S38 | ochoa | E3 ubiquitin-protein ligase RING1 (EC 2.3.2.27) (Polycomb complex protein RING1) (RING finger protein 1) (RING-type E3 ubiquitin transferase RING1) (Really interesting new gene 1 protein) | Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity. {ECO:0000269|PubMed:16359901}. |
| Q07866 | KLC1 | S162 | ochoa | Kinesin light chain 1 (KLC 1) | Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport (PubMed:21385839). The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (By similarity). {ECO:0000250|UniProtKB:P37285, ECO:0000269|PubMed:21385839}. |
| Q08999 | RBL2 | S639 | ochoa|psp | Retinoblastoma-like protein 2 (130 kDa retinoblastoma-associated protein) (p130) (Retinoblastoma-related protein 2) (RBR-2) (pRb2) | Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor. |
| Q08999 | RBL2 | S1112 | ochoa|psp | Retinoblastoma-like protein 2 (130 kDa retinoblastoma-associated protein) (p130) (Retinoblastoma-related protein 2) (RBR-2) (pRb2) | Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor. |
| Q08AM6 | VAC14 | S517 | ochoa | Protein VAC14 homolog (Tax1-binding protein 2) | Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes into a star-shaped structure and nucleates the assembly of the complex. The pentamer binds a single copy each of PIKFYVE and FIG4 and coordinates both PIKfyve kinase activity and FIG4 phosphatase activity, being required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:33098764). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. {ECO:0000269|PubMed:15542851, ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:33098764}. |
| Q09666 | AHNAK | S559 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q12830 | BPTF | S763 | ochoa | Nucleosome-remodeling factor subunit BPTF (Bromodomain and PHD finger-containing transcription factor) (Fetal Alz-50 clone 1 protein) (Fetal Alzheimer antigen) | Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:14609955, PubMed:28801535). The NURF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NURF-5 ISWI chromatin remodeling complex (PubMed:28801535). Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development (PubMed:14609955). Histone-binding protein which binds to H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of active genes (PubMed:16728976, PubMed:16728978). Binds to histone H3 tails dimethylated on 'Lys-4' (H3K4Me2) to a lesser extent (PubMed:16728976, PubMed:16728978, PubMed:18042461). May also regulate transcription through direct binding to DNA or transcription factors (PubMed:10575013). {ECO:0000269|PubMed:10575013, ECO:0000269|PubMed:14609955, ECO:0000269|PubMed:16728976, ECO:0000269|PubMed:16728978, ECO:0000269|PubMed:18042461, ECO:0000269|PubMed:28801535}. |
| Q12888 | TP53BP1 | S500 | 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}. |
| Q13023 | AKAP6 | S1073 | 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. |
| Q13315 | ATM | S794 | psp | Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated) | Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217). May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, ECO:0000269|PubMed:9843217}. |
| Q13323 | BIK | S124 | psp | Bcl-2-interacting killer (Apoptosis inducer NBK) (BIP1) (BP4) | Accelerates programmed cell death. Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. Does not interact with BAX. {ECO:0000269|PubMed:8521816}. |
| Q13370 | PDE3B | S22 | ochoa | cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (EC 3.1.4.17) (CGIPDE1) (CGIP1) (Cyclic GMP-inhibited phosphodiesterase B) (CGI-PDE B) | Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological process (PubMed:14592490, PubMed:21393242). Regulates angiogenesis by inhibiting the cAMP-dependent guanine nucleotide exchange factor RAPGEF3 and downstream phosphatidylinositol 3-kinase gamma-mediated signaling (PubMed:21393242). Controls cardiac contractility by reducing cAMP concentration in cardiocytes (By similarity). {ECO:0000250|UniProtKB:Q61409, ECO:0000269|PubMed:14592490, ECO:0000269|PubMed:21393242}. |
| Q13415 | ORC1 | S273 | ochoa|psp | Origin recognition complex subunit 1 (Replication control protein 1) | Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The 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. |
| Q13522 | PPP1R1A | S47 | ochoa | Protein phosphatase 1 regulatory subunit 1A (Protein phosphatase inhibitor 1) (I-1) (IPP-1) | Inhibitor of protein-phosphatase 1. This protein may be important in hormonal control of glycogen metabolism. Hormones that elevate intracellular cAMP increase I-1 activity in many tissues. I-1 activation may impose cAMP control over proteins that are not directly phosphorylated by PKA. Following a rise in intracellular calcium, I-1 is inactivated by calcineurin (or PP2B). Does not inhibit type-2 phosphatases. |
| Q13522 | PPP1R1A | S67 | ochoa|psp | Protein phosphatase 1 regulatory subunit 1A (Protein phosphatase inhibitor 1) (I-1) (IPP-1) | Inhibitor of protein-phosphatase 1. This protein may be important in hormonal control of glycogen metabolism. Hormones that elevate intracellular cAMP increase I-1 activity in many tissues. I-1 activation may impose cAMP control over proteins that are not directly phosphorylated by PKA. Following a rise in intracellular calcium, I-1 is inactivated by calcineurin (or PP2B). Does not inhibit type-2 phosphatases. |
| Q13618 | CUL3 | S737 | ochoa | Cullin-3 (CUL-3) | Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21670212, PubMed:21840486, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:27664236). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205). By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205). The BCR(KBTBD4) E3 ubiquitin ligase complex targets CoREST corepressor complex components RCOR1, KDM1A/LSD1 and HDAC2 for proteasomal degradation with RCOR1 likely to be the primary target while degradation of KDM1A and HDAC2 is likely due to their association with RCOR1 (PubMed:33417871). It also targets RCOR3, MIER2 and MIER3 for proteasomal degradation as well as associated proteins ZNF217 and RREB1 with degradation being dependent on the presence of an ELM2 domain in the target proteins (PubMed:36997086). The BCR(ARMC5) complex mediates premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation by mediating ubiquitination of Pol II subunit POLR2A (PubMed:35687106, PubMed:38225631, PubMed:39504960, PubMed:39667934). Required for 'Lys-63'-linked ubiquitination of large ribosomal subunit protein MRPL12 (PubMed:37526061). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27664236, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:33417871, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:36997086, ECO:0000269|PubMed:37526061, ECO:0000269|PubMed:38225631, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}. |
| Q14258 | TRIM25 | S46 | ochoa | E3 ubiquitin/ISG15 ligase TRIM25 (EC 6.3.2.n3) (Estrogen-responsive finger protein) (RING finger protein 147) (RING-type E3 ubiquitin transferase) (EC 2.3.2.27) (RING-type E3 ubiquitin transferase TRIM25) (Tripartite motif-containing protein 25) (Ubiquitin/ISG15-conjugating enzyme TRIM25) (Zinc finger protein 147) | Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase (PubMed:16352599). Involved in innate immune defense against viruses by mediating ubiquitination of RIGI and IFIH1 (PubMed:17392790, PubMed:29357390, PubMed:30193849, PubMed:31710640, PubMed:33849980, PubMed:36045682). Mediates 'Lys-63'-linked polyubiquitination of the RIGI N-terminal CARD-like region and may play a role in signal transduction that leads to the production of interferons in response to viral infection (PubMed:17392790, PubMed:23950712). Mediates 'Lys-63'-linked polyubiquitination of IFIH1 (PubMed:30193849). Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway (PubMed:16352599, PubMed:17069755). Mediates estrogen action in various target organs (PubMed:22452784). Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784). Plays a role in promoting the restart of stalled replication forks via interaction with the KHDC3L-OOEP scaffold and subsequent ubiquitination of BLM, resulting in the recruitment and retainment of BLM at DNA replication forks (By similarity). Plays an essential role in the antiviral activity of ZAP/ZC3HAV1; an antiviral protein which inhibits the replication of certain viruses. Mechanistically, mediates 'Lys-63'-linked polyubiquitination of ZAP/ZC3HAV1 that is required for its optimal binding to target mRNA (PubMed:28060952, PubMed:28202764). Also mediates the ubiquitination of various substrates implicated in stress granule formation, nonsense-mediated mRNA decay, nucleoside synthesis and mRNA translation and stability (PubMed:36067236). {ECO:0000250|UniProtKB:Q61510, ECO:0000269|PubMed:16352599, ECO:0000269|PubMed:17069755, ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:22452784, ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:29357390, ECO:0000269|PubMed:30193849, ECO:0000269|PubMed:31710640, ECO:0000269|PubMed:33849980, ECO:0000269|PubMed:36045682, ECO:0000269|PubMed:36067236}. |
| Q14315 | FLNC | S762 | ochoa | Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) | Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}. |
| Q14500 | KCNJ12 | S405 | ochoa | ATP-sensitive inward rectifier potassium channel 12 (Inward rectifier K(+) channel Kir2.2) (IRK-2) (Inward rectifier K(+) channel Kir2.2v) (Potassium channel, inwardly rectifying subfamily J member 12) | Inward rectifying potassium channel that probably participates in controlling the resting membrane potential in electrically excitable cells. Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. {ECO:0000269|PubMed:12417321, ECO:0000269|PubMed:20921230, ECO:0000269|PubMed:7859381, ECO:0000269|PubMed:8647284}. |
| Q14653 | IRF3 | S123 | psp | Interferon regulatory factor 3 (IRF-3) | Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049179, PubMed:25636800, PubMed:27302953, PubMed:31340999, PubMed:36603579, PubMed:8524823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995, PubMed:36603579, PubMed:8524823). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:36603579). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953, PubMed:36603579). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148, PubMed:36603579). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31340999, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:36603579, ECO:0000269|PubMed:8524823, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}. |
| 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}. |
| Q14690 | PDCD11 | S1360 | 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}. |
| Q14761 | PTPRCAP | S163 | ochoa|psp | Protein tyrosine phosphatase receptor type C-associated protein (PTPRC-associated protein) (CD45-associated protein) (CD45-AP) (Lymphocyte phosphatase-associated phosphoprotein) | None |
| Q14789 | GOLGB1 | S967 | 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 | S543 | 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}. |
| Q14814 | MEF2D | S110 | ochoa|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}. |
| Q14865 | ARID5B | S1002 | ochoa | AT-rich interactive domain-containing protein 5B (ARID domain-containing protein 5B) (MRF1-like protein) (Modulator recognition factor 2) (MRF-2) | Transcription coactivator that binds to the 5'-AATA[CT]-3' core sequence and plays a key role in adipogenesis and liver development. Acts by forming a complex with phosphorylated PHF2, which mediates demethylation at Lys-336, leading 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. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes. Overexpression leads to induction of smooth muscle marker genes, suggesting that it may also act as a regulator of smooth muscle cell differentiation and proliferation. Represses the cytomegalovirus enhancer. {ECO:0000269|PubMed:21532585}. |
| Q14914 | PTGR1 | S88 | ochoa | Prostaglandin reductase 1 (PRG-1) (15-oxoprostaglandin 13-reductase) (EC 1.3.1.48) (Dithiolethione-inducible gene 1 protein) (D3T-inducible gene 1 protein) (DIG-1) (Leukotriene B4 12-hydroxydehydrogenase) (NAD(P)H-dependent alkenal/one oxidoreductase) (EC 1.3.1.74) | NAD(P)H-dependent oxidoreductase involved in metabolic inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins (PG), leukotrienes (LT) and lipoxins (LX) (PubMed:25619643). Catalyzes with high efficiency the reduction of the 13,14 double bond of 15-oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-oxo-PGF2-alpha (PubMed:25619643). Catalyzes with lower efficiency the oxidation of the hydroxyl group at C12 of LTB4 and its derivatives, converting them into biologically less active 12-oxo-LTB4 metabolites (By similarity) (PubMed:25619643). Reduces 15-oxo-LXA4 to 13,14 dihydro-15-oxo-LXA4, enhancing neutrophil recruitment at the inflammatory site (By similarity). May play a role in metabolic detoxification of alkenals and ketones. Reduces alpha,beta-unsaturated alkenals and ketones, particularly those with medium-chain length, showing highest affinity toward (2E)-decenal and (3E)-3-nonen-2-one (PubMed:25619643). May inactivate 4-hydroxy-2-nonenal, a cytotoxic lipid constituent of oxidized low-density lipoprotein particles (By similarity). {ECO:0000250|UniProtKB:P97584, ECO:0000250|UniProtKB:Q29073, ECO:0000269|PubMed:25619643}. |
| Q14BN4 | SLMAP | S148 | 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}. |
| 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}. |
| Q15386 | UBE3C | S672 | ochoa | Ubiquitin-protein ligase E3C (EC 2.3.2.26) (HECT-type ubiquitin transferase E3C) (Homologous to E6AP carboxyl terminus homologous protein 2) (HectH2) (RTA-associated ubiquitin ligase) (RAUL) | E3 ubiquitin-protein ligase that specifically catalyzes 'Lys-29'- and 'Lys-48'-linked polyubiquitin chains (PubMed:11278995, PubMed:12692129, PubMed:16341092, PubMed:16601690, PubMed:24158444, PubMed:24811749, PubMed:25752573, PubMed:25752577, PubMed:32039437, PubMed:33637724, PubMed:34239127). Accepts ubiquitin from the E2 ubiquitin-conjugating enzyme UBE2D1 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:32039437, PubMed:9575161). Associates with the proteasome and promotes elongation of ubiquitin chains on substrates bound to the 26S proteasome (PubMed:24158444, PubMed:28396413, PubMed:31375563). Also catalyzes 'Lys-29'- and 'Lys-48'-linked ubiquitination of 26S proteasome subunit ADRM1/RPN13 in response to proteotoxic stress, impairing the ability of the proteasome to bind and degrade ubiquitin-conjugated proteins (PubMed:24811749, PubMed:31375563). Acts as a negative regulator of autophagy by mediating 'Lys-29'- and 'Lys-48'-linked ubiquitination of PIK3C3/VPS34, promoting its degradation (PubMed:33637724). Can assemble unanchored poly-ubiquitin chains in either 'Lys-29'- or 'Lys-48'-linked polyubiquitin chains; with some preference for 'Lys-48' linkages (PubMed:11278995, PubMed:16601690, PubMed:25752577). Acts as a negative regulator of type I interferon by mediating 'Lys-48'-linked ubiquitination of IRF3 and IRF7, leading to their degradation by the proteasome (PubMed:21167755). Catalyzes ubiquitination and degradation of CAND2 (PubMed:12692129). {ECO:0000269|PubMed:11278995, ECO:0000269|PubMed:12692129, ECO:0000269|PubMed:16341092, ECO:0000269|PubMed:16601690, ECO:0000269|PubMed:21167755, ECO:0000269|PubMed:24158444, ECO:0000269|PubMed:24811749, ECO:0000269|PubMed:25752573, ECO:0000269|PubMed:25752577, ECO:0000269|PubMed:28396413, ECO:0000269|PubMed:31375563, ECO:0000269|PubMed:32039437, ECO:0000269|PubMed:33637724, ECO:0000269|PubMed:34239127, ECO:0000269|PubMed:9575161}. |
| Q15468 | STIL | S1111 | ochoa | SCL-interrupting locus protein (TAL-1-interrupting locus protein) | Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CPAP to the base of the procentriole to initiate procentriole assembly (PubMed:22020124). In complex with STIL acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility (PubMed:29712910, PubMed:32107292). {ECO:0000269|PubMed:16024801, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:29712910, ECO:0000269|PubMed:32107292, ECO:0000269|PubMed:9372240}. |
| 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 | S469 | ochoa|psp | 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}. |
| Q15643 | TRIP11 | S1313 | 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}. |
| Q15652 | JMJD1C | S2053 | ochoa | Probable JmjC domain-containing histone demethylation protein 2C (EC 1.14.11.-) (Jumonji domain-containing protein 1C) (Thyroid receptor-interacting protein 8) (TR-interacting protein 8) (TRIP-8) | Probable histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May be involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes (By similarity). {ECO:0000250}. |
| Q15746 | MYLK | S305 | ochoa | Myosin light chain kinase, smooth muscle (MLCK) (smMLCK) (EC 2.7.11.18) (Kinase-related protein) (KRP) (Telokin) [Cleaved into: Myosin light chain kinase, smooth muscle, deglutamylated form] | Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, ECO:0000269|PubMed:20453870}. |
| Q16828 | DUSP6 | S197 | psp | Dual specificity protein phosphatase 6 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity protein phosphatase PYST1) (Mitogen-activated protein kinase phosphatase 3) (MAP kinase phosphatase 3) (MKP-3) | Dual specificity protein phosphatase, which mediates dephosphorylation and inactivation of MAP kinases (PubMed:8670865). Has a specificity for the ERK family (PubMed:8670865). Plays an important role in alleviating chronic postoperative pain (By similarity). Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (By similarity). Also important for dephosphorylation of MAPK1/3 in local wound tissue, which further contributes to resolution of acute pain (By similarity). Promotes cell differentiation by regulating MAPK1/MAPK3 activity and regulating the expression of AP1 transcription factors (PubMed:29043977). {ECO:0000250|UniProtKB:Q9DBB1, ECO:0000269|PubMed:29043977, ECO:0000269|PubMed:8670865}. |
| Q16831 | UPP1 | S61 | ochoa | Uridine phosphorylase 1 (UPase 1) (UrdPase 1) (EC 2.4.2.3) | Catalyzes the reversible phosphorylytic cleavage of uridine to uracil and ribose-1-phosphate which can then be utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis (PubMed:7488099). Shows broad substrate specificity and can also accept deoxyuridine and other analogous compounds (Probable). {ECO:0000269|PubMed:7488099, ECO:0000305|PubMed:13737038}. |
| Q16849 | PTPRN | S226 | ochoa | Receptor-type tyrosine-protein phosphatase-like N (R-PTP-N) (Islet cell antigen 512) (ICA 512) (Islet cell autoantigen 3) (PTP IA-2) [Cleaved into: ICA512-N-terminal fragment (ICA512-NTF); ICA512-transmembrane fragment (ICA512-TMF); ICA512-cleaved cytosolic fragment (ICA512-CCF)] | Plays a role in vesicle-mediated secretory processes (PubMed:24843546). Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets (By similarity). Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation (PubMed:24843546). Plays a role in insulin secretion in response to glucose stimuli (PubMed:24843546). Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain (By similarity). In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). Seems to lack intrinsic enzyme activity (By similarity). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). {ECO:0000250|UniProtKB:Q60673, ECO:0000269|PubMed:24843546}.; FUNCTION: [ICA512-transmembrane fragment]: ICA512-TMF regulates dynamics and exocytosis of insulin secretory granules (SGs); binding of ICA512-TMF to SNTB2/beta-2-syntrophin is proposed to restrain SGs mobility and exocytosis by tethering them to the actin cytoskeleton depending on UTRN; the function is inhibited by cytoplasmic ICA512-CFF dimerizing with ICA512-TMF and displacing SNTB2. {ECO:0000269|PubMed:18824546, ECO:0000269|PubMed:20886068}.; FUNCTION: [ICA512-cleaved cytosolic fragment]: ICA512-CCF translocated to the nucleus promotes expression of insulin and other granule-related genes; the function implicates binding to and regulating activity of STAT5B probably by preventing its dephosphorylation and potentially by inducing its sumoylation by recruiting PIAS4 (PubMed:15596545, PubMed:16622421, PubMed:18178618). Enhances pancreatic beta-cell proliferation by converging with signaling by STAT5B and STAT3 (PubMed:15596545, PubMed:16622421, PubMed:18178618). ICA512-CCF located in the cytoplasm regulates dynamics and exocytosis of insulin secretory granules (SGs) by dimerizing with ICA512-TMF and displacing SNTB2 thus enhancing SGs mobility and exocytosis (PubMed:18824546, PubMed:20886068). {ECO:0000269|PubMed:15596545, ECO:0000269|PubMed:16622421, ECO:0000269|PubMed:18178618, ECO:0000269|PubMed:18824546, ECO:0000269|PubMed:20886068}. |
| Q16890 | TPD52L1 | S144 | ochoa | Tumor protein D53 (hD53) (Tumor protein D52-like 1) | None |
| Q17R98 | ZNF827 | S66 | 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}. |
| Q1HG44 | DUOXA2 | S296 | ochoa | Dual oxidase maturation factor 2 (Dual oxidase activator 2) | Required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX2. May play a role in thyroid hormone synthesis. {ECO:0000269|PubMed:16651268}. |
| Q2LD37 | BLTP1 | S3196 | 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}. |
| Q2TBE0 | CWF19L2 | S479 | ochoa | CWF19-like protein 2 | None |
| Q32P28 | P3H1 | S505 | ochoa | Prolyl 3-hydroxylase 1 (EC 1.14.11.7) (Growth suppressor 1) (Leucine- and proline-enriched proteoglycan 1) (Leprecan-1) | Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts. {ECO:0000269|PubMed:10951563}. |
| Q3MIN7 | RGL3 | S52 | ochoa | Ral guanine nucleotide dissociation stimulator-like 3 (RalGDS-like 3) | Guanine nucleotide exchange factor (GEF) for Ral-A. Potential effector of GTPase HRas and Ras-related protein M-Ras. Negatively regulates Elk-1-dependent gene induction downstream of HRas and MEKK1 (By similarity). {ECO:0000250}. |
| Q4AC94 | C2CD3 | S1606 | 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}. |
| Q4J6C6 | PREPL | S410 | ochoa | Prolyl endopeptidase-like (EC 3.4.21.-) (Prolylendopeptidase-like) | Serine peptidase whose precise substrate specificity remains unclear (PubMed:16143824, PubMed:16385448, PubMed:28726805). Does not cleave peptides after a arginine or lysine residue (PubMed:16143824). Regulates trans-Golgi network morphology and sorting by regulating the membrane binding of the AP-1 complex (PubMed:23321636). May play a role in the regulation of synaptic vesicle exocytosis (PubMed:24610330). {ECO:0000269|PubMed:16143824, ECO:0000269|PubMed:16385448, ECO:0000269|PubMed:23321636, ECO:0000269|PubMed:24610330, ECO:0000269|PubMed:28726805}. |
| Q567U6 | CCDC93 | S305 | ochoa | Coiled-coil domain-containing protein 93 | Component of the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of composed of the CCC subcomplex and the retriever subcomplex (PubMed:37172566, PubMed:38459129). Component of the CCC complex, which is involved in the regulation of endosomal recycling of surface proteins, including integrins, signaling receptor and channels (PubMed:37172566, PubMed:38459129). The CCC complex associates with SNX17, retriever and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of numerous cargos such as integrins ITGA5:ITGB1 (PubMed:25355947, PubMed:28892079). Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes and is dependent on its interaction with WASHC2C (PubMed:25355947). {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079, ECO:0000269|PubMed:37172566, ECO:0000269|PubMed:38459129}.; FUNCTION: (Microbial infection) The CCC complex, in collaboration with the heterotrimeric retriever complex, mediates the exit of human papillomavirus to the cell surface. {ECO:0000269|PubMed:28892079}. |
| Q5FBB7 | SGO1 | S507 | psp | Shugoshin 1 (Serologically defined breast cancer antigen NY-BR-85) (Shugoshin-like 1) | Plays a central role in chromosome cohesion during mitosis by preventing premature dissociation of cohesin complex from centromeres after prophase, when most of cohesin complex dissociates from chromosomes arms. May act by preventing phosphorylation of the STAG2 subunit of cohesin complex at the centromere, ensuring cohesin persistence at centromere until cohesin cleavage by ESPL1/separase at anaphase. Essential for proper chromosome segregation during mitosis and this function requires interaction with PPP2R1A. Its phosphorylated form is necessary for chromosome congression and for the proper attachment of spindle microtubule to the kinetochore. Necessary for kinetochore localization of PLK1 and CENPF. May play a role in the tension sensing mechanism of the spindle-assembly checkpoint by regulating PLK1 kinetochore affinity. Isoform 3 plays a role in maintaining centriole cohesion involved in controlling spindle pole integrity. Involved in centromeric enrichment of AUKRB in prometaphase. {ECO:0000269|PubMed:15604152, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:15737064, ECO:0000269|PubMed:16580887, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:20739936}. |
| Q5JSZ5 | PRRC2B | S288 | ochoa | Protein PRRC2B (HLA-B-associated transcript 2-like 1) (Proline-rich coiled-coil protein 2B) | None |
| Q5JTD0 | TJAP1 | S345 | ochoa | Tight junction-associated protein 1 (Protein incorporated later into tight junctions) (Tight junction protein 4) | Plays a role in regulating the structure of the Golgi apparatus. {ECO:0000250|UniProtKB:Q9DCD5}. |
| Q5SRE5 | NUP188 | S54 | ochoa | Nucleoporin NUP188 (hNup188) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope (Probable). Required for proper protein transport into the nucleus (PubMed:32275884). {ECO:0000269|PubMed:32275884, ECO:0000305|PubMed:32275884}. |
| 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}. |
| Q5T0D9 | TPRG1L | S227 | ochoa | Tumor protein p63-regulated gene 1-like protein (Mossy fiber terminal-associated vertebrate-specific presynaptic protein) (Protein FAM79A) | Presynaptic protein involved in the synaptic transmission tuning. Regulates synaptic release probability by decreasing the calcium sensitivity of release. {ECO:0000250|UniProtKB:A8WCF8}. |
| Q5T8I9 | HENMT1 | S329 | ochoa | Small RNA 2'-O-methyltransferase (EC 2.1.1.386) (HEN1 methyltransferase homolog 1) | Methyltransferase that adds a 2'-O-methyl group at the 3'-end of piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. This probably protects the 3'-end of piRNAs from uridylation activity and subsequent degradation. Stabilization of piRNAs is essential for gametogenesis. {ECO:0000250|UniProtKB:Q8CAE2}. |
| Q5VWN6 | TASOR2 | S219 | ochoa | Protein TASOR 2 | None |
| Q5VZK9 | CARMIL1 | S1151 | ochoa | F-actin-uncapping protein LRRC16A (CARMIL homolog) (Capping protein regulator and myosin 1 linker protein 1) (Capping protein, Arp2/3 and myosin-I linker homolog 1) (Capping protein, Arp2/3 and myosin-I linker protein 1) (Leucine-rich repeat-containing protein 16A) | Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:19846667). {ECO:0000269|PubMed:16054028, ECO:0000269|PubMed:19846667}. |
| Q5VZL5 | ZMYM4 | S1030 | 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}. |
| Q66K14 | TBC1D9B | S363 | 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}. |
| Q68DA7 | FMN1 | S554 | ochoa | Formin-1 (Limb deformity protein homolog) | Plays a role in the formation of adherens junction and the polymerization of linear actin cables. {ECO:0000250}. |
| Q6DN90 | IQSEC1 | S515 | 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}. |
| Q6IPM2 | IQCE | S322 | ochoa | IQ domain-containing protein E | Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling (By similarity). Required for proper limb morphogenesis (PubMed:28488682). {ECO:0000250|UniProtKB:Q6PCQ0, ECO:0000269|PubMed:28488682}. |
| Q6IQ26 | DENND5A | S52 | ochoa | DENN domain-containing protein 5A (Rab6-interacting protein 1) (Rab6IP1) | Guanine nucleotide exchange factor (GEF) which may activate RAB6A and RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. Involved in the negative regulation of neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:G3V7Q0, ECO:0000269|PubMed:20937701}. |
| Q6IQ55 | TTBK2 | S422 | 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}. |
| Q6KC79 | NIPBL | S231 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6NYC8 | PPP1R18 | S530 | ochoa | Phostensin (Protein phosphatase 1 F-actin cytoskeleton-targeting subunit) (Protein phosphatase 1 regulatory subunit 18) | [Isoform 1]: May target protein phosphatase 1 to F-actin cytoskeleton. {ECO:0000269|PubMed:24434620}.; FUNCTION: [Isoform 4]: May target protein phosphatase 1 to F-actin cytoskeleton. {ECO:0000269|PubMed:17374523}. |
| Q6P2E9 | EDC4 | S1154 | ochoa | Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) | In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}. |
| Q6P3S1 | DENND1B | S690 | 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}. |
| Q6P5Q4 | LMOD2 | S186 | ochoa | Leiomodin-2 (Cardiac leiomodin) (C-LMOD) (Leiomodin) | Mediates nucleation of actin filaments and thereby promotes actin polymerization (PubMed:18403713, PubMed:25250574, PubMed:26370058, PubMed:26417072). Plays a role in the regulation of actin filament length (By similarity). Required for normal sarcomere organization in the heart, and for normal heart function (PubMed:18403713). {ECO:0000250|UniProtKB:Q3UHZ5, ECO:0000269|PubMed:18403713, ECO:0000269|PubMed:25250574, ECO:0000269|PubMed:26370058, ECO:0000269|PubMed:26417072}. |
| Q6PIZ9 | TRAT1 | S157 | ochoa | T-cell receptor-associated transmembrane adapter 1 (T-cell receptor-interacting molecule) (TRIM) (pp29/30) | Stabilizes the TCR (T-cell antigen receptor)/CD3 complex at the surface of T-cells. {ECO:0000269|PubMed:11390434}. |
| Q6PJG2 | MIDEAS | S148 | ochoa | Mitotic deacetylase-associated SANT domain protein (ELM2 and SANT domain-containing protein 1) | None |
| Q6R327 | RICTOR | S265 | 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}. |
| Q6UX15 | LAYN | S286 | ochoa | Layilin | Receptor for hyaluronate. {ECO:0000269|PubMed:11294894}. |
| Q6V0I7 | FAT4 | S4655 | ochoa | Protocadherin Fat 4 (hFat4) (Cadherin family member 14) (FAT tumor suppressor homolog 4) (Fat-like cadherin protein FAT-J) | Cadherins are calcium-dependent cell adhesion proteins. FAT4 plays a role in the maintenance of planar cell polarity as well as in inhibition of YAP1-mediated neuroprogenitor cell proliferation and differentiation (By similarity). {ECO:0000250}. |
| Q6ZSZ6 | TSHZ1 | S765 | ochoa | Teashirt homolog 1 (Antigen NY-CO-33) (Serologically defined colon cancer antigen 33) | Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential). {ECO:0000305}. |
| Q6ZUT9 | DENND5B | S822 | ochoa | DENN domain-containing protein 5B (Rab6IP1-like protein) | Guanine nucleotide exchange factor (GEF) which may activate RAB39A and/or RAB39B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}. |
| Q70CQ2 | USP34 | S3503 | ochoa | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| Q711Q0 | CEFIP | S116 | 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}. |
| Q71F56 | MED13L | S878 | ochoa | Mediator of RNA polymerase II transcription subunit 13-like (Mediator complex subunit 13-like) (Thyroid hormone receptor-associated protein 2) (Thyroid hormone receptor-associated protein complex 240 kDa component-like) | 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. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway. |
| Q76I76 | SSH2 | S236 | 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}. |
| Q7L2H7 | EIF3M | S337 | ochoa | Eukaryotic translation initiation factor 3 subunit M (eIF3m) (Fetal lung protein B5) (hFL-B5) (PCI domain-containing protein 1) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17403899, 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:17403899). 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_03012, ECO:0000269|PubMed:17403899, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) May favor virus entry in case of infection with herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2). {ECO:0000269|PubMed:15919898}. |
| Q7Z2Z1 | TICRR | S1078 | 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}. |
| Q7Z4H7 | HAUS6 | S406 | 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}. |
| Q86T82 | USP37 | S462 | ochoa | Ubiquitin carboxyl-terminal hydrolase 37 (EC 3.4.19.12) (Deubiquitinating enzyme 37) (Ubiquitin thioesterase 37) (Ubiquitin-specific-processing protease 37) | Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response (PubMed:26299517, PubMed:27296872, PubMed:31911859, PubMed:34509474). Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872). Also plays an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability (PubMed:34509474). Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM (PubMed:34606619). Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM (PubMed:34606619). Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI (PubMed:31911859). Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination (PubMed:26299517). {ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:26299517, ECO:0000269|PubMed:27296872, ECO:0000269|PubMed:31911859, ECO:0000269|PubMed:34509474, ECO:0000269|PubMed:34606619}. |
| Q86T90 | KIAA1328 | S273 | ochoa | Protein hinderin | Competes with SMC1 for binding to SMC3. May affect the availability of SMC3 to engage in the formation of multimeric protein complexes. {ECO:0000269|PubMed:15656913}. |
| Q86T90 | KIAA1328 | S499 | ochoa | Protein hinderin | Competes with SMC1 for binding to SMC3. May affect the availability of SMC3 to engage in the formation of multimeric protein complexes. {ECO:0000269|PubMed:15656913}. |
| Q86VP6 | CAND1 | S638 | ochoa | Cullin-associated NEDD8-dissociated protein 1 (Cullin-associated and neddylation-dissociated protein 1) (TBP-interacting protein of 120 kDa A) (TBP-interacting protein 120A) (p120 CAND1) | Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes. {ECO:0000269|PubMed:12504025, ECO:0000269|PubMed:12504026, ECO:0000269|PubMed:12609982, ECO:0000269|PubMed:16449638, ECO:0000269|PubMed:21249194, ECO:0000269|PubMed:23453757}. |
| Q86W42 | THOC6 | S180 | ochoa | THO complex subunit 6 (Functional spliceosome-associated protein 35) (fSAP35) (WD repeat-containing protein 58) | Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Plays a key structural role in the oligomerization of the THO-DDX39B complex (PubMed:33191911). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15998806, PubMed:17190602). Plays a role in apoptosis negative control involved in brain development (PubMed:15833825, PubMed:23621916). {ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:23621916, ECO:0000269|PubMed:33191911}.; FUNCTION: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. {ECO:0000269|PubMed:18974867}. |
| Q86W50 | METTL16 | S498 | ochoa | RNA N(6)-adenosine-methyltransferase METTL16 (EC 2.1.1.348) (Methyltransferase 10 domain-containing protein) (Methyltransferase-like protein 16) (U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase) (EC 2.1.1.346) | RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753, PubMed:30197297, PubMed:30197299, PubMed:33428944, PubMed:33930289). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753, PubMed:30197297, PubMed:30197299). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (PubMed:28525753, PubMed:33930289). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200, PubMed:32266935). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311). {ECO:0000269|PubMed:27872311, ECO:0000269|PubMed:28525753, ECO:0000269|PubMed:29051200, ECO:0000269|PubMed:30197297, ECO:0000269|PubMed:30197299, ECO:0000269|PubMed:32266935, ECO:0000269|PubMed:33428944}. |
| Q86XL3 | ANKLE2 | S662 | ochoa|psp | Ankyrin repeat and LEM domain-containing protein 2 (LEM domain-containing protein 4) | Involved in mitotic nuclear envelope reassembly by promoting dephosphorylation of BAF/BANF1 during mitotic exit (PubMed:22770216). Coordinates the control of BAF/BANF1 dephosphorylation by inhibiting VRK1 kinase and promoting dephosphorylation of BAF/BANF1 by protein phosphatase 2A (PP2A), thereby facilitating nuclear envelope assembly (PubMed:22770216). May regulate nuclear localization of VRK1 in non-dividing cells (PubMed:31735666). It is unclear whether it acts as a real PP2A regulatory subunit or whether it is involved in recruitment of the PP2A complex (PubMed:22770216). Involved in brain development (PubMed:25259927). {ECO:0000269|PubMed:22770216, ECO:0000269|PubMed:25259927, ECO:0000269|PubMed:31735666}. |
| Q86XP1 | DGKH | S1075 | ochoa | Diacylglycerol kinase eta (DAG kinase eta) (EC 2.7.1.107) (Diglyceride kinase eta) (DGK-eta) | Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:12810723, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable) (PubMed:12810723, PubMed:23949095). Plays a key role in promoting cell growth (PubMed:19710016). Activates the Ras/B-Raf/C-Raf/MEK/ERK signaling pathway induced by EGF (PubMed:19710016). Regulates the recruitment of RAF1 and BRAF from cytoplasm to membranes and their heterodimerization (PubMed:19710016). {ECO:0000269|PubMed:12810723, ECO:0000269|PubMed:19710016, ECO:0000269|PubMed:23949095, ECO:0000305}. |
| Q8IUD6 | RNF135 | S184 | ochoa | E3 ubiquitin-protein ligase RNF135 (EC 2.3.2.27) (RIG-I E3 ubiquitin ligase) (REUL) (RING finger protein 135) (RING finger protein leading to RIG-I activation) (Riplet) (RING-type E3 ubiquitin transferase RNF135) | E2-dependent E3 ubiquitin-protein ligase that functions as a RIGI coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response (PubMed:19017631, PubMed:19484123, PubMed:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIGI oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway (PubMed:19017631, PubMed:21147464, PubMed:28469175, PubMed:31006531). Through a ubiquitin-independent parallel mechanism, which consists in bridging RIGI filaments forming on longer viral RNAs, further activates the RIG-I signaling pathway (PubMed:31006531). This second mechanism that synergizes with the ubiquitin-dependent one would thereby allow an RNA length-dependent regulation of the RIG-I signaling pathway (Probable). Associated with the E2 ligase UBE2N, also constitutively synthesizes unanchored 'Lys-63'-linked polyubiquitin chains that may also activate the RIG-I signaling pathway (PubMed:28469175, PubMed:31006531). {ECO:0000269|PubMed:19017631, ECO:0000269|PubMed:19484123, ECO:0000269|PubMed:21147464, ECO:0000269|PubMed:23950712, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:31006531, ECO:0000305|PubMed:31006531}. |
| Q8IUF8 | RIOX2 | S47 | ochoa | Ribosomal oxygenase 2 (60S ribosomal protein L27a histidine hydroxylase) (Bifunctional lysine-specific demethylase and histidyl-hydroxylase MINA) (EC 1.14.11.79) (Histone lysine demethylase MINA) (MYC-induced nuclear antigen) (Mineral dust-induced gene protein) (Nucleolar protein 52) (Ribosomal oxygenase MINA) (ROX) | Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Is involved in the demethylation of trimethylated 'Lys-9' on histone H3 (H3K9me3), leading to an increase in ribosomal RNA expression. Also catalyzes the hydroxylation of 60S ribosomal protein L27a on 'His-39'. May play an important role in cell growth and survival. May be involved in ribosome biogenesis, most likely during the assembly process of pre-ribosomal particles. {ECO:0000269|PubMed:12091391, ECO:0000269|PubMed:14695334, ECO:0000269|PubMed:15534111, ECO:0000269|PubMed:15819408, ECO:0000269|PubMed:15897898, ECO:0000269|PubMed:17317935, ECO:0000269|PubMed:19502796, ECO:0000269|PubMed:23103944}. |
| Q8IUG5 | MYO18B | S2226 | ochoa | Unconventional myosin-XVIIIb | May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. May play a role in the control of tumor development and progression; restored MYO18B expression in lung cancer cells suppresses anchorage-independent growth. |
| Q8IVW6 | ARID3B | S165 | ochoa | AT-rich interactive domain-containing protein 3B (ARID domain-containing protein 3B) (Bright and dead ringer protein) (Bright-like protein) | Transcription factor which may be involved in neuroblastoma growth and malignant transformation. Favors nuclear targeting of ARID3A. {ECO:0000269|PubMed:16951138, ECO:0000269|PubMed:17400556}. |
| Q8IWE2 | FAM114A1 | S120 | ochoa | Protein NOXP20 (Nervous system overexpressed protein 20) (Protein FAM114A1) | May play a role in neuronal cell development. {ECO:0000250}. |
| Q8IWU2 | LMTK2 | S886 | 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. |
| Q8IYD8 | FANCM | S1448 | ochoa | 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}. |
| Q8IYM9 | TRIM22 | S87 | ochoa | E3 ubiquitin-protein ligase TRIM22 (EC 2.3.2.27) (50 kDa-stimulated trans-acting factor) (RING finger protein 94) (RING-type E3 ubiquitin transferase TRIM22) (Staf-50) (Tripartite motif-containing protein 22) | Interferon-induced E3 ubiquitin ligase that plays important roles in innate and adaptive immunity (PubMed:25683609, PubMed:35777501). Restricts the replication of many viruses including HIV-1, encephalomyocarditis virus (EMCV), hepatitis B virus (HBV), hepatitis C virus (HCV) or Zika virus (ZIKV) (PubMed:25683609, PubMed:35777501, PubMed:36042495). Mechanistically, negatively regulates HCV replication by promoting ubiquitination and subsequent degradation of viral NS5A (PubMed:25683609). Also acts by promoting the degradation of Zika virus NS1 and NS3 proteins through proteasomal degradation (PubMed:36042495). Acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter (PubMed:26683615). Also plays a role in antiviral immunity by co-regulating together with NT5C2 the RIGI/NF-kappa-B pathway by promoting 'Lys-63'-linked ubiquitination of RIGI, while NT5C2 is responsible for 'Lys-48'-linked ubiquitination of RIGI (PubMed:36159777). Participates in adaptive immunity by suppressing the amount of MHC class II protein in a negative feedback manner in order to limit the extent of MHC class II induction (PubMed:35777501). {ECO:0000269|PubMed:18389079, ECO:0000269|PubMed:18656448, ECO:0000269|PubMed:19218198, ECO:0000269|PubMed:19585648, ECO:0000269|PubMed:25683609, ECO:0000269|PubMed:26683615, ECO:0000269|PubMed:35777501, ECO:0000269|PubMed:36042495, ECO:0000269|PubMed:36159777}. |
| Q8IZ21 | PHACTR4 | S427 | ochoa | Phosphatase and actin regulator 4 | Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway (By similarity). {ECO:0000250}. |
| Q8IZD4 | DCP1B | S448 | ochoa | mRNA-decapping enzyme 1B (EC 3.6.1.62) | May play a role in the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. May remove the 7-methyl guanine cap structure from mRNA molecules, yielding a 5'-phosphorylated mRNA fragment and 7m-GDP (By similarity). {ECO:0000250|UniProtKB:Q9NPI6}. |
| Q8N2S1 | LTBP4 | S300 | ochoa | Latent-transforming growth factor beta-binding protein 4 (LTBP-4) | Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta. {ECO:0000250|UniProtKB:Q14766}. |
| Q8N302 | AGGF1 | S329 | 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}. |
| Q8N4X5 | AFAP1L2 | S165 | ochoa | Actin filament-associated protein 1-like 2 (AFAP1-like protein 2) | May play a role in a signaling cascade by enhancing the kinase activity of SRC. Contributes to SRC-regulated transcription activation. {ECO:0000269|PubMed:17412687}. |
| 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}. |
| Q8N8K9 | KIAA1958 | S272 | ochoa | Uncharacterized protein KIAA1958 | None |
| Q8ND30 | PPFIBP2 | S40 | 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}. |
| 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}. |
| Q8NEZ4 | KMT2C | S4006 | 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}. |
| Q8NG08 | HELB | S711 | ochoa | DNA helicase B (hDHB) (EC 3.6.4.12) | 5'-3' DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection (PubMed:25617833, PubMed:26774285). Recruitment to single-stranded DNA (ssDNA) following DNA damage leads to inhibit the nucleases catalyzing resection, such as EXO1, BLM and DNA2, possibly via the 5'-3' ssDNA translocase activity of HELB (PubMed:26774285). As cells approach S phase, DNA end resection is promoted by the nuclear export of HELB following phosphorylation (PubMed:26774285). Acts independently of TP53BP1 (PubMed:26774285). Unwinds duplex DNA with 5'-3' polarity. Has single-strand DNA-dependent ATPase and DNA helicase activities. Prefers ATP and dATP as substrates (PubMed:12181327). During S phase, may facilitate cellular recovery from replication stress (PubMed:22194613). {ECO:0000269|PubMed:12181327, ECO:0000269|PubMed:22194613, ECO:0000269|PubMed:25617833, ECO:0000269|PubMed:26774285}. |
| Q8NG08 | HELB | S1048 | ochoa | DNA helicase B (hDHB) (EC 3.6.4.12) | 5'-3' DNA helicase involved in DNA damage response by acting as an inhibitor of DNA end resection (PubMed:25617833, PubMed:26774285). Recruitment to single-stranded DNA (ssDNA) following DNA damage leads to inhibit the nucleases catalyzing resection, such as EXO1, BLM and DNA2, possibly via the 5'-3' ssDNA translocase activity of HELB (PubMed:26774285). As cells approach S phase, DNA end resection is promoted by the nuclear export of HELB following phosphorylation (PubMed:26774285). Acts independently of TP53BP1 (PubMed:26774285). Unwinds duplex DNA with 5'-3' polarity. Has single-strand DNA-dependent ATPase and DNA helicase activities. Prefers ATP and dATP as substrates (PubMed:12181327). During S phase, may facilitate cellular recovery from replication stress (PubMed:22194613). {ECO:0000269|PubMed:12181327, ECO:0000269|PubMed:22194613, ECO:0000269|PubMed:25617833, ECO:0000269|PubMed:26774285}. |
| Q8NHM5 | KDM2B | S497 | ochoa | Lysine-specific demethylase 2B (EC 1.14.11.27) (CXXC-type zinc finger protein 2) (F-box and leucine-rich repeat protein 10) (F-box protein FBL10) (F-box/LRR-repeat protein 10) (JmjC domain-containing histone demethylation protein 1B) (Jumonji domain-containing EMSY-interactor methyltransferase motif protein) (Protein JEMMA) (Protein-containing CXXC domain 2) ([Histone-H3]-lysine-36 demethylase 1B) | Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}. |
| Q8NHV4 | NEDD1 | S89 | 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}. |
| Q8TDJ6 | DMXL2 | S473 | ochoa | DmX-like protein 2 (Rabconnectin-3) | May serve as a scaffold protein for MADD and RAB3GA on synaptic vesicles (PubMed:11809763). Plays a role in the brain as a key controller of neuronal and endocrine homeostatic processes (By similarity). {ECO:0000250|UniProtKB:Q8BPN8, ECO:0000269|PubMed:11809763}. |
| Q8TDZ2 | MICAL1 | S625 | ochoa | [F-actin]-monooxygenase MICAL1 (EC 1.14.13.225) (EC 1.6.3.1) (Molecule interacting with CasL protein 1) (MICAL-1) (NEDD9-interacting protein with calponin homology and LIM domains) | 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 (PubMed:29343822). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023, PubMed:29343822). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels (By similarity). May act as Rab effector protein and play a role in vesicle trafficking. Promotes endosomal tubule extension by associating with RAB8 (RAB8A or RAB8B), RAB10 and GRAF (GRAF1/ARHGAP26 or GRAF2/ARHGAP10) on the endosomal membrane which may connect GRAFs to Rabs, thereby participating in neosynthesized Rab8-Rab10-Rab11-dependent protein export (PubMed:32344433). {ECO:0000250|UniProtKB:Q8VDP3, ECO:0000269|PubMed:18305261, ECO:0000269|PubMed:21864500, ECO:0000269|PubMed:26845023, ECO:0000269|PubMed:28230050, ECO:0000269|PubMed:29343822, ECO:0000269|PubMed:32344433, ECO:0000305|PubMed:27552051}. |
| Q8TER5 | ARHGEF40 | S931 | ochoa | Rho guanine nucleotide exchange factor 40 (Protein SOLO) | May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}. |
| Q8TF44 | C2CD4C | S156 | ochoa | C2 calcium-dependent domain-containing protein 4C (Nuclear-localized factor 3) (Protein FAM148C) | None |
| Q8WUY3 | PRUNE2 | S1803 | 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}. |
| Q8WV28 | BLNK | S432 | ochoa | B-cell linker protein (B-cell adapter containing a SH2 domain protein) (B-cell adapter containing a Src homology 2 domain protein) (Cytoplasmic adapter protein) (Src homology 2 domain-containing leukocyte protein of 65 kDa) (SLP-65) | Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis. {ECO:0000269|PubMed:10583958, ECO:0000269|PubMed:15270728, ECO:0000269|PubMed:16912232, ECO:0000269|PubMed:9697839}. |
| Q8WYP5 | AHCTF1 | S2154 | 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}. |
| Q8WYQ5 | DGCR8 | S95 | ochoa|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}. |
| Q92576 | PHF3 | S1722 | ochoa | PHD finger protein 3 | None |
| Q92817 | EVPL | S1263 | ochoa | Envoplakin (210 kDa cornified envelope precursor protein) (210 kDa paraneoplastic pemphigus antigen) (p210) | Component of the cornified envelope of keratinocytes. May link the cornified envelope to desmosomes and intermediate filaments. |
| Q92830 | KAT2A | S372 | psp | Histone acetyltransferase KAT2A (EC 2.3.1.48) (General control of amino acid synthesis protein 5-like 2) (Histone acetyltransferase GCN5) (hGCN5) (Histone glutaryltransferase KAT2A) (EC 2.3.1.-) (Histone succinyltransferase KAT2A) (EC 2.3.1.-) (Lysine acetyltransferase 2A) (STAF97) | Protein lysine acyltransferase that can act as a acetyltransferase, glutaryltransferase, succinyltransferase or malonyltransferase, depending on the context (PubMed:29211711, PubMed:35995428). Acts as a histone lysine succinyltransferase: catalyzes succinylation of histone H3 on 'Lys-79' (H3K79succ), with a maximum frequency around the transcription start sites of genes (PubMed:29211711). Succinylation of histones gives a specific tag for epigenetic transcription activation (PubMed:29211711). Association with the 2-oxoglutarate dehydrogenase complex, which provides succinyl-CoA, is required for histone succinylation (PubMed:29211711). In different complexes, functions either as an acetyltransferase (HAT) or as a succinyltransferase: in the SAGA and ATAC complexes, acts as a histone acetyltransferase (PubMed:17301242, PubMed:19103755, PubMed:29211711). Has significant histone acetyltransferase activity with core histones, but not with nucleosome core particles (PubMed:17301242, PubMed:19103755, PubMed:21131905). Has a a strong preference for acetylation of H3 at 'Lys-9' (H3K9ac) (PubMed:21131905). Acetylation of histones gives a specific tag for epigenetic transcription activation (PubMed:17301242, PubMed:19103755, PubMed:29211711). Recruited by the XPC complex at promoters, where it specifically mediates acetylation of histone variant H2A.Z.1/H2A.Z, thereby promoting expression of target genes (PubMed:29973595, PubMed:31527837). Involved in long-term memory consolidation and synaptic plasticity: acts by promoting expression of a hippocampal gene expression network linked to neuroactive receptor signaling (By similarity). Acts as a positive regulator of T-cell activation: upon TCR stimulation, recruited to the IL2 promoter following interaction with NFATC2 and catalyzes acetylation of histone H3 at 'Lys-9' (H3K9ac), leading to promote IL2 expression (By similarity). Required for growth and differentiation of craniofacial cartilage and bone by regulating acetylation of histone H3 at 'Lys-9' (H3K9ac) (By similarity). Regulates embryonic stem cell (ESC) pluripotency and differentiation (By similarity). Also acetylates non-histone proteins, such as CEBPB, MRE11, PPARGC1A, PLK4 and TBX5 (PubMed:16753578, PubMed:17301242, PubMed:27796307, PubMed:29174768, PubMed:38128537). Involved in heart and limb development by mediating acetylation of TBX5, acetylation regulating nucleocytoplasmic shuttling of TBX5 (PubMed:29174768). Acts as a negative regulator of centrosome amplification by mediating acetylation of PLK4 (PubMed:27796307). Acts as a negative regulator of gluconeogenesis by mediating acetylation and subsequent inactivation of PPARGC1A (PubMed:16753578, PubMed:23142079). Also acts as a histone glutaryltransferase: catalyzes glutarylation of histone H4 on 'Lys-91' (H4K91glu), a mark that destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes (PubMed:31542297). {ECO:0000250|UniProtKB:Q9JHD2, ECO:0000269|PubMed:16753578, ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:23142079, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:29211711, ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837, ECO:0000269|PubMed:31542297, ECO:0000269|PubMed:35995428, ECO:0000269|PubMed:38128537}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. {ECO:0000269|PubMed:11384967}. |
| Q92870 | APBB2 | S31 | 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}. |
| Q92995 | USP13 | S630 | ochoa | Ubiquitin carboxyl-terminal hydrolase 13 (EC 3.4.19.12) (Deubiquitinating enzyme 13) (Isopeptidase T-3) (ISOT-3) (Ubiquitin thioesterase 13) (Ubiquitin-specific-processing protease 13) | Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response (PubMed:21571647, PubMed:32772043, PubMed:33592542). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy (PubMed:32101753). Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB (PubMed:32772043). In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1 (PubMed:33592542). Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion (PubMed:36585612). Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1 (PubMed:23940278, PubMed:28534493). {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:32101753, ECO:0000269|PubMed:32772043, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:36585612}. |
| Q96AC1 | FERMT2 | S523 | ochoa | Fermitin family homolog 2 (Kindlin-2) (Mitogen-inducible gene 2 protein) (MIG-2) (Pleckstrin homology domain-containing family C member 1) (PH domain-containing family C member 1) | Scaffolding protein that enhances integrin activation mediated by TLN1 and/or TLN2, but activates integrins only weakly by itself. Binds to membranes enriched in phosphoinositides. Enhances integrin-mediated cell adhesion onto the extracellular matrix and cell spreading; this requires both its ability to interact with integrins and with phospholipid membranes. Required for the assembly of focal adhesions. Participates in the connection between extracellular matrix adhesion sites and the actin cytoskeleton and also in the orchestration of actin assembly and cell shape modulation. Recruits FBLIM1 to focal adhesions. Plays a role in the TGFB1 and integrin signaling pathways. Stabilizes active CTNNB1 and plays a role in the regulation of transcription mediated by CTNNB1 and TCF7L2/TCF4 and in Wnt signaling. {ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18458155, ECO:0000269|PubMed:21325030, ECO:0000269|PubMed:22030399, ECO:0000269|PubMed:22078565, ECO:0000269|PubMed:22699938}. |
| Q96AE4 | FUBP1 | S147 | ochoa | Far upstream element-binding protein 1 (FBP) (FUSE-binding protein 1) (DNA helicase V) (hDH V) | Regulates MYC expression by binding to a single-stranded far-upstream element (FUSE) upstream of the MYC promoter. May act both as activator and repressor of transcription. {ECO:0000269|PubMed:8125259}. |
| Q96AY4 | TTC28 | S2271 | ochoa | Tetratricopeptide repeat protein 28 (TPR repeat protein 28) (TPR repeat-containing big gene cloned at Keio) | During mitosis, may be involved in the condensation of spindle midzone microtubules, leading to the formation of midbody. {ECO:0000269|PubMed:23036704}. |
| Q96DA6 | DNAJC19 | S70 | ochoa | Mitochondrial import inner membrane translocase subunit TIM14 (DnaJ homolog subfamily C member 19) | Mitochondrial co-chaperone which forms a complex with prohibitins to regulate cardiolipin remodeling (By similarity). May be a component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. May act as a co-chaperone that stimulate the ATP-dependent activity (By similarity). {ECO:0000250|UniProtKB:Q07914, ECO:0000250|UniProtKB:Q9CQV7}. |
| Q96GS4 | BORCS6 | S61 | ochoa | BLOC-1-related complex subunit 6 (Lysosome-dispersing protein) (Lyspersin) | As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor. {ECO:0000269|PubMed:25898167}. |
| Q96HA1 | POM121 | S108 | 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}. |
| Q96IT1 | ZNF496 | S299 | ochoa | Zinc finger protein 496 (Zinc finger protein with KRAB and SCAN domains 17) | DNA-binding transcription factor that can both act as an activator and a repressor. {ECO:0000250}. |
| Q96JB2 | COG3 | S212 | 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}. |
| Q96JH7 | VCPIP1 | S131 | 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 | S736 | 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}. |
| Q96KP1 | EXOC2 | S404 | ochoa | Exocyst complex component 2 (Exocyst complex component Sec5) | Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. {ECO:0000269|PubMed:12459492, ECO:0000269|PubMed:32639540}. |
| Q96L73 | NSD1 | S822 | ochoa | Histone-lysine N-methyltransferase, H3 lysine-36 specific (EC 2.1.1.357) (Androgen receptor coactivator 267 kDa protein) (Androgen receptor-associated protein of 267 kDa) (H3-K36-HMTase) (Lysine N-methyltransferase 3B) (Nuclear receptor-binding SET domain-containing protein 1) (NR-binding SET domain-containing protein) | Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. |
| Q96P16 | RPRD1A | S156 | ochoa | Regulation of nuclear pre-mRNA domain-containing protein 1A (Cyclin-dependent kinase inhibitor 2B-related protein) (p15INK4B-related protein) | Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle. {ECO:0000269|PubMed:22231121, ECO:0000269|PubMed:24399136, ECO:0000269|PubMed:24997600}. |
| Q96QE3 | ATAD5 | S756 | ochoa | ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) | Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}. |
| Q96RY7 | IFT140 | S360 | ochoa | Intraflagellar transport protein 140 homolog (WD and tetratricopeptide repeats protein 2) | 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) (PubMed:20889716, PubMed:22503633). Plays a pivotal role in proper development and function of ciliated cells through its role in ciliogenesis and/or cilium maintenance (PubMed:22503633). Required for the development and maintenance of the outer segments of rod and cone photoreceptor cells. Plays a role in maintenance and the delivery of opsin to the outer segment of photoreceptor cells (By similarity). {ECO:0000250|UniProtKB:E9PY46, ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:22503633, ECO:0000269|PubMed:28724397}. |
| Q96S38 | RPS6KC1 | S596 | ochoa | Ribosomal protein S6 kinase delta-1 (S6K-delta-1) (EC 2.7.11.1) (52 kDa ribosomal protein S6 kinase) (Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein) (SPHK1-binding protein) | May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell (PubMed:12077123). Plays a role in the recruitment of PRDX3 to early endosomes (PubMed:15750338). {ECO:0000269|PubMed:12077123, ECO:0000269|PubMed:15750338}. |
| Q96SK2 | TMEM209 | S222 | 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}. |
| 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}. |
| Q96T23 | RSF1 | S473 | 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 | S1278 | 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}. |
| Q99496 | RNF2 | S41 | ochoa | E3 ubiquitin-protein ligase RING2 (EC 2.3.2.27) (Huntingtin-interacting protein 2-interacting protein 3) (HIP2-interacting protein 3) (Protein DinG) (RING finger protein 1B) (RING1b) (RING finger protein 2) (RING finger protein BAP-1) (RING-type E3 ubiquitin transferase RING2) | E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation (PubMed:15386022, PubMed:16359901, PubMed:21772249, PubMed:25355358, PubMed:25519132, PubMed:26151332, PubMed:33864376). H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation (By similarity). Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development (PubMed:16359901, PubMed:26151332). PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility (PubMed:26151332). E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4 (PubMed:21772249). Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (Probable). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes (By similarity). Also acts as a negative regulator of autophagy by mediating ubiquitination of AMBRA1, leading to its subsequent degradation (By similarity). {ECO:0000250|UniProtKB:Q9CQJ4, ECO:0000269|PubMed:11513855, ECO:0000269|PubMed:15386022, ECO:0000269|PubMed:16359901, ECO:0000269|PubMed:16714294, ECO:0000269|PubMed:20696397, ECO:0000269|PubMed:21772249, ECO:0000269|PubMed:25355358, ECO:0000269|PubMed:25519132, ECO:0000269|PubMed:26151332, ECO:0000269|PubMed:33864376, ECO:0000305}. |
| Q99569 | PKP4 | S814 | 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}. |
| Q99593 | TBX5 | S41 | ochoa | T-box transcription factor TBX5 (T-box protein 5) | DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation (PubMed:25725155, PubMed:25963046, PubMed:26917986, PubMed:27035640, PubMed:29174768, PubMed:8988164). Binds to the core DNA motif of NPPA promoter (PubMed:26926761). {ECO:0000269|PubMed:25725155, ECO:0000269|PubMed:25963046, ECO:0000269|PubMed:26917986, ECO:0000269|PubMed:26926761, ECO:0000269|PubMed:27035640, ECO:0000269|PubMed:29174768, ECO:0000269|PubMed:8988164}. |
| Q99650 | OSMR | S877 | ochoa | Oncostatin-M-specific receptor subunit beta (Interleukin-31 receptor subunit beta) (IL-31 receptor subunit beta) (IL-31R subunit beta) (IL-31R-beta) (IL-31RB) | Associates with IL31RA to form the IL31 receptor. Binds IL31 to activate STAT3 and possibly STAT1 and STAT5. Capable of transducing OSM-specific signaling events. {ECO:0000269|PubMed:15184896, ECO:0000269|PubMed:8999038}. |
| Q99685 | MGLL | S196 | ochoa | Monoglyceride lipase (MGL) (EC 3.1.1.23) (HU-K5) (Lysophospholipase homolog) (Lysophospholipase-like) (Monoacylglycerol lipase) (MAGL) | Converts monoacylglycerides to free fatty acids and glycerol (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (PubMed:20079333). {ECO:0000269|PubMed:19029917, ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}. |
| Q99719 | SEPTIN5 | S327 | ochoa|psp | Septin-5 (Cell division control-related protein 1) (CDCrel-1) (Peanut-like protein 1) | Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential). May play a role in platelet secretion (By similarity). {ECO:0000250, ECO:0000305}. |
| Q99728 | BARD1 | S496 | ochoa | BRCA1-associated RING domain protein 1 (BARD-1) (EC 2.3.2.27) (RING-type E3 ubiquitin transferase BARD1) | E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage. {ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:20351172}. |
| Q99814 | EPAS1 | S383 | 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}. |
| Q9BQA1 | WDR77 | S176 | ochoa | 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}. |
| Q9BQI5 | SGIP1 | S151 | ochoa | SH3-containing GRB2-like protein 3-interacting protein 1 (Endophilin-3-interacting protein) | May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis. {ECO:0000250|UniProtKB:Q8VD37}. |
| Q9BQK8 | LPIN3 | S221 | ochoa | Phosphatidate phosphatase LPIN3 (EC 3.1.3.4) (Lipin-3) (Lipin-3-like) | Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis therefore regulates fatty acid metabolism. {ECO:0000250|UniProtKB:Q99PI4}. |
| Q9BTE3 | MCMBP | S298 | ochoa | Mini-chromosome maintenance complex-binding protein (MCM-BP) (MCM-binding protein) | Associated component of the MCM complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion. {ECO:0000269|PubMed:20090939, ECO:0000269|PubMed:21196493}. |
| Q9BV86 | NTMT1 | S63 | ochoa | 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}. |
| Q9BXL6 | CARD14 | S60 | 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}. |
| Q9BY89 | KIAA1671 | S749 | ochoa | Uncharacterized protein KIAA1671 | None |
| Q9BYV9 | BACH2 | S409 | ochoa | Transcription regulator protein BACH2 (BTB and CNC homolog 2) | Transcriptional regulator that acts as a repressor or activator (By similarity). Binds to Maf recognition elements (MARE) (By similarity). Plays an important role in coordinating transcription activation and repression by MAFK (By similarity). Induces apoptosis in response to oxidative stress through repression of the antiapoptotic factor HMOX1 (PubMed:17018862). Positively regulates the nuclear import of actin (By similarity). Is a key regulator of adaptive immunity, crucial for the maintenance of regulatory T-cell function and B-cell maturation (PubMed:28530713). {ECO:0000250|UniProtKB:P97303, ECO:0000269|PubMed:17018862, ECO:0000269|PubMed:28530713}. |
| Q9BYW2 | SETD2 | S131 | 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}. |
| Q9BYX4 | IFIH1 | S490 | ochoa | Interferon-induced helicase C domain-containing protein 1 (EC 3.6.4.13) (Clinically amyopathic dermatomyositis autoantigen 140 kDa) (CADM-140 autoantigen) (Helicase with 2 CARD domains) (Helicard) (Interferon-induced with helicase C domain protein 1) (Melanoma differentiation-associated protein 5) (MDA-5) (Murabutide down-regulated protein) (RIG-I-like receptor 2) (RLR-2) (RNA helicase-DEAD box protein 116) | Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines (PubMed:28594402, PubMed:32169843, PubMed:33727702). Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length) (PubMed:22160685). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus (PubMed:28606988). Detects coronavirus SARS-CoV-2 (PubMed:33440148, PubMed:33514628). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines. {ECO:0000269|PubMed:14645903, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19656871, ECO:0000269|PubMed:21217758, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:22160685, ECO:0000269|PubMed:28594402, ECO:0000269|PubMed:28606988, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:33514628, ECO:0000269|PubMed:33727702}. |
| Q9BZK3 | NACA4P | S113 | ochoa | Putative nascent polypeptide-associated complex subunit alpha-like protein (Alpha-NAC pseudogene 1) (NAC-alpha pseudogene 1) (NACA family member 4, pseudogene) | None |
| 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}. |
| Q9H040 | SPRTN | S268 | ochoa | DNA-dependent metalloprotease SPRTN (EC 3.4.24.-) (DNA damage protein targeting VCP) (DVC1) (Protein with SprT-like domain at the N terminus) (Spartan) | DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:27852435, PubMed:27871365, PubMed:27871366, PubMed:30893605, PubMed:32649882, PubMed:36608669). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:27852435, PubMed:27871365, PubMed:27871366, PubMed:32649882, PubMed:36608669). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (PubMed:27852435, PubMed:27871365, PubMed:27871366, PubMed:32649882). Catalyzes proteolytic cleavage of the HMCES DNA-protein cross-link following unfolding by the BRIP1/FANCJ helicase (PubMed:36608669). Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (PubMed:27871366). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By similarity). SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). Involved in recruitment of VCP/p97 to sites of DNA damage (PubMed:22902628, PubMed:23042605, PubMed:23042607, PubMed:32152270). Also acts as an activator of CHEK1 during normal DNA replication by mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from chromatin and subsequent activation (PubMed:31316063). Does not activate CHEK1 in response to DNA damage (PubMed:31316063). May also act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA (PubMed:22681887, PubMed:22894931, PubMed:22902628, PubMed:22987070). Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis (PubMed:22681887). {ECO:0000250|UniProtKB:A0A1L8G2K9, ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628, ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:32649882, ECO:0000269|PubMed:36608669}. |
| Q9H078 | CLPB | S426 | ochoa | Mitochondrial disaggregase (EC 3.6.1.-) (Suppressor of potassium transport defect 3) [Cleaved into: Mitochondrial disaggregase, cleaved form] | Functions as a regulatory ATPase and participates in secretion/protein trafficking process. Has ATP-dependent protein disaggregase activity and is required to maintain the solubility of key mitochondrial proteins (PubMed:32573439, PubMed:34115842, PubMed:35247700, PubMed:36170828, PubMed:36745679). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117). Plays a role in granulocyte differentiation (PubMed:34115842). {ECO:0000269|PubMed:31522117, ECO:0000269|PubMed:32573439, ECO:0000269|PubMed:34115842, ECO:0000269|PubMed:35247700, ECO:0000269|PubMed:36170828, ECO:0000269|PubMed:36745679}. |
| Q9H081 | MIS12 | S185 | ochoa | Protein MIS12 homolog | Part of the MIS12 complex which is required for normal chromosome alignment and segregation and for kinetochore formation during mitosis (PubMed:12515822, PubMed:15502821, PubMed:16585270). Essential for proper kinetochore microtubule attachments (PubMed:23891108). {ECO:0000269|PubMed:12515822, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:16585270, ECO:0000269|PubMed:23891108}. |
| Q9H2J7 | SLC6A15 | S687 | ochoa | Sodium-dependent neutral amino acid transporter B(0)AT2 (Sodium- and chloride-dependent neurotransmitter transporter NTT73) (Sodium-coupled branched-chain amino-acid transporter 1) (Solute carrier family 6 member 15) (Transporter v7-3) | Functions as a sodium-dependent neutral amino acid transporter. Exhibits preference for the branched-chain amino acids, particularly leucine, valine and isoleucine and methionine. Can also transport low-affinity substrates such as alanine, phenylalanine, glutamine and pipecolic acid. Mediates the saturable, pH-sensitive and electrogenic cotransport of proline and sodium ions with a stoichiometry of 1:1. May have a role as transporter for neurotransmitter precursors into neurons. In contrast to other members of the neurotransmitter transporter family, does not appear to be chloride-dependent. {ECO:0000269|PubMed:16226721}. |
| Q9H2K2 | TNKS2 | S666 | ochoa | Poly [ADP-ribose] polymerase tankyrase-2 (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 6) (ARTD6) (Poly [ADP-ribose] polymerase 5B) (Protein poly-ADP-ribosyltransferase tankyrase-2) (EC 2.4.2.-) (TNKS-2) (TRF1-interacting ankyrin-related ADP-ribose polymerase 2) (Tankyrase II) (Tankyrase-2) (TANK2) (Tankyrase-like protein) (Tankyrase-related protein) | Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:11739745, PubMed:11802774, PubMed:19759537, PubMed:21478859, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:11802774, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:23622245, ECO:0000269|PubMed:25043379}. |
| Q9H2U1 | DHX36 | S963 | ochoa | ATP-dependent DNA/RNA helicase DHX36 (EC 3.6.4.12) (EC 3.6.4.13) (DEAD/H box polypeptide 36) (DEAH-box protein 36) (G4-resolvase-1) (G4R1) (MLE-like protein 1) (RNA helicase associated with AU-rich element protein) | Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:16150737, PubMed:18854321, PubMed:20472641, PubMed:21586581). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:14731398, PubMed:18279852, PubMed:21993297, PubMed:22238380, PubMed:25579584). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-DNA and G4-RNA) (PubMed:16150737, PubMed:18842585, PubMed:20472641, PubMed:21586581, PubMed:24369427, PubMed:26195789). Plays a role in genomic integrity (PubMed:22238380). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (PubMed:20472641, PubMed:21149580, PubMed:21846770, PubMed:22238380, PubMed:24151078, PubMed:25579584). Plays a role in transcriptional regulation (PubMed:21586581, PubMed:21993297). Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:21993297). Plays a role in post-transcriptional regulation (PubMed:27940037). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (PubMed:27940037). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (PubMed:24369427, PubMed:26489465). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (PubMed:24369427). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (PubMed:26489465). Also binds to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (PubMed:14731398, PubMed:18279852). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (PubMed:14731398). 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). Required for early embryonic development and hematopoiesis. Involved in the regulation of cardioblast differentiation and proliferation during heart development. Involved in spermatogonia differentiation. May play a role in ossification (By similarity). {ECO:0000250|UniProtKB:D4A2Z8, ECO:0000250|UniProtKB:Q05B79, ECO:0000250|UniProtKB:Q8VHK9, ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:16150737, ECO:0000269|PubMed:18279852, ECO:0000269|PubMed:18842585, ECO:0000269|PubMed:18854321, ECO:0000269|PubMed:20472641, ECO:0000269|PubMed:21149580, ECO:0000269|PubMed:21586581, ECO:0000269|PubMed:21846770, ECO:0000269|PubMed:21993297, ECO:0000269|PubMed:22238380, ECO:0000269|PubMed:24151078, ECO:0000269|PubMed:24369427, ECO:0000269|PubMed:25579584, ECO:0000269|PubMed:26195789, ECO:0000269|PubMed:26489465, ECO:0000269|PubMed:27940037}. |
| Q9H2Y7 | ZNF106 | S893 | 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}. |
| Q9H4I2 | ZHX3 | S577 | ochoa | Zinc fingers and homeoboxes protein 3 (Triple homeobox protein 1) (Zinc finger and homeodomain protein 3) | Acts as a transcriptional repressor. Involved in the early stages of mesenchymal stem cell (MSC) osteogenic differentiation. Is a regulator of podocyte gene expression during primary glomerula disease. Binds to promoter DNA. {ECO:0000269|PubMed:12659632, ECO:0000269|PubMed:21174497}. |
| Q9H582 | ZNF644 | S1214 | ochoa | Zinc finger protein 644 (Zinc finger motif enhancer-binding protein 2) (Zep-2) | May be involved in transcriptional regulation. |
| Q9H5I5 | PIEZO2 | S1857 | 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}. |
| Q9H714 | RUBCNL | S29 | ochoa | Protein associated with UVRAG as autophagy enhancer (Pacer) (Protein Rubicon-like) | Regulator of autophagy that promotes autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns(3)P) in late steps of autophagy (PubMed:28306502, PubMed:30704899). Acts by antagonizing RUBCN, thereby stimulating phosphatidylinositol 3-kinase activity of the PI3K/PI3KC3 complex (PubMed:28306502). Following anchorage to the autophagosomal SNARE STX17, promotes the recruitment of PI3K/PI3KC3 and HOPS complexes to the autophagosome to regulate the fusion specificity of autophagosomes with late endosomes/lysosomes (PubMed:28306502). Binds phosphoinositides phosphatidylinositol 3-phosphate (PtdIns(3)P), 4-phosphate (PtdIns(4)P) and 5-phosphate (PtdIns(5)P) (PubMed:28306502). In addition to its role in autophagy, acts as a regulator of lipid and glycogen homeostasis (By similarity). May act as a tumor suppressor (Probable). {ECO:0000250|UniProtKB:Q3TD16, ECO:0000269|PubMed:28306502, ECO:0000269|PubMed:30704899, ECO:0000305|PubMed:23522960}. |
| Q9H9R9 | DBNDD1 | S119 | ochoa | Dysbindin domain-containing protein 1 | None |
| Q9HA38 | ZMAT3 | S158 | ochoa | Zinc finger matrin-type protein 3 (Zinc finger protein WIG-1) (p53-activated gene 608 protein) | Acts as a bona fide target gene of p53/TP53. May play a role in the TP53-dependent growth regulatory pathway. May contribute to TP53-mediated apoptosis by regulation of TP53 expression and translocation to the nucleus and nucleolus. {ECO:0000269|PubMed:11571644}. |
| Q9HAD4 | WDR41 | S19 | ochoa | WD repeat-containing protein 41 | Non-catalytic component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:27103069, PubMed:27193190, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:27103069). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro, however WDR42 is shown not be an essential complex component for this function (PubMed:32303654). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27103069, PubMed:27617292). {ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531, ECO:0000269|PubMed:32303654}. |
| Q9HAV4 | XPO5 | S826 | ochoa | Exportin-5 (Exp5) (Ran-binding protein 21) | Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and release of the cargo from the export receptor. XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi). Mediates nuclear export of isoform 5 of ADAR/ADAR1 in a RanGTP-dependent manner.; FUNCTION: Mediates the nuclear export of micro-RNA precursors, which form short hairpins (PubMed:14631048, PubMed:14681208, PubMed:15613540). Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference. In some circumstances can also mediate the nuclear export of deacylated and aminoacylated tRNAs. Specifically recognizes dsRNAs that lack a 5'-overhang in a sequence-independent manner, have only a short 3'-overhang, and that have a double-stranded length of at least 15 base-pairs (PubMed:19965479). Binding is dependent on Ran-GTP (PubMed:19965479). {ECO:0000269|PubMed:14631048, ECO:0000269|PubMed:14681208, ECO:0000269|PubMed:15613540, ECO:0000269|PubMed:19965479}.; FUNCTION: (Microbial infection) Mediates the nuclear export of adenovirus VA1 dsRNA. {ECO:0000269|PubMed:12509441}. |
| Q9HAW4 | CLSPN | S846 | 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}. |
| Q9HCM4 | EPB41L5 | S550 | ochoa | Band 4.1-like protein 5 (Erythrocyte membrane protein band 4.1-like 5) | Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells. {ECO:0000269|PubMed:17920587}. |
| Q9NP74 | PALMD | S489 | ochoa | Palmdelphin (Paralemmin-like protein) | None |
| Q9NQC3 | RTN4 | S991 | ochoa | Reticulon-4 (Foocen) (Neurite outgrowth inhibitor) (Nogo protein) (Neuroendocrine-specific protein) (NSP) (Neuroendocrine-specific protein C homolog) (RTN-x) (Reticulon-5) | Required to induce the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:24262037, PubMed:25612671, PubMed:27619977). They regulate membrane morphogenesis in the ER by promoting tubular ER production (PubMed:24262037, PubMed:25612671, PubMed:27619977, PubMed:27786289). They influence nuclear envelope expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). However each isoform have specific functions mainly depending on their tissue expression specificities (Probable). {ECO:0000269|PubMed:24262037, ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412, ECO:0000269|PubMed:27619977, ECO:0000269|PubMed:27786289, ECO:0000305}.; FUNCTION: [Isoform A]: Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS (PubMed:10667797, PubMed:11201742). Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Acts as a negative regulator of central nervous system angiogenesis. Inhibits spreading, migration and sprouting of primary brain microvascular endothelial cells (MVECs). Also induces the retraction of MVECs lamellipodia and filopodia in a ROCK pathway-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742, ECO:0000269|PubMed:19699797}.; FUNCTION: [Isoform B]: Mainly function in endothelial cells and vascular smooth muscle cells, is also involved in immune system regulation (Probable). Modulator of vascular remodeling, promotes the migration of endothelial cells but inhibits the migration of vascular smooth muscle cells. Regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Inhibits serine palmitoyltransferase, SPTLC1, the rate-limiting enzyme of the novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine-1-phosphate (S1P). Required to promote macrophage homing and functions such as cytokine/chemokine gene expression involved in angiogenesis, arteriogenesis and tissue repair. Mediates ICAM1 induced transendothelial migration of leukocytes such as monocytes and neutrophils and acute inflammation. Necessary for immune responses triggered by nucleic acid sensing TLRs, such as TLR9, is required for proper TLR9 location to endolysosomes. Also involved in immune response to LPS. Plays a role in liver regeneration through the modulation of hepatocytes proliferation (By similarity). Reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration (PubMed:11126360). With isoform C, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:11126360, ECO:0000269|PubMed:16965550, ECO:0000305}.; FUNCTION: [Isoform C]: Regulates cardiomyocyte apoptosis upon hypoxic conditions (By similarity). With isoform B, inhibits BACE1 activity and amyloid precursor protein processing (PubMed:16965550). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:16965550}. |
| Q9NR48 | ASH1L | S22 | ochoa | Histone-lysine N-methyltransferase ASH1L (EC 2.1.1.359) (EC 2.1.1.367) (ASH1-like protein) (huASH1) (Absent small and homeotic disks protein 1 homolog) (Lysine N-methyltransferase 2H) | Histone methyltransferase specifically trimethylating 'Lys-36' of histone H3 forming H3K36me3 (PubMed:21239497). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). The physiological significance of the H3K9me1 activity is unclear (By similarity). {ECO:0000250|UniProtKB:Q99MY8, ECO:0000269|PubMed:21239497}. |
| Q9NR80 | ARHGEF4 | S62 | 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}. |
| 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}. |
| Q9NVH2 | INTS7 | S644 | 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}. |
| Q9NWL6 | ASNSD1 | S396 | ochoa | Asparagine synthetase domain-containing protein 1 (HCV NS3-transactivated protein 1) | None |
| Q9NYM9 | BET1L | S70 | ochoa | BET1-like protein (Golgi SNARE with a size of 15 kDa) (GOS-15) (GS15) (Vesicle transport protein GOS15) | Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex. Required for the integrity of the Golgi complex (By similarity). {ECO:0000250|UniProtKB:O35152}. |
| Q9NYV6 | RRN3 | S44 | ochoa|psp | RNA polymerase I-specific transcription initiation factor RRN3 (Transcription initiation factor IA) (TIF-IA) | Required for efficient transcription initiation by RNA polymerase I (Pol I). Required for the formation of the competent pre-initiation complex (PIC). {ECO:0000250, ECO:0000269|PubMed:10758157, ECO:0000269|PubMed:11250903, ECO:0000269|PubMed:11265758, ECO:0000269|PubMed:15805466}. |
| Q9NZV8 | KCND2 | S552 | psp | A-type voltage-gated potassium channel KCND2 (Potassium voltage-gated channel subfamily D member 2) (Voltage-gated potassium channel subunit Kv4.2) | Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:11507158, PubMed:14623880, PubMed:14695263, PubMed:14980201, PubMed:15454437, PubMed:16934482, PubMed:19171772, PubMed:24501278, PubMed:24811166, PubMed:34552243, PubMed:35597238). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:14623880, PubMed:14980201, PubMed:15454437, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (PubMed:35597238). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10551270, ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278, ECO:0000269|PubMed:24811166, ECO:0000269|PubMed:34552243, ECO:0000269|PubMed:35597238}. |
| Q9P244 | LRFN1 | S718 | ochoa | Leucine-rich repeat and fibronectin type III domain-containing protein 1 (Synaptic adhesion-like molecule 2) | Promotes neurite outgrowth in hippocampal neurons. Involved in the regulation and maintenance of excitatory synapses. Induces the clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1, GRIA1 and GRIN1 (By similarity). {ECO:0000250}. |
| Q9P260 | RELCH | S453 | 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}. |
| Q9P275 | USP36 | S682 | ochoa | Ubiquitin carboxyl-terminal hydrolase 36 (EC 2.3.2.-) (EC 3.4.19.12) (Deubiquitinating enzyme 36) (Ubiquitin thioesterase 36) (Ubiquitin-specific-processing protease 36) | Deubiquitinase essential for the regulation of nucleolar structure and function (PubMed:19208757, PubMed:22902402, PubMed:29273634). Required for cell and organism viability (PubMed:19208757, PubMed:22902402, PubMed:29273634). Plays an important role in ribosomal RNA processing and protein synthesis, which is mediated, at least in part, through deubiquitination of DHX33, NPM1 and FBL, regulating their protein stability (PubMed:19208757, PubMed:22902402, PubMed:29273634, PubMed:36912080). Functions as a transcriptional repressor by deubiquiting histone H2B at the promoters of genes critical for cellular differentiation, such as CDKN1A, thereby preventing histone H3 'Lys-4' trimethylation (H3K4) (PubMed:29274341). Specifically deubiquitinates MYC in the nucleolus, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 3 of FBXW7 (FBW7gamma) in the nucleolus and counteracting ubiquitination of MYC by the SCF(FBW7) complex (PubMed:25775507). In contrast, it does not interact with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm (PubMed:25775507). Interacts to and regulates the actions of E3 ubiquitin-protein ligase NEDD4L over substrates such as NTRK1, KCNQ2 and KCNQ3, affecting their expression an functions (PubMed:27445338). Deubiquitinates SOD2, regulates SOD2 protein stability (PubMed:21268071). Deubiquitinase activity is required to control selective autophagy activation by ubiquitinated proteins (PubMed:22622177). Promotes CEP63 stabilization through 'Lys-48'-linked deubiquitination leading to increased stability (PubMed:35989368). Acts as a SUMO ligase to promote EXOSC10 sumoylation critical for the nucleolar RNA exosome function in rRNA processing (PubMed:36912080). Binds to pre-rRNAs (PubMed:36912080). {ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:21268071, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:22902402, ECO:0000269|PubMed:25775507, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:29273634, ECO:0000269|PubMed:29274341, ECO:0000269|PubMed:35989368, ECO:0000269|PubMed:36912080}. |
| Q9P2D1 | CHD7 | S301 | ochoa | Chromodomain-helicase-DNA-binding protein 7 (CHD-7) (EC 3.6.4.-) (ATP-dependent helicase CHD7) | ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP (PubMed:28533432). Probable transcription regulator. May be involved in the in 45S precursor rRNA production. {ECO:0000269|PubMed:22646239, ECO:0000269|PubMed:28533432}. |
| Q9P2D3 | HEATR5B | S1737 | ochoa | HEAT repeat-containing protein 5B | 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}. |
| Q9P2N6 | KANSL3 | S633 | ochoa | KAT8 regulatory NSL complex subunit 3 (NSL complex protein NSL3) (Non-specific lethal 3 homolog) (Serum inhibited-related protein) (Testis development protein PRTD) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). Within the NSL complex, KANSL3 is required to promote KAT8 association with mitochondrial DNA (PubMed:27768893). Required for transcription of intraciliary transport genes in both ciliated and non-ciliated cells (By similarity). This is necessary for cilium assembly in ciliated cells and for organization of the microtubule cytoskeleton in non-ciliated cells (By similarity). Also required within the NSL complex to maintain nuclear architecture stability by promoting KAT8-mediated acetylation of lamin LMNA (By similarity). Plays an essential role in spindle assembly during mitosis (PubMed:26243146). Acts as a microtubule minus-end binding protein which stabilizes microtubules and promotes their assembly (PubMed:26243146). Indispensable during early embryonic development where it is required for proper lineage specification and maintenance during peri-implantation development and is essential for implantation (By similarity). {ECO:0000250|UniProtKB:A2RSY1, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}. |
| Q9UBS8 | RNF14 | S348 | 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}. |
| Q9UBU6 | FAM8A1 | S229 | ochoa | Protein FAM8A1 (Autosomal highly conserved protein) | Plays a role in the assembly of the HRD1 complex, a complex involved in the ubiquitin-proteasome-dependent process of ER-associated degradation (ERAD). {ECO:0000269|PubMed:28827405}. |
| Q9UDT6 | CLIP2 | S294 | ochoa | CAP-Gly domain-containing linker protein 2 (Cytoplasmic linker protein 115) (CLIP-115) (Cytoplasmic linker protein 2) (Williams-Beuren syndrome chromosomal region 3 protein) (Williams-Beuren syndrome chromosomal region 4 protein) | Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations (By similarity). {ECO:0000250}. |
| Q9UER7 | DAXX | S178 | ochoa|psp | Death domain-associated protein 6 (Daxx) (hDaxx) (ETS1-associated protein 1) (EAP1) (Fas death domain-associated protein) | Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as a histone chaperone that facilitates deposition of histone H3.3. Acts as a targeting component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S-phase and telomeres, and the in vitro remodeling of H3.3-containing nucleosomes. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upon neuronal activation associates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML-NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV). Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (PubMed:15016915). {ECO:0000269|PubMed:12140263, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:17942542, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:24530302}. |
| Q9UGU0 | TCF20 | S1167 | 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}. |
| Q9UHL9 | GTF2IRD1 | S448 | ochoa | General transcription factor II-I repeat domain-containing protein 1 (GTF2I repeat domain-containing protein 1) (General transcription factor III) (MusTRD1/BEN) (Muscle TFII-I repeat domain-containing protein 1) (Slow-muscle-fiber enhancer-binding protein) (USE B1-binding protein) (Williams-Beuren syndrome chromosomal region 11 protein) (Williams-Beuren syndrome chromosomal region 12 protein) | May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation. May repress GTF2I transcriptional functions, by preventing its nuclear residency, or by inhibiting its transcriptional activation. May contribute to slow-twitch fiber type specificity during myogenesis and in regenerating muscles. Binds troponin I slow-muscle fiber enhancer (USE B1). Binds specifically and with high affinity to the EFG sequences derived from the early enhancer of HOXC8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:11438732}. |
| Q9UIF8 | BAZ2B | S405 | 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}. |
| Q9UJC3 | HOOK1 | S167 | ochoa | Protein Hook homolog 1 (h-hook1) (hHK1) | Component of the FTS/Hook/FHIP complex (FHF complex) (PubMed:18799622, PubMed:32073997). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex) (PubMed:18799622). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). Required for spermatid differentiation. Probably involved in the positioning of the microtubules of the manchette and the flagellum in relation to the membrane skeleton (By similarity). {ECO:0000250|UniProtKB:Q8BIL5, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}. |
| Q9UJF2 | RASAL2 | S663 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UKL0 | RCOR1 | S460 | 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}. |
| Q9UKT4 | FBXO5 | S98 | ochoa | F-box only protein 5 (Early mitotic inhibitor 1) | Regulator of APC activity during mitotic and meiotic cell cycle (PubMed:16921029, PubMed:17234884, PubMed:17485488, PubMed:17875940, PubMed:23708001, PubMed:23708605). During mitotic cell cycle plays a role as both substrate and inhibitor of APC-FZR1 complex (PubMed:16921029, PubMed:17234884, PubMed:17485488, PubMed:17875940, PubMed:23708001, PubMed:23708605, PubMed:29875408). During G1 phase, plays a role as substrate of APC-FZR1 complex E3 ligase (PubMed:29875408). Then switches as an inhibitor of APC-FZR1 complex during S and G2 leading to cell-cycle commitment (PubMed:29875408). As APC inhibitor, prevents the degradation of APC substrates at multiple levels: by interacting with APC and blocking access of APC substrates to the D-box coreceptor, formed by FZR1 and ANAPC10; by suppressing ubiquitin ligation and chain elongation by APC by preventing the UBE2C and UBE2S activities (PubMed:16921029, PubMed:23708001, PubMed:23708605). Plays a role in genome integrity preservation by coordinating DNA replication with mitosis through APC inhibition in interphase to stabilize CCNA2 and GMNN in order to promote mitosis and prevent rereplication and DNA damage-induced cellular senescence (PubMed:17234884, PubMed:17485488, PubMed:17875940). During oocyte maturation, plays a role in meiosis through inactivation of APC-FZR1 complex. Inhibits APC through RPS6KA2 interaction that increases FBXO5 affiniy for CDC20 leading to the metaphase arrest of the second meiotic division before fertilization (By similarity). Controls entry into the first meiotic division through inactivation of APC-FZR1 complex (By similarity). Promotes migration and osteogenic differentiation of mesenchymal stem cells (PubMed:29850565). {ECO:0000250|UniProtKB:Q7TSG3, ECO:0000269|PubMed:16921029, ECO:0000269|PubMed:17234884, ECO:0000269|PubMed:17485488, ECO:0000269|PubMed:17875940, ECO:0000269|PubMed:23708001, ECO:0000269|PubMed:23708605, ECO:0000269|PubMed:29850565, ECO:0000269|PubMed:29875408}. |
| Q9ULD9 | ZNF608 | S1402 | ochoa | Zinc finger protein 608 (Renal carcinoma antigen NY-REN-36) | Transcription factor, which represses ZNF609 transcription. {ECO:0000250|UniProtKB:Q56A10}. |
| Q9ULJ3 | ZBTB21 | S605 | ochoa | Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) | Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}. |
| Q9ULT0 | TTC7A | S51 | ochoa | Tetratricopeptide repeat protein 7A (TPR repeat protein 7A) | Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:24417819). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, plays a central role in bridging PI4KA to EFR3B and HYCC1, via direct interactions (By similarity). {ECO:0000250|UniProtKB:Q86TV6, ECO:0000269|PubMed:23229899, ECO:0000269|PubMed:24417819}. |
| Q9UPQ4 | TRIM35 | S65 | ochoa | E3 ubiquitin-protein ligase TRIM35 (EC 2.3.2.27) (Hemopoietic lineage switch protein 5) | E3 ubiquitin-protein ligase that participates in multiple biological processes including cell death, glucose metabolism, and in particular, the innate immune response. Mediates 'Lys-63'-linked polyubiquitination of TRAF3 thereby promoting type I interferon production via RIG-I signaling pathway (PubMed:32562145). Can also catalyze 'Lys-48'-linked polyubiquitination and proteasomal degradation of viral proteins such as influenza virus PB2 (PubMed:32562145). Acts as a negative feedback regulator of TLR7- and TLR9-triggered signaling. Mechanistically, promotes the 'Lys-48'-linked ubiquitination of IRF7 and induces its degradation via a proteasome-dependent pathway (PubMed:25907537). Reduces FGFR1-dependent tyrosine phosphorylation of PKM, inhibiting PKM-dependent lactate production, glucose metabolism, and cell growth (PubMed:25263439). {ECO:0000269|PubMed:25263439, ECO:0000269|PubMed:25907537, ECO:0000269|PubMed:32562145}. |
| Q9UPV0 | CEP164 | S1374 | ochoa | Centrosomal protein of 164 kDa (Cep164) | Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1. {ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:18283122, ECO:0000269|PubMed:23348840}. |
| 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}. |
| Q9UQ84 | EXO1 | S598 | ochoa | Exonuclease 1 (hExo1) (EC 3.1.-.-) (Exonuclease I) (hExoI) | 5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts directed by strand breaks located either 5' or 3' to the mismatch. Also exhibits endonuclease activity against 5'-overhanging flap structures similar to those generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. Required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Essential for male and female meiosis. {ECO:0000269|PubMed:10364235, ECO:0000269|PubMed:10608837, ECO:0000269|PubMed:11809771, ECO:0000269|PubMed:11842105, ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12704184, ECO:0000269|PubMed:14636568, ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:15225546, ECO:0000269|PubMed:15886194, ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:9685493}. |
| Q9UQR1 | ZNF148 | S412 | 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. |
| Q9Y222 | DMTF1 | S701 | ochoa | Cyclin-D-binding Myb-like transcription factor 1 (hDMTF1) (Cyclin-D-interacting Myb-like protein 1) (hDMP1) | Transcriptional activator which activates the CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting p53/TP53-dependent growth arrest (By similarity). Binds to the consensus sequence 5'-CCCG[GT]ATGT-3' (By similarity). Isoform 1 may cooperate with MYB to activate transcription of the ANPEP gene. Isoform 2 may antagonize transcriptional activation by isoform 1. {ECO:0000250, ECO:0000269|PubMed:12917399}. |
| Q9Y232 | CDYL | S149 | ochoa | Chromodomain Y-like protein (CDY-like) (Crotonyl-CoA hydratase) (EC 4.2.1.-) | [Isoform 2]: Chromatin reader protein that recognizes and binds histone H3 trimethylated at 'Lys-9', dimethylated at 'Lys-27' and trimethylated at 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3, respectively) (PubMed:19808672, PubMed:28402439). Part of multimeric repressive chromatin complexes, where it is required for transmission and restoration of repressive histone marks, thereby preserving the epigenetic landscape (PubMed:28402439). Required for chromatin targeting and maximal enzymatic activity of Polycomb repressive complex 2 (PRC2); acts as a positive regulator of PRC2 activity by bridging the pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring nucleosomes (PubMed:22009739). Acts as a corepressor for REST by facilitating histone-lysine N-methyltransferase EHMT2 recruitment and H3K9 dimethylation at REST target genes for repression (PubMed:19061646). Involved in X chromosome inactivation in females: recruited to Xist RNA-coated X chromosome and facilitates propagation of H3K9me2 by anchoring EHMT2 (By similarity). Promotes EZH2 accumulation and H3K27me3 methylation at DNA double strand breaks (DSBs), thereby facilitating transcriptional repression at sites of DNA damage and homology-directed repair of DSBs (PubMed:29177481). Required for neuronal migration during brain development by repressing expression of RHOA (By similarity). By repressing the expression of SCN8A, contributes to the inhibition of intrinsic neuronal excitability and epileptogenesis (By similarity). In addition to acting as a chromatin reader, acts as a hydro-lyase (PubMed:28803779). Shows crotonyl-coA hydratase activity by mediating the conversion of crotonyl-CoA ((2E)-butenoyl-CoA) to beta-hydroxybutyryl-CoA (3-hydroxybutanoyl-CoA), thereby acting as a negative regulator of histone crotonylation (PubMed:28803779). Histone crotonylation is required during spermatogenesis; down-regulation of histone crotonylation by CDYL regulates the reactivation of sex chromosome-linked genes in round spermatids and histone replacement in elongating spermatids (By similarity). By regulating histone crotonylation and trimethylation of H3K27, may be involved in stress-induced depression-like behaviors, possibly by regulating VGF expression (By similarity). {ECO:0000250|UniProtKB:Q9WTK2, ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:22009739, ECO:0000269|PubMed:28402439, ECO:0000269|PubMed:28803779, ECO:0000269|PubMed:29177481}.; FUNCTION: [Isoform 1]: Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the presence of a N-terminal extension that inactivates the chromo domain (PubMed:19808672). {ECO:0000269|PubMed:19808672}.; FUNCTION: [Isoform 3]: Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the absence of the chromo domain (PubMed:19808672). Acts as a negative regulator of isoform 2 by displacing isoform 2 from chromatin. {ECO:0000269|PubMed:19808672}. |
| Q9Y250 | LZTS1 | S254 | ochoa | Leucine zipper putative tumor suppressor 1 (F37/esophageal cancer-related gene-coding leucine-zipper motif) (Fez1) | Involved in the regulation of cell growth. May stabilize the active CDC2-cyclin B1 complex and thereby contribute to the regulation of the cell cycle and the prevention of uncontrolled cell proliferation. May act as a tumor suppressor. {ECO:0000269|PubMed:10097140, ECO:0000269|PubMed:11464283, ECO:0000269|PubMed:11504921}. |
| Q9Y2I6 | NINL | S191 | ochoa | Ninein-like protein | Involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly. Involved in vesicle transport in photoreceptor cells (By similarity). May play a role in ovarian carcinogenesis. {ECO:0000250|UniProtKB:G9G127, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:16254247, ECO:0000269|PubMed:18538832}. |
| Q9Y2J2 | EPB41L3 | S762 | 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}. |
| 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}. |
| Q9Y2X3 | NOP58 | S351 | 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}. |
| Q9Y3M8 | STARD13 | S416 | ochoa | StAR-related lipid transfer protein 13 (46H23.2) (Deleted in liver cancer 2 protein) (DLC-2) (Rho GTPase-activating protein) (START domain-containing protein 13) (StARD13) | GTPase-activating protein for RhoA, and perhaps for Cdc42. May be involved in regulation of cytoskeletal reorganization, cell proliferation and cell motility. Acts a tumor suppressor in hepatocellular carcinoma cells. {ECO:0000269|PubMed:14697242, ECO:0000269|PubMed:16217026}. |
| Q9Y4B5 | MTCL1 | S923 | ochoa | Microtubule cross-linking factor 1 (Coiled-coil domain-containing protein 165) (PAR-1-interacting protein) (SOGA family member 2) | Microtubule-associated factor involved in the late phase of epithelial polarization and microtubule dynamics regulation (PubMed:23902687). Plays a role in the development and maintenance of non-centrosomal microtubule bundles at the lateral membrane in polarized epithelial cells (PubMed:23902687). Required for faithful chromosome segregation during mitosis (PubMed:33587225). {ECO:0000269|PubMed:23902687, ECO:0000269|PubMed:33587225}. |
| 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}. |
| Q9Y5A7 | NUB1 | S489 | ochoa | NEDD8 ultimate buster 1 (Negative regulator of ubiquitin-like proteins 1) (Renal carcinoma antigen NY-REN-18) | Specific down-regulator of the NEDD8 conjugation system. Recruits NEDD8, UBD, and their conjugates to the proteasome for degradation. Isoform 1 promotes the degradation of NEDD8 more efficiently than isoform 2. {ECO:0000269|PubMed:16707496}. |
| Q9Y6M5 | SLC30A1 | S426 | ochoa | Proton-coupled zinc antiporter SLC30A1 (Solute carrier family 30 member 1) (Zinc transporter 1) | Zinc ion:proton antiporter that could function at the plasma membrane mediating zinc efflux from cells against its electrochemical gradient protecting them from intracellular zinc accumulation and toxicity (PubMed:31471319). Alternatively, could prevent the transport to the plasma membrane of CACNB2, the L-type calcium channels regulatory subunit, through a yet to be defined mechanism. By modulating the expression of these channels at the plasma membrane, could prevent calcium and zinc influx into cells. By the same mechanism, could also prevent L-type calcium channels-mediated heavy metal influx into cells (By similarity). In some cells, could also function as a zinc ion:proton antiporter mediating zinc entry into the lumen of cytoplasmic vesicles. In macrophages, can increase zinc ions concentration into the lumen of cytoplasmic vesicles containing engulfed bacteria and could help inactivate them (PubMed:32441444). Forms a complex with TMC6/EVER1 and TMC8/EVER2 at the ER membrane of keratynocytes which facilitates zinc uptake into the ER (PubMed:18158319). Down-regulates the activity of transcription factors induced by zinc and cytokines (PubMed:18158319). {ECO:0000250|UniProtKB:Q62720, ECO:0000269|PubMed:18158319, ECO:0000269|PubMed:31471319, ECO:0000269|PubMed:32441444}. |
| V9GYD0 | ARL2-SNX15 | S45 | ochoa | ARL2-SNX15 readthrough (NMD candidate) | None |
| O00418 | EEF2K | S135 | Sugiyama | 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}. |
| Q5R3I4 | TTC38 | S362 | Sugiyama | Tetratricopeptide repeat protein 38 (TPR repeat protein 38) | None |
| Q6ULP2 | AFTPH | S151 | Sugiyama | Aftiphilin | 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}. |
| P52788 | SMS | S145 | Sugiyama | Spermine synthase (SPMSY) (EC 2.5.1.22) (Spermidine aminopropyltransferase) | Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM). {ECO:0000269|PubMed:18367445, ECO:0000269|PubMed:18550699, ECO:0000269|PubMed:23696453, ECO:0000269|PubMed:23897707}. |
| 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}. |
| Q8TDU6 | GPBAR1 | S310 | PSP | G-protein coupled bile acid receptor 1 (G-protein coupled receptor GPCR19) (hGPCR19) (Membrane-type receptor for bile acids) (M-BAR) (hBG37) (BG37) | Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids. {ECO:0000269|PubMed:12419312, ECO:0000269|PubMed:12524422}. |
| P07814 | EPRS1 | S1350 | 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}. |
| P35658 | NUP214 | S430 | Sugiyama | Nuclear pore complex protein Nup214 (214 kDa nucleoporin) (Nucleoporin Nup214) (Protein CAN) | Part of the nuclear pore complex (PubMed:9049309). Has a critical role in nucleocytoplasmic transport (PubMed:31178128). May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex (PubMed:31178128, PubMed:8108440). {ECO:0000269|PubMed:31178128, ECO:0000269|PubMed:9049309, ECO:0000303|PubMed:8108440}.; FUNCTION: (Microbial infection) Required for capsid disassembly of the human adenovirus 5 (HadV-5) leading to release of the viral genome to the nucleus (in vitro). {ECO:0000269|PubMed:25410864}. |
| 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}. |
| Q9P2J9 | PDP2 | S118 | Sugiyama | [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 2, mitochondrial (PDP 2) (EC 3.1.3.43) (Pyruvate dehydrogenase phosphatase catalytic subunit 2) (PDPC 2) | Mitochondrial enzyme that catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating the conversion of pyruvate into acetyl-CoA (By similarity). Acts as a crucial regulator of T cell metabolism and function, with a particular focus on T-helper Th17 (By similarity). {ECO:0000250|UniProtKB:O88484, ECO:0000250|UniProtKB:Q504M2}. |
| P57059 | SIK1 | S117 | 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}. |
| Q9H3D4 | TP63 | S310 | SIGNOR | 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}. |
| Q59H18 | TNNI3K | S430 | Sugiyama | Serine/threonine-protein kinase TNNI3K (EC 2.7.11.1) (Cardiac ankyrin repeat kinase) (Cardiac troponin I-interacting kinase) (TNNI3-interacting kinase) | May play a role in cardiac physiology. {ECO:0000303|PubMed:12721663}. |
| O95816 | BAG2 | S157 | Sugiyama | BAG family molecular chaperone regulator 2 (BAG-2) (Bcl-2-associated athanogene 2) | Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release (PubMed:24318877, PubMed:9873016). {ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:9873016}. |
| Q9UBE8 | NLK | S232 | Sugiyama | Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1) | Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}. |
| A1A4S6 | ARHGAP10 | S374 | ochoa | Rho GTPase-activating protein 10 (GTPase regulator associated with focal adhesion kinase 2) (GRAF2) (Graf-related protein 2) (Rho-type GTPase-activating protein 10) | GTPase-activating protein that catalyzes the conversion of active GTP-bound Rho GTPases to their inactive GDP-bound form, thus suppressing various Rho GTPase-mediated cellular processes (PubMed:11432776). Also converts Cdc42 to an inactive GDP-bound state (PubMed:11432776). Essential for PTKB2 regulation of cytoskeletal organization via Rho family GTPases. Inhibits PAK2 proteolytic fragment PAK-2p34 kinase activity and changes its localization from the nucleus to the perinuclear region. Stabilizes PAK-2p34 thereby increasing stimulation of cell death (By similarity). Associates with MICAL1 on the endosomal membrane to promote Rab8-Rab10-dependent tubule extension. After dissociation with MICAL1, recruits WDR44 which connects the endoplasmic reticulum (ER) with the endosomal tubule, thereby participating in the export of a subset of neosynthesized proteins (PubMed:32344433). {ECO:0000250|UniProtKB:Q6Y5D8, ECO:0000269|PubMed:11432776, ECO:0000269|PubMed:32344433}. |
| A1L390 | PLEKHG3 | S743 | 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}. |
| A7KAX9 | ARHGAP32 | S1181 | 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}. |
| A8MVW0 | FAM171A2 | S357 | ochoa | Protein FAM171A2 | None |
| B2RNG4 | TRIM6-TRIM34 | S441 | ochoa | RING-type E3 ubiquitin transferase (EC 2.3.2.27) | None |
| H0YIS7 | RNASEK-C17orf49 | S182 | ochoa | BPTF-associated chromatin complex component 1 (BPTF-associated protein of 18 kDa) (Chromatin complexes subunit BAP18) | Component of chromatin complexes such as the MLL1/MLL and NURF complexes. {ECO:0000256|ARBA:ARBA00059556}. |
| O00159 | MYO1C | S592 | ochoa | Unconventional myosin-Ic (Myosin I beta) (MMI-beta) (MMIb) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes. {ECO:0000269|PubMed:24636949}.; FUNCTION: [Isoform 3]: Involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation. {ECO:0000250|UniProtKB:Q9WTI7}. |
| 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). |
| O00287 | RFXAP | S237 | 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. |
| O00411 | POLRMT | S666 | ochoa | DNA-directed RNA polymerase, mitochondrial (MtRPOL) (EC 2.7.7.6) | DNA-dependent RNA polymerase catalyzes the transcription of mitochondrial DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:21278163, PubMed:33602924). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (PubMed:29149603). In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:29149603). Has DNA primase activity (PubMed:18685103, PubMed:33602924). Catalyzes the synthesis of short RNA primers that are necessary for the initiation of lagging-strand DNA synthesis from the origin of light-strand DNA replication (OriL) (PubMed:18685103, PubMed:33602924). {ECO:0000269|PubMed:18685103, ECO:0000269|PubMed:21278163, ECO:0000269|PubMed:29149603, ECO:0000269|PubMed:33602924}. |
| O00443 | PIK3C2A | S329 | ochoa | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3K-C2-alpha) (PtdIns-3-kinase C2 subunit alpha) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphoinositide 3-kinase-C2-alpha) | Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465). {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:31034465, ECO:0000269|PubMed:9337861}. |
| O00562 | PITPNM1 | S600 | ochoa | Membrane-associated phosphatidylinositol transfer protein 1 (Drosophila retinal degeneration B homolog) (Phosphatidylinositol transfer protein, membrane-associated 1) (PITPnm 1) (Pyk2 N-terminal domain-interacting receptor 2) (NIR-2) | Catalyzes the transfer of phosphatidylinositol (PI) between membranes (PubMed:10531358, PubMed:22822086). Binds PI, phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC (PubMed:22822086). Regulates RHOA activity, and plays a role in cytoskeleton remodeling (PubMed:11909959). Necessary for normal completion of cytokinesis (PubMed:15125835). Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus (PubMed:15723057). Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus (PubMed:15545272). Required for protein export from the endoplasmic reticulum and the Golgi (PubMed:15723057). Binds calcium ions (PubMed:10022914). {ECO:0000269|PubMed:10022914, ECO:0000269|PubMed:10531358, ECO:0000269|PubMed:11909959, ECO:0000269|PubMed:15545272, ECO:0000269|PubMed:15723057, ECO:0000269|PubMed:22822086}. |
| O14529 | CUX2 | S927 | ochoa | Homeobox protein cut-like 2 (Homeobox protein cux-2) | Transcription factor involved in the control of neuronal proliferation and differentiation in the brain. Regulates dendrite development and branching, dendritic spine formation, and synaptogenesis in cortical layers II-III. Binds to DNA in a sequence-specific manner. {ECO:0000250|UniProtKB:P70298}. |
| O14545 | TRAFD1 | S98 | ochoa | TRAF-type zinc finger domain-containing protein 1 (Protein FLN29) | Negative feedback regulator that controls excessive innate immune responses. Regulates both Toll-like receptor 4 (TLR4) and DDX58/RIG1-like helicases (RLH) pathways. May inhibit the LTR pathway by direct interaction with TRAF6 and attenuation of NF-kappa-B activation. May negatively regulate the RLH pathway downstream from MAVS and upstream of NF-kappa-B and IRF3 (By similarity). {ECO:0000250, ECO:0000269|PubMed:16221674}. |
| O14617 | AP3D1 | S1068 | ochoa | AP-3 complex subunit delta-1 (AP-3 complex subunit delta) (Adaptor-related protein complex 3 subunit delta-1) (Delta-adaptin) | Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. Involved in process of CD8+ T-cell and NK cell degranulation (PubMed:26744459). In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals (By similarity). {ECO:0000250|UniProtKB:O54774, ECO:0000269|PubMed:26744459}. |
| O14654 | IRS4 | S251 | ochoa | Insulin receptor substrate 4 (IRS-4) (160 kDa phosphotyrosine protein) (py160) (Phosphoprotein of 160 kDa) (pp160) | Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2. {ECO:0000269|PubMed:10531310, ECO:0000269|PubMed:10594015, ECO:0000269|PubMed:12639902, ECO:0000269|PubMed:17408801, ECO:0000269|PubMed:9553137}. |
| O14737 | PDCD5 | S57 | ochoa | Programmed cell death protein 5 (TF-1 cell apoptosis-related protein 19) (Protein TFAR19) | May function in the process of apoptosis. |
| O15067 | PFAS | S128 | ochoa | Phosphoribosylformylglycinamidine synthase (FGAM synthase) (FGAMS) (EC 6.3.5.3) (Formylglycinamide ribonucleotide amidotransferase) (FGAR amidotransferase) (FGAR-AT) (Formylglycinamide ribotide amidotransferase) (Phosphoribosylformylglycineamide amidotransferase) | Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate. {ECO:0000305|PubMed:10548741}. |
| 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}. |
| O15417 | TNRC18 | S1136 | ochoa | Trinucleotide repeat-containing gene 18 protein (Long CAG trinucleotide repeat-containing gene 79 protein) | None |
| O15516 | CLOCK | S106 | psp | Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 8) (bHLHe8) | Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). {ECO:0000250|UniProtKB:O08785, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}. |
| O43164 | PJA2 | S216 | ochoa | E3 ubiquitin-protein ligase Praja-2 (Praja2) (EC 2.3.2.27) (RING finger protein 131) (RING-type E3 ubiquitin transferase Praja-2) | Has E2-dependent E3 ubiquitin-protein ligase activity (PubMed:12036302, PubMed:21423175). Responsible for ubiquitination of cAMP-dependent protein kinase type I and type II-alpha/beta regulatory subunits and for targeting them for proteasomal degradation. Essential for PKA-mediated long-term memory processes (PubMed:21423175). Through the ubiquitination of MFHAS1, positively regulates the TLR2 signaling pathway that leads to the activation of the downstream p38 and JNK MAP kinases and promotes the polarization of macrophages toward the pro-inflammatory M1 phenotype (PubMed:28471450). Plays a role in ciliogenesis by ubiquitinating OFD1 (PubMed:33934390). {ECO:0000269|PubMed:12036302, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:28471450, ECO:0000269|PubMed:33934390}. |
| O43182 | ARHGAP6 | S384 | ochoa | Rho GTPase-activating protein 6 (Rho-type GTPase-activating protein 6) (Rho-type GTPase-activating protein RhoGAPX-1) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Could regulate the interactions of signaling molecules with the actin cytoskeleton. Promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. {ECO:0000269|PubMed:10699171}. |
| O43194 | GPR39 | S411 | 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}. |
| O43542 | XRCC3 | S225 | psp | DNA repair protein XRCC3 (X-ray repair cross-complementing protein 3) | Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA, thought to repair chromosomal fragmentation, translocations and deletions. Part of the RAD51 paralog protein complex CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, CX3 acts downstream of RAD51 recruitment; the complex binds predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junctions of replication forks. Involved in HJ resolution and thus in processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex and seems to involve GEN1 during mitotic cell cycle progression. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and RAD51C. {ECO:0000269|PubMed:14716019, ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23108668, ECO:0000269|PubMed:23149936}. |
| O43683 | BUB1 | S176 | ochoa|psp | Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) | Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}. |
| O43747 | AP1G1 | S369 | ochoa | 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}. |
| O60240 | PLIN1 | S81 | ochoa | Perilipin-1 (Lipid droplet-associated protein) | Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels. {ECO:0000269|PubMed:23399566}. |
| O60264 | SMARCA5 | S137 | ochoa | SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin A5) (EC 3.6.4.-) (Sucrose nonfermenting protein 2 homolog) (hSNF2H) | ATPase that possesses intrinsic ATP-dependent nucleosome-remodeling activity (PubMed:12972596, PubMed:28801535). Catalytic subunit of ISWI chromatin-remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair; this may require intact histone H4 tails (PubMed:10880450, PubMed:12198550, PubMed:12434153, PubMed:12972596, PubMed:23911928, PubMed:28801535). Within the ISWI chromatin-remodeling complexes, slides edge- and center-positioned histone octamers away from their original location on the DNA template (PubMed:28801535). Catalytic activity and histone octamer sliding propensity is regulated and determined by components of the ISWI chromatin-remodeling complexes (PubMed:28801535). The BAZ1A/ACF1-, BAZ1B/WSTF-, BAZ2A/TIP5- and BAZ2B-containing ISWI chromatin-remodeling complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template in an ATP-dependent manner (PubMed:14759371, PubMed:15543136, PubMed:28801535). The CECR2- and RSF1-containing ISWI chromatin-remodeling complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). Binds to core histones together with RSF1, and is required for the assembly of regular nucleosome arrays by the RSF-5 ISWI chromatin-remodeling complex (PubMed:12972596). Involved in DNA replication and together with BAZ1A/ACF1 is required for replication of pericentric heterochromatin in S-phase (PubMed:12434153). Probably plays a role in repression of RNA polymerase I dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter (By similarity). Essential component of the WICH-5 ISWI chromatin-remodeling complex (also called the WICH complex), a chromatin-remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure (PubMed:11980720, PubMed:15543136). The WICH-5 ISWI chromatin-remodeling complex regulates the transcription of various genes, has a role in RNA polymerase I transcription (By similarity). Within the B-WICH complex has a role in RNA polymerase III transcription (PubMed:16603771). Mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes (By similarity). Essential component of NoRC-5 ISWI chromatin-remodeling complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing (By similarity). {ECO:0000250|UniProtKB:Q91ZW3, ECO:0000269|PubMed:10880450, ECO:0000269|PubMed:11980720, ECO:0000269|PubMed:12198550, ECO:0000269|PubMed:12434153, ECO:0000269|PubMed:12972596, ECO:0000269|PubMed:14759371, ECO:0000269|PubMed:15543136, ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:23911928, ECO:0000269|PubMed:28801535}. |
| O60271 | SPAG9 | S387 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| O60602 | TLR5 | S805 | psp | Toll-like receptor 5 (Toll/interleukin-1 receptor-like protein 3) | Pattern recognition receptor (PRR) located on the cell surface that participates in the activation of innate immunity and inflammatory response (PubMed:11323673, PubMed:18490781). Recognizes small molecular motifs named pathogen-associated molecular pattern (PAMPs) expressed by pathogens and microbe-associated molecular patterns (MAMPs) usually expressed by resident microbiota (PubMed:29934223). Upon ligand binding such as bacterial flagellins, recruits intracellular adapter proteins MYD88 and TRIF leading to NF-kappa-B activation, cytokine secretion and induction of the inflammatory response (PubMed:11489966, PubMed:20855887). Plays thereby an important role in the relationship between the intestinal epithelium and enteric microbes and contributes to the gut microbiota composition throughout life (By similarity). {ECO:0000250|UniProtKB:Q9JLF7, ECO:0000269|PubMed:11323673, ECO:0000269|PubMed:11489966, ECO:0000269|PubMed:18490781, ECO:0000269|PubMed:20855887, ECO:0000269|PubMed:29934223}. |
| 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}. |
| O60673 | REV3L | S400 | ochoa | DNA polymerase zeta catalytic subunit (EC 2.7.7.7) (Protein reversionless 3-like) (REV3-like) (hREV3) | Catalytic subunit of the DNA polymerase zeta complex, an error-prone polymerase specialized in translesion DNA synthesis (TLS). Lacks an intrinsic 3'-5' exonuclease activity and thus has no proofreading function. {ECO:0000269|PubMed:24449906}. |
| O75665 | OFD1 | S735 | ochoa|psp | Centriole and centriolar satellite protein OFD1 (Oral-facial-digital syndrome 1 protein) (Protein 71-7A) | Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250|UniProtKB:Q80Z25, ECO:0000269|PubMed:33934390}. |
| O75665 | OFD1 | S844 | ochoa | Centriole and centriolar satellite protein OFD1 (Oral-facial-digital syndrome 1 protein) (Protein 71-7A) | Component of the centrioles controlling mother and daughter centrioles length. Recruits to the centriole IFT88 and centriole distal appendage-specific proteins including CEP164 (By similarity). Involved in the biogenesis of the cilium, a centriole-associated function. The cilium is a cell surface projection found in many vertebrate cells required to transduce signals important for development and tissue homeostasis (PubMed:33934390). Plays an important role in development by regulating Wnt signaling and the specification of the left-right axis. Only OFD1 localized at the centriolar satellites is removed by autophagy, which is an important step in the ciliogenesis regulation (By similarity). {ECO:0000250|UniProtKB:Q80Z25, ECO:0000269|PubMed:33934390}. |
| O75815 | BCAR3 | S375 | 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}. |
| 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}. |
| O75865 | TRAPPC6A | S35 | psp | Trafficking protein particle complex subunit 6A (TRAPP complex subunit 6A) | May play a role in vesicular transport during the biogenesis of melanosomes. {ECO:0000250|UniProtKB:Q78XR0}. |
| O75943 | RAD17 | S86 | ochoa | Cell cycle checkpoint protein RAD17 (hRad17) (RF-C/activator 1 homolog) | Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). Has a weak ATPase activity required for binding to chromatin (PubMed:10208430, PubMed:11418864, PubMed:11687627, PubMed:11799063, PubMed:12672690, PubMed:14624239, PubMed:15235112). Participates in the recruitment of the 9-1-1 (RAD1-RAD9-HUS1) complex and RHNO1 onto chromatin, and in CHEK1 activation (PubMed:21659603). Involved in homologous recombination by mediating recruitment of the MRN complex to DNA damage sites (PubMed:24534091). May also serve as a sensor of DNA replication progression (PubMed:12578958, PubMed:14500819, PubMed:15538388). {ECO:0000269|PubMed:10208430, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11687627, ECO:0000269|PubMed:11799063, ECO:0000269|PubMed:12578958, ECO:0000269|PubMed:12672690, ECO:0000269|PubMed:14500819, ECO:0000269|PubMed:14624239, ECO:0000269|PubMed:15235112, ECO:0000269|PubMed:15538388, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:24534091}. |
| O76094 | SRP72 | S81 | 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}. |
| O94915 | FRYL | S1258 | ochoa | Protein furry homolog-like (ALL1-fused gene from chromosome 4p12 protein) | Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching (By similarity). May function as a transcriptional activator. {ECO:0000250, ECO:0000269|PubMed:16061630}. |
| O95069 | KCNK2 | S348 | ochoa|psp | Potassium channel subfamily K member 2 (Outward rectifying potassium channel protein TREK-1) (TREK-1 K(+) channel subunit) (Two pore domain potassium channel TREK1) (Two pore potassium channel TPKC1) (K2P2.1) | K(+) channel that conducts voltage-dependent outward rectifying currents upon membrane depolarization. Voltage sensing is coupled to K(+) electrochemical gradient in an 'ion flux gating' mode where outward but not inward ion flow opens the gate. Converts to voltage-independent 'leak' conductance mode upon stimulation by various stimuli including mechanical membrane stretch, acidic pH, heat and lipids. Reversibly converts between a voltage-insensitive K(+) 'leak' channel and a voltage-dependent outward rectifying K(+) channel in a phosphorylation-dependent manner (By similarity) (PubMed:10321245, PubMed:10784345, PubMed:11319556, PubMed:23169818, PubMed:30573346, PubMed:38605031). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (By similarity). In trigeminal ganglia sensory neurons, the heterodimer of KCNK2/TREK-1 and KCNK18/TRESK inhibits neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). At trigeminal A-beta afferent nerves, the heterodimer of KCNK2/TREK-1 and KCNK4/TRAAK is mostly coexpressed at nodes of Ranvier where it conducts voltage-independent mechanosensitive and thermosensitive currents, allowing rapid action potential repolarization, high speed and high frequence saltatory conduction on myelinated nerves to ensure prompt sensory responses (By similarity). In hippocampal astrocytes, the heterodimer of KCNK2/TREK-1 and KCNK1/TWIK-1 allows passive K(+) conductance under basal conditions, but changes ion selectivity and becomes permeable to L-glutamate and Cl(-) ions upon binding to G-protein subunit GNG4 in stimulated astrocytes. Mediates rapid L-glutamate release in response to activation of G-protein-coupled receptors, such as F2R and CNR1 (By similarity). In hippocampal pyramidal neurons, the homodimer of KCNK2/TREK-1 contributes to gamma-aminobutyric acid (GABA) B-induced slow inhibitory postsynaptic potential. Associates with AKAP5 and Gs-protein-coupled receptor B2AR at postsynaptic dense bodies and converts to a leak channel no longer sensitive to stimulation by arachidonic acid, acidic pH or mechanical stress, nor inhibited by Gq-coupled receptors but still under the negative control of Gs-coupled receptors (By similarity). Permeable to other monovalent cations such as Rb(+) and Cs(+) (By similarity). {ECO:0000250|UniProtKB:P97438, ECO:0000250|UniProtKB:Q920B6, ECO:0000269|PubMed:10321245, ECO:0000269|PubMed:10784345, ECO:0000269|PubMed:11319556, ECO:0000269|PubMed:23169818, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:38605031}.; FUNCTION: [Isoform 4]: Does not display channel activity but reduces the channel activity of isoform 1 and isoform 2 and reduces cell surface expression of isoform 2. {ECO:0000250|UniProtKB:Q920B6}. |
| O95140 | MFN2 | S442 | psp | Mitofusin-2 (EC 3.6.5.-) (Transmembrane GTPase MFN2) | Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion (PubMed:11181170, PubMed:11950885, PubMed:19889647, PubMed:26214738, PubMed:28114303). Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events (PubMed:28114303). Overexpression induces the formation of mitochondrial networks (PubMed:28114303). Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the regulation of vascular smooth muscle cell proliferation (By similarity). Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:23620051). Is required for PRKN recruitment to dysfunctional mitochondria (PubMed:23620051). Involved in the control of unfolded protein response (UPR) upon ER stress including activation of apoptosis and autophagy during ER stress (By similarity). Acts as an upstream regulator of EIF2AK3 and suppresses EIF2AK3 activation under basal conditions (By similarity). {ECO:0000250|UniProtKB:Q80U63, ECO:0000250|UniProtKB:Q8R500, ECO:0000269|PubMed:11181170, ECO:0000269|PubMed:11950885, ECO:0000269|PubMed:19889647, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:26085578, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:28114303, ECO:0000305}. |
| O95149 | SNUPN | S340 | ochoa | Snurportin-1 (RNA U transporter 1) | Functions as an U snRNP-specific nuclear import adapter. Involved in the trimethylguanosine (m3G)-cap-dependent nuclear import of U snRNPs. Binds specifically to the terminal m3G-cap U snRNAs. {ECO:0000269|PubMed:10209022, ECO:0000269|PubMed:15920472, ECO:0000269|PubMed:16030253, ECO:0000269|PubMed:38413582, ECO:0000269|PubMed:9670026}. |
| O95263 | PDE8B | S517 | ochoa | High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B (HsPDE8B) (EC 3.1.4.53) (Cell proliferation-inducing gene 22 protein) | Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in specific signaling in the thyroid gland. |
| O95476 | CTDNEP1 | S49 | ochoa | CTD nuclear envelope phosphatase 1 (EC 3.1.3.16) (Serine/threonine-protein phosphatase dullard) | Serine/threonine protein phosphatase forming with CNEP1R1 an active phosphatase complex that dephosphorylates and may activate LPIN1 and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol. May antagonize BMP signaling. {ECO:0000269|PubMed:17420445, ECO:0000269|PubMed:22134922}. |
| O95477 | ABCA1 | S2234 | ochoa | Phospholipid-transporting ATPase ABCA1 (EC 7.6.2.1) (ATP-binding cassette sub-family A member 1) (ATP-binding cassette transporter 1) (ABC-1) (ATP-binding cassette 1) (Cholesterol efflux regulatory protein) | Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981, PubMed:35974019). Thereby, participates in phospholipid transfer to apolipoproteins to form nascent high density lipoproteins/HDLs (PubMed:14754908). Transports preferentially phosphatidylcholine over phosphatidylserine (PubMed:24097981). May play a similar role in the efflux of intracellular cholesterol to apolipoproteins and the formation of nascent high density lipoproteins/HDLs (PubMed:10533863, PubMed:14754908, PubMed:24097981, PubMed:35974019). Translocates phospholipids from the outer face of the plasma membrane and forces it through its gateway and annulus into an elongated hydrophobic tunnel in its extracellular domain (PubMed:35974019). {ECO:0000269|PubMed:10533863, ECO:0000269|PubMed:14754908, ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:35974019}. |
| O95613 | PCNT | S2044 | 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}. |
| 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}. |
| O95758 | PTBP3 | S165 | 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}. |
| O95801 | TTC4 | S234 | ochoa | Tetratricopeptide repeat protein 4 (TPR repeat protein 4) | May act as a co-chaperone for HSP90AB1 (PubMed:18320024). Promotes Sendai virus (SeV)-induced host cell innate immune responses (PubMed:29251827). {ECO:0000269|PubMed:18320024, ECO:0000269|PubMed:29251827}. |
| O96028 | NSD2 | S54 | ochoa | Histone-lysine N-methyltransferase NSD2 (EC 2.1.1.357) (Multiple myeloma SET domain-containing protein) (MMSET) (Nuclear SET domain-containing protein 2) (Protein trithorax-5) (Wolf-Hirschhorn syndrome candidate 1 protein) | Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:19808676, PubMed:22099308, PubMed:27571355, PubMed:29728617, PubMed:33941880). Also monomethylates nucleosomal histone H3 at 'Lys-36' (H3K36me) in vitro (PubMed:22099308). Does not trimethylate nucleosomal histone H3 at 'Lys-36' (H3K36me3) (PubMed:22099308). However, specifically trimethylates histone H3 at 'Lys-36' (H3K36me3) at euchromatic regions in embryonic stem (ES) cells (By similarity). By methylating histone H3 at 'Lys-36', involved in the regulation of gene transcription during various biological processes (PubMed:16115125, PubMed:22099308, PubMed:29728617). In ES cells, associates with developmental transcription factors such as SALL1 and represses inappropriate gene transcription mediated by histone deacetylation (By similarity). During heart development, associates with transcription factor NKX2-5 to repress transcription of NKX2-5 target genes (By similarity). Plays an essential role in adipogenesis, by regulating expression of genes involved in pre-adipocyte differentiation (PubMed:29728617). During T-cell receptor (TCR) and CD28-mediated T-cell activation, promotes the transcription of transcription factor BCL6 which is required for follicular helper T (Tfh) cell differentiation (By similarity). During B-cell development, required for the generation of the B1 lineage (By similarity). During B2 cell activation, may contribute to the control of isotype class switch recombination (CRS), splenic germinal center formation, and the humoral immune response (By similarity). Plays a role in class switch recombination of the immunoglobulin heavy chain (IgH) locus during B-cell activation (By similarity). By regulating the methylation of histone H3 at 'Lys-36' and histone H4 at 'Lys-20' at the IgH locus, involved in TP53BP1 recruitment to the IgH switch region and promotes the transcription of IgA (By similarity). {ECO:0000250|UniProtKB:Q8BVE8, ECO:0000269|PubMed:16115125, ECO:0000269|PubMed:19808676, ECO:0000269|PubMed:22099308, ECO:0000269|PubMed:27571355, ECO:0000269|PubMed:29728617, ECO:0000269|PubMed:33941880}.; FUNCTION: [Isoform 1]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2). {ECO:0000269|PubMed:22099308}.; FUNCTION: [Isoform 4]: Histone methyltransferase which specifically dimethylates nucleosomal histone H3 at 'Lys-36' (H3K36me2) (PubMed:22099308). Methylation of histone H3 at 'Lys-27' is controversial (PubMed:18172012, PubMed:22099308). Mono-, di- or tri-methylates histone H3 at 'Lys-27' (H3K27me, H3K27me2 and H3K27me3) (PubMed:18172012). Does not methylate histone H3 at 'Lys-27' (PubMed:22099308). May act as a transcription regulator that binds DNA and suppresses IL5 transcription through HDAC recruitment (PubMed:11152655, PubMed:18172012). {ECO:0000269|PubMed:11152655, ECO:0000269|PubMed:18172012, ECO:0000269|PubMed:22099308}. |
| P00338 | LDHA | S161 | ochoa|psp | L-lactate dehydrogenase A chain (LDH-A) (EC 1.1.1.27) (Cell proliferation-inducing gene 19 protein) (LDH muscle subunit) (LDH-M) (Renal carcinoma antigen NY-REN-59) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:11276087}. |
| P00441 | SOD1 | S26 | ochoa | Superoxide dismutase [Cu-Zn] (EC 1.15.1.1) (Superoxide dismutase 1) (hSod1) | Destroys radicals which are normally produced within the cells and which are toxic to biological systems. {ECO:0000269|PubMed:24140062}. |
| P01009 | SERPINA1 | S261 | ochoa | Alpha-1-antitrypsin (Alpha-1 protease inhibitor) (Alpha-1-antiproteinase) (Serpin A1) [Cleaved into: Short peptide from AAT (SPAAT)] | Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.; FUNCTION: [Short peptide from AAT]: Reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE). |
| 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}. |
| P04035 | HMGCR | S504 | ochoa | 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) (EC 1.1.1.34) | Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis (PubMed:21357570, PubMed:2991281, PubMed:36745799, PubMed:6995544). HMGCR is the main target of statins, a class of cholesterol-lowering drugs (PubMed:11349148, PubMed:18540668, PubMed:36745799). {ECO:0000269|PubMed:11349148, ECO:0000269|PubMed:18540668, ECO:0000269|PubMed:21357570, ECO:0000269|PubMed:2991281, ECO:0000269|PubMed:36745799, ECO:0000269|PubMed:6995544}. |
| P04350 | TUBB4A | S95 | 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. |
| P05062 | ALDOB | S272 | 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}. |
| P05107 | ITGB2 | S346 | 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 | S842 | 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}. |
| P07195 | LDHB | S162 | ochoa|psp | L-lactate dehydrogenase B chain (LDH-B) (EC 1.1.1.27) (LDH heart subunit) (LDH-H) (Renal carcinoma antigen NY-REN-46) | Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+). {ECO:0000269|PubMed:27618187}. |
| P07437 | TUBB | S95 | 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. |
| P07864 | LDHC | S161 | ochoa | L-lactate dehydrogenase C chain (LDH-C) (EC 1.1.1.27) (Cancer/testis antigen 32) (CT32) (LDH testis subunit) (LDH-X) | Possible role in sperm motility. |
| P07900 | HSP90AA1 | S72 | 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}. |
| P08047 | SP1 | S702 | 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}. |
| P08195 | SLC3A2 | S406 | 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}. |
| P08238 | HSP90AB1 | S452 | 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}. |
| P09211 | GSTP1 | S185 | psp | Glutathione S-transferase P (EC 2.5.1.18) (GST class-pi) (GSTP1-1) | Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration. {ECO:0000269|PubMed:21046276, ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9084911}. |
| P10070 | GLI2 | S149 | psp | Zinc finger protein GLI2 (GLI family zinc finger protein 2) (Tax helper protein) | Functions as a transcription regulator in the hedgehog (Hh) pathway (PubMed:18455992, PubMed:26565916). Functions as a transcriptional activator (PubMed:19878745, PubMed:24311597, PubMed:9557682). May also function as transcriptional repressor (By similarity). Requires STK36 for full transcriptional activator activity. Required for normal embryonic development (PubMed:15994174, PubMed:20685856). {ECO:0000250|UniProtKB:Q0VGT2, ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:26565916, ECO:0000269|PubMed:9557682, ECO:0000305|PubMed:20685856}.; FUNCTION: [Isoform 1]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 2]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 3]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 4]: Involved in the smoothened (SHH) signaling pathway. {ECO:0000269|PubMed:18455992}.; FUNCTION: [Isoform 1]: Acts as a transcriptional activator in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 2]: (Microbial infection) Acts as a transcriptional activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 3]: (Microbial infection) Acts as a transcriptional activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 4]: (Microbial infection) Acts as a transcriptional activators in T-cell leukemia virus type 1 (HTLV-1)-infected cells in a Tax-dependent manner. Binds to the DNA sequence 5'-GAACCACCCA-3' which is part of the Tax-responsive element (TRE-2S) regulatory element that augments the Tax-dependent enhancer of HTLV-1 (PubMed:9557682). {ECO:0000269|PubMed:15994174, ECO:0000269|PubMed:9557682}.; FUNCTION: [Isoform 5]: Acts as a transcriptional repressor. {ECO:0000269|PubMed:15994174}. |
| P10398 | ARAF | S162 | ochoa | Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks) | Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789). {ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:36402789}.; FUNCTION: [Isoform 2]: Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. {ECO:0000269|PubMed:22609986}. |
| P11142 | HSPA8 | S153 | ochoa | Heat shock cognate 71 kDa protein (EC 3.6.4.10) (Heat shock 70 kDa protein 8) (Heat shock protein family A member 8) (Lipopolysaccharide-associated protein 1) (LAP-1) (LPS-associated protein 1) | Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, chaperone-mediated autophagy, activation of proteolysis of misfolded proteins, formation and dissociation of protein complexes, and antigen presentation. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661, PubMed:2799391, PubMed:36586411). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:12526792, PubMed:21148293, PubMed:21150129, PubMed:23018488, PubMed:24732912, PubMed:27916661). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24121476, PubMed:24318877, PubMed:26865365, PubMed:27474739). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Substrate recognition component in chaperone-mediated autophagy (CMA), a selective protein degradation process that mediates degradation of proteins with a -KFERQ motif: HSPA8/HSC70 specifically recognizes and binds cytosolic proteins bearing a -KFERQ motif and promotes their recruitment to the surface of the lysosome where they bind to lysosomal protein LAMP2 (PubMed:11559757, PubMed:2799391, PubMed:36586411). KFERQ motif-containing proteins are eventually transported into the lysosomal lumen where they are degraded (PubMed:11559757, PubMed:2799391, PubMed:36586411). In conjunction with LAMP2, facilitates MHC class II presentation of cytoplasmic antigens by guiding antigens to the lysosomal membrane for interaction with LAMP2 which then elicits MHC class II presentation of peptides to the cell membrane (PubMed:15894275). Participates in the ER-associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). It is recruited to clathrin-coated vesicles through its interaction with DNAJC6 leading to activation of HSPA8/HSC70 ATPase activity and therefore uncoating of clathrin-coated vesicles (By similarity). {ECO:0000250|UniProtKB:P19120, ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:11559757, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15894275, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000269|PubMed:2799391, ECO:0000269|PubMed:36586411, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}. |
| P13569 | CFTR | S1045 | psp | Cystic fibrosis transmembrane conductance regulator (CFTR) (ATP-binding cassette sub-family C member 7) (Channel conductance-controlling ATPase) (EC 5.6.1.6) (cAMP-dependent chloride channel) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:12727866, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:29393851, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}. |
| P15056 | BRAF | S399 | ochoa|psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P15056 | BRAF | S675 | psp | Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) | Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}. |
| P15374 | UCHL3 | S151 | ochoa | Ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCH-L3) (EC 3.4.19.12) (Ubiquitin thioesterase L3) | Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3'', and exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders. {ECO:0000269|PubMed:19154770, ECO:0000269|PubMed:21762696, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:2530630, ECO:0000269|PubMed:9790970}. |
| 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}. |
| P18031 | PTPN1 | S243 | psp | Tyrosine-protein phosphatase non-receptor type 1 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1B) (PTP-1B) | Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET. {ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21135139, ECO:0000269|PubMed:22169477}. |
| P18615 | NELFE | S51 | ochoa|psp | Negative elongation factor E (NELF-E) (RNA-binding protein RD) | Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:10199401, PubMed:27256882). 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:11940650, PubMed:12612062, PubMed:27256882). Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA (PubMed:18303858, PubMed:27256882, PubMed:27282391). {ECO:0000269|PubMed:10199401, ECO:0000269|PubMed:11940650, ECO:0000269|PubMed:12612062, ECO:0000269|PubMed:18303858, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27282391}.; FUNCTION: (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II. {ECO:0000269|PubMed:23884411}. |
| P19525 | EIF2AK2 | S97 | ochoa|psp | Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) | IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. |
| P21283 | ATP6V1C1 | S362 | ochoa | V-type proton ATPase subunit C 1 (V-ATPase subunit C 1) (Vacuolar proton pump subunit C 1) | 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). Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity (By similarity). {ECO:0000250|UniProtKB:P21282, ECO:0000250|UniProtKB:P31412, ECO:0000269|PubMed:33065002}. |
| P21333 | FLNA | S219 | 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 | S1981 | 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 | S293 | 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}. |
| P25445 | FAS | S225 | 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}. |
| P25963 | NFKBIA | S63 | psp | NF-kappa-B inhibitor alpha (I-kappa-B-alpha) (IkB-alpha) (IkappaBalpha) (Major histocompatibility complex enhancer-binding protein MAD3) | Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:36651806, PubMed:7479976). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed:7479976, PubMed:7628694, PubMed:7796813, PubMed:7878466). {ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:36651806, ECO:0000269|PubMed:7479976, ECO:0000269|PubMed:7628694, ECO:0000269|PubMed:7796813, ECO:0000269|PubMed:7878466}. |
| P26639 | TARS1 | S339 | ochoa | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P26641 | EEF1G | S33 | ochoa | Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) | Probably plays a role in anchoring the complex to other cellular components. |
| P26641 | EEF1G | S304 | ochoa | Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) | Probably plays a role in anchoring the complex to other cellular components. |
| P27105 | STOM | S161 | 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. |
| P31350 | RRM2 | S26 | ochoa | Ribonucleoside-diphosphate reductase subunit M2 (EC 1.17.4.1) (Ribonucleotide reductase small chain) (Ribonucleotide reductase small subunit) | Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling. |
| P31751 | AKT2 | S447 | ochoa | RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-2) (Protein kinase B beta) (PKB beta) (RAC protein kinase beta) (RAC-PK-beta) | Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (PubMed:21432781, PubMed:21620960). In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth (PubMed:31204173). Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion (By similarity). Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation (PubMed:23444369). {ECO:0000250|UniProtKB:Q60823, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:31204173, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.; FUNCTION: Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity). {ECO:0000250|UniProtKB:Q60823}. |
| P31939 | ATIC | S450 | ochoa | Bifunctional purine biosynthesis protein ATIC (AICAR transformylase/inosine monophosphate cyclohydrolase) (ATIC) [Cleaved into: Bifunctional purine biosynthesis protein ATIC, N-terminally processed] [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase) (AICAR formyltransferase) (AICAR transformylase); Inosine 5'-monophosphate cyclohydrolase (IMP cyclohydrolase) (EC 3.5.4.10) (IMP synthase) (Inosinicase)] | Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571). {ECO:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:9378707}. |
| P31947 | SFN | S45 | 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}. |
| P32119 | PRDX2 | S112 | ochoa | Peroxiredoxin-2 (EC 1.11.1.24) (Natural killer cell-enhancing factor B) (NKEF-B) (PRP) (Thiol-specific antioxidant protein) (TSA) (Thioredoxin peroxidase 1) (Thioredoxin-dependent peroxide reductase 1) (Thioredoxin-dependent peroxiredoxin 2) | Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2). {ECO:0000269|PubMed:9497357}. |
| P32929 | CTH | S377 | psp | Cystathionine gamma-lyase (CGL) (CSE) (EC 4.4.1.1) (Cysteine desulfhydrase) (Cysteine-protein sulfhydrase) (Gamma-cystathionase) (Homocysteine desulfhydrase) (EC 4.4.1.2) | Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate (PubMed:10212249, PubMed:18476726, PubMed:19261609, PubMed:19961860). Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione (PubMed:18476726). Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce the endogenous gaseous signaling molecule hydrogen sulfide (H2S) (PubMed:10212249, PubMed:19019829, PubMed:19261609, PubMed:19961860). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer's disease) (PubMed:19261609). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (PubMed:19261609). Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function (PubMed:22169477). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (Probable) (PubMed:29254196). Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (By similarity). Can also accept homoserine as substrate (By similarity). Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity). {ECO:0000250|UniProtKB:P18757, ECO:0000250|UniProtKB:Q8VCN5, ECO:0000269|PubMed:10212249, ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19019829, ECO:0000269|PubMed:19261609, ECO:0000269|PubMed:19961860, ECO:0000269|PubMed:22169477, ECO:0000269|PubMed:29254196, ECO:0000303|PubMed:18476726, ECO:0000305|PubMed:18476726, ECO:0000305|PubMed:19019829}. |
| P35251 | RFC1 | S190 | 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}. |
| P35372 | OPRM1 | S268 | psp | Mu-type opioid receptor (M-OR-1) (MOR-1) (Mu opiate receptor) (Mu opioid receptor) (MOP) (hMOP) | Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity). {ECO:0000250|UniProtKB:P33535, ECO:0000269|PubMed:10529478, ECO:0000269|PubMed:12068084, ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, ECO:0000303|PubMed:19300905}.; FUNCTION: [Isoform 12]: Couples to GNAS and is proposed to be involved in excitatory effects. {ECO:0000269|PubMed:20525224}.; FUNCTION: [Isoform 16]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}.; FUNCTION: [Isoform 17]: Does not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity. {ECO:0000269|PubMed:16580639}. |
| P35579 | MYH9 | S1328 | 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}. |
| P35680 | HNF1B | S75 | ochoa | Hepatocyte nuclear factor 1-beta (HNF-1-beta) (HNF-1B) (Homeoprotein LFB3) (Transcription factor 2) (TCF-2) (Variant hepatic nuclear factor 1) (vHNF1) | Transcription factor that binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:17924661, PubMed:7900999). Binds to the FPC element in the cAMP regulatory unit of the PLAU gene (By similarity). Transcriptional activity is increased by coactivator PCBD1 (PubMed:24204001). {ECO:0000250|UniProtKB:Q03365, ECO:0000269|PubMed:17924661, ECO:0000269|PubMed:24204001, ECO:0000269|PubMed:7900999}. |
| P35749 | MYH11 | S998 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P35790 | CHKA | Y197 | psp | Choline kinase alpha (CK) (EC 2.7.1.32) (CHETK-alpha) (Ethanolamine kinase) (EK) (EC 2.7.1.82) | Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis (PubMed:17007874, PubMed:19915674, PubMed:23416529, PubMed:34077757). Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis (PubMed:17007874, PubMed:19915674). Has higher activity with choline (PubMed:17007874, PubMed:19915674). May contribute to tumor cell growth (PubMed:19915674). {ECO:0000269|PubMed:17007874, ECO:0000269|PubMed:19915674, ECO:0000269|PubMed:23416529, ECO:0000269|PubMed:34077757}.; FUNCTION: [Isoform 1]: This isoform plays a key role in lipolysis of lipid droplets following glucose deprivation (PubMed:34077757). In response to glucose deprivation, phosphorylated by AMPK, promoting localization to lipid droplets (PubMed:34077757). Phosphorylation is followed by acetylation by KAT5, leading to dissociation of the homodimer into a monomer (PubMed:34077757). Monomeric CHKA isoform 1 is converted into a tyrosine-protein kinase, which phosphorylates lipid droplet structural proteins PLIN2 and PLIN3, leading to lipolysis of lipid droplets (PubMed:34077757). {ECO:0000269|PubMed:34077757}. |
| P35968 | KDR | S803 | ochoa | Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}. |
| P38398 | BRCA1 | S1286 | 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}. |
| P38646 | HSPA9 | S200 | ochoa | Stress-70 protein, mitochondrial (EC 3.6.4.10) (75 kDa glucose-regulated protein) (GRP-75) (Heat shock 70 kDa protein 9) (Heat shock protein family A member 9) (Mortalin) (MOT) (Peptide-binding protein 74) (PBP74) | Mitochondrial chaperone that plays a key role in mitochondrial protein import, folding, and assembly. Plays an essential role in the protein quality control system, the correct folding of proteins, the re-folding of misfolded proteins, and the targeting of proteins for subsequent degradation. These processes are achieved through cycles of ATP binding, ATP hydrolysis, and ADP release, mediated by co-chaperones (PubMed:18632665, PubMed:25615450, PubMed:28848044, PubMed:30933555, PubMed:31177526). In mitochondria, it associates with the TIM (translocase of the inner membrane) protein complex to assist in the import and folding of mitochondrial proteins (By similarity). Plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis, interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). Regulates mitochondrial calcium-dependent apoptosis by coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria-associated endoplasmic reticulum (ER) membrane to facilitate calcium transport from the ER lumen to the mitochondria intermembrane space, providing calcium for the downstream calcium channel MCU, which releases it into the mitochondrial matrix (By similarity). Although primarily located in the mitochondria, it is also found in other cellular compartments. In the cytosol, it associates with proteins involved in signaling, apoptosis, or senescence. It may play a role in cell cycle regulation via its interaction with and promotion of degradation of TP53 (PubMed:24625977, PubMed:26634371). May play a role in the control of cell proliferation and cellular aging (By similarity). Protects against reactive oxygen species (ROS) (By similarity). Extracellular HSPA9 plays a cytoprotective role by preventing cell lysis following immune attack by the membrane attack complex by disrupting formation of the complex (PubMed:16091382). {ECO:0000250|UniProtKB:P0CS90, ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:16091382, ECO:0000269|PubMed:18632665, ECO:0000269|PubMed:21123823, ECO:0000269|PubMed:24625977, ECO:0000269|PubMed:25615450, ECO:0000269|PubMed:26634371, ECO:0000269|PubMed:26702583, ECO:0000269|PubMed:28848044, ECO:0000269|PubMed:30933555, ECO:0000269|PubMed:31177526}. |
| P39880 | CUX1 | S974 | ochoa | Homeobox protein cut-like 1 (CCAAT displacement protein) (CDP) (CDP/Cux p200) (Homeobox protein cux-1) [Cleaved into: CDP/Cux p110] | Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}. |
| P40425 | PBX2 | S101 | 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 | S69 | ochoa | Malate dehydrogenase, mitochondrial (EC 1.1.1.37) | None |
| P41134 | ID1 | S36 | psp | DNA-binding protein inhibitor ID-1 (Class B basic helix-loop-helix protein 24) (bHLHb24) (Inhibitor of DNA binding 1) (Inhibitor of differentiation 1) | Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Inhibits skeletal muscle and cardiac myocyte differentiation. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250}. |
| P41235 | HNF4A | S303 | 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}. |
| P42224 | STAT1 | S640 | ochoa | Signal transducer and activator of transcription 1-alpha/beta (Transcription factor ISGF-3 components p91/p84) | Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:12764129, PubMed:12855578, PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, PubMed:9724754). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B promoter and activation of IL12B transcription (PubMed:32209697). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity). {ECO:0000250|UniProtKB:P42225, ECO:0000269|PubMed:12764129, ECO:0000269|PubMed:12855578, ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:23940278, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:34508746, ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:8156998, ECO:0000269|PubMed:9724754, ECO:0000303|PubMed:15526160}. |
| P42575 | CASP2 | S139 | psp | Caspase-2 (CASP-2) (EC 3.4.22.55) (Neural precursor cell expressed developmentally down-regulated protein 2) (NEDD-2) (Protease ICH-1) [Cleaved into: Caspase-2 subunit p18; Caspase-2 subunit p13; Caspase-2 subunit p12] | Is a regulator of the cascade of caspases responsible for apoptosis execution (PubMed:11156409, PubMed:15073321, PubMed:8087842). Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269|PubMed:11156409, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 1]: Acts as a positive regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000269|PubMed:11156409}. |
| P42575 | CASP2 | S157 | ochoa|psp | Caspase-2 (CASP-2) (EC 3.4.22.55) (Neural precursor cell expressed developmentally down-regulated protein 2) (NEDD-2) (Protease ICH-1) [Cleaved into: Caspase-2 subunit p18; Caspase-2 subunit p13; Caspase-2 subunit p12] | Is a regulator of the cascade of caspases responsible for apoptosis execution (PubMed:11156409, PubMed:15073321, PubMed:8087842). Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (PubMed:15073321). Associates with PIDD1 and CRADD to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis in response to genotoxic stress (PubMed:15073321). {ECO:0000269|PubMed:11156409, ECO:0000269|PubMed:15073321, ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 1]: Acts as a positive regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 2]: Acts as a negative regulator of apoptosis. {ECO:0000269|PubMed:8087842}.; FUNCTION: [Isoform 3]: May function as an endogenous apoptosis inhibitor that antagonizes caspase activation and cell death. {ECO:0000269|PubMed:11156409}. |
| P42685 | FRK | S220 | ochoa | Tyrosine-protein kinase FRK (EC 2.7.10.2) (FYN-related kinase) (Nuclear tyrosine protein kinase RAK) (Protein-tyrosine kinase 5) | Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents its ubiquitination and degradation, possibly by reducing its binding to NEDD4. May function as a tumor suppressor. {ECO:0000269|PubMed:19345329}. |
| P43246 | MSH2 | S479 | ochoa | DNA mismatch repair protein Msh2 (hMSH2) (MutS protein homolog 2) | Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containing DNA strand (PubMed:26300262). ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:17611581, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:26300262, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}. |
| P47897 | QARS1 | S70 | ochoa | Glutamine--tRNA ligase (EC 6.1.1.18) (Glutaminyl-tRNA synthetase) (GlnRS) | Glutamine--tRNA ligase (PubMed:26869582). Plays a critical role in brain development (PubMed:24656866). {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}. |
| P48637 | GSS | S181 | 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}. |
| P48730 | CSNK1D | S298 | psp | Casein kinase I isoform delta (CKI-delta) (CKId) (EC 2.7.11.1) (Tau-protein kinase CSNK1D) (EC 2.7.11.26) | Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (By similarity). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. {ECO:0000250|UniProtKB:Q9DC28, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:16027726, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:19043076, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:20407760, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:20696890, ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:21084295, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092}. |
| P49589 | CARS1 | S305 | ochoa | Cysteine--tRNA ligase, cytoplasmic (EC 6.1.1.16) (Cysteinyl-tRNA synthetase) (CysRS) | Catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys). {ECO:0000269|PubMed:11347887, ECO:0000269|PubMed:30824121}. |
| P49736 | MCM2 | S878 | ochoa | DNA replication licensing factor MCM2 (EC 3.6.4.12) (Minichromosome maintenance protein 2 homolog) (Nuclear protein BM28) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (PubMed:8175912). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (PubMed:26196677). {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:8175912}. |
| P49757 | NUMB | S284 | ochoa | 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}. |
| P49815 | TSC2 | S540 | psp | 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}. |
| P49815 | TSC2 | S923 | 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 | S34 | 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}. |
| P51587 | BRCA2 | S1339 | ochoa | Breast cancer type 2 susceptibility protein (Fanconi anemia group D1 protein) | Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180). {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180}. |
| P51825 | AFF1 | S750 | ochoa | AF4/FMR2 family member 1 (ALL1-fused gene from chromosome 4 protein) (Protein AF-4) (Protein FEL) (Proto-oncogene AF4) | None |
| P51826 | AFF3 | S755 | ochoa | AF4/FMR2 family member 3 (Lymphoid nuclear protein related to AF4) (Protein LAF-4) | Putative transcription activator that may function in lymphoid development and oncogenesis. Binds, in vitro, to double-stranded DNA. |
| P52565 | ARHGDIA | S24 | ochoa | Rho GDP-dissociation inhibitor 1 (Rho GDI 1) (Rho-GDI alpha) | Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}. |
| P52888 | THOP1 | S172 | ochoa | Thimet oligopeptidase (EC 3.4.24.15) (Endopeptidase 24.15) (MP78) | Involved in the metabolism of neuropeptides under 20 amino acid residues long. Involved in cytoplasmic peptide degradation (PubMed:17251185, PubMed:7639763). Able to degrade the amyloid-beta precursor protein and generate amyloidogenic fragments (PubMed:17251185, PubMed:7639763). Also acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By similarity). {ECO:0000250|UniProtKB:P24155, ECO:0000269|PubMed:17251185, ECO:0000269|PubMed:7639763}. |
| P53814 | SMTN | S579 | 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}. |
| P55055 | NR1H2 | S431 | psp | Oxysterols receptor LXR-beta (Liver X receptor beta) (Nuclear receptor NER) (Nuclear receptor subfamily 1 group H member 2) (Ubiquitously-expressed nuclear receptor) | Nuclear receptor that exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920). Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Induces LPCAT3-dependent phospholipid remodeling in endoplasmic reticulum (ER) membranes of hepatocytes, driving SREBF1 processing and lipogenesis (By similarity). Via LPCAT3, triggers the incorporation of arachidonate into phosphatidylcholines of ER membranes, increasing membrane dynamics and enabling triacylglycerols transfer to nascent very low-density lipoprotein (VLDL) particles (By similarity). Via LPCAT3 also counteracts lipid-induced ER stress response and inflammation, likely by modulating SRC kinase membrane compartmentalization and limiting the synthesis of lipid inflammatory mediators (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex (PubMed:20159957). {ECO:0000250|UniProtKB:Q60644, ECO:0000269|PubMed:20159957, ECO:0000269|PubMed:25661920}. |
| P56373 | P2RX3 | S178 | psp | P2X purinoceptor 3 (P2X3) (ATP receptor) (Purinergic receptor) | Extracellular ATP-activated non-selective cation channel (PubMed:10440098, PubMed:27626375, PubMed:29674445, PubMed:31232692). Plays particularly important role in sensory neurons where its activation is critical for gustatory, nociceptive responses, visceral reflexes and sensory hypersensitization (By similarity). {ECO:0000250|UniProtKB:Q3UR32, ECO:0000269|PubMed:10440098, ECO:0000269|PubMed:27626375, ECO:0000269|PubMed:29674445, ECO:0000269|PubMed:31232692}. |
| P57078 | RIPK4 | S420 | ochoa | Receptor-interacting serine/threonine-protein kinase 4 (EC 2.7.11.1) (Ankyrin repeat domain-containing protein 3) (PKC-delta-interacting protein kinase) | Serine/threonine protein kinase (By similarity). Required for embryonic skin development and correct skin homeostasis in adults, via phosphorylation of PKP1 and subsequent promotion of keratinocyte differentiation and cell adhesion (By similarity). It is a direct transcriptional target of TP63 (PubMed:22197488). Plays a role in NF-kappa-B activation (PubMed:12446564). {ECO:0000250|UniProtKB:Q9ERK0, ECO:0000269|PubMed:12446564, ECO:0000269|PubMed:22197488}. |
| P61019 | RAB2A | S67 | ochoa | Ras-related protein Rab-2A (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 (PubMed:37821429). RAB2A regulates autophagy by promoting autophagosome-lysosome fusion via recruitment of the HOPS endosomal tethering complex; this process involves autophagosomal RAB2A and lysosomal RAB39A recruitment of HOPS subcomplexes VPS39-VPS11 and VPS41-VPS16-VPS18-VPS33A, respectively, which assemble into a functional complex to mediate membrane tethering and SNAREs-driven membrane fusion (PubMed:37821429). Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi (PubMed:26209634). Together with RAB2B, redundantly required for efficient autophagic flux (PubMed:28483915). {ECO:0000269|PubMed:26209634, ECO:0000269|PubMed:28483915, ECO:0000269|PubMed:37821429}. |
| P62314 | SNRPD1 | S59 | 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}. |
| P68371 | TUBB4B | S95 | 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. |
| P68871 | HBB | S90 | 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. |
| P78348 | ASIC1 | S40 | psp | Acid-sensing ion channel 1 (ASIC1) (Amiloride-sensitive cation channel 2, neuronal) (Brain sodium channel 2) | Forms voltage-independent, pH-gated trimeric sodium channels that act as postsynaptic excitatory receptors in the nervous system, playing a crucial role in regulating synaptic plasticity, learning, and memory (PubMed:21036899, PubMed:32915133, PubMed:34319232). Upon extracellular pH drop this channel elicits transient, fast activating, and completely desensitizing inward currents (PubMed:21036899). Displays high selectivity for sodium ions but can also permit the permeation of other cations (PubMed:21036899). Regulates more or less directly intracellular calcium concentration and CaMKII phosphorylation, and thereby the density of dendritic spines. Modulates neuronal activity in the circuits underlying innate fear (By similarity). {ECO:0000250|UniProtKB:Q6NXK8, ECO:0000269|PubMed:21036899, ECO:0000269|PubMed:32915133, ECO:0000269|PubMed:34319232}.; FUNCTION: [Isoform Asic1a]: Has high selectivity for sodium ions, but can also be permeable to other cations including calcium, lithium and potassium. {ECO:0000269|PubMed:21036899}.; FUNCTION: [Isoform Asic1b]: Produces acid activated currents with a reduced amplitude and inactivates faster (PubMed:21036899). Has high selectivity for sodium ions but also supports a calcium-mediated current which is sustained and maintained as long as acidic conditions are present (PubMed:21036899). Also potentially permeable to lithium and potassium (PubMed:21036899). {ECO:0000269|PubMed:21036899}.; FUNCTION: [Isoform 1]: Has no measurable proton-gated sodium channel activity in vitro. {ECO:0000269|PubMed:21036899}. |
| P78371 | CCT2 | S54 | psp | T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| P78413 | IRX4 | S258 | ochoa | Iroquois-class homeodomain protein IRX-4 (Homeodomain protein IRXA3) (Iroquois homeobox protein 4) | Likely to be an important mediator of ventricular differentiation during cardiac development. |
| P78527 | PRKDC | S2827 | 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}. |
| P84022 | SMAD3 | S309 | psp | Mothers against decapentaplegic homolog 3 (MAD homolog 3) (Mad3) (Mothers against DPP homolog 3) (hMAD-3) (JV15-2) (SMAD family member 3) (SMAD 3) (Smad3) (hSMAD3) | Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. {ECO:0000269|PubMed:10995748, ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:15588252, ECO:0000269|PubMed:16156666, ECO:0000269|PubMed:16751101, ECO:0000269|PubMed:16862174, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:19218245, ECO:0000269|PubMed:19289081, ECO:0000269|PubMed:9732876, ECO:0000269|PubMed:9892009}. |
| P98174 | FGD1 | S116 | ochoa | FYVE, RhoGEF and PH domain-containing protein 1 (Faciogenital dysplasia 1 protein) (Rho/Rac guanine nucleotide exchange factor FGD1) (Rho/Rac GEF) (Zinc finger FYVE domain-containing protein 3) | Activates CDC42, a member of the Ras-like family of Rho- and Rac proteins, by exchanging bound GDP for free GTP. Plays a role in regulating the actin cytoskeleton and cell shape. {ECO:0000269|PubMed:8969170}. |
| Q00536 | CDK16 | S119 | ochoa|psp | Cyclin-dependent kinase 16 (EC 2.7.11.22) (Cell division protein kinase 16) (PCTAIRE-motif protein kinase 1) (Serine/threonine-protein kinase PCTAIRE-1) | Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}. |
| Q00536 | CDK16 | S391 | psp | Cyclin-dependent kinase 16 (EC 2.7.11.22) (Cell division protein kinase 16) (PCTAIRE-motif protein kinase 1) (Serine/threonine-protein kinase PCTAIRE-1) | Protein kinase that plays a role in vesicle-mediated transport processes and exocytosis. Regulates GH1 release by brain neurons. Phosphorylates NSF, and thereby regulates NSF oligomerization. Required for normal spermatogenesis. Regulates neuron differentiation and dendrite development (By similarity). Plays a role in the regulation of insulin secretion in response to changes in blood glucose levels. Can phosphorylate CCNY at 'Ser-336' (in vitro). {ECO:0000250, ECO:0000269|PubMed:22184064, ECO:0000269|PubMed:22796189, ECO:0000269|PubMed:22798068}. |
| Q01196 | RUNX1 | S295 | ochoa | Runt-related transcription factor 1 (Acute myeloid leukemia 1 protein) (Core-binding factor subunit alpha-2) (CBF-alpha-2) (Oncogene AML-1) (Polyomavirus enhancer-binding protein 2 alpha B subunit) (PEA2-alpha B) (PEBP2-alpha B) (SL3-3 enhancer factor 1 alpha B subunit) (SL3/AKV core-binding factor alpha B subunit) | Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). Essential for the development of normal hematopoiesis (PubMed:17431401). Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter (PubMed:10207087, PubMed:14970218). Inhibits KAT6B-dependent transcriptional activation (By similarity). Involved in lineage commitment of immature T cell precursors. CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation. CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing (By similarity). Controls the anergy and suppressive function of regulatory T-cells (Treg) by associating with FOXP3. Activates the expression of IL2 and IFNG and down-regulates the expression of TNFRSF18, IL2RA and CTLA4, in conventional T-cells (PubMed:17377532). Positively regulates the expression of RORC in T-helper 17 cells (By similarity). {ECO:0000250|UniProtKB:Q03347, ECO:0000269|PubMed:10207087, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:14970218, ECO:0000269|PubMed:17377532, ECO:0000269|PubMed:17431401, ECO:0000305}.; FUNCTION: Isoform AML-1G shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. {ECO:0000250|UniProtKB:Q03347}.; FUNCTION: Isoform AML-1L interferes with the transactivation activity of RUNX1. {ECO:0000269|PubMed:9199349}. |
| Q02556 | IRF8 | S232 | ochoa | Interferon regulatory factor 8 (IRF-8) (Interferon consensus sequence-binding protein) (H-ICSBP) (ICSBP) | Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:25122610). Can both act as a transcriptional activator or repressor (By similarity). Plays a negative regulatory role in cells of the immune system (By similarity). Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (By similarity). Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (By similarity). Positively regulates macroautophagy in dendritic cells (PubMed:29434592). Acts as a transcriptional repressor of osteoclast differentiation factors such as NFATC1 and EEIG1 (By similarity). {ECO:0000250|UniProtKB:P23611, ECO:0000269|PubMed:25122610, ECO:0000269|PubMed:29434592}. |
| Q02818 | NUCB1 | S86 | 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}. |
| Q04206 | RELA | S529 | psp | Transcription factor p65 (Nuclear factor NF-kappa-B p65 subunit) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3) | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Besides its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752, ECO:0000269|PubMed:33440148}. |
| Q04637 | EIF4G1 | S314 | 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}. |
| Q05209 | PTPN12 | S551 | 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}. |
| Q07817 | BCL2L1 | S145 | psp | Bcl-2-like protein 1 (Bcl2-L-1) (Apoptosis regulator Bcl-X) | Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.; FUNCTION: Isoform Bcl-X(L) also regulates presynaptic plasticity, including neurotransmitter release and recovery, number of axonal mitochondria as well as size and number of synaptic vesicle clusters. During synaptic stimulation, increases ATP availability from mitochondria through regulation of mitochondrial membrane ATP synthase F(1)F(0) activity and regulates endocytic vesicle retrieval in hippocampal neurons through association with DMN1L and stimulation of its GTPase activity in synaptic vesicles. May attenuate inflammation impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785). {ECO:0000269|PubMed:17418785}.; FUNCTION: Isoform Bcl-X(S) promotes apoptosis. |
| Q07869 | PPARA | S230 | psp | Peroxisome proliferator-activated receptor alpha (PPAR-alpha) (Nuclear receptor subfamily 1 group C member 1) | Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as a transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2. {ECO:0000269|PubMed:10195690, ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:7629123, ECO:0000269|PubMed:7684926, ECO:0000269|PubMed:9556573}. |
| 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}. |
| Q08043 | ACTN3 | S319 | ochoa | Alpha-actinin-3 (Alpha-actinin skeletal muscle isoform 3) (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. |
| Q08345 | DDR1 | S788 | psp | Epithelial discoidin domain-containing receptor 1 (Epithelial discoidin domain receptor 1) (EC 2.7.10.1) (CD167 antigen-like family member A) (Cell adhesion kinase) (Discoidin receptor tyrosine kinase) (HGK2) (Mammary carcinoma kinase 10) (MCK-10) (Protein-tyrosine kinase 3A) (Protein-tyrosine kinase RTK-6) (TRK E) (Tyrosine kinase DDR) (Tyrosine-protein kinase CAK) (CD antigen CD167a) | Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11. {ECO:0000250, ECO:0000269|PubMed:12065315, ECO:0000269|PubMed:16234985, ECO:0000269|PubMed:16337946, ECO:0000269|PubMed:19401332, ECO:0000269|PubMed:20093046, ECO:0000269|PubMed:20432435, ECO:0000269|PubMed:20884741, ECO:0000269|PubMed:21044884, ECO:0000269|PubMed:9659899}. |
| Q08999 | RBL2 | S1068 | ochoa|psp | Retinoblastoma-like protein 2 (130 kDa retinoblastoma-associated protein) (p130) (Retinoblastoma-related protein 2) (RBR-2) (pRb2) | Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor. |
| Q09472 | EP300 | S19 | psp | Histone acetyltransferase p300 (p300 HAT) (EC 2.3.1.48) (E1A-associated protein p300) (Histone butyryltransferase p300) (EC 2.3.1.-) (Histone crotonyltransferase p300) (EC 2.3.1.-) (Protein 2-hydroxyisobutyryltransferase p300) (EC 2.3.1.-) (Protein lactyltransferas p300) (EC 2.3.1.-) (Protein propionyltransferase p300) (EC 2.3.1.-) | Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling (PubMed:23415232, PubMed:23934153, PubMed:8945521). Acetylates all four core histones in nucleosomes (PubMed:23415232, PubMed:23934153, PubMed:8945521). Histone acetylation gives an epigenetic tag for transcriptional activation (PubMed:23415232, PubMed:23934153, PubMed:8945521). Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability (PubMed:23415232). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905, PubMed:23911289). Also able to acetylate histone lysine residues that are already monomethylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Catalyzes formation of histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRMT1, SIRT2, STAT3 or GLUL (PubMed:12929931, PubMed:15653507, PubMed:16285960, PubMed:16762839, PubMed:18722353, PubMed:18782771, PubMed:26990986). Acetylates 'Lys-131' of ALX1 and acts as its coactivator (PubMed:12929931). Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of p53/TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (PubMed:18722353). Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis (PubMed:11511361, PubMed:15448695). Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription (PubMed:18451878). Acetylates HDAC1 leading to its inactivation and modulation of transcription (PubMed:16762839). Acetylates 'Lys-247' of EGR2 (By similarity). Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2 (PubMed:12586840). Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement (PubMed:14752053). Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity (PubMed:15890677). Acetylates STAT3 at different sites, promoting both STAT3 dimerization and activation and recruitment to chromatin (PubMed:15653507, PubMed:16285960, PubMed:18782771). Acetylates BCL6 which disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity (PubMed:12402037). Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter (PubMed:14645221). Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity (PubMed:16617102). Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity (PubMed:20955178). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates MEF2D (PubMed:21030595). Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degradation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990). Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity). Acetylates PCK1 and promotes PCK1 anaplerotic activity (PubMed:30193097). Acetylates RXRA and RXRG (PubMed:17761950). Acetylates isoform M2 of PKM (PKM2), promoting its homodimerization and conversion into a protein kinase (PubMed:24120661). Acetylates RPTOR in response to leucine, leading to activation of the mTORC1 complex (PubMed:30197302, PubMed:32561715). Acetylates RICTOR, leading to activation of the mTORC2 complex (PubMed:22084251). Mediates cAMP-gene regulation by binding specifically to phosphorylated CREBBP (PubMed:8917528). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA or propanoyl-CoA (propionyl-CoA), and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation or propionylation, respectively (PubMed:17267393, PubMed:25818647, PubMed:29775581, PubMed:31645732). Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25818647). Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low (PubMed:25818647). Also acts as a histone butyryltransferase; butyrylation marks active promoters (PubMed:17267393). Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription (PubMed:31645732). Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes (PubMed:29775581). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493). {ECO:0000250|UniProtKB:B2RWS6, ECO:0000269|PubMed:10733570, ECO:0000269|PubMed:11430825, ECO:0000269|PubMed:11511361, ECO:0000269|PubMed:11701890, ECO:0000269|PubMed:12402037, ECO:0000269|PubMed:12586840, ECO:0000269|PubMed:12929931, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:14752053, ECO:0000269|PubMed:15186775, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:16285960, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16762839, ECO:0000269|PubMed:17267393, ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:18722353, ECO:0000269|PubMed:18782771, ECO:0000269|PubMed:18995842, ECO:0000269|PubMed:20810990, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21131905, ECO:0000269|PubMed:22084251, ECO:0000269|PubMed:23415232, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:23934153, ECO:0000269|PubMed:24120661, ECO:0000269|PubMed:24939902, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:25818647, ECO:0000269|PubMed:26990986, ECO:0000269|PubMed:29775581, ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:30197302, ECO:0000269|PubMed:31645732, ECO:0000269|PubMed:32561715, ECO:0000269|PubMed:37731000, ECO:0000269|PubMed:8917528, ECO:0000269|PubMed:8945521, ECO:0000305|PubMed:20955178}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. {ECO:0000269|PubMed:10545121, ECO:0000269|PubMed:11080476}. |
| Q09666 | AHNAK | S5589 | ochoa | Neuroblast differentiation-associated protein AHNAK (Desmoyokin) | May be required for neuronal cell differentiation. |
| Q0VF96 | CGNL1 | S349 | ochoa | Cingulin-like protein 1 (Junction-associated coiled-coil protein) (Paracingulin) | May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons. {ECO:0000269|PubMed:22891260}. |
| Q12906 | ILF3 | S190 | ochoa | Interleukin enhancer-binding factor 3 (Double-stranded RNA-binding protein 76) (DRBP76) (M-phase phosphoprotein 4) (MPP4) (Nuclear factor associated with dsRNA) (NFAR) (Nuclear factor of activated T-cells 90 kDa) (NF-AT-90) (Translational control protein 80) (TCP80) | RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs (PubMed:28625552). As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (PubMed:14731398). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response (PubMed:21123651, PubMed:34110282). Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs (PubMed:21123651, PubMed:28625552). {ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:28625552, ECO:0000269|PubMed:9442054}.; FUNCTION: (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3. {ECO:0000269|PubMed:26891316}. |
| Q12959 | DLG1 | S684 | ochoa | Disks large homolog 1 (Synapse-associated protein 97) (SAP-97) (SAP97) (hDlg) | Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Promotes epithelial cell layer barrier function via maintaining cell-cell adhesion (By similarity). May also play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel. During long-term depression in hippocampal neurons, it recruits ADAM10 to the plasma membrane (PubMed:23676497). {ECO:0000250|UniProtKB:A0A8C0TYJ0, ECO:0000250|UniProtKB:Q811D0, ECO:0000269|PubMed:10656683, ECO:0000269|PubMed:12445884, ECO:0000269|PubMed:14699157, ECO:0000269|PubMed:15263016, ECO:0000269|PubMed:19213956, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:23676497}. |
| Q12968 | NFATC3 | S366 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 3 (NF-ATc3) (NFATc3) (NFATx) (T-cell transcription factor NFAT4) (NF-AT4) (NF-AT4c) | Acts as a regulator of transcriptional activation. Binds to the TNFSF11/RANKL promoter region and promotes TNFSF11 transcription (By similarity). Binding to the TNFSF11 promoter region is increased by high levels of Ca(2+) which induce NFATC3 expression and may lead to regulation of TNFSF11 expression in osteoblasts (By similarity). Plays a role in promoting mesenteric arterial wall remodeling in response to the intermittent hypoxia-induced increase in EDN1 and ROCK signaling (By similarity). As a result NFATC3 colocalizes with F-actin filaments, translocates to the nucleus and promotes transcription of the smooth muscle hypertrophy and differentiation marker ACTA2 (By similarity). Promotes lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC4 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). In conjunction with NFATC4, involved in embryonic heart development via maintenance of cardiomyocyte survival, proliferation and differentiation (By similarity). Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (PubMed:18815128). Required for thymocyte maturation during DN3 to DN4 transition and during positive selection (By similarity). Positively regulates macrophage-derived polymicrobial clearance, via binding to the promoter region and promoting transcription of NOS2 resulting in subsequent generation of nitric oxide (By similarity). Involved in Ca(2+)-mediated transcriptional responses upon Ca(2+) influx via ORAI1 CRAC channels. {ECO:0000250|UniProtKB:A0A0G2JTY4, ECO:0000250|UniProtKB:P97305, ECO:0000269|PubMed:18815128, ECO:0000269|PubMed:32415068}. |
| Q13023 | AKAP6 | S1563 | 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. |
| Q13029 | PRDM2 | S876 | ochoa | PR domain zinc finger protein 2 (EC 2.1.1.355) (GATA-3-binding protein G3B) (Lysine N-methyltransferase 8) (MTB-ZF) (MTE-binding protein) (PR domain-containing protein 2) (Retinoblastoma protein-interacting zinc finger protein) (Zinc finger protein RIZ) | S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates 'Lys-9' of histone H3. May function as a DNA-binding transcription factor. Binds to the macrophage-specific TPA-responsive element (MTE) of the HMOX1 (heme oxygenase 1) gene and may act as a transcriptional activator of this gene. {ECO:0000269|PubMed:14633678}. |
| Q13045 | FLII | S860 | ochoa | Protein flightless-1 homolog | Is a regulator of actin polymerization, required for proper myofibril organization and regulation of the length of sarcomeric thin filaments (By similarity). It also plays a role in the assembly of cardiomyocyte cell adhesion complexes (By similarity). Regulates cytoskeletal rearrangements involved in cytokinesis and cell migration, by inhibiting Rac1-dependent paxillin phosphorylation (By similarity). May play a role as coactivator in transcriptional activation by hormone-activated nuclear receptors (NR) and acts in cooperation with NCOA2 and CARM1 (PubMed:14966289). Involved in estrogen hormone signaling. {ECO:0000250|UniProtKB:Q9JJ28, ECO:0000269|PubMed:14966289}. |
| Q13085 | ACACA | S50 | ochoa | Acetyl-CoA carboxylase 1 (ACC1) (EC 6.4.1.2) (Acetyl-Coenzyme A carboxylase alpha) (ACC-alpha) | Cytosolic enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting step of de novo fatty acid biosynthesis (PubMed:20457939, PubMed:20952656, PubMed:29899443). This is a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (PubMed:20457939, PubMed:20952656, PubMed:29899443). {ECO:0000269|PubMed:20457939, ECO:0000269|PubMed:20952656, ECO:0000269|PubMed:29899443}. |
| Q13191 | CBLB | S761 | 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}. |
| Q13315 | ATM | S2996 | ochoa|psp | Serine-protein kinase ATM (EC 2.7.11.1) (Ataxia telangiectasia mutated) (A-T mutated) | Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217). May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (PubMed:26344566). {ECO:0000250|UniProtKB:Q62388, ECO:0000269|PubMed:10550055, ECO:0000269|PubMed:10766245, ECO:0000269|PubMed:10802669, ECO:0000269|PubMed:10839545, ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11375976, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12556884, ECO:0000269|PubMed:14871926, ECO:0000269|PubMed:15448695, ECO:0000269|PubMed:15456891, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:16086026, ECO:0000269|PubMed:16858402, ECO:0000269|PubMed:17923702, ECO:0000269|PubMed:19431188, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:21757780, ECO:0000269|PubMed:24534091, ECO:0000269|PubMed:26240375, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:26774286, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:30171069, ECO:0000269|PubMed:30612738, ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:30952868, ECO:0000269|PubMed:35076389, ECO:0000269|PubMed:38128537, ECO:0000269|PubMed:9733514, ECO:0000269|PubMed:9733515, ECO:0000269|PubMed:9843217}. |
| Q13501 | SQSTM1 | S399 | ochoa | Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) | Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}. |
| Q13506 | NAB1 | S174 | 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}. |
| Q13772 | NCOA4 | S553 | 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}. |
| Q13835 | PKP1 | S142 | ochoa | Plakophilin-1 (Band 6 protein) (B6P) | A component of desmosome cell-cell junctions which are required for positive regulation of cellular adhesion (PubMed:23444369). Plays a role in desmosome protein expression regulation and localization to the desmosomal plaque, thereby maintaining cell sheet integrity and anchorage of desmosomes to intermediate filaments (PubMed:10852826, PubMed:23444369). Required for localization of DSG3 and YAP1 to the cell membrane in keratinocytes in response to mechanical strain, via the formation of an interaction complex composed of DSG3, YAP1, PKP1 and YWHAG (PubMed:31835537). Positively regulates differentiation of keratinocytes, potentially via promoting localization of DSG1 at desmosome cell junctions (By similarity). Required for calcium-independent development and maturation of desmosome plaques specifically at lateral cell-cell contacts in differentiating keratinocytes (By similarity). Plays a role in the maintenance of DSG3 protein abundance, DSG3 clustering and localization of these clusters to the cell membrane in keratinocytes (By similarity). May also promote keratinocyte proliferation and morphogenesis during postnatal development (PubMed:9326952). Required for tight junction inside-out transepidermal barrier function of the skin (By similarity). Promotes Wnt-mediated proliferation and differentiation of ameloblasts, via facilitating TJP1/ZO-1 localization to tight junctions (By similarity). Binds single-stranded DNA (ssDNA), and may thereby play a role in sensing DNA damage and promoting cell survival (PubMed:20613778). Positively regulates cap-dependent translation and as a result cell proliferation, via recruitment of EIF4A1 to the initiation complex and promotion of EIF4A1 ATPase activity (PubMed:20156963, PubMed:23444369). Regulates the mRNA stability and protein abundance of desmosome components PKP2, PKP3, DSC2 and DSP, potentially via its interaction with FXR1 (PubMed:25225333). {ECO:0000250|UniProtKB:P97350, ECO:0000269|PubMed:10852826, ECO:0000269|PubMed:20156963, ECO:0000269|PubMed:20613778, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:25225333, ECO:0000269|PubMed:31835537, ECO:0000269|PubMed:9326952}. |
| Q13885 | TUBB2A | S95 | 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. |
| Q14202 | ZMYM3 | S1045 | 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}. |
| Q14254 | FLOT2 | S385 | ochoa | Flotillin-2 (Epidermal surface antigen) (ESA) (Membrane component chromosome 17 surface marker 1) | May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. May be involved in epidermal cell adhesion and epidermal structure and function. |
| Q14432 | PDE3A | S402 | ochoa | cGMP-inhibited 3',5'-cyclic phosphodiesterase 3A (EC 3.1.4.17) (Cyclic GMP-inhibited phosphodiesterase A) (CGI-PDE A) (cGMP-inhibited cAMP phosphodiesterase) (cGI-PDE) | Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099). {ECO:0000269|PubMed:1315035, ECO:0000269|PubMed:25961942, ECO:0000269|PubMed:27975297, ECO:0000269|PubMed:31420216, ECO:0000269|PubMed:34707099, ECO:0000269|PubMed:8155697, ECO:0000269|PubMed:8695850}. |
| Q14669 | TRIP12 | S278 | 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 | S209 | 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}. |
| Q14684 | RRP1B | S278 | 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}. |
| Q14699 | RFTN1 | S555 | ochoa | Raftlin (Cell migration-inducing gene 2 protein) (Raft-linking protein) | Involved in protein trafficking via association with clathrin and AP2 complex (PubMed:21266579, PubMed:27022195). Upon bacterial lipopolysaccharide stimulation, mediates internalization of TLR4 to endosomes in dendritic cells and macrophages; and internalization of poly(I:C) to TLR3-positive endosomes in myeloid dendritic cells and epithelial cells; resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production (PubMed:21266579, PubMed:27022195). Involved in T-cell antigen receptor-mediated signaling by regulating tyrosine kinase LCK localization, T-cell dependent antibody production and cytokine secretion (By similarity). May regulate B-cell antigen receptor-mediated signaling (PubMed:12805216). May play a pivotal role in the formation and/or maintenance of lipid rafts (PubMed:12805216). {ECO:0000250|UniProtKB:Q6A0D4, ECO:0000269|PubMed:12805216, ECO:0000269|PubMed:21266579, ECO:0000269|PubMed:27022195}. |
| Q14739 | LBR | S357 | ochoa | Delta(14)-sterol reductase LBR (Delta-14-SR) (EC 1.3.1.70) (3-beta-hydroxysterol Delta (14)-reductase) (C-14 sterol reductase) (C14SR) (Integral nuclear envelope inner membrane protein) (LMN2R) (Lamin-B receptor) (Sterol C14-reductase) | Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis (PubMed:12618959, PubMed:16784888, PubMed:21327084, PubMed:27336722, PubMed:9630650). Plays a critical role in myeloid cell cholesterol biosynthesis which is essential to both myeloid cell growth and functional maturation (By similarity). Mediates the activation of NADPH oxidases, perhaps by maintaining critical levels of cholesterol required for membrane lipid raft formation during neutrophil differentiation (By similarity). Anchors the lamina and the heterochromatin to the inner nuclear membrane (PubMed:10828963). {ECO:0000250|UniProtKB:Q3U9G9, ECO:0000269|PubMed:10828963, ECO:0000269|PubMed:12618959, ECO:0000269|PubMed:16784888, ECO:0000269|PubMed:21327084, ECO:0000269|PubMed:27336722, ECO:0000269|PubMed:9630650}. |
| Q14966 | ZNF638 | S1658 | 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}. |
| Q14CW9 | ATXN7L3 | S281 | ochoa | Ataxin-7-like protein 3 (SAGA-associated factor 11 homolog) | Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B (PubMed:18206972, PubMed:21746879). The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. Within the complex, it is required to recruit USP22 and ENY2 into the SAGA complex (PubMed:18206972). Regulates H2B monoubiquitination (H2Bub1) levels. Affects subcellular distribution of ENY2, USP22 and ATXN7L3B (PubMed:27601583). {ECO:0000255|HAMAP-Rule:MF_03047, ECO:0000269|PubMed:18206972, ECO:0000269|PubMed:21746879, ECO:0000269|PubMed:27601583}. |
| Q15029 | EFTUD2 | S944 | ochoa | 116 kDa U5 small nuclear ribonucleoprotein component (Elongation factor Tu GTP-binding domain-containing protein 2) (SNU114 homolog) (hSNU114) (U5 snRNP-specific protein, 116 kDa) (U5-116 kDa) | Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes (PubMed:25092792, PubMed:28076346, PubMed:28502770, PubMed:28781166, PubMed:29301961, PubMed:29360106, PubMed:29361316, PubMed:30315277, PubMed:30705154). Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (PubMed:16723661). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:16723661, ECO:0000269|PubMed:25092792, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30315277, ECO:0000269|PubMed:30705154, ECO:0000305|PubMed:33509932}. |
| Q15058 | KIF14 | S1186 | 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}. |
| Q15139 | PRKD1 | S205 | ochoa|psp | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q15149 | PLEC | S2802 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15149 | PLEC | S3461 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15149 | PLEC | 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}. |
| Q15149 | PLEC | S3975 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15149 | PLEC | S3993 | ochoa | Plectin (PCN) (PLTN) (Hemidesmosomal protein 1) (HD1) (Plectin-1) | Interlinks intermediate filaments with microtubules and microfilaments and anchors intermediate filaments to desmosomes or hemidesmosomes. Could also bind muscle proteins such as actin to membrane complexes in muscle. May be involved not only in the filaments network, but also in the regulation of their dynamics. Structural component of muscle. Isoform 9 plays a major role in the maintenance of myofiber integrity. {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:21109228}. |
| Q15149 | PLEC | S4365 | 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}. |
| Q15154 | PCM1 | S372 | psp | 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}. |
| 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}. |
| Q15468 | STIL | S428 | psp | SCL-interrupting locus protein (TAL-1-interrupting locus protein) | Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CPAP to the base of the procentriole to initiate procentriole assembly (PubMed:22020124). In complex with STIL acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility (PubMed:29712910, PubMed:32107292). {ECO:0000269|PubMed:16024801, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:29712910, ECO:0000269|PubMed:32107292, ECO:0000269|PubMed:9372240}. |
| Q15468 | STIL | S719 | ochoa | SCL-interrupting locus protein (TAL-1-interrupting locus protein) | Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1 (PubMed:16024801, PubMed:9372240). Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CPAP to the base of the procentriole to initiate procentriole assembly (PubMed:22020124). In complex with STIL acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility (PubMed:29712910, PubMed:32107292). {ECO:0000269|PubMed:16024801, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:29712910, ECO:0000269|PubMed:32107292, ECO:0000269|PubMed:9372240}. |
| Q15643 | TRIP11 | S1335 | 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}. |
| Q15646 | OASL | S396 | ochoa | 2'-5'-oligoadenylate synthase-like protein (2'-5'-OAS-related protein) (2'-5'-OAS-RP) (59 kDa 2'-5'-oligoadenylate synthase-like protein) (Thyroid receptor-interacting protein 14) (TR-interacting protein 14) (TRIP-14) (p59 OASL) (p59OASL) | Does not have 2'-5'-OAS activity, but can bind double-stranded RNA. Displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. {ECO:0000269|PubMed:18931074, ECO:0000269|PubMed:20074559, ECO:0000269|PubMed:9826176}. |
| Q15742 | NAB2 | S479 | ochoa | NGFI-A-binding protein 2 (EGR-1-binding protein 2) (Melanoma-associated delayed early response protein) (Protein MADER) | Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2. Isoform 2 lacks repression ability (By similarity). {ECO:0000250}. |
| Q15788 | NCOA1 | S620 | ochoa | Nuclear receptor coactivator 1 (NCoA-1) (EC 2.3.1.48) (Class E basic helix-loop-helix protein 74) (bHLHe74) (Protein Hin-2) (RIP160) (Renal carcinoma antigen NY-REN-52) (Steroid receptor coactivator 1) (SRC-1) | Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3. {ECO:0000269|PubMed:10449719, ECO:0000269|PubMed:12954634, ECO:0000269|PubMed:7481822, ECO:0000269|PubMed:9223281, ECO:0000269|PubMed:9223431, ECO:0000269|PubMed:9296499, ECO:0000269|PubMed:9427757}. |
| Q15911 | ZFHX3 | S571 | 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}. |
| Q16512 | PKN1 | S916 | ochoa|psp | Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) | PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. |
| Q16513 | PKN2 | S163 | ochoa | Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2) | PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936, ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}. |
| Q16656 | NRF1 | S102 | psp | Nuclear respiratory factor 1 (NRF-1) (Alpha palindromic-binding protein) (Alpha-pal) | Transcription factor that activates the expression of the EIF2S1 (EIF2-alpha) gene. Links the transcriptional modulation of key metabolic genes to cellular growth and development. Implicated in the control of nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. |
| Q16665 | HIF1A | S696 | 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}. |
| Q16891 | IMMT | S356 | 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}. |
| Q18PE1 | DOK7 | S246 | ochoa | Protein Dok-7 (Downstream of tyrosine kinase 7) | Probable muscle-intrinsic activator of MUSK that plays an essential role in neuromuscular synaptogenesis. Acts in aneural activation of MUSK and subsequent acetylcholine receptor (AchR) clustering in myotubes. Induces autophosphorylation of MUSK. {ECO:0000269|PubMed:20603078}. |
| Q1ED39 | KNOP1 | S387 | ochoa | Lysine-rich nucleolar protein 1 (Protein FAM191A) (Testis-specific gene 118 protein) | None |
| Q2TB10 | ZNF800 | S387 | ochoa | Zinc finger protein 800 | May be involved in transcriptional regulation. |
| Q3KR37 | GRAMD1B | S88 | ochoa | Protein Aster-B (GRAM domain-containing protein 1B) | Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis in the adrenal gland and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). {ECO:0000250|UniProtKB:Q80TI0}. |
| Q4G0A6 | MINDY4 | S392 | ochoa | Probable ubiquitin carboxyl-terminal hydrolase MINDY-4 (EC 3.4.19.12) (Probable deubiquitinating enzyme MINDY-4) | Probable hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins. {ECO:0000250|UniProtKB:Q8NBR6}. |
| Q53QZ3 | ARHGAP15 | S217 | 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}. |
| Q5FWE3 | PRRT3 | S924 | ochoa | Proline-rich transmembrane protein 3 | None |
| Q5JVF3 | PCID2 | S24 | ochoa | PCI domain-containing protein 2 (CSN12-like protein) | Required for B-cell survival through the regulation of the expression of cell-cycle checkpoint MAD2L1 protein during B cell differentiation (By similarity). As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (PubMed:22307388). Binds and stabilizes BRCA2 and is thus involved in the control of R-loop-associated DNA damage and transcription-associated genomic instability (PubMed:24896180). Blocks the activity of the SRCAP chromatin remodeling complex by interacting with SRCAP complex member ZNHIT1 and inhibiting its interaction with the complex (By similarity). This prevents the deposition of histone variant H2AZ1/H2A.Z at the nucleosomes of key lymphoid fate regulator genes which suppresses their expression and restricts lymphoid lineage commitment (By similarity). {ECO:0000250|UniProtKB:Q8BFV2, ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:24896180, ECO:0000305|PubMed:23591820}. |
| Q5TGY3 | AHDC1 | S135 | 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}. |
| 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}. |
| Q5VTT5 | MYOM3 | S1309 | 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}. |
| Q5VUA4 | ZNF318 | S214 | 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}. |
| Q5VWG9 | TAF3 | S199 | 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}. |
| Q5VZ89 | DENND4C | S1115 | 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}. |
| Q63HN8 | RNF213 | S4118 | 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}. |
| Q6DT37 | CDC42BPG | S1514 | ochoa | Serine/threonine-protein kinase MRCK gamma (EC 2.7.11.1) (CDC42-binding protein kinase gamma) (DMPK-like gamma) (Myotonic dystrophy kinase-related CDC42-binding kinase gamma) (MRCK gamma) (MRCKG) (Myotonic dystrophy protein kinase-like gamma) (Myotonic dystrophy protein kinase-like alpha) | May act as a downstream effector of CDC42 in cytoskeletal reorganization. Contributes to the actomyosin contractility required for cell invasion, through the regulation of MYPT1 and thus MLC2 phosphorylation (By similarity). {ECO:0000250|UniProtKB:Q5VT25, ECO:0000269|PubMed:15194684}. |
| Q6FI81 | CIAPIN1 | S201 | ochoa | 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}. |
| Q6ISB3 | GRHL2 | S81 | ochoa | Grainyhead-like protein 2 homolog (Brother of mammalian grainyhead) (Transcription factor CP2-like 3) | Transcription factor playing an important role in primary neurulation and in epithelial development (PubMed:25152456, PubMed:29309642). Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes (By similarity). During embryogenesis, plays unique and cooperative roles with GRHL3 in establishing distinct zones of primary neurulation. Essential for closure 3 (rostral end of the forebrain), functions cooperatively with GRHL3 in closure 2 (forebrain/midbrain boundary) and posterior neuropore closure (By similarity). Regulates epithelial morphogenesis acting as a target gene-associated transcriptional activator of apical junctional complex components. Up-regulates of CLDN3 and CLDN4, as well as of RAB25, which increases the CLDN4 protein and its localization at tight junctions (By similarity). Comprises an essential component of the transcriptional machinery that establishes appropriate expression levels of CLDN4 and CDH1 in different types of epithelia. Exhibits functional redundancy with GRHL3 in epidermal morphogenetic events and epidermal wound repair (By similarity). In lung, forms a regulatory loop with NKX2-1 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). In keratinocytes, plays a role in telomerase activation during cellular proliferation, regulates TERT expression by binding to TERT promoter region and inhibiting DNA methylation at the 5'-CpG island, possibly by interfering with DNMT1 enzyme activity (PubMed:19015635, PubMed:20938050). In addition, impairs keratinocyte differentiation and epidermal function by inhibiting the expression of genes clustered at the epidermal differentiation complex (EDC) as well as GRHL1 and GRHL3 through epigenetic mechanisms (PubMed:23254293). {ECO:0000250|UniProtKB:Q8K5C0, ECO:0000269|PubMed:19015635, ECO:0000269|PubMed:20938050, ECO:0000269|PubMed:20978075, ECO:0000269|PubMed:23254293, ECO:0000269|PubMed:25152456, ECO:0000269|PubMed:29309642, ECO:0000305|PubMed:12175488}. |
| Q6KC79 | NIPBL | S228 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6KC79 | NIPBL | S255 | ochoa | Nipped-B-like protein (Delangin) (SCC2 homolog) | Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with MAU2/SCC4 which mediates the loading of the cohesin complex onto chromatin (PubMed:22628566, PubMed:28914604). Plays a role in cohesin loading at sites of DNA damage. Its recruitment to double-strand breaks (DSBs) sites occurs in a CBX3-, RNF8- and RNF168-dependent manner whereas its recruitment to UV irradiation-induced DNA damage sites occurs in a ATM-, ATR-, RNF8- and RNF168-dependent manner (PubMed:28167679). Along with ZNF609, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others (By similarity). {ECO:0000250|UniProtKB:Q6KCD5, ECO:0000269|PubMed:22628566, ECO:0000269|PubMed:28167679, ECO:0000269|PubMed:28914604}. |
| Q6NYC8 | PPP1R18 | S145 | ochoa | Phostensin (Protein phosphatase 1 F-actin cytoskeleton-targeting subunit) (Protein phosphatase 1 regulatory subunit 18) | [Isoform 1]: May target protein phosphatase 1 to F-actin cytoskeleton. {ECO:0000269|PubMed:24434620}.; FUNCTION: [Isoform 4]: May target protein phosphatase 1 to F-actin cytoskeleton. {ECO:0000269|PubMed:17374523}. |
| Q6P2E9 | EDC4 | S656 | ochoa | Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) | In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}. |
| Q6P996 | PDXDC1 | S718 | ochoa | Pyridoxal-dependent decarboxylase domain-containing protein 1 (EC 4.1.1.-) | None |
| Q6TDP4 | KLHL17 | S374 | ochoa | Kelch-like protein 17 (Actinfilin) | Substrate-recognition component of some cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes. The BCR(KLHL17) complex mediates the ubiquitination and subsequent degradation of GLUR6. May play a role in the actin-based neuronal function (By similarity). {ECO:0000250}. |
| Q6UUV7 | CRTC3 | S343 | ochoa | CREB-regulated transcription coactivator 3 (Transducer of regulated cAMP response element-binding protein 3) (TORC-3) (Transducer of CREB protein 3) | Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:14506290, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:15466468, ECO:0000269|PubMed:16817901, ECO:0000269|PubMed:16980408, ECO:0000269|PubMed:17210223, ECO:0000269|PubMed:17644518}. |
| Q6UXF1 | TMEM108 | S539 | ochoa | Transmembrane protein 108 (Retrolinkin) | Transmembrane protein required for proper cognitive functions. Involved in the development of dentate gyrus (DG) neuron circuitry, is necessary for AMPA receptors surface expression and proper excitatory postsynaptic currents of DG granule neurons. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Through the interaction with DST, mediates the docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport. In hippocampal neurons, required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2 early endocytic trafficking and mediate signaling from early endosomes. {ECO:0000250|UniProtKB:Q8BHE4}. |
| Q6WCQ1 | MPRIP | S662 | 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}. |
| Q6Y7W6 | GIGYF2 | S649 | 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}. |
| Q6ZMR3 | LDHAL6A | S161 | ochoa | L-lactate dehydrogenase A-like 6A (LDHA-like protein 6A) (EC 1.1.1.27) | Catalyzes the interconversion of L-lactate and pyruvate with nicotinamide adenine dinucleotide NAD(+) as a coenzyme (PubMed:18351441). Significantly increases the transcriptional activity of JUN, when overexpressed. {ECO:0000269|PubMed:18351441}. |
| Q6ZRV2 | FAM83H | S436 | 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}. |
| Q6ZSZ6 | TSHZ1 | S880 | ochoa | Teashirt homolog 1 (Antigen NY-CO-33) (Serologically defined colon cancer antigen 33) | Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential). {ECO:0000305}. |
| Q6ZUJ8 | PIK3AP1 | S426 | ochoa | Phosphoinositide 3-kinase adapter protein 1 (B-cell adapter for phosphoinositide 3-kinase) (B-cell phosphoinositide 3-kinase adapter protein 1) | Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL. {ECO:0000269|PubMed:15893754}. |
| Q6ZV73 | FGD6 | S226 | 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}. |
| 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}. |
| 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}. |
| Q7KZI7 | MARK2 | S477 | ochoa | Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}. |
| Q7L2J0 | MEPCE | S183 | ochoa | 7SK snRNA methylphosphate capping enzyme (MePCE) (EC 2.1.1.-) (Bicoid-interacting protein 3 homolog) (Bin3 homolog) | S-adenosyl-L-methionine-dependent methyltransferase that adds a methylphosphate cap at the 5'-end of 7SK snRNA (7SK RNA), leading to stabilize it (PubMed:17643375, PubMed:19906723, PubMed:30559425). Also has a non-enzymatic function as part of the 7SK RNP complex: the 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:17643375). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC) (PubMed:28254838). In the 7SK RNP complex, MEPCE is required to stabilize 7SK RNA and facilitate the assembly of 7SK RNP complex (PubMed:19906723, PubMed:38100593). MEPCE has a non-enzymatic function in the 7SK RNP complex; interaction with LARP7 within the 7SK RNP complex occluding its catalytic center (PubMed:19906723). Also required for stability of U6 snRNAs (PubMed:38100593). {ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:19906723, ECO:0000269|PubMed:28254838, ECO:0000269|PubMed:30559425, ECO:0000269|PubMed:38100593}. |
| Q7L591 | DOK3 | S439 | ochoa | Docking protein 3 (Downstream of tyrosine kinase 3) | DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK3 is a negative regulator of JNK signaling in B-cells through interaction with INPP5D/SHIP1. May modulate ABL1 function (By similarity). {ECO:0000250}. |
| Q7L9B9 | EEPD1 | S160 | ochoa | Endonuclease/exonuclease/phosphatase family domain-containing protein 1 | None |
| Q7Z2Z1 | TICRR | S1115 | psp | 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 | S271 | 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}. |
| Q7Z3J2 | VPS35L | S108 | ochoa | VPS35 endosomal protein-sorting factor-like (Esophageal cancer-associated protein) | Acts as a component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1) (PubMed:28892079). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes (PubMed:28892079). In the endosomes, drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling (PubMed:28892079). Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association with the CCC complex and cooperation with the WASH complex on early endosomes. Seems not to be required for CCC complex stability (PubMed:25355947). {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}.; FUNCTION: (Microbial infection) The heterotrimeric retriever complex, in collaboration with the CCC complex, mediates the exit of human papillomavirus to the cell surface. {ECO:0000269|PubMed:28892079}. |
| Q7Z401 | DENND4A | S1429 | 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}. |
| Q7Z402 | TMC7 | S86 | ochoa | Transmembrane channel-like protein 7 | Acts as an inhibitory modulator of PIEZO2 mechanosensitive channel in dorsal root ganglion (DRG) neurons through physical interactions or interference with the interaction between PIEZO2 and the cytoskeleton. {ECO:0000250|UniProtKB:Q8C428}. |
| Q7Z406 | MYH14 | S1324 | ochoa | Myosin-14 (Myosin heavy chain 14) (Myosin heavy chain, non-muscle IIc) (Non-muscle myosin heavy chain IIc) (NMHC II-C) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. {ECO:0000250}. |
| Q7Z418 | KCNK18 | S262 | psp | Potassium channel subfamily K member 18 (TWIK-related individual potassium channel) (TWIK-related spinal cord potassium channel) | K(+) channel that conducts outward and inward rectifying currents at depolarized and hyperpolarized membrane potentials, respectively. The outward rectifying currents are voltage-dependent, coupled to K(+) electrochemical gradient across the membrane, whereas the inward currents can be induced in response to activation of Ca(2+)-mobilizing receptors (PubMed:12754259, PubMed:15562060, PubMed:20871611, PubMed:22355750, PubMed:26919430, PubMed:30573346). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties. In trigeminal ganglia sensory neurons, the heterodimers of KCNK18/TRESK and KCNK2/TREK-1 or KCNK10/TREK-2 inhibit neuronal firing and neurogenic inflammation by stabilizing the resting membrane potential at K(+) equilibrium potential as well as by regulating the threshold of action potentials and the spike frequency (By similarity). In thymocytes, conducts K(+) currents upon T cell receptor (TCR) signaling leading to sustained Ca(2+) influx and NF-kappa-B activation, FOXP3 transcription and positive selection of regulatory T cell (Treg) progenitor subsets (PubMed:34702947). Appears to mediate the analgesics effects of hydroxy-alpha-sanshool, a metabolite naturally present in Schezuan pepper and other Xanthoxylum plants (By similarity). {ECO:0000250|UniProtKB:Q6VV64, ECO:0000269|PubMed:12754259, ECO:0000269|PubMed:15562060, ECO:0000269|PubMed:20871611, ECO:0000269|PubMed:22355750, ECO:0000269|PubMed:26919430, ECO:0000269|PubMed:30573346, ECO:0000269|PubMed:34702947}. |
| Q86SQ7 | SDCCAG8 | S51 | 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}. |
| Q86T24 | ZBTB33 | S259 | ochoa | Transcriptional regulator Kaiso (Zinc finger and BTB domain-containing protein 33) | Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' and also binds to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. May contribute to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1 (PubMed:23251453). {ECO:0000269|PubMed:11445535, ECO:0000269|PubMed:14527417, ECO:0000269|PubMed:15548582, ECO:0000269|PubMed:15817151, ECO:0000269|PubMed:16354688, ECO:0000269|PubMed:23251453}. |
| Q86U86 | PBRM1 | S681 | 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}. |
| Q86UR5 | RIMS1 | S1493 | ochoa | Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1) (RIM 1) (Rab-3-interacting protein 2) | Rab effector involved in exocytosis (By similarity). May act as scaffold protein that regulates neurotransmitter release at the active zone. Essential for maintaining normal probability of neurotransmitter release and for regulating release during short-term synaptic plasticity (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000250|UniProtKB:Q99NE5, ECO:0000269|PubMed:23999003}. |
| Q86UW6 | N4BP2 | S906 | ochoa | NEDD4-binding protein 2 (N4BP2) (EC 3.-.-.-) (BCL-3-binding protein) | Has 5'-polynucleotide kinase and nicking endonuclease activity. May play a role in DNA repair or recombination. {ECO:0000269|PubMed:12730195}. |
| Q86UZ6 | ZBTB46 | S324 | 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}. |
| Q86YS3 | RAB11FIP4 | S253 | ochoa | Rab11 family-interacting protein 4 (FIP4-Rab11) (Rab11-FIP4) (Arfophilin-2) | Acts as a regulator of endocytic traffic by participating in membrane delivery. Required for the abscission step in cytokinesis, possibly by acting as an 'address tag' delivering recycling endosome membranes to the cleavage furrow during late cytokinesis. In case of infection by HCMV (human cytomegalovirus), may participate in egress of the virus out of nucleus; this function is independent of ARF6. {ECO:0000269|PubMed:12470645}. |
| Q86YV0 | RASAL3 | S72 | ochoa | RAS protein activator like-3 | Functions as a Ras GTPase-activating protein. Plays an important role in the expansion and functions of natural killer T (NKT) cells in the liver by negatively regulating RAS activity and the down-stream ERK signaling pathway. {ECO:0000250|UniProtKB:Q8C2K5}. |
| Q86Z02 | HIPK1 | S350 | ochoa | Homeodomain-interacting protein kinase 1 (EC 2.7.11.1) (Nuclear body-associated kinase 2) | Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:24559171). {ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:24559171}. |
| Q8HWS3 | RFX6 | S21 | ochoa | DNA-binding protein RFX6 (Regulatory factor X 6) (Regulatory factor X domain-containing protein 1) | Transcription factor required to direct islet cell differentiation during endocrine pancreas development. Specifically required for the differentiation of 4 of the 5 islet cell types and for the production of insulin (PubMed:20148032, PubMed:25497100). Not required for pancreatic PP (polypeptide-producing) cells differentiation. Acts downstream of NEUROG3 and regulates the transcription factors involved in beta-cell maturation and function, thereby restricting the expression of the beta-cell differentiation and specification genes, and thus the beta-cell fate choice. Activates transcription by forming a heterodimer with RFX3 and binding to the X-box in the promoter of target genes (PubMed:20148032). Involved in glucose-stimulated insulin secretion by promoting insulin and L-type calcium channel gene transcription (PubMed:25497100). {ECO:0000269|PubMed:20148032, ECO:0000269|PubMed:25497100}. |
| Q8IUC4 | RHPN2 | S639 | ochoa | Rhophilin-2 (76 kDa RhoB effector protein) (GTP-Rho-binding protein 2) (p76RBE) | Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity. {ECO:0000269|PubMed:12221077}. |
| Q8IW35 | CEP97 | S413 | ochoa | Centrosomal protein of 97 kDa (Cep97) (Leucine-rich repeat and IQ domain-containing protein 2) | Acts as a key negative regulator of ciliogenesis in collaboration with CCP110 by capping the mother centriole thereby preventing cilia formation (PubMed:17719545, PubMed:30375385). Required for recruitment of CCP110 to the centrosome (PubMed:17719545). {ECO:0000269|PubMed:17719545, ECO:0000269|PubMed:30375385}. |
| Q8IWB9 | TEX2 | S196 | ochoa | Testis-expressed protein 2 (Transmembrane protein 96) | During endoplasmic reticulum (ER) stress or when cellular ceramide levels increase, may induce contacts between the ER and medial-Golgi complex to facilitate non-vesicular transport of ceramides from the ER to the Golgi complex where they are converted to complex sphingolipids, preventing toxic ceramide accumulation. {ECO:0000269|PubMed:28011845}. |
| Q8IWZ3 | ANKHD1 | S1658 | ochoa | Ankyrin repeat and KH domain-containing protein 1 (HIV-1 Vpr-binding ankyrin repeat protein) (Multiple ankyrin repeats single KH domain) (hMASK) | May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}. |
| Q8IX12 | CCAR1 | S1080 | ochoa | 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}. |
| Q8IX15 | HOMEZ | S351 | ochoa | Homeobox and leucine zipper protein Homez (Homeodomain leucine zipper-containing factor) | May function as a transcriptional regulator. |
| Q8IX90 | SKA3 | S313 | 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}. |
| Q8IXM2 | BACC1 | S141 | ochoa | BPTF-associated chromatin complex component 1 (BPTF-associated protein of 18 kDa) (Chromatin complexes subunit BAP18) | Component of chromatin complexes such as the MLL1/MLL and NURF complexes. |
| Q8IYD8 | FANCM | S1794 | ochoa | 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}. |
| Q8IYJ3 | SYTL1 | S470 | ochoa | Synaptotagmin-like protein 1 (Exophilin-7) (Protein JFC1) | May play a role in vesicle trafficking (By similarity). Binds phosphatidylinositol 3,4,5-trisphosphate. Acts as a RAB27A effector protein and may play a role in cytotoxic granule exocytosis in lymphocytes (By similarity). {ECO:0000250, ECO:0000269|PubMed:11278853, ECO:0000269|PubMed:18266782}. |
| Q8N103 | TAGAP | S68 | ochoa | T-cell activation Rho GTPase-activating protein (T-cell activation GTPase-activating protein) | May function as a GTPase-activating protein and may play important roles during T-cell activation. {ECO:0000269|PubMed:15177553}. |
| Q8N163 | CCAR2 | S626 | ochoa | Cell cycle and apoptosis regulator protein 2 (Cell division cycle and apoptosis regulator protein 2) (DBIRD complex subunit KIAA1967) (Deleted in breast cancer gene 1 protein) (DBC-1) (DBC.1) (NET35) (p30 DBC) | Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions (PubMed:22446626). Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis (PubMed:18235501, PubMed:18235502, PubMed:23352644). Inhibits SUV39H1 methyltransferase activity (PubMed:19218236). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:19131338). Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress (PubMed:23398316). Regulates the circadian expression of the core clock components NR1D1 and BMAL1 (PubMed:23398316). Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses the transcriptional activator activity of BRCA1 (PubMed:20160719). Inhibits SIRT1 in a CHEK2 and PSEM3-dependent manner and inhibits the activity of CHEK2 in vitro (PubMed:25361978). {ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502, ECO:0000269|PubMed:19131338, ECO:0000269|PubMed:19218236, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:22446626, ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:25732823}. |
| Q8N3C0 | ASCC3 | S452 | ochoa | Activating signal cointegrator 1 complex subunit 3 (EC 5.6.2.4) (ASC-1 complex subunit p200) (ASC1p200) (Helicase, ATP binding 1) (Trip4 complex subunit p200) | ATPase involved both in DNA repair and rescue of stalled ribosomes (PubMed:22055184, PubMed:28757607, PubMed:32099016, PubMed:32579943, PubMed:36302773). 3'-5' DNA helicase involved in repair of alkylated DNA: promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3-methylcytosine (3mC) within double-stranded regions (PubMed:22055184). Also involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (PubMed:28757607, PubMed:32099016, PubMed:32579943, PubMed:36302773). Drives the splitting of stalled ribosomes that are ubiquitinated in a ZNF598-dependent manner, as part of the ribosome quality control trigger (RQT) complex (PubMed:28757607, PubMed:32099016, PubMed:32579943, PubMed:36302773). Part of the ASC-1 complex that enhances NF-kappa-B, SRF and AP1 transactivation (PubMed:12077347). {ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:22055184, ECO:0000269|PubMed:28757607, ECO:0000269|PubMed:32099016, ECO:0000269|PubMed:32579943, ECO:0000269|PubMed:36302773}. |
| Q8N8S7 | ENAH | S541 | ochoa | Protein enabled homolog | 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. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:11696321, ECO:0000269|PubMed:18158903}. |
| Q8NC74 | RBBP8NL | S283 | ochoa | RBBP8 N-terminal-like protein | None |
| Q8NCF5 | NFATC2IP | S390 | ochoa | NFATC2-interacting protein (45 kDa NF-AT-interacting protein) (45 kDa NFAT-interacting protein) (Nuclear factor of activated T-cells, cytoplasmic 2-interacting protein) | In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}. |
| Q8NDI1 | EHBP1 | S408 | ochoa | EH domain-binding protein 1 | May play a role in actin reorganization. Links clathrin-mediated endocytosis to the actin cytoskeleton. May act as Rab effector protein and play a role in vesicle trafficking (PubMed:14676205, PubMed:27552051). Required for perinuclear sorting and insulin-regulated recycling of SLC2A4/GLUT4 in adipocytes (By similarity). {ECO:0000250|UniProtKB:Q69ZW3, ECO:0000269|PubMed:14676205, ECO:0000305|PubMed:27552051}. |
| Q8NEM2 | SHCBP1 | S269 | ochoa | SHC SH2 domain-binding protein 1 | May play a role in signaling pathways governing cellular proliferation, cell growth and differentiation. May be a component of a novel signaling pathway downstream of Shc. Acts as a positive regulator of FGF signaling in neural progenitor cells. {ECO:0000250|UniProtKB:Q9Z179}. |
| Q8NEV8 | EXPH5 | S1753 | 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}. |
| Q8NF91 | SYNE1 | S8325 | 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}. |
| Q8NF91 | SYNE1 | S8688 | 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}. |
| Q8NFF5 | FLAD1 | S106 | ochoa | FAD synthase (EC 2.7.7.2) (FAD pyrophosphorylase) (FMN adenylyltransferase) (Flavin adenine dinucleotide synthase) [Includes: Molybdenum cofactor biosynthesis protein-like region; FAD synthase region] | Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. {ECO:0000269|PubMed:16643857, ECO:0000269|PubMed:27259049}. |
| Q8NFP9 | NBEA | S1529 | 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}. |
| Q8NHM5 | KDM2B | S832 | ochoa | Lysine-specific demethylase 2B (EC 1.14.11.27) (CXXC-type zinc finger protein 2) (F-box and leucine-rich repeat protein 10) (F-box protein FBL10) (F-box/LRR-repeat protein 10) (JmjC domain-containing histone demethylation protein 1B) (Jumonji domain-containing EMSY-interactor methyltransferase motif protein) (Protein JEMMA) (Protein-containing CXXC domain 2) ([Histone-H3]-lysine-36 demethylase 1B) | Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}. |
| Q8TB72 | PUM2 | S82 | ochoa | Pumilio homolog 2 (Pumilio-2) | Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (, PubMed:21397187). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:22345517). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). May regulate DCUN1D3 mRNA levels (PubMed:25349211). May support proliferation and self-renewal of stem cells. Binds specifically to miRNA MIR199A precursor, with PUM1, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25349211, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233}. |
| Q8TC05 | MDM1 | S242 | ochoa | Nuclear protein MDM1 | Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules (PubMed:26337392). {ECO:0000269|PubMed:26337392}. |
| Q8TC05 | MDM1 | S683 | ochoa | Nuclear protein MDM1 | Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules (PubMed:26337392). {ECO:0000269|PubMed:26337392}. |
| Q8TD22 | SFXN5 | S36 | ochoa | Sideroflexin-5 | Mitochondrial amino-acid transporter (By similarity). Transports citrate (By similarity). Does not act as a serine transporter: not able to mediate transport of serine into mitochondria (By similarity) (PubMed:30442778). In brown adipose tissue, plays a role in the regulation of UCP1-dependent thermogenesis probably by supporting mitochondrial glycerol-3-phosphate utilization (By similarity). {ECO:0000250|UniProtKB:Q8CFD0, ECO:0000250|UniProtKB:Q925N0, ECO:0000250|UniProtKB:Q9H9B4, ECO:0000269|PubMed:30442778}. |
| Q8TDD1 | DDX54 | S696 | ochoa | ATP-dependent RNA helicase DDX54 (EC 3.6.4.13) (ATP-dependent RNA helicase DP97) (DEAD box RNA helicase 97 kDa) (DEAD box protein 54) | Has RNA-dependent ATPase activity. Represses the transcriptional activity of nuclear receptors. {ECO:0000269|PubMed:12466272}. |
| Q8TEK3 | DOT1L | S297 | 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}. |
| Q8TEK3 | DOT1L | S764 | 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 | S1438 | ochoa | Rho guanine nucleotide exchange factor 40 (Protein SOLO) | May act as a guanine nucleotide exchange factor (GEF). {ECO:0000250}. |
| Q8WUD1 | RAB2B | S67 | ochoa | Ras-related protein Rab-2B (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. Regulates the compacted morphology of the Golgi (Probable). Promotes cytosolic DNA-induced innate immune responses. Regulates IFN responses against DNA viruses by regulating the CGAS-STING signaling axis (By similarity). Together with RAB2A redundantly required for efficient autophagic flux (PubMed:28483915). {ECO:0000250|UniProtKB:P59279, ECO:0000269|PubMed:28483915, ECO:0000305|PubMed:26209634}. |
| Q8WUX9 | CHMP7 | S429 | ochoa | Charged multivesicular body protein 7 (Chromatin-modifying protein 7) | ESCRT-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope (NE) during late anaphase (PubMed:26040712). Together with SPAST, the ESCRT-III complex promotes NE sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712, PubMed:28242692). Recruited to the reforming NE during anaphase by LEMD2 (PubMed:28242692). Plays a role in the endosomal sorting pathway (PubMed:16856878). {ECO:0000269|PubMed:16856878, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:28242692}. |
| Q8WWW8 | GAB3 | S346 | ochoa | GRB2-associated-binding protein 3 (GRB2-associated binder 3) (Growth factor receptor bound protein 2-associated protein 3) | None |
| Q8WXH0 | SYNE2 | S3145 | 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}. |
| Q8WYP5 | AHCTF1 | S528 | 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}. |
| Q8WYR1 | PIK3R5 | S507 | ochoa | Phosphoinositide 3-kinase regulatory subunit 5 (PI3-kinase regulatory subunit 5) (PI3-kinase p101 subunit) (Phosphatidylinositol 4,5-bisphosphate 3-kinase regulatory subunit) (PtdIns-3-kinase regulatory subunit) (Protein FOAP-2) (PtdIns-3-kinase p101) (p101-PI3K) | Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG (By similarity). {ECO:0000250}. |
| Q92551 | IP6K1 | S139 | ochoa | Inositol hexakisphosphate kinase 1 (InsP6 kinase 1) (EC 2.7.4.21) (Inositol hexaphosphate kinase 1) | Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4. |
| Q92551 | IP6K1 | S175 | ochoa | Inositol hexakisphosphate kinase 1 (InsP6 kinase 1) (EC 2.7.4.21) (Inositol hexaphosphate kinase 1) | Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4. |
| Q92667 | AKAP1 | S570 | ochoa | A-kinase anchor protein 1, mitochondrial (A-kinase anchor protein 149 kDa) (AKAP 149) (Dual specificity A-kinase-anchoring protein 1) (D-AKAP-1) (Protein kinase A-anchoring protein 1) (PRKA1) (Spermatid A-kinase anchor protein 84) (S-AKAP84) | Binds to type I and II regulatory subunits of protein kinase A and anchors them to the cytoplasmic face of the mitochondrial outer membrane (By similarity). Involved in mitochondrial-mediated antiviral innate immunity (PubMed:31522117). Promotes translocation of NDUFS1 into mitochondria to regulate mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) activity (By similarity). {ECO:0000250|UniProtKB:O08715, ECO:0000269|PubMed:31522117}. |
| Q92698 | RAD54L | S572 | psp | DNA repair and recombination protein RAD54-like (EC 3.6.4.12) (RAD54 homolog) (hHR54) (hRAD54) | Plays an essential role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks (PubMed:11459989, PubMed:12205100, PubMed:24798879, PubMed:27264870, PubMed:32457312, PubMed:9774452). Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Also plays an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA (By similarity). {ECO:0000250|UniProtKB:P32863, ECO:0000269|PubMed:11459989, ECO:0000269|PubMed:12205100, ECO:0000269|PubMed:24798879, ECO:0000269|PubMed:27264870, ECO:0000269|PubMed:32457312, ECO:0000269|PubMed:9774452}. |
| Q92750 | TAF4B | S252 | ochoa | Transcription initiation factor TFIID subunit 4B (Transcription initiation factor TFIID 105 kDa subunit) (TAF(II)105) (TAFII-105) (TAFII105) | Cell type-specific subunit of the general transcription factor TFIID that may function as a gene-selective coactivator in certain cells. TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. TAF4B is a transcriptional coactivator of the p65/RELA NF-kappa-B subunit. Involved in the activation of a subset of antiapoptotic genes including TNFAIP3. May be involved in regulating folliculogenesis. Through interaction with OCBA/POU2AF1, acts as a coactivator of B-cell-specific transcription. Plays a role in spermiogenesis and oogenesis. {ECO:0000250|UniProtKB:G5E8Z2, ECO:0000269|PubMed:10828057, ECO:0000269|PubMed:10849440, ECO:0000269|PubMed:16088961, ECO:0000303|PubMed:24431330}. |
| Q92785 | DPF2 | S94 | 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}. |
| Q92794 | KAT6A | S941 | ochoa | Histone acetyltransferase KAT6A (EC 2.3.1.48) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 3) (MYST-3) (Monocytic leukemia zinc finger protein) (Runt-related transcription factor-binding protein 2) (Zinc finger protein 220) | Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12771199, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17925393, ECO:0000269|PubMed:23431171}. |
| Q92900 | UPF1 | S1089 | psp | 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}. |
| Q92917 | GPKOW | S388 | ochoa | G-patch domain and KOW motifs-containing protein (G-patch domain-containing protein 5) (Protein MOS2 homolog) (Protein T54) | RNA-binding protein involved in pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:25296192, ECO:0000305|PubMed:33509932}. |
| Q92932 | PTPRN2 | S652 | ochoa | Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) (EC 3.1.3.-) (EC 3.1.3.48) (Islet cell autoantigen-related protein) (IAR) (ICAAR) (Phogrin) [Cleaved into: IA-2beta60] | Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate (By similarity). Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolysis of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments (PubMed:26620550). {ECO:0000250|UniProtKB:P80560, ECO:0000250|UniProtKB:Q63475, ECO:0000269|PubMed:26620550}. |
| Q92985 | IRF7 | S479 | psp | Interferon regulatory factor 7 (IRF-7) | Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:28342865, PubMed:28768858). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:17574024, PubMed:32972995). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Induces transcription of ubiquitin hydrolase USP25 mRNA in response to lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent manner (By similarity). Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages (By similarity) (PubMed:11073981, PubMed:12374802, PubMed:15361868, PubMed:17404045). {ECO:0000250|UniProtKB:P70434, ECO:0000269|PubMed:11073981, ECO:0000269|PubMed:12374802, ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:17404045, ECO:0000269|PubMed:17574024, ECO:0000269|PubMed:28342865, ECO:0000269|PubMed:28768858, ECO:0000269|PubMed:32972995}. |
| Q92995 | USP13 | S239 | ochoa | Ubiquitin carboxyl-terminal hydrolase 13 (EC 3.4.19.12) (Deubiquitinating enzyme 13) (Isopeptidase T-3) (ISOT-3) (Ubiquitin thioesterase 13) (Ubiquitin-specific-processing protease 13) | Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy, endoplasmic reticulum-associated degradation (ERAD), cell cycle progression or DNA damage response (PubMed:21571647, PubMed:32772043, PubMed:33592542). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms with NEDD4 a deubiquitination complex, which subsequently stabilizes VPS34 to promote autophagy (PubMed:32101753). Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Regulates the cell cycle progression by stabilizing cell cycle proteins such as SKP2 and AURKB (PubMed:32772043). In addition, plays an important role in maintaining genomic stability and in DNA replication checkpoint activation via regulation of RAP80 and TOPBP1 (PubMed:33592542). Deubiquitinates the multifunctional protein HMGB1 and subsequently drives its nucleocytoplasmic localization and its secretion (PubMed:36585612). Positively regulates type I and type II interferon signalings by deubiquitinating STAT1 but negatively regulates antiviral response by deubiquitinating STING1 (PubMed:23940278, PubMed:28534493). {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:32101753, ECO:0000269|PubMed:32772043, ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:36585612}. |
| Q96AD5 | PNPLA2 | S428 | ochoa | Patatin-like phospholipase domain-containing protein 2 (EC 3.1.1.3) (Adipose triglyceride lipase) (Calcium-independent phospholipase A2-zeta) (iPLA2-zeta) (EC 3.1.1.4) (Desnutrin) (Pigment epithelium-derived factor receptor) (PEDF-R) (TTS2.2) (Transport-secretion protein 2) (TTS2) | Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (PubMed:15364929, PubMed:15550674, PubMed:16150821, PubMed:16239926, PubMed:17603008, PubMed:34903883). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone and acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (By similarity). Also possesses acylglycerol transacylase and phospholipase A2 activities (PubMed:15364929, PubMed:17032652, PubMed:17603008). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides (PubMed:17603008). Regulates adiposome size and may be involved in the degradation of adiposomes (PubMed:16239926). Catalyzes the formation of an ester bond between hydroxy fatty acids and fatty acids derived from triglycerides or diglycerides to generate fatty acid esters of hydroxy fatty acids (FAHFAs) in adipocytes (PubMed:35676490). Acts antagonistically with LDAH in regulation of cellular lipid stores (PubMed:28578400). Inhibits LDAH-stimulated lipid droplet fusion (PubMed:28578400). May play an important role in energy homeostasis (By similarity). May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion (By similarity). {ECO:0000250|UniProtKB:Q8BJ56, ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:16150821, ECO:0000269|PubMed:16239926, ECO:0000269|PubMed:17032652, ECO:0000269|PubMed:17603008, ECO:0000269|PubMed:28578400, ECO:0000269|PubMed:34903883, ECO:0000269|PubMed:35676490}. |
| Q96CN4 | EVI5L | S722 | ochoa | EVI5-like protein (Ecotropic viral integration site 5-like protein) | Functions as a GTPase-activating protein (GAP) with a broad specificity. {ECO:0000269|PubMed:16923123}. |
| Q96ED9 | HOOK2 | S163 | 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}. |
| Q96EV2 | RBM33 | S54 | ochoa | RNA-binding protein 33 (Proline-rich protein 8) (RNA-binding motif protein 33) | RNA reader protein, which recognizes and binds specific RNAs, thereby regulating RNA metabolic processes, such as mRNA export, mRNA stability and/or translation (PubMed:35589130, PubMed:37257451). Binds a subset of intronless RNAs containing GC-rich elements, such as NORAD, and promotes their nuclear export by recruiting target RNAs to components of the NXF1-NXT1 RNA export machinery (PubMed:35589130). Specifically recognizes and binds N6-methyladenosine (m6A)-containing mRNAs, promoting their demethylation by ALKBH5 (PubMed:37257451). Acts as an molecular adapter, which (1) promotes ALKBH5 recruitment to m6A-containing transcripts and (2) activates ALKBH5 demethylase activity by recruiting SENP1, leading to ALKBH5 deSUMOylation and subsequent activation (PubMed:37257451). {ECO:0000269|PubMed:35589130, ECO:0000269|PubMed:37257451}. |
| Q96F46 | IL17RA | S554 | ochoa|psp | Interleukin-17 receptor A (IL-17 receptor A) (IL-17RA) (CDw217) (CD antigen CD217) | Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911633, PubMed:9367539). Receptor for IL17F (PubMed:17911633, PubMed:19838198). Binds to IL17A with higher affinity than to IL17F (PubMed:17911633). Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (PubMed:16785495). Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (PubMed:18684971). Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16785495, PubMed:17911633, PubMed:18684971, PubMed:21350122, PubMed:24120361). Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (By similarity). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity). Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, providing for production of virus-specific IgM antibodies at first line of host defense (By similarity). Receptor for IL17C as part of a heterodimeric complex with IL17RE (PubMed:21993848). {ECO:0000250|UniProtKB:Q60943, ECO:0000269|PubMed:16785495, ECO:0000269|PubMed:17911633, ECO:0000269|PubMed:18684971, ECO:0000269|PubMed:19838198, ECO:0000269|PubMed:21350122, ECO:0000269|PubMed:21993848, ECO:0000269|PubMed:24120361, ECO:0000269|PubMed:9367539}.; FUNCTION: (Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway. {ECO:0000269|PubMed:33723527}. |
| Q96FF7 | MISP3 | S26 | ochoa | Uncharacterized protein MISP3 (MISP family member 3) | None |
| Q96FS4 | SIPA1 | S304 | ochoa | Signal-induced proliferation-associated protein 1 (Sipa-1) (GTPase-activating protein Spa-1) (p130 SPA-1) | GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state (PubMed:9346962). Affects cell cycle progression (By similarity). {ECO:0000250|UniProtKB:P46062, ECO:0000269|PubMed:9346962}. |
| Q96GS4 | BORCS6 | S89 | ochoa | BLOC-1-related complex subunit 6 (Lysosome-dispersing protein) (Lyspersin) | As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end-directed kinesin motor. {ECO:0000269|PubMed:25898167}. |
| Q96LT9 | RNPC3 | S21 | ochoa | RNA-binding region-containing protein 3 (RNA-binding motif protein 40) (RNA-binding protein 40) (U11/U12 small nuclear ribonucleoprotein 65 kDa protein) (U11/U12 snRNP 65 kDa protein) (U11/U12-65K) | Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'-stem-loop of m(7)G-capped U12 snRNA. {ECO:0000269|PubMed:16096647, ECO:0000269|PubMed:19447915, ECO:0000269|PubMed:24480542, ECO:0000269|PubMed:29255062}. |
| Q96MY1 | NOL4L | S179 | ochoa | Nucleolar protein 4-like | None |
| Q96N46 | TTC14 | S733 | ochoa | Tetratricopeptide repeat protein 14 (TPR repeat protein 14) | None |
| Q96NE9 | FRMD6 | S544 | ochoa | FERM domain-containing protein 6 (Willin) | None |
| Q96P47 | AGAP3 | S219 | 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}. |
| Q96PY5 | FMNL2 | S406 | 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}. |
| Q96Q89 | KIF20B | S1586 | 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}. |
| Q96RR4 | CAMKK2 | S511 | psp | Calcium/calmodulin-dependent protein kinase kinase 2 (CaM-KK 2) (CaM-kinase kinase 2) (CaMKK 2) (EC 2.7.11.17) (Calcium/calmodulin-dependent protein kinase kinase beta) (CaM-KK beta) (CaM-kinase kinase beta) (CaMKK beta) | Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching. {ECO:0000250, ECO:0000269|PubMed:11395482, ECO:0000269|PubMed:12935886, ECO:0000269|PubMed:21957496, ECO:0000269|PubMed:9662074}. |
| Q96SN8 | CDK5RAP2 | S1238 | 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}. |
| Q96ST2 | IWS1 | S621 | 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}. |
| Q99504 | EYA3 | S438 | ochoa | Protein phosphatase EYA3 (EC 3.1.3.48) (Eyes absent homolog 3) | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1 (PubMed:19234442, PubMed:19351884). Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1, and seems to coactivate SIX2, SIX4 and SIX5. The repression of precursor cell proliferation in myoblasts by SIX1 is switched to activation through recruitment of EYA3 to the SIX1-DACH1 complex and seems to be dependent on EYA3 phosphatase activity (By similarity). May be involved in development of the eye. {ECO:0000250|UniProtKB:P97480, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19351884}. |
| Q99618 | CDCA3 | S225 | 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}. |
| Q9BS91 | SLC35A5 | S394 | 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}. |
| Q9BUA3 | SPINDOC | S121 | ochoa | Spindlin interactor and repressor of chromatin-binding protein (SPIN1-docking protein) (SPIN-DOC) | Chromatin protein that stabilizes SPIN1 and enhances its association with histone H3 trimethylated at both 'Lys-4' and 'Lys-9' (H3K4me3K9me3) (PubMed:33574238). Positively regulates poly-ADP-ribosylation in response to DNA damage; acts by facilitating PARP1 ADP-ribosyltransferase activity (PubMed:34737271). {ECO:0000269|PubMed:33574238, ECO:0000269|PubMed:34737271}. |
| Q9BV35 | SLC25A23 | S417 | ochoa | Mitochondrial adenyl nucleotide antiporter SLC25A23 (Mitochondrial ATP-Mg/Pi carrier protein 2) (Short calcium-binding mitochondrial carrier protein 3) (SCaMC-3) (Solute carrier family 25 member 23) | Electroneutral antiporter that mediates the transport of adenine nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenine nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenine nucleotide-dependent metabolic pathways (PubMed:15123600). Also acts as a regulator of mitochondrial calcium uptake and can probably transport trace amounts of other divalent metal cations in complex with ATP (PubMed:24430870, PubMed:28695448). In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides (PubMed:15123600). {ECO:0000269|PubMed:15123600, ECO:0000269|PubMed:24430870, ECO:0000269|PubMed:28695448}. |
| Q9BVA1 | TUBB2B | S95 | 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}. |
| Q9BVI0 | PHF20 | S332 | ochoa | PHD finger protein 20 (Glioma-expressed antigen 2) (Hepatocellular carcinoma-associated antigen 58) (Novel zinc finger protein) (Transcription factor TZP) | Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. Not required for maintaining the global histone H4 'Lys-16' acetylation (H4K16ac) levels or locus specific histone acetylation, but instead works downstream in transcriptional regulation of MOF target genes (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Contributes to methyllysine-dependent p53/TP53 stabilization and up-regulation after DNA damage. {ECO:0000250, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22864287}. |
| Q9BXK5 | BCL2L13 | S426 | ochoa | Bcl-2-like protein 13 (Bcl2-L-13) (Bcl-rambo) (Protein Mil1) | May promote the activation of caspase-3 and apoptosis. |
| Q9BXK5 | BCL2L13 | S444 | ochoa | Bcl-2-like protein 13 (Bcl2-L-13) (Bcl-rambo) (Protein Mil1) | May promote the activation of caspase-3 and apoptosis. |
| Q9BXW6 | OSBPL1A | S490 | 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}. |
| Q9BYJ4 | TRIM34 | S87 | ochoa | E3 ubiquitin-protein ligase TRIM34 (EC 2.3.2.27) (Interferon-responsive finger protein 1) (RING finger protein 21) | Functions as antiviral protein and contributes to the defense against retroviral infections (PubMed:17156811, PubMed:32282853). Acts as a capsid-specific restriction factor with the help of TRIM5 and prevents infection from non-host-adapted retroviruses (PubMed:32282853). During influenza A virus infection, promotes programmed cell death by targeting ZBP1 for 'Lys-63'-linked polyubiquitination (PubMed:35065966). In turn, promotes ZBP1 recruitment of RIPK3 to mediate virus-induced programmed necrosis (PubMed:35065966). Negatively regulates the function of mitochondria by enhancing mitochondrial depolarization leading to cytochrome c release and mitochondria-dependent apoptosis (PubMed:31956709). Also promotes the formation of multinucleated giant cells by means of cell fusion and phagocytosis in epithelial cells (PubMed:31487507). {ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:31487507, ECO:0000269|PubMed:31956709, ECO:0000269|PubMed:32282853, ECO:0000269|PubMed:35065966}. |
| Q9BZ71 | PITPNM3 | S612 | ochoa | Membrane-associated phosphatidylinositol transfer protein 3 (Phosphatidylinositol transfer protein, membrane-associated 3) (PITPnm 3) (Pyk2 N-terminal domain-interacting receptor 1) (NIR-1) | Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (in vitro) (By similarity). Binds calcium ions. {ECO:0000250}. |
| Q9C010 | PKIB | S53 | ochoa | cAMP-dependent protein kinase inhibitor beta (PKI-beta) | 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. {ECO:0000250}. |
| Q9C035 | TRIM5 | S86 | ochoa | Tripartite motif-containing protein 5 (EC 2.3.2.27) (RING finger protein 88) (RING-type E3 ubiquitin transferase TRIM5) | Capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses. Blocks viral replication early in the life cycle, after viral entry but before reverse transcription. In addition to acting as a capsid-specific restriction factor, also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Binding to the viral capsid triggers its E3 ubiquitin ligase activity, and in concert with the heterodimeric ubiquitin conjugating enzyme complex UBE2V1-UBE2N (also known as UBC13-UEV1A complex) generates 'Lys-63'-linked polyubiquitin chains, which in turn are catalysts in the autophosphorylation of the MAP3K7/TAK1 complex (includes TAK1, TAB2, and TAB3). Activation of the MAP3K7/TAK1 complex by autophosphorylation results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes, thereby leading to an innate immune response in the infected cell. Restricts infection by N-tropic murine leukemia virus (N-MLV), equine infectious anemia virus (EIAV), simian immunodeficiency virus of macaques (SIVmac), feline immunodeficiency virus (FIV), and bovine immunodeficiency virus (BIV) (PubMed:17156811). Plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2 (PubMed:25127057). Also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction (PubMed:25127057). {ECO:0000269|PubMed:12878161, ECO:0000269|PubMed:17156811, ECO:0000269|PubMed:18312418, ECO:0000269|PubMed:21035162, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:21632761, ECO:0000269|PubMed:22291694, ECO:0000269|PubMed:25127057}. |
| Q9C0B5 | ZDHHC5 | S274 | 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}. |
| Q9C0K0 | BCL11B | S493 | ochoa | B-cell lymphoma/leukemia 11B (BCL-11B) (B-cell CLL/lymphoma 11B) (COUP-TF-interacting protein 2) (Radiation-induced tumor suppressor gene 1 protein) (hRit1) | Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC-rich response element (By similarity). May also function in the P53-signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q99PV8, ECO:0000269|PubMed:16809611, ECO:0000269|PubMed:27959755}. |
| Q9GZY8 | MFF | S229 | 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}. |
| Q9H165 | BCL11A | S114 | ochoa | BCL11 transcription factor A (B-cell CLL/lymphoma 11A) (B-cell lymphoma/leukemia 11A) (BCL-11A) (COUP-TF-interacting protein 1) (Ecotropic viral integration site 9 protein homolog) (EVI-9) (Zinc finger protein 856) | Transcription factor (PubMed:16704730, PubMed:29606353). Associated with the BAF SWI/SNF chromatin remodeling complex (PubMed:23644491, PubMed:39607926). Binds to the 5'-TGACCA-3' sequence motif in regulatory regions of target genes, including a distal promoter of the HBG1 hemoglobin subunit gamma-1 gene (PubMed:29606353, PubMed:39423807). Involved in regulation of the developmental switch from gamma- to beta-globin, probably via direct repression of HBG1; hence indirectly repressing fetal hemoglobin (HbF) level (PubMed:26375765, PubMed:29606353, PubMed:39423807, PubMed:39607926). Involved in brain development (PubMed:27453576). May play a role in hematopoiesis (By similarity). Essential factor in lymphopoiesis required for B-cell formation in fetal liver (By similarity). May function as a modulator of the transcriptional repression activity of NR2F2 (By similarity). {ECO:0000250|UniProtKB:Q9QYE3, ECO:0000269|PubMed:16704730, ECO:0000269|PubMed:23644491, ECO:0000269|PubMed:29606353, ECO:0000269|PubMed:39423807, ECO:0000269|PubMed:39607926, ECO:0000303|PubMed:26375765, ECO:0000303|PubMed:27453576}. |
| Q9H2X6 | HIPK2 | S359 | ochoa|psp | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| Q9H422 | HIPK3 | S357 | ochoa | Homeodomain-interacting protein kinase 3 (EC 2.7.11.1) (Androgen receptor-interacting nuclear protein kinase) (ANPK) (Fas-interacting serine/threonine-protein kinase) (FIST) (Homolog of protein kinase YAK1) | Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}. |
| Q9H4A3 | WNK1 | S2002 | ochoa | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9H4B7 | TUBB1 | S95 | ochoa | Tubulin beta-1 chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9H4M7 | PLEKHA4 | S201 | ochoa | Pleckstrin homology domain-containing family A member 4 (PH domain-containing family A member 4) (Phosphoinositol 3-phosphate-binding protein 1) (PEPP-1) | Binds specifically to phosphatidylinositol 3-phosphate (PtdIns3P), but not to other phosphoinositides. {ECO:0000269|PubMed:11001876}. |
| Q9H5I5 | PIEZO2 | S2059 | 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 | S246 | ochoa | Pecanex-like protein 3 (Pecanex homolog protein 3) | None |
| Q9H6K1 | ILRUN | S272 | ochoa | Protein ILRUN (Inflammation and lipid regulator with UBA-like and NBR1-like domains protein) | Negative regulator of innate antiviral response. Blocks IRF3-dependent cytokine production such as IFNA, IFNB and TNF (PubMed:29802199). Interacts with IRF3 and inhibits IRF3 recruitment to type I IFN promoter sequences while also reducing nuclear levels of the coactivators EP300 and CREBBP (PubMed:29802199). {ECO:0000269|PubMed:29802199}. |
| Q9H6S3 | EPS8L2 | S231 | ochoa | Epidermal growth factor receptor kinase substrate 8-like protein 2 (EPS8-like protein 2) (Epidermal growth factor receptor pathway substrate 8-related protein 2) (EPS8-related protein 2) | Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton. In the cochlea, is required for stereocilia maintenance in adult hair cells (By similarity). {ECO:0000250|UniProtKB:Q99K30, ECO:0000269|PubMed:14565974}. |
| Q9H7D7 | WDR26 | S121 | ochoa | WD repeat-containing protein 26 (CUL4- and DDB1-associated WDR protein 2) (Myocardial ischemic preconditioning up-regulated protein 2) | G-beta-like protein involved in cell signal transduction (PubMed:15378603, PubMed:19446606, PubMed:22065575, PubMed:23625927, PubMed:26895380, PubMed:27098453). Acts as a negative regulator in MAPK signaling pathway (PubMed:15378603). Functions as a scaffolding protein to promote G beta:gamma-mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes (PubMed:22065575, PubMed:23625927). 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). Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta-catenin destruction complex, thus negatively regulating CTNNB1 degradation (PubMed:27098453). Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration (PubMed:26895380). Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria (PubMed:19446606). Also protects cells by promoting hypoxia-mediated autophagy and mitophagy (By similarity). {ECO:0000250|UniProtKB:F1LTR1, ECO:0000269|PubMed:15378603, ECO:0000269|PubMed:19446606, ECO:0000269|PubMed:23625927, ECO:0000269|PubMed:26895380, ECO:0000269|PubMed:27098453, ECO:0000269|PubMed:29911972}. |
| Q9H7N4 | SCAF1 | S30 | ochoa | Splicing factor, arginine/serine-rich 19 (SR-related C-terminal domain-associated factor 1) (SR-related and CTD-associated factor 1) (SR-related-CTD-associated factor) (SCAF) (Serine arginine-rich pre-mRNA splicing factor SR-A1) (SR-A1) | May function in pre-mRNA splicing. {ECO:0000250}. |
| Q9H7P9 | PLEKHG2 | S1227 | 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}. |
| Q9HB07 | MYG1 | S120 | ochoa | 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}. |
| Q9HB14 | KCNK13 | S343 | ochoa | Potassium channel subfamily K member 13 (Tandem pore domain halothane-inhibited potassium channel 1) (THIK-1) | K(+) channel that conducts outward rectifying tonic currents potentiated by purinergic signals (PubMed:24163367, PubMed:25148687, PubMed:30472253, PubMed:38409076). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:25148687). Contributes most of K(+) currents at the plasma membrane of resting microglia. Maintains a depolarized membrane potential required for proper ramified microglia morphology and phagocytosis, selectively mediating microglial pruning of presynaptic compartments at hippocampal excitatory synapses (PubMed:38409076). Upon local release of ATP caused by neuronal injury or infection, it is potentiated by P2RY12 and P2RX7 receptor signaling and contributes to ATP-triggered K(+) efflux underlying microglial NLRP3 inflammasome assembly and IL1B release (By similarity) (PubMed:38409076). {ECO:0000250|UniProtKB:Q8R1P5, ECO:0000269|PubMed:24163367, ECO:0000269|PubMed:25148687, ECO:0000269|PubMed:30472253, ECO:0000269|PubMed:38409076}. |
| 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}. |
| Q9NPQ8 | RIC8A | S32 | ochoa | Chaperone Ric-8A (Synembryn-A) | Chaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity: folds GNAI1, GNAO1, GNA13 and GNAQ (By similarity). Does not fold G(s) G-alpha proteins GNAS nor GNAL (By similarity). Also acts as a guanine nucleotide exchange factor (GEF) for G alpha proteins by stimulating exchange of bound GDP for free GTP (By similarity). Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein (GNAI1), possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex (By similarity). Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation (PubMed:16629901). {ECO:0000250|UniProtKB:Q80ZG1, ECO:0000269|PubMed:16629901}. |
| Q9NR48 | ASH1L | S179 | ochoa | Histone-lysine N-methyltransferase ASH1L (EC 2.1.1.359) (EC 2.1.1.367) (ASH1-like protein) (huASH1) (Absent small and homeotic disks protein 1 homolog) (Lysine N-methyltransferase 2H) | Histone methyltransferase specifically trimethylating 'Lys-36' of histone H3 forming H3K36me3 (PubMed:21239497). Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro (By similarity). The physiological significance of the H3K9me1 activity is unclear (By similarity). {ECO:0000250|UniProtKB:Q99MY8, ECO:0000269|PubMed:21239497}. |
| Q9NRY4 | ARHGAP35 | S591 | ochoa | Rho GTPase-activating protein 35 (Glucocorticoid receptor DNA-binding factor 1) (Glucocorticoid receptor repression factor 1) (GRF-1) (Rho GAP p190A) (p190-A) | Rho GTPase-activating protein (GAP) (PubMed:19673492, PubMed:28894085). Binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:19673492). This binding is inhibited by phosphorylation by PRKCA (PubMed:19673492). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (By similarity). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signals from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity). Represses transcription of the glucocorticoid receptor by binding to the cis-acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function is however unclear and would need additional experimental evidences (PubMed:1894621). {ECO:0000250|UniProtKB:P81128, ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621, ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}. |
| Q9NS91 | RAD18 | S55 | ochoa | E3 ubiquitin-protein ligase RAD18 (EC 2.3.2.27) (Postreplication repair protein RAD18) (hHR18) (hRAD18) (RING finger protein 73) (RING-type E3 ubiquitin transferase RAD18) | E3 ubiquitin-protein ligase involved in postreplication repair of UV-damaged DNA. Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. Associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. Has ssDNA binding activity. {ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:21659603}. |
| Q9NX02 | NLRP2 | S107 | ochoa | NACHT, LRR and PYD domains-containing protein 2 (Nucleotide-binding site protein 1) (PYRIN domain and NACHT domain-containing protein 1) (PYRIN-containing APAF1-like protein 2) | Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature pro-inflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of pro-inflammatory caspases. {ECO:0000269|PubMed:15456791}. |
| Q9NYA4 | MTMR4 | S616 | ochoa | Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR4 (EC 3.1.3.95) (FYVE domain-containing dual specificity protein phosphatase 2) (FYVE-DSP2) (Myotubularin-related protein 4) (Phosphatidylinositol-3,5-bisphosphate 3-phosphatase) (Zinc finger FYVE domain-containing protein 11) | 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:11302699, PubMed:16787938, PubMed:20736309, PubMed:27625994, PubMed:29962048, PubMed:30944173). 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, in a subset of endosomal membranes to negatively regulate both endocytic recycling and trafficking and/or maturation of endosomes toward lysosomes (PubMed:16787938, PubMed:20736309, PubMed:29962048). Through phosphatidylinositol 3-phosphate turnover in phagosome membranes regulates phagocytosis and phagosome maturation (PubMed:31543504). By decreasing phosphatidylinositol 3-monophosphate (PI3P) levels in immune cells it can also regulate the innate immune response (PubMed:30944173). Beside its lipid phosphatase activity, can also function as a molecular adapter to regulate midbody abscission during mitotic cytokinesis (PubMed:25659891). Can also negatively regulate TGF-beta and BMP signaling through Smad proteins dephosphorylation and retention in endosomes (PubMed:20061380, PubMed:23150675). {ECO:0000269|PubMed:11302699, ECO:0000269|PubMed:16787938, ECO:0000269|PubMed:20061380, ECO:0000269|PubMed:20736309, ECO:0000269|PubMed:23150675, ECO:0000269|PubMed:25659891, ECO:0000269|PubMed:27625994, ECO:0000269|PubMed:29962048, ECO:0000269|PubMed:30944173, ECO:0000269|PubMed:31543504}. |
| Q9NZ09 | UBAP1 | S249 | 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}. |
| Q9NZJ5 | EIF2AK3 | S1096 | ochoa | Eukaryotic translation initiation factor 2-alpha kinase 3 (EC 2.7.11.1) (PRKR-like endoplasmic reticulum kinase) (Pancreatic eIF2-alpha kinase) (HsPEK) (Protein tyrosine kinase EIF2AK3) (EC 2.7.10.2) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR) (PubMed:10026192, PubMed:10677345, PubMed:11907036, PubMed:12086964, PubMed:25925385, PubMed:31023583). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognizes and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation (PubMed:10677345, PubMed:27917829, PubMed:31023583). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:10026192, PubMed:10677345, PubMed:31023583, PubMed:33384352). The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes (PubMed:31023583). In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites (PubMed:39116259). In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity). {ECO:0000250|UniProtKB:Q9Z2B5, ECO:0000269|PubMed:10026192, ECO:0000269|PubMed:10677345, ECO:0000269|PubMed:11907036, ECO:0000269|PubMed:12086964, ECO:0000269|PubMed:25925385, ECO:0000269|PubMed:27917829, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:33384352, ECO:0000269|PubMed:39116259}. |
| Q9NZN5 | ARHGEF12 | S824 | ochoa | Rho guanine nucleotide exchange factor 12 (Leukemia-associated RhoGEF) | May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13. {ECO:0000269|PubMed:11094164}. |
| Q9P206 | NHSL3 | S418 | ochoa | NHS-like protein 3 | Able to directly activate the TNF-NFkappaB signaling pathway. {ECO:0000269|PubMed:32854746}. |
| Q9P258 | RCC2 | S290 | ochoa | Protein RCC2 (RCC1-like protein TD-60) (Telophase disk protein of 60 kDa) | Multifunctional protein that may affect its functions by regulating the activity of small GTPases, such as RAC1 and RALA (PubMed:12919680, PubMed:25074804, PubMed:26158537, PubMed:28869598). Required for normal progress through the cell cycle, both during interphase and during mitosis (PubMed:12919680, PubMed:23388455, PubMed:26158537). Required for the presence of normal levels of MAD2L1, AURKB and BIRC5 on inner centromeres during mitosis, and for normal attachment of kinetochores to mitotic spindles (PubMed:12919680, PubMed:26158537). Required for normal organization of the microtubule cytoskeleton in interphase cells (PubMed:23388455). Functions as guanine nucleotide exchange factor (GEF) for RALA (PubMed:26158537). Interferes with the activation of RAC1 by guanine nucleotide exchange factors (PubMed:25074804). Prevents accumulation of active, GTP-bound RAC1, and suppresses RAC1-mediated reorganization of the actin cytoskeleton and formation of membrane protrusions (PubMed:25074804, PubMed:28869598). Required for normal cellular responses to contacts with the extracellular matrix of adjacent cells, and for directional cell migration in response to a fibronectin gradient (in vitro) (PubMed:25074804, PubMed:28869598). {ECO:0000269|PubMed:12919680, ECO:0000269|PubMed:23388455, ECO:0000269|PubMed:25074804, ECO:0000269|PubMed:26158537, ECO:0000269|PubMed:28869598}. |
| Q9P265 | DIP2B | S50 | ochoa | Disco-interacting protein 2 homolog B (DIP2 homolog B) | Negatively regulates axonal outgrowth and is essential for normal synaptic transmission. Not required for regulation of axon polarity. Promotes acetylation of alpha-tubulin. {ECO:0000250|UniProtKB:Q3UH60}. |
| Q9P2N6 | KANSL3 | S876 | ochoa | KAT8 regulatory NSL complex subunit 3 (NSL complex protein NSL3) (Non-specific lethal 3 homolog) (Serum inhibited-related protein) (Testis development protein PRTD) | Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). Within the NSL complex, KANSL3 is required to promote KAT8 association with mitochondrial DNA (PubMed:27768893). Required for transcription of intraciliary transport genes in both ciliated and non-ciliated cells (By similarity). This is necessary for cilium assembly in ciliated cells and for organization of the microtubule cytoskeleton in non-ciliated cells (By similarity). Also required within the NSL complex to maintain nuclear architecture stability by promoting KAT8-mediated acetylation of lamin LMNA (By similarity). Plays an essential role in spindle assembly during mitosis (PubMed:26243146). Acts as a microtubule minus-end binding protein which stabilizes microtubules and promotes their assembly (PubMed:26243146). Indispensable during early embryonic development where it is required for proper lineage specification and maintenance during peri-implantation development and is essential for implantation (By similarity). {ECO:0000250|UniProtKB:A2RSY1, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}. |
| 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}. |
| Q9UBY9 | HSPB7 | S46 | ochoa | Heat shock protein beta-7 (HspB7) (Cardiovascular heat shock protein) (cvHsp) | None |
| Q9UDT6 | CLIP2 | S170 | ochoa | CAP-Gly domain-containing linker protein 2 (Cytoplasmic linker protein 115) (CLIP-115) (Cytoplasmic linker protein 2) (Williams-Beuren syndrome chromosomal region 3 protein) (Williams-Beuren syndrome chromosomal region 4 protein) | Seems to link microtubules to dendritic lamellar body (DLB), a membranous organelle predominantly present in bulbous dendritic appendages of neurons linked by dendrodendritic gap junctions. May operate in the control of brain-specific organelle translocations (By similarity). {ECO:0000250}. |
| Q9UEW8 | STK39 | S315 | ochoa | STE20/SPS1-related proline-alanine-rich protein kinase (Ste-20-related kinase) (EC 2.7.11.1) (DCHT) (Serine/threonine-protein kinase 39) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:21321328). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:12740379, PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities (By similarity). Phosphorylates RELT (By similarity). {ECO:0000250|UniProtKB:Q9Z1W9, ECO:0000269|PubMed:12740379, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:34289367}. |
| Q9UGN4 | CD300A | S217 | ochoa | CMRF35-like molecule 8 (CLM-8) (CD300 antigen-like family member A) (CMRF-35-H9) (CMRF35-H9) (CMRF35-H) (IRC1/IRC2) (Immunoglobulin superfamily member 12) (IgSF12) (Inhibitory receptor protein 60) (IRp60) (NK inhibitory receptor) (CD antigen CD300a) | Inhibitory receptor which may contribute to the down-regulation of cytolytic activity in natural killer (NK) cells, and to the down-regulation of mast cell degranulation (PubMed:10746781, PubMed:16339535, PubMed:9701027). Negatively regulates the Toll-like receptor (TLR) signaling mediated by MYD88 but not TRIF through activation of PTPN6 (PubMed:22043923). {ECO:0000269|PubMed:10746781, ECO:0000269|PubMed:16339535, ECO:0000269|PubMed:22043923, ECO:0000269|PubMed:9701027}. |
| Q9UGU0 | TCF20 | S1303 | ochoa | Transcription factor 20 (TCF-20) (Nuclear factor SPBP) (Protein AR1) (Stromelysin-1 PDGF-responsive element-binding protein) (SPRE-binding protein) | Transcriptional activator that binds to the regulatory region of MMP3 and thereby controls stromelysin expression. It stimulates the activity of various transcriptional activators such as JUN, SP1, PAX6 and ETS1, suggesting a function as a coactivator. {ECO:0000269|PubMed:10995766}. |
| Q9UHB7 | AFF4 | S703 | 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}. |
| Q9UHB7 | AFF4 | S706 | 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}. |
| Q9UHD2 | TBK1 | S509 | ochoa | Serine/threonine-protein kinase TBK1 (EC 2.7.11.1) (NF-kappa-B-activating kinase) (T2K) (TANK-binding kinase 1) | Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents (PubMed:10581243, PubMed:11839743, PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:15485837, PubMed:18583960, PubMed:21138416, PubMed:23453971, PubMed:23453972, PubMed:23746807, PubMed:25636800, PubMed:26611359, PubMed:32404352, PubMed:34363755, PubMed:32298923). Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X (PubMed:12692549, PubMed:12702806, PubMed:14703513, PubMed:15367631, PubMed:18583960, PubMed:25636800). This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB (PubMed:12702806, PubMed:15367631, PubMed:25636800, PubMed:32972995). In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:23453971, PubMed:23453972, PubMed:23746807). Plays a key role in IRF3 activation: acts by first phosphorylating innate adapter proteins MAVS, STING1 and TICAM1 on their pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800, PubMed:30842653, PubMed:37926288). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce expression of interferons (PubMed:25636800). Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes (PubMed:21931631). Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus (PubMed:10783893, PubMed:15489227). Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy (PubMed:21617041). Phosphorylates SMCR8 component of the C9orf72-SMCR8 complex, promoting autophagosome maturation (PubMed:27103069). Phosphorylates ATG8 proteins MAP1LC3C and GABARAPL2, thereby preventing their delipidation and premature removal from nascent autophagosomes (PubMed:31709703). Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, which leads to a negative impact on insulin sensitivity (By similarity). Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C (PubMed:21270402). Phosphorylates Borna disease virus (BDV) P protein (PubMed:16155125). Plays an essential role in the TLR3- and IFN-dependent control of herpes virus HSV-1 and HSV-2 infections in the central nervous system (PubMed:22851595). Acts both as a positive and negative regulator of the mTORC1 complex, depending on the context: activates mTORC1 in response to growth factors by catalyzing phosphorylation of MTOR, while it limits the mTORC1 complex by promoting phosphorylation of RPTOR (PubMed:29150432, PubMed:31530866). Acts as a positive regulator of the mTORC2 complex by mediating phosphorylation of MTOR, leading to increased phosphorylation and activation of AKT1 (By similarity). Phosphorylates and activates AKT1 (PubMed:21464307). Involved in the regulation of TNF-induced RIPK1-mediated cell death, probably acting via CYLD phosphorylation that in turn controls RIPK1 ubiquitination status (PubMed:34363755). Also participates in the differentiation of T follicular regulatory cells together with the receptor ICOS (PubMed:27135603). {ECO:0000250|UniProtKB:Q9WUN2, ECO:0000269|PubMed:10581243, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11839743, ECO:0000269|PubMed:12692549, ECO:0000269|PubMed:12702806, ECO:0000269|PubMed:14703513, ECO:0000269|PubMed:15367631, ECO:0000269|PubMed:15485837, ECO:0000269|PubMed:15489227, ECO:0000269|PubMed:16155125, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21270402, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:21931631, ECO:0000269|PubMed:22851595, ECO:0000269|PubMed:23453971, ECO:0000269|PubMed:23453972, ECO:0000269|PubMed:23746807, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:26611359, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27135603, ECO:0000269|PubMed:29150432, ECO:0000269|PubMed:30842653, ECO:0000269|PubMed:31530866, ECO:0000269|PubMed:31709703, ECO:0000269|PubMed:32298923, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:34363755, ECO:0000269|PubMed:37926288}. |
| Q9UJ70 | NAGK | S74 | ochoa | N-acetyl-D-glucosamine kinase (N-acetylglucosamine kinase) (EC 2.7.1.59) (GlcNAc kinase) (Muramyl dipeptide kinase) (EC 2.7.1.-) (N-acetyl-D-mannosamine kinase) (EC 2.7.1.60) | Converts endogenous N-acetylglucosamine (GlcNAc), a major component of complex carbohydrates, from lysosomal degradation or nutritional sources into GlcNAc 6-phosphate (PubMed:22692205). Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway: although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded (PubMed:22692205). Also has N-acetylmannosamine (ManNAc) kinase activity (By similarity). Also involved in innate immunity by promoting detection of bacterial peptidoglycan by NOD2: acts by catalyzing phosphorylation of muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, to generate 6-O-phospho-muramyl dipeptide, which acts as a direct ligand for NOD2 (PubMed:36002575). {ECO:0000250|UniProtKB:Q9QZ08, ECO:0000269|PubMed:22692205, ECO:0000269|PubMed:36002575}. |
| Q9UK58 | CCNL1 | S65 | ochoa | Cyclin-L1 (Cyclin-L) | Involved in pre-mRNA splicing. Functions in association with cyclin-dependent kinases (CDKs) (PubMed:18216018). Inhibited by the CDK-specific inhibitor CDKN1A/p21 (PubMed:11980906). May play a role in the regulation of RNA polymerase II (pol II). May be a candidate proto-oncogene in head and neck squamous cell carcinomas (HNSCC) (PubMed:12414649, PubMed:15700036). {ECO:0000269|PubMed:11980906, ECO:0000269|PubMed:12414649, ECO:0000269|PubMed:15700036, ECO:0000269|PubMed:18216018}. |
| Q9UKM9 | RALY | S177 | ochoa | RNA-binding protein Raly (Autoantigen p542) (Heterogeneous nuclear ribonucleoprotein C-like 2) (hnRNP core protein C-like 2) (hnRNP associated with lethal yellow protein homolog) | RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver. Binds the lipid-responsive non-coding RNA LeXis and is required for LeXis-mediated effect on cholesterogenesis (By similarity). May be a heterogeneous nuclear ribonucleoprotein (hnRNP) (PubMed:9376072). {ECO:0000250|UniProtKB:Q64012, ECO:0000269|PubMed:9376072}. |
| Q9UKZ1 | CNOT11 | S339 | 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. |
| Q9ULC8 | ZDHHC8 | S286 | ochoa | Palmitoyltransferase ZDHHC8 (EC 2.3.1.225) (Zinc finger DHHC domain-containing protein 8) (DHHC-8) (Zinc finger protein 378) | Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and therefore functions in several unrelated biological processes (Probable). Through the palmitoylation of ABCA1 regulates the localization of the transporter to the plasma membrane and thereby regulates its function in cholesterol and phospholipid efflux (Probable). Could also pamitoylate the D(2) dopamine receptor DRD2 and regulate its stability and localization to the plasma membrane (Probable). Could also play a role in glutamatergic transmission (By similarity). {ECO:0000250|UniProtKB:Q5Y5T5, ECO:0000305|PubMed:19556522, ECO:0000305|PubMed:23034182, ECO:0000305|PubMed:26535572}.; FUNCTION: (Microbial infection) Able to palmitoylate SARS coronavirus-2/SARS-CoV-2 spike protein following its synthesis in the endoplasmic reticulum (ER). In the infected cell, promotes spike biogenesis by protecting it from premature ER degradation, increases half-life and controls the lipid organization of its immediate membrane environment. Once the virus has formed, spike palmitoylation controls fusion with the target cell. {ECO:0000269|PubMed:34599882}. |
| Q9ULH1 | ASAP1 | S910 | 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}. |
| Q9ULW0 | TPX2 | S310 | ochoa|psp | Targeting protein for Xklp2 (Differentially expressed in cancerous and non-cancerous lung cells 2) (DIL-2) (Hepatocellular carcinoma-associated antigen 519) (Hepatocellular carcinoma-associated antigen 90) (Protein fls353) (Restricted expression proliferation-associated protein 100) (p100) | Spindle assembly factor required for normal assembly of mitotic spindles. Required for normal assembly of microtubules during apoptosis. Required for chromatin and/or kinetochore dependent microtubule nucleation. Mediates AURKA localization to spindle microtubules (PubMed:18663142, PubMed:19208764, PubMed:37728657). Activates AURKA by promoting its autophosphorylation at 'Thr-288' and protects this residue against dephosphorylation (PubMed:18663142, PubMed:19208764). TPX2 is inactivated upon binding to importin-alpha (PubMed:26165940). At the onset of mitosis, GOLGA2 interacts with importin-alpha, liberating TPX2 from importin-alpha, allowing TPX2 to activate AURKA kinase and stimulate local microtubule nucleation (PubMed:26165940). {ECO:0000269|PubMed:18663142, ECO:0000269|PubMed:19208764, ECO:0000269|PubMed:26165940}. |
| Q9UMS6 | SYNPO2 | S365 | 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}. |
| Q9UNA1 | ARHGAP26 | S584 | ochoa | Rho GTPase-activating protein 26 (GTPase regulator associated with focal adhesion kinase) (GRAF1) (Oligophrenin-1-like protein) (Rho-type GTPase-activating protein 26) | GTPase-activating protein for RHOA and CDC42. Facilitates mitochondrial quality control by promoting Parkin-mediated recruitment of autophagosomes to damaged mitochondria (PubMed:38081847). Negatively regulates the growth of human parainfluenza virus type 2 by inhibiting hPIV-2-mediated RHOA activation via interaction with two of its viral proteins P and V (PubMed:27512058). {ECO:0000269|PubMed:27512058, ECO:0000269|PubMed:38081847}.; FUNCTION: [Isoform 2]: Associates with MICAL1 on the endosomal membrane to promote Rab8-Rab10-dependent tubule extension. After dissociation of MICAL1, recruits WDR44 which connects the endoplasmic reticulum (ER) with the endosomal tubule, thereby participating in the export of a subset of neosynthesized proteins. {ECO:0000269|PubMed:32344433}. |
| Q9UNK0 | STX8 | S159 | ochoa | Syntaxin-8 | Vesicle trafficking protein that functions in the early secretory pathway, possibly by mediating retrograde transport from cis-Golgi membranes to the ER. |
| Q9UNL2 | SSR3 | S105 | ochoa | Translocon-associated protein subunit gamma (TRAP-gamma) (Signal sequence receptor subunit gamma) (SSR-gamma) | TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. |
| Q9UPM8 | AP4E1 | S665 | ochoa | AP-4 complex subunit epsilon-1 (AP-4 adaptor complex subunit epsilon) (Adaptor-related protein complex 4 subunit epsilon-1) (Epsilon subunit of AP-4) (Epsilon-adaptin) | Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}. |
| Q9UPN4 | CEP131 | S512 | 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}. |
| Q9UPU5 | USP24 | S1371 | ochoa | Ubiquitin carboxyl-terminal hydrolase 24 (EC 3.4.19.12) (Deubiquitinating enzyme 24) (Ubiquitin thioesterase 24) (Ubiquitin-specific-processing protease 24) | Ubiquitin-specific protease that regulates cell survival in various contexts through modulating the protein stability of some of its substrates including DDB2, MCL1 or TP53. Plays a positive role on ferritinophagy where ferritin is degraded in lysosomes and releases free iron. {ECO:0000269|PubMed:23159851, ECO:0000269|PubMed:29695420}. |
| Q9UQ13 | SHOC2 | S297 | psp | Leucine-rich repeat protein SHOC-2 (Protein soc-2 homolog) (Protein sur-8 homolog) | Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates activation of the MAPK pathway (PubMed:10783161, PubMed:16630891, PubMed:25137548, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). Acts as a scaffolding protein in the SMP complex (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:10783161, PubMed:16630891, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670). {ECO:0000269|PubMed:10783161, ECO:0000269|PubMed:16630891, ECO:0000269|PubMed:25137548, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35830882, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670}. |
| Q9UQB8 | BAIAP2 | S384 | 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}. |
| Q9Y316 | MEMO1 | S86 | ochoa | Protein MEMO1 (C21orf19-like protein) (Hepatitis C virus NS5A-transactivated protein 7) (HCV NS5A-transactivated protein 7) (Mediator of ErbB2-driven cell motility 1) (Mediator of cell motility 1) (Memo-1) | May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. Mediator of ERBB2 signaling. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Is required for breast carcinoma cell migration. {ECO:0000269|PubMed:15156151, ECO:0000269|PubMed:20937854}. |
| 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}. |
| Q9Y485 | DMXL1 | S466 | ochoa | DmX-like protein 1 (X-like 1 protein) | None |
| Q9Y490 | TLN1 | S1225 | 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}. |
| Q9Y4H2 | IRS2 | S550 | 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}. |
| Q9Y5A9 | YTHDF2 | S39 | ochoa|psp | YTH domain-containing family protein 2 (DF2) (CLL-associated antigen KW-14) (High-glucose-regulated protein 8) (Renal carcinoma antigen NY-REN-2) | Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:25412658, PubMed:25412661, PubMed:32492408). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting m6A-dependent degradation of neural development-related mRNA targets (By similarity). Inhibits neural specification of induced pluripotent stem cells by binding to methylated neural-specific mRNAs and promoting their degradation, thereby restraining neural differentiation (PubMed:32169943). Regulates circadian regulation of hepatic lipid metabolism: acts by promoting m6A-dependent degradation of PPARA transcripts (PubMed:30428350). Regulates the innate immune response to infection by inhibiting the type I interferon response: acts by binding to m6A-containing IFNB transcripts and promoting their degradation (PubMed:30559377). May also act as a promoter of cap-independent mRNA translation following heat shock stress: upon stress, relocalizes to the nucleus and specifically binds mRNAs with some m6A methylation mark at their 5'-UTR, protecting demethylation of mRNAs by FTO, thereby promoting cap-independent mRNA translation (PubMed:26458103). Regulates mitotic entry by promoting the phase-specific m6A-dependent degradation of WEE1 transcripts (PubMed:32267835). Promotes formation of phase-separated membraneless compartments, such as P-bodies or stress granules, by undergoing liquid-liquid phase separation upon binding to mRNAs containing multiple m6A-modified residues: polymethylated mRNAs act as a multivalent scaffold for the binding of YTHDF proteins, juxtaposing their disordered regions and thereby leading to phase separation (PubMed:31292544, PubMed:31388144, PubMed:31642031, PubMed:32451507). The resulting mRNA-YTHDF complexes then partition into different endogenous phase-separated membraneless compartments, such as P-bodies, stress granules or neuronal RNA granules (PubMed:31292544). May also recognize and bind RNAs modified by C5-methylcytosine (m5C) and act as a regulator of rRNA processing (PubMed:31815440). {ECO:0000250|UniProtKB:Q91YT7, ECO:0000269|PubMed:22575960, ECO:0000269|PubMed:24284625, ECO:0000269|PubMed:25412658, ECO:0000269|PubMed:25412661, ECO:0000269|PubMed:26046440, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:28106072, ECO:0000269|PubMed:30065315, ECO:0000269|PubMed:30428350, ECO:0000269|PubMed:30559377, ECO:0000269|PubMed:30930054, ECO:0000269|PubMed:31292544, ECO:0000269|PubMed:31388144, ECO:0000269|PubMed:31642031, ECO:0000269|PubMed:31815440, ECO:0000269|PubMed:32169943, ECO:0000269|PubMed:32267835, ECO:0000269|PubMed:32451507, ECO:0000269|PubMed:32492408}.; FUNCTION: (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282). {ECO:0000269|PubMed:29447282}.; FUNCTION: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627). {ECO:0000269|PubMed:29659627}. |
| Q9Y5K6 | CD2AP | S550 | 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}. |
| Q9Y5Z4 | HEBP2 | S141 | ochoa | Heme-binding protein 2 (Placental protein 23) (PP23) (Protein SOUL) | Can promote mitochondrial permeability transition and facilitate necrotic cell death under different types of stress conditions. {ECO:0000269|PubMed:17098234}. |
| Q9Y6A5 | TACC3 | S71 | 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 | S1528 | 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}. |
| Q9Y6R0 | NUMBL | S313 | 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}. |
| O15530 | PDPK1 | S176 | Sugiyama | 3-phosphoinositide-dependent protein kinase 1 (hPDK1) (EC 2.7.11.1) | Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9445477, PubMed:9707564, PubMed:9768361). Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), TSSK3, protein kinase PKN (PKN1 and PKN2) (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9707564, PubMed:9768361). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage (PubMed:10226025, PubMed:12167717, PubMed:9094314). Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta (PubMed:17327236). Activates PPARG transcriptional activity and promotes adipocyte differentiation (By similarity). Activates the NF-kappa-B pathway via phosphorylation of IKKB (PubMed:16207722). The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II (PubMed:14585963). Controls proliferation, survival, and growth of developing pancreatic cells (By similarity). Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells (By similarity). Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis (PubMed:17371830). Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response (By similarity). Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses (By similarity). Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages (By similarity). {ECO:0000250|UniProtKB:Q9Z2A0, ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9368760, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9445477, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.; FUNCTION: [Isoform 3]: Catalytically inactive. {ECO:0000269|PubMed:9445477}. |
| Q6A1A2 | PDPK2P | S149 | Sugiyama | Putative 3-phosphoinositide-dependent protein kinase 2 (EC 2.7.11.1) (3-phosphoinositide-dependent protein kinase 2 pseudogene) | Phosphorylates and activates not only PKB/AKT, but also PKA, PKC-zeta, RPS6KA1 and RPS6KB1. May play a general role in signaling processes and in development (By similarity). {ECO:0000250}. |
| O60664 | PLIN3 | S225 | 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}. |
| P02786 | TFRC | S620 | Sugiyama | Transferrin receptor protein 1 (TR) (TfR) (TfR1) (Trfr) (T9) (p90) (CD antigen CD71) [Cleaved into: Transferrin receptor protein 1, serum form (sTfR)] | Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. Positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (PubMed:26214738). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity). {ECO:0000250|UniProtKB:Q62351, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.; FUNCTION: (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus. {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.; FUNCTION: (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762, ECO:0000269|PubMed:36779763}.; FUNCTION: (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells. {ECO:0000269|PubMed:36779762}. |
| Q04864 | REL | S516 | GPS6 | 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. |
| Q13347 | EIF3I | S197 | Sugiyama | Eukaryotic translation initiation factor 3 subunit I (eIF3i) (Eukaryotic translation initiation factor 3 subunit 2) (TGF-beta receptor-interacting protein 1) (TRIP-1) (eIF-3-beta) (eIF3 p36) | Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). {ECO:0000255|HAMAP-Rule:MF_03008, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}. |
| Q14160 | SCRIB | S917 | Sugiyama | 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}. |
| P07900 | HSP90AA1 | S460 | Sugiyama | Heat shock protein HSP 90-alpha (EC 3.6.4.10) (Heat shock 86 kDa) (HSP 86) (HSP86) (Heat shock protein family C member 1) (Lipopolysaccharide-associated protein 2) (LAP-2) (LPS-associated protein 2) (Renal carcinoma antigen NY-REN-38) | Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812). {ECO:0000269|PubMed:11274138, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:15937123, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:27353360, ECO:0000269|PubMed:29127155, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}.; FUNCTION: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion. {ECO:0000305|PubMed:22066472}. |
| Q92538 | GBF1 | S174 | Sugiyama | Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (BFA-resistant GEF 1) | Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER) (PubMed:12047556, PubMed:12808027, PubMed:16926190, PubMed:17956946, PubMed:18003980, PubMed:19039328, PubMed:24213530). Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adaptor protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5) (PubMed:23386609). Has GEF activity towards ARF1 (PubMed:15616190). Has in vitro GEF activity towards ARF5 (By similarity). Involved in the processing of PSAP (PubMed:17666033). Required for the assembly of the Golgi apparatus (PubMed:12808027, PubMed:18003980). The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions (PubMed:18063581, PubMed:23418352). May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate (PubMed:19461073, PubMed:22185782). In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex (PubMed:22573891). Plays a role in maintaining mitochondrial morphology (PubMed:25190516). {ECO:0000250|UniProtKB:Q9R1D7, ECO:0000269|PubMed:12047556, ECO:0000269|PubMed:12808027, ECO:0000269|PubMed:15616190, ECO:0000269|PubMed:16926190, ECO:0000269|PubMed:17666033, ECO:0000269|PubMed:17956946, ECO:0000269|PubMed:18003980, ECO:0000269|PubMed:18063581, ECO:0000269|PubMed:19461073, ECO:0000269|PubMed:22185782, ECO:0000269|PubMed:22573891, ECO:0000269|PubMed:23386609, ECO:0000269|PubMed:23418352, ECO:0000269|PubMed:24213530, ECO:0000269|PubMed:25190516, ECO:0000305|PubMed:19039328, ECO:0000305|PubMed:22573891}. |
| 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}. |
| 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}. |
| Q9NQR4 | NIT2 | S133 | Sugiyama | Omega-amidase NIT2 (EC 3.5.1.3) (Nitrilase homolog 2) | Has omega-amidase activity (PubMed:19595734, PubMed:22674578). The role of omega-amidase is to remove potentially toxic intermediates by converting 2-oxoglutaramate and 2-oxosuccinamate to biologically useful 2-oxoglutarate and oxaloacetate, respectively (PubMed:19595734). {ECO:0000269|PubMed:19595734, ECO:0000269|PubMed:22674578}. |
| O14646 | CHD1 | S1017 | Sugiyama | 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}. |
| P41091 | EIF2S3 | S412 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 3 (EC 3.6.5.3) (Eukaryotic translation initiation factor 2 subunit gamma X) (eIF2-gamma X) (eIF2gX) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA (PubMed:31836389). This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC) (By similarity). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex (By similarity). In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). {ECO:0000250|UniProtKB:P05198, ECO:0000269|PubMed:31836389}. |
| Q14694 | USP10 | S265 | Sugiyama | Ubiquitin carboxyl-terminal hydrolase 10 (EC 3.4.19.12) (Deubiquitinating enzyme 10) (Ubiquitin thioesterase 10) (Ubiquitin-specific-processing protease 10) | Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}. |
| Q2VIR3 | EIF2S3B | S412 | Sugiyama | Eukaryotic translation initiation factor 2 subunit 3B (EC 3.6.5.3) (Eukaryotic translation initiation factor 2 subunit gamma A) (eIF-2-gamma A) (eIF-2gA) | Member of the eIF2 complex that functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B (By similarity). {ECO:0000250|UniProtKB:P05198}. |
| O00443 | PIK3C2A | S58 | Sugiyama | Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3K-C2-alpha) (PtdIns-3-kinase C2 subunit alpha) (EC 2.7.1.137) (EC 2.7.1.153) (EC 2.7.1.154) (Phosphoinositide 3-kinase-C2-alpha) | Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. Involved in the regulation of ciliogenesis and trafficking of ciliary components (PubMed:31034465). {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:31034465, ECO:0000269|PubMed:9337861}. |
| P51811 | XK | S63 | ELM | Endoplasmic reticulum membrane adapter protein XK (Kell complex 37 kDa component) (Kx antigen) (Membrane transport protein XK) (XK-related protein 1) | Recruits the lipid transfer protein VPS13A from lipid droplets to the endoplasmic reticulum (ER) membrane. {ECO:0000269|PubMed:32845802}. |
| P26639 | TARS1 | S577 | Sugiyama | Threonine--tRNA ligase 1, cytoplasmic (EC 6.1.1.3) (Threonyl-tRNA synthetase) (ThrRS) (Threonyl-tRNA synthetase 1) | Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity). {ECO:0000250|UniProtKB:Q9D0R2, ECO:0000269|PubMed:25824639, ECO:0000269|PubMed:31374204}. |
| P13674 | P4HA1 | S387 | Sugiyama | Prolyl 4-hydroxylase subunit alpha-1 (4-PH alpha-1) (EC 1.14.11.2) (Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1) | Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. {ECO:0000269|PubMed:9211872}. |
| Q7L5Y9 | MAEA | S226 | Sugiyama | E3 ubiquitin-protein transferase MAEA (EC 2.3.2.27) (Cell proliferation-inducing gene 5 protein) (Erythroblast macrophage protein) (Human lung cancer oncogene 10 protein) (HLC-10) (Macrophage erythroblast attacher) (P44EMLP) | Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex (PubMed:29911972). MAEA is required for normal cell proliferation (PubMed:29911972). The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (PubMed:29911972). Plays a role in erythroblast enucleation during erythrocyte maturation and in the development of mature macrophages (By similarity). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (PubMed:9763581). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis. Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (By similarity). May contribute to nuclear architecture and cells division events (Probable). {ECO:0000250|UniProtKB:Q4VC33, ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:9763581, ECO:0000305|PubMed:16510120}. |
| P10398 | ARAF | S528 | Sugiyama | Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks) | Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade. Phosphorylates PFKFB2 (PubMed:36402789). {ECO:0000269|PubMed:22609986, ECO:0000269|PubMed:36402789}.; FUNCTION: [Isoform 2]: Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation. {ECO:0000269|PubMed:22609986}. |
| P31939 | ATIC | S202 | Sugiyama | Bifunctional purine biosynthesis protein ATIC (AICAR transformylase/inosine monophosphate cyclohydrolase) (ATIC) [Cleaved into: Bifunctional purine biosynthesis protein ATIC, N-terminally processed] [Includes: Phosphoribosylaminoimidazolecarboxamide formyltransferase (EC 2.1.2.3) (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase) (AICAR formyltransferase) (AICAR transformylase); Inosine 5'-monophosphate cyclohydrolase (IMP cyclohydrolase) (EC 3.5.4.10) (IMP synthase) (Inosinicase)] | Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571). {ECO:0000269|PubMed:10985775, ECO:0000269|PubMed:11948179, ECO:0000269|PubMed:14756554, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:9378707}. |
| Q96SB3 | PPP1R9B | S94 | ELM|iPTMNet|EPSD | Neurabin-2 (Neurabin-II) (Protein phosphatase 1 regulatory subunit 9B) (Spinophilin) | Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha-adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1 (By similarity). Required for hepatocyte growth factor (HGF)-induced cell migration. {ECO:0000250, ECO:0000269|PubMed:19151759}. |
| Q13057 | COASY | S507 | Sugiyama | Bifunctional coenzyme A synthase (CoA synthase) (NBP) (POV-2) [Includes: Phosphopantetheine adenylyltransferase (EC 2.7.7.3) (Dephospho-CoA pyrophosphorylase) (Pantetheine-phosphate adenylyltransferase) (PPAT); Dephospho-CoA kinase (DPCK) (EC 2.7.1.24) (Dephosphocoenzyme A kinase) (DPCOAK)] | Bifunctional enzyme that catalyzes the fourth and fifth sequential steps of CoA biosynthetic pathway. The fourth reaction is catalyzed by the phosphopantetheine adenylyltransferase, coded by the coaD domain; the fifth reaction is catalyzed by the dephospho-CoA kinase, coded by the coaE domain. May act as a point of CoA biosynthesis regulation. {ECO:0000269|PubMed:11923312, ECO:0000269|PubMed:24360804}. |
| Q15181 | PPA1 | S127 | Sugiyama | Inorganic pyrophosphatase (EC 3.6.1.1) (Pyrophosphate phospho-hydrolase) (PPase) | None |
| P51617 | IRAK1 | S344 | Sugiyama | Interleukin-1 receptor-associated kinase 1 (IRAK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}. |
| P29144 | TPP2 | S164 | Sugiyama | Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) | Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}. |
| P49327 | FASN | S2039 | Sugiyama | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| Q96AG4 | LRRC59 | S47 | Sugiyama | Leucine-rich repeat-containing protein 59 (Ribosome-binding protein p34) (p34) [Cleaved into: Leucine-rich repeat-containing protein 59, N-terminally processed] | Required for nuclear import of FGF1, but not that of FGF2. Might regulate nuclear import of exogenous FGF1 by facilitating interaction with the nuclear import machinery and by transporting cytosolic FGF1 to, and possibly through, the nuclear pores. {ECO:0000269|PubMed:22321063}. |
| Q9NQ48 | LZTFL1 | S209 | Sugiyama | Leucine zipper transcription factor-like protein 1 | Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function. {ECO:0000269|PubMed:20233871, ECO:0000269|PubMed:22072986, ECO:0000269|PubMed:22510444}. |
| Q8WWH5 | TRUB1 | S268 | Sugiyama | Pseudouridylate synthase TRUB1 (EC 5.4.99.-) (TruB pseudouridine synthase homolog 1) (tRNA pseudouridine 55 synthase TRUB1) (Psi55 synthase TRUB1) (EC 5.4.99.25) | Pseudouridine synthase that catalyzes pseudouridylation of mRNAs and tRNAs (PubMed:28073919, PubMed:31477916, PubMed:32926445). Mediates pseudouridylation of mRNAs with the consensus sequence 5'-GUUCNANNC-3', harboring a stem-loop structure (PubMed:28073919, PubMed:31477916). Constitutes the major pseudouridine synthase acting on mRNAs (PubMed:28073919). Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs (PubMed:32926445, PubMed:33023933). Promotes the processing of pri-let-7 microRNAs (pri-miRNAs) independently of its RNA pseudouridylate synthase activity (PubMed:32926445). Acts by binding to the stem-loop structure on pri-let-7, preventing LIN28-binding (LIN28A and/or LIN28B), thereby enhancing the interaction between pri-let-7 and the microprocessor DGCR8, which mediates miRNA maturation (PubMed:32926445). {ECO:0000269|PubMed:28073919, ECO:0000269|PubMed:31477916, ECO:0000269|PubMed:32926445, ECO:0000269|PubMed:33023933}. |
| Q9H3N1 | TMX1 | S92 | Sugiyama | Thioredoxin-related transmembrane protein 1 (Protein disulfide-isomerase TMX1) (EC 5.3.4.1) (Thioredoxin domain-containing protein 1) (Transmembrane Trx-related protein) | Thiredoxin domain-containing protein that participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyze dithiol-disulfide exchange reactions (PubMed:11152479, PubMed:37648867). Acts as a key inhibitor of the alternative triglyceride biosynthesis pathway by inhibiting the activity of TMEM68/DIESL at the endoplasmic reticulum, thereby restricting accumulation of triacylglycerol (PubMed:37648867). The alternative triglyceride biosynthesis pathway mediates formation of triacylglycerol from diacylglycerol and membrane phospholipids (PubMed:37648867). Acts as a protein disulfide isomerase by catalyzing formation or reduction of disulfide bonds (PubMed:22228764, PubMed:29932915). Specifically mediates formation of disulfide bonds of transmembrane proteins at the endoplasmic reticulum membrane (PubMed:22228764). Involved in endoplasmic reticulum-associated degradation (ERAD) via its protein disulfide isomerase activity by acting on folding-defective polypeptides at the endoplasmic reticulum membrane (PubMed:29932915). Acts as a negative regulator of platelet aggregation following secretion in the extracellular space (PubMed:30425049). Acts as a regulator of endoplasmic reticulum-mitochondria contact sites via its ability to regulate redox signals (PubMed:27502484, PubMed:31304984). Regulates endoplasmic reticulum-mitochondria Ca(2+) flux (PubMed:27502484). {ECO:0000269|PubMed:11152479, ECO:0000269|PubMed:22228764, ECO:0000269|PubMed:27502484, ECO:0000269|PubMed:29932915, ECO:0000269|PubMed:30425049, ECO:0000269|PubMed:31304984, ECO:0000269|PubMed:37648867}. |
| Q13233 | MAP3K1 | S1358 | Sugiyama | Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1) (EC 2.3.2.27) | Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). {ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:9808624}. |
| Q13464 | ROCK1 | S407 | 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}. |
| Q13882 | PTK6 | S147 | Sugiyama | Protein-tyrosine kinase 6 (EC 2.7.10.2) (Breast tumor kinase) (Tyrosine-protein kinase BRK) | Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Phosphorylates the GTPase-activating protein ARAP1 following EGF stimulation which enhances EGFR signaling by delaying EGFR down-regulation (PubMed:20554524). Also associates with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways. {ECO:0000269|PubMed:20554524}.; FUNCTION: [Isoform 2]: Inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins. |
| O14910 | LIN7A | S157 | Sugiyama | Protein lin-7 homolog A (Lin-7A) (hLin-7) (Mammalian lin-seven protein 1) (MALS-1) (Tax interaction protein 33) (TIP-33) (Vertebrate lin-7 homolog 1) (Veli-1) | Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. {ECO:0000250|UniProtKB:Q8JZS0, ECO:0000269|PubMed:12967566}. |
| Q9NUP9 | LIN7C | S142 | Sugiyama | Protein lin-7 homolog C (Lin-7C) (Mammalian lin-seven protein 3) (MALS-3) (Vertebrate lin-7 homolog 3) (Veli-3) | Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity). This complex may have the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Ensures the proper localization of GRIN2B (subunit 2B of the NMDA receptor) to neuronal postsynaptic density and may function in localizing synaptic vesicles at synapses where it is recruited by beta-catenin and cadherin. Required to localize Kir2 channels, GABA transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the basolateral membrane of epithelial cells. {ECO:0000250|UniProtKB:O88952}. |
| Q5S007 | LRRK2 | S1253 | 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 | S1536 | 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}. |
| O43143 | DHX15 | S656 | Sugiyama | ATP-dependent RNA helicase DHX15 (EC 3.6.4.13) (ATP-dependent RNA helicase #46) (DEAH box protein 15) (Splicing factor Prp43) (hPrp43) | RNA helicase involved in mRNA processing and antiviral innate immunity (PubMed:19103666, PubMed:19432882, PubMed:24782566, PubMed:24990078, PubMed:32179686, PubMed:34161762). Pre-mRNA processing factor involved in disassembly of spliceosomes after the release of mature mRNA (PubMed:19103666). In cooperation with TFIP11 seem to be involved in the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns (PubMed:19103666). Plays a key role in antiviral innate immunity by promoting both MAVS-dependent signaling and NLRP6 inflammasome (PubMed:24782566, PubMed:24990078, PubMed:34161762). Acts as an RNA virus sensor: recognizes and binds viral double stranded RNA (dsRNA) and activates the MAVS-dependent signaling to produce interferon-beta and interferon lambda-3 (IFNL3) (PubMed:24782566, PubMed:24990078, PubMed:34161762). Involved in intestinal antiviral innate immunity together with NLRP6: recognizes and binds viral dsRNA and promotes activation of the NLRP6 inflammasome in intestinal epithelial cells to restrict infection by enteric viruses (PubMed:34161762). The NLRP6 inflammasome acts by promoting maturation and secretion of IL18 in the extracellular milieu (PubMed:34161762). Also involved in antibacterial innate immunity by promoting Wnt-induced antimicrobial protein expression in Paneth cells (By similarity). {ECO:0000250|UniProtKB:O35286, ECO:0000269|PubMed:19103666, ECO:0000269|PubMed:19432882, ECO:0000269|PubMed:24782566, ECO:0000269|PubMed:24990078, ECO:0000269|PubMed:32179686, ECO:0000269|PubMed:34161762}. |
| Q8IY84 | NIM1K | S119 | Sugiyama | Serine/threonine-protein kinase NIM1 (EC 2.7.11.1) (NIM1 serine/threonine-protein kinase) | None |
| Q8TD08 | MAPK15 | S191 | 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}. |
| Q96GD4 | AURKB | S22 | 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}. |
| Q99558 | MAP3K14 | S856 | Sugiyama | Mitogen-activated protein kinase kinase kinase 14 (EC 2.7.11.25) (NF-kappa-beta-inducing kinase) (HsNIK) (Serine/threonine-protein kinase NIK) | Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Phosphorylates CHUK/IKKA, thereby promoting proteolytic processing of NFKB2/P100, which leads to NF-kappa-B activation via the non-canonical pathway (PubMed:25406581, PubMed:29230214). Has an essential role in the non-canonical NF-kappa-B signaling that regulates genes encoding molecules involved in B-cell survival, lymphoid organogenesis, and immune response (PubMed:25406581). Could act in a receptor-selective manner. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:25406581}. |
| Q9Y383 | LUC7L2 | S50 | Sugiyama | Putative RNA-binding protein Luc7-like 2 | May bind to RNA via its Arg/Ser-rich domain. |
| Q01081 | U2AF1 | S19 | Sugiyama | 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}. |
| Q8WU68 | U2AF1L4 | S19 | Sugiyama | Splicing factor U2AF 26 kDa subunit (U2 auxiliary factor 26) (U2 small nuclear RNA auxiliary factor 1-like protein 4) (U2AF1-like 4) (U2(RNU2) small nuclear RNA auxiliary factor 1-like protein 3) (U2 small nuclear RNA auxiliary factor 1-like protein 3) (U2AF1-like protein 3) | RNA-binding protein that function as a pre-mRNA splicing factor. 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. Acts by enhancing the binding of U2AF2 to weak pyrimidine tracts. Also participates in the regulation of alternative pre-mRNA splicing. Activates exon 5 skipping of PTPRC during T-cell activation; an event reversed by GFI1. Binds to RNA at the AG dinucleotide at the 3'-splice site (By similarity). Shows a preference for AGC or AGA (By similarity). {ECO:0000250|UniProtKB:Q8BGJ9}. |
| P50570 | DNM2 | S357 | Sugiyama | Dynamin-2 (EC 3.6.5.5) (Dynamin 2) (Dynamin II) | Catalyzes the hydrolysis of GTP and utilizes this energy to mediate vesicle scission at plasma membrane during endocytosis and filament remodeling at many actin structures during organization of the actin cytoskeleton (PubMed:15731758, PubMed:19605363, PubMed:19623537, PubMed:33713620, PubMed:34744632). Plays an important role in vesicular trafficking processes, namely clathrin-mediated endocytosis (CME), exocytic and clathrin-coated vesicle from the trans-Golgi network, and PDGF stimulated macropinocytosis (PubMed:15731758, PubMed:19623537, PubMed:33713620). During vesicular trafficking process, associates to the membrane, through lipid binding, and self-assembles into ring-like structure through oligomerization to form a helical polymer around the vesicle membrane and leading to vesicle scission (PubMed:17636067, PubMed:34744632, PubMed:36445308). Plays a role in organization of the actin cytoskeleton by mediating arrangement of stress fibers and actin bundles in podocytes (By similarity). During organization of the actin cytoskeleton, self-assembles into ring-like structure that directly bundles actin filaments to form typical membrane tubules decorated with dynamin spiral polymers (By similarity). Self-assembly increases GTPase activity and the GTP hydrolysis causes the rapid depolymerization of dynamin spiral polymers, and results in dispersion of actin bundles (By similarity). Remodels, through its interaction with CTTN, bundled actin filaments in a GTPase-dependent manner and plays a role in orchestrating the global actomyosin cytoskeleton (PubMed:19605363). The interaction with CTTN stabilizes the interaction of DNM2 and actin filaments and stimulates the intrinsic GTPase activity that results in actin filament-barbed ends and increases the sensitivity of filaments in bundles to the actin depolymerizing factor, CFL1 (By similarity). Plays a role in the autophagy process, by participating in the formation of ATG9A vesicles destined for the autophagosomes through its interaction with SNX18 (PubMed:29437695), by mediating recycling endosome scission leading to autophagosome release through MAP1LC3B interaction (PubMed:29437695, PubMed:32315611). Also regulates maturation of apoptotic cell corpse-containing phagosomes by recruiting PIK3C3 to the phagosome membrane (By similarity). Also plays a role in cytokinesis (By similarity). May participate in centrosome cohesion through its interaction with TUBG1 (By similarity). Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Involved in membrane tubulation (PubMed:24135484). {ECO:0000250|UniProtKB:P39052, ECO:0000250|UniProtKB:P39054, ECO:0000269|PubMed:15731758, ECO:0000269|PubMed:17636067, ECO:0000269|PubMed:19605363, ECO:0000269|PubMed:19623537, ECO:0000269|PubMed:24135484, ECO:0000269|PubMed:29437695, ECO:0000269|PubMed:32315611, ECO:0000269|PubMed:33713620, ECO:0000269|PubMed:34744632, ECO:0000269|PubMed:36445308}. |
| Q9NRA0 | SPHK2 | S377 | Sugiyama | Sphingosine kinase 2 (SK 2) (SPK 2) (EC 2.7.1.91) | Catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-dihydrosphingosine, D-erythro-sphingosine and L-threo-dihydrosphingosine. Binds phosphoinositides (PubMed:12954646, PubMed:19168031). In contrast to prosurvival SPHK1, has a positive effect on intracellular ceramide levels, inhibits cells growth and enhances apoptosis (PubMed:16118219). In mitochondria, is important for cytochrome-c oxidase assembly and mitochondrial respiration. The SPP produced in mitochondria binds PHB2 and modulates the regulation via PHB2 of complex IV assembly and respiration (PubMed:20959514). In nucleus, plays a role in epigenetic regulation of gene expression. Interacts with HDAC1 and HDAC2 and, through SPP production, inhibits their enzymatic activity, preventing the removal of acetyl groups from lysine residues with histones. Up-regulates acetylation of histone H3-K9, histone H4-K5 and histone H2B-K12 (PubMed:19729656). In nucleus, may have an inhibitory effect on DNA synthesis and cell cycle (PubMed:12954646, PubMed:16103110). In mast cells, is the main regulator of SPP production which mediates calcium influx, NF-kappa-B activation, cytokine production, such as TNF and IL6, and degranulation of mast cells (By similarity). In dopaminergic neurons, is involved in promoting mitochondrial functions regulating ATP and ROS levels (By similarity). Also involved in the regulation of glucose and lipid metabolism (By similarity). {ECO:0000250|UniProtKB:Q9JIA7, ECO:0000269|PubMed:12954646, ECO:0000269|PubMed:16103110, ECO:0000269|PubMed:16118219, ECO:0000269|PubMed:19168031, ECO:0000269|PubMed:19729656, ECO:0000269|PubMed:20959514}. |
| Q9UK32 | RPS6KA6 | S555 | Sugiyama | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
| Q8WWI1 | LMO7 | S1410 | Sugiyama | LIM domain only protein 7 (LMO-7) (F-box only protein 20) (LOMP) | None |
| Q08211 | DHX9 | S623 | Sugiyama | ATP-dependent RNA helicase A (EC 3.6.4.13) (DEAH box protein 9) (DExH-box helicase 9) (Leukophysin) (LKP) (Nuclear DNA helicase II) (NDH II) (RNA helicase A) | Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:24990949, PubMed:25062910, PubMed:28221134, PubMed:9111062, PubMed:37467750). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:10198287, PubMed:9111062). Also binds to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11038348, PubMed:11149922, PubMed:11416126, PubMed:15355351, PubMed:28221134, PubMed:9323138, PubMed:9662397). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Also acts as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:10924507, PubMed:11402034, PubMed:9162007). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588). {ECO:0000250|UniProtKB:O70133, ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:11038348, ECO:0000269|PubMed:11149922, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11416126, ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:12711669, ECO:0000269|PubMed:15355351, ECO:0000269|PubMed:1537828, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20669935, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:21561811, ECO:0000269|PubMed:22190748, ECO:0000269|PubMed:24049074, ECO:0000269|PubMed:24990949, ECO:0000269|PubMed:25062910, ECO:0000269|PubMed:28221134, ECO:0000269|PubMed:28355180, ECO:0000269|PubMed:28636595, ECO:0000269|PubMed:37467750, ECO:0000269|PubMed:9111062, ECO:0000269|PubMed:9162007, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9662397}.; FUNCTION: (Microbial infection) Plays a role in HIV-1 replication and virion infectivity (PubMed:11096080, PubMed:19229320, PubMed:25149208, PubMed:27107641). Enhances HIV-1 transcription by facilitating the binding of RNA polymerase II holoenzyme to the proviral DNA (PubMed:11096080, PubMed:25149208). Binds (via DRBM domain 2) to the HIV-1 TAR RNA and stimulates HIV-1 transcription of transactivation response element (TAR)-containing mRNAs (PubMed:11096080, PubMed:9892698). Involved also in HIV-1 mRNA splicing and transport (PubMed:25149208). Positively regulates HIV-1 gag mRNA translation, through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Binds (via DRBM domains) to a HIV-1 double-stranded RNA region of the primer binding site (PBS)-segment of the 5'-UTR, and hence stimulates DHX9 incorporation into virions and virion infectivity (PubMed:27107641). Also plays a role as a cytosolic viral MyD88-dependent DNA and RNA sensors in plasmacytoid dendritic cells (pDCs), and hence induce antiviral innate immune responses (PubMed:20696886, PubMed:21957149). Binds (via the OB-fold region) to viral single-stranded DNA unmethylated C-phosphate-G (CpG) oligonucleotide (PubMed:20696886). {ECO:0000269|PubMed:11096080, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:20696886, ECO:0000269|PubMed:21957149, ECO:0000269|PubMed:25149208, ECO:0000269|PubMed:27107641, ECO:0000269|PubMed:9892698}. |
| O95347 | SMC2 | S664 | Sugiyama | Structural maintenance of chromosomes protein 2 (SMC protein 2) (SMC-2) (Chromosome-associated protein E) (hCAP-E) (XCAP-E 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}. |
| A0A087WV96 | CYP3A7-CYP3A51P | S139 | ochoa | Cytochrome P450 3A (EC 1.14.14.-) | Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. {ECO:0000256|RuleBase:RU368049}. |
| A0A087WZ62 | None | S246 | ochoa | Mannosyltransferase (EC 2.4.1.-) | None |
| A0AVT1 | UBA6 | S951 | ochoa | Ubiquitin-like modifier-activating enzyme 6 (Ubiquitin-activating enzyme 6) (EC 6.2.1.45) (Monocyte protein 4) (MOP-4) (Ubiquitin-activating enzyme E1-like protein 2) (E1-L2) | 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:35970836, PubMed:35986001). Specific for ubiquitin, does not activate ubiquitin-like peptides. Also activates UBD/FAT10 conjugation via adenylation of its C-terminal glycine (PubMed:17889673, PubMed:35970836, PubMed:35986001). Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility. {ECO:0000269|PubMed:15202508, ECO:0000269|PubMed:17597759, ECO:0000269|PubMed:17889673, ECO:0000269|PubMed:35970836, ECO:0000269|PubMed:35986001}. |
| A0MZ66 | SHTN1 | S249 | ochoa | Shootin-1 (Shootin1) | Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth. Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth. In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons. {ECO:0000250|UniProtKB:A0MZ67, ECO:0000250|UniProtKB:Q8K2Q9}. |
| A5YKK6 | CNOT1 | S1061 | ochoa | CCR4-NOT transcription complex subunit 1 (CCR4-associated factor 1) (Negative regulator of transcription subunit 1 homolog) (NOT1H) (hNOT1) | Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity. Plays a role in rapid sperm motility via mediating timely mRNA turnover (By similarity). {ECO:0000250|UniProtKB:Q6ZQ08, ECO:0000269|PubMed:10637334, ECO:0000269|PubMed:16778766, ECO:0000269|PubMed:21278420, ECO:0000269|PubMed:21976065, ECO:0000269|PubMed:21984185, ECO:0000269|PubMed:22367759, ECO:0000269|PubMed:23644599, ECO:0000269|PubMed:27558897, ECO:0000269|PubMed:32354837}. |
| A6NJG2 | SOWAHD | S22 | ochoa | Ankyrin repeat domain-containing protein SOWAHD (Ankyrin repeat domain-containing protein 58) (Protein sosondowah homolog D) | None |
| A8MV72 | None | S205 | ochoa | Putative UPF0607 protein ENSP00000382826 | None |
| A8MVW0 | FAM171A2 | S669 | ochoa | Protein FAM171A2 | None |
| F5H5P2 | None | S381 | ochoa | 2-oxoisovalerate dehydrogenase subunit alpha (EC 1.2.4.4) (Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain) | Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction. {ECO:0000256|ARBA:ARBA00037052, ECO:0000256|RuleBase:RU365014}. |
| F8WAN1 | SPECC1L-ADORA2A | S171 | ochoa | SPECC1L-ADORA2A readthrough (NMD candidate) | None |
| O00255 | MEN1 | S583 | psp | Menin | Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates 'Lys-4' of histone H3 (H3K4). Functions as a transcriptional regulator. Binds to the TERT promoter and represses telomerase expression. Plays a role in TGFB1-mediated inhibition of cell-proliferation, possibly regulating SMAD3 transcriptional activity. Represses JUND-mediated transcriptional activation on AP1 sites, as well as that mediated by NFKB subunit RELA. Positively regulates HOXC8 and HOXC6 gene expression. May be involved in normal hematopoiesis through the activation of HOXA9 expression (By similarity). May be involved in DNA repair. {ECO:0000250|UniProtKB:O88559, ECO:0000269|PubMed:11274402, ECO:0000269|PubMed:11526476, ECO:0000269|PubMed:12837246, ECO:0000269|PubMed:12874027, ECO:0000269|PubMed:14992727, ECO:0000269|PubMed:22327296}. |
| O00273 | DFFA | S228 | 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). |
| O00327 | BMAL1 | S78 | psp | Basic helix-loop-helix ARNT-like protein 1 (Aryl hydrocarbon receptor nuclear translocator-like protein 1) (Basic-helix-loop-helix-PAS protein MOP3) (Brain and muscle ARNT-like 1) (Class E basic helix-loop-helix protein 5) (bHLHe5) (Member of PAS protein 3) (PAS domain-containing protein 3) (bHLH-PAS protein JAP3) | Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART and KLF11. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (PubMed:28985504). Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (By similarity). Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B) (By similarity). {ECO:0000250|UniProtKB:Q9WTL8, ECO:0000269|PubMed:11441146, ECO:0000269|PubMed:12738229, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:23955654, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}.; FUNCTION: (Microbial infection) Regulates SARS coronavirus-2/SARS-CoV-2 entry and replication in lung epithelial cells probably through the post-transcriptional regulation of ACE2 and interferon-stimulated gene expression. {ECO:0000269|PubMed:34545347}. |
| O00560 | SDCBP | S36 | ochoa | Syntenin-1 (Melanoma differentiation-associated protein 9) (MDA-9) (Pro-TGF-alpha cytoplasmic domain-interacting protein 18) (TACIP18) (Scaffold protein Pbp1) (Syndecan-binding protein 1) | Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:11498591, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:26539120, ECO:0000303|PubMed:26291527}. |
| O14490 | DLGAP1 | S406 | psp | Disks large-associated protein 1 (DAP-1) (Guanylate kinase-associated protein) (hGKAP) (PSD-95/SAP90-binding protein 1) (SAP90/PSD-95-associated protein 1) (SAPAP1) | Part of the postsynaptic scaffold in neuronal cells. |
| O14497 | ARID1A | S1516 | ochoa | AT-rich interactive domain-containing protein 1A (ARID domain-containing protein 1A) (B120) (BRG1-associated factor 250) (BAF250) (BRG1-associated factor 250a) (BAF250A) (Osa homolog 1) (hOSA1) (SWI-like protein) (SWI/SNF complex protein p270) (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1) (hELD) | Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). {ECO:0000250|UniProtKB:A2BH40, ECO:0000303|PubMed:12672490, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}. |
| O14523 | C2CD2L | S532 | 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}. |
| 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. |
| O14920 | IKBKB | S177 | psp | Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK-2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:9346484}. |
| O14939 | PLD2 | S243 | psp | Phospholipase D2 (PLD 2) (hPLD2) (EC 3.1.4.4) (Choline phosphatase 2) (PLD1C) (Phosphatidylcholine-hydrolyzing phospholipase D2) | Function as phospholipase selective for phosphatidylcholine (PubMed:9582313). May have a role in signal-induced cytoskeletal regulation and/or endocytosis (By similarity). {ECO:0000250|UniProtKB:P97813, ECO:0000269|PubMed:9582313}. |
| O14980 | XPO1 | S450 | ochoa | Exportin-1 (Exp1) (Chromosome region maintenance 1 protein homolog) | Mediates the nuclear export of cellular proteins (cargos) bearing a leucine-rich nuclear export signal (NES) and of RNAs. In the nucleus, in association with RANBP3, binds cooperatively to the NES on its target protein and to the GTPase RAN in its active GTP-bound form (Ran-GTP). Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Involved in U3 snoRNA transport from Cajal bodies to nucleoli. Binds to late precursor U3 snoRNA bearing a TMG cap. {ECO:0000269|PubMed:15574332, ECO:0000269|PubMed:20921223, ECO:0000269|PubMed:9311922, ECO:0000269|PubMed:9323133}.; FUNCTION: (Microbial infection) Mediates the export of unspliced or incompletely spliced RNAs out of the nucleus from different viruses including HIV-1, HTLV-1 and influenza A. Interacts with, and mediates the nuclear export of HIV-1 Rev and HTLV-1 Rex proteins. Involved in HTLV-1 Rex multimerization. {ECO:0000269|PubMed:14612415, ECO:0000269|PubMed:9837918}. |
| O14981 | BTAF1 | S257 | 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. |
| O14983 | ATP2A1 | S362 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) (SR Ca(2+)-ATPase 1) (EC 7.2.2.10) (Calcium pump 1) (Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) | Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (By similarity). Contributes to calcium sequestration involved in muscular excitation/contraction (PubMed:10914677). {ECO:0000250|UniProtKB:P04191, ECO:0000269|PubMed:10914677}. |
| O15027 | SEC16A | S846 | psp | Protein transport protein Sec16A (SEC16 homolog A) (p250) | Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17005010, PubMed:17192411, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity). {ECO:0000250|UniProtKB:E9QAT4, ECO:0000269|PubMed:17005010, ECO:0000269|PubMed:17192411, ECO:0000269|PubMed:17428803, ECO:0000269|PubMed:21768384, ECO:0000269|PubMed:22355596, ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28442536, ECO:0000269|PubMed:29300766}. |
| O15061 | SYNM | S1141 | 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}. |
| O15151 | MDM4 | S161 | ochoa | Protein Mdm4 (Double minute 4 protein) (Mdm2-like p53-binding protein) (Protein Mdmx) (p53-binding protein Mdm4) | Along with MDM2, contributes to TP53 regulation (PubMed:32300648). Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions. {ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:32300648}. |
| O15195 | VILL | S784 | ochoa | Villin-like protein | Possible tumor suppressor. |
| O15503 | INSIG1 | S125 | 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}. |
| O43166 | SIPA1L1 | S1508 | 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}. |
| O43175 | PHGDH | S362 | ochoa | D-3-phosphoglycerate dehydrogenase (3-PGDH) (EC 1.1.1.95) (2-oxoglutarate reductase) (EC 1.1.1.399) (Malate dehydrogenase) (EC 1.1.1.37) | Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate. {ECO:0000269|PubMed:11751922, ECO:0000269|PubMed:25406093}. |
| O43182 | ARHGAP6 | S837 | ochoa | Rho GTPase-activating protein 6 (Rho-type GTPase-activating protein 6) (Rho-type GTPase-activating protein RhoGAPX-1) | GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Could regulate the interactions of signaling molecules with the actin cytoskeleton. Promotes continuous elongation of cytoplasmic processes during cell motility and simultaneous retraction of the cell body changing the cell morphology. {ECO:0000269|PubMed:10699171}. |
| O43314 | PPIP5K2 | S1180 | ochoa | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC 2.7.4.24) (Diphosphoinositol pentakisphosphate kinase 2) (Histidine acid phosphatase domain-containing protein 1) (InsP6 and PP-IP5 kinase 2) (VIP1 homolog 2) (hsVIP2) | Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4 (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation (PubMed:17690096, PubMed:17702752, PubMed:21222653, PubMed:29590114). Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4 (PubMed:17690096, PubMed:17702752). Required for normal hearing (PubMed:29590114). {ECO:0000269|PubMed:17690096, ECO:0000269|PubMed:17702752, ECO:0000269|PubMed:21222653, ECO:0000269|PubMed:29590114}. |
| O43399 | TPD52L2 | S96 | ochoa | Tumor protein D54 (hD54) (Tumor protein D52-like 2) | None |
| O43426 | SYNJ1 | S830 | ochoa | Synaptojanin-1 (EC 3.1.3.36) (Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1) | Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:23804563, PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity). {ECO:0000250|UniProtKB:O18964, ECO:0000250|UniProtKB:Q62910, ECO:0000269|PubMed:23804563, ECO:0000269|PubMed:27435091}. |
| O43432 | EIF4G3 | S1157 | ochoa | Eukaryotic translation initiation factor 4 gamma 3 (eIF-4-gamma 3) (eIF-4G 3) (eIF4G 3) (eIF-4-gamma II) (eIF4GII) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:9418880). Functional homolog of EIF4G1 (PubMed:9418880). {ECO:0000269|PubMed:9418880}. |
| O43663 | PRC1 | S532 | ochoa | Protein regulator of cytokinesis 1 | Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle. Acts as an oncogene for promoting bladder cancer cells proliferation, apoptosis inhibition and carcinogenic progression (PubMed:17409436). {ECO:0000269|PubMed:12082078, ECO:0000269|PubMed:15297875, ECO:0000269|PubMed:15625105, ECO:0000269|PubMed:16431929, ECO:0000269|PubMed:17409436, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:20691902, ECO:0000269|PubMed:9885575}. |
| O43683 | BUB1 | S318 | ochoa | Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) | Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}. |
| 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}. |
| O60240 | PLIN1 | S130 | ochoa | Perilipin-1 (Lipid droplet-associated protein) | Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels. {ECO:0000269|PubMed:23399566}. |
| O60271 | SPAG9 | S229 | ochoa | C-Jun-amino-terminal kinase-interacting protein 4 (JIP-4) (JNK-interacting protein 4) (Cancer/testis antigen 89) (CT89) (Human lung cancer oncogene 6 protein) (HLC-6) (JNK-associated leucine-zipper protein) (JLP) (Mitogen-activated protein kinase 8-interacting protein 4) (Proliferation-inducing protein 6) (Protein highly expressed in testis) (PHET) (Sperm surface protein) (Sperm-associated antigen 9) (Sperm-specific protein) (Sunday driver 1) | The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:14743216). Regulates lysosomal positioning by acting as an adapter protein which links PIP4P1-positive lysosomes to the dynein-dynactin complex (PubMed:29146937). Assists PIKFYVE selective functionality in microtubule-based endosome-to-TGN trafficking (By similarity). {ECO:0000250|UniProtKB:Q58A65, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:29146937}. |
| 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}. |
| O60346 | PHLPP1 | S1359 | psp | PH domain leucine-rich repeat-containing protein phosphatase 1 (EC 3.1.3.16) (Pleckstrin homology domain-containing family E member 1) (PH domain-containing family E member 1) (Suprachiasmatic nucleus circadian oscillatory protein) (hSCOP) | 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 AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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 suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). 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 (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}. |
| O60361 | NME2P1 | S107 | ochoa | Putative nucleoside diphosphate kinase (NDK) (NDP kinase) (EC 2.7.4.6) | Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). {ECO:0000250}. |
| O60524 | NEMF | S936 | 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}. |
| O60566 | BUB1B | S270 | 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}. |
| O60664 | PLIN3 | S130 | ochoa | Perilipin-3 (47 kDa mannose 6-phosphate receptor-binding protein) (47 kDa MPR-binding protein) (Cargo selection protein TIP47) (Mannose-6-phosphate receptor-binding protein 1) (Placental protein 17) (PP17) | Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177). {ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:9590177}. |
| O60701 | UGDH | S40 | ochoa | UDP-glucose 6-dehydrogenase (UDP-Glc dehydrogenase) (UDP-GlcDH) (UDPGDH) (EC 1.1.1.22) | Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21502315, PubMed:21961565, PubMed:22123821, PubMed:23106432, PubMed:25478983, PubMed:27966912, PubMed:30420606, PubMed:30457329). Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (By similarity). Required for proper brain and neuronal development (PubMed:32001716). {ECO:0000250|UniProtKB:O70475, ECO:0000269|PubMed:21502315, ECO:0000269|PubMed:21961565, ECO:0000269|PubMed:22123821, ECO:0000269|PubMed:23106432, ECO:0000269|PubMed:25478983, ECO:0000269|PubMed:27966912, ECO:0000269|PubMed:30420606, ECO:0000269|PubMed:30457329, ECO:0000269|PubMed:32001716}. |
| O60841 | EIF5B | S708 | ochoa | Eukaryotic translation initiation factor 5B (eIF-5B) (EC 3.6.5.3) (Translation initiation factor IF-2) | Plays a role in translation initiation (PubMed:10659855, PubMed:35732735). Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon (PubMed:10659855, PubMed:35732735). Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex (PubMed:12569173, PubMed:35732735). Is released after formation of the 80S initiation complex (PubMed:35732735). Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes (PubMed:10659855, PubMed:35732735). In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit (PubMed:10659855). {ECO:0000269|PubMed:10659855, ECO:0000269|PubMed:12569173, ECO:0000269|PubMed:35732735}. |
| O75110 | ATP9A | S629 | ochoa | Probable phospholipid-transporting ATPase IIA (EC 7.6.2.1) (ATPase class II type 9A) | Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation (PubMed:27733620, PubMed:30213940, PubMed:36604604). Also involved in endosome to trans-Golgi network retrograde transport (PubMed:27733620, PubMed:30213940). In complex with MON2 and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS, a transporter of Wnt morphogens in developing tissues. Participates in the formation of endosomal carriers that direct WLS trafficking back to Golgi, away from lysosomal degradation (PubMed:30213940). Appears to be implicated in intercellular communication by negatively regulating the release of exosomes (PubMed:30947313). The flippase activity towards membrane lipids and its role in membrane asymmetry remains to be proved (PubMed:30947313). Required for the maintenance of neurite morphology and synaptic transmission (By similarity). {ECO:0000250|UniProtKB:O70228, ECO:0000269|PubMed:27733620, ECO:0000269|PubMed:30213940, ECO:0000269|PubMed:30947313, ECO:0000269|PubMed:36604604}. |
| O75362 | ZNF217 | S407 | 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}. |
| O75420 | GIGYF1 | S411 | ochoa | GRB10-interacting GYF protein 1 (PERQ amino acid-rich with GYF domain-containing protein 1) | May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling. May increase IGF1 receptor phosphorylation under IGF1 stimulation as well as phosphorylation of IRS1 and SHC1 (By similarity). {ECO:0000250, ECO:0000269|PubMed:12771153}. |
| O75469 | NR1I2 | S167 | 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}. |
| O75569 | PRKRA | S22 | ochoa | Interferon-inducible double-stranded RNA-dependent protein kinase activator A (PKR-associated protein X) (PKR-associating protein X) (Protein activator of the interferon-induced protein kinase) (Protein kinase, interferon-inducible double-stranded RNA-dependent activator) | Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner (By similarity). {ECO:0000250, ECO:0000269|PubMed:10336432, ECO:0000269|PubMed:11238927, ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:16982605, ECO:0000269|PubMed:17452327, ECO:0000269|PubMed:9687506}. |
| O75691 | UTP20 | S788 | ochoa | Small subunit processome component 20 homolog (Down-regulated in metastasis protein) (Novel nucleolar protein 73) (NNP73) (Protein Key-1A6) | 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. Involved in 18S pre-rRNA processing. Associates with U3 snoRNA. {ECO:0000269|PubMed:17498821, ECO:0000269|PubMed:34516797}. |
| O75995 | SASH3 | S243 | ochoa | SAM and SH3 domain-containing protein 3 (SH3 protein expressed in lymphocytes homolog) | May function as a signaling adapter protein in lymphocytes. {ECO:0000250|UniProtKB:Q8K352}. |
| O76039 | CDKL5 | S388 | 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}. |
| O94806 | PRKD3 | S731 | ochoa|psp | 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}. |
| O94906 | PRPF6 | S279 | ochoa | Pre-mRNA-processing factor 6 (Androgen receptor N-terminal domain-transactivating protein 1) (ANT-1) (PRP6 homolog) (U5 snRNP-associated 102 kDa protein) (U5-102 kDa protein) | Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:20118938, PubMed:21549338, PubMed:28781166). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation. {ECO:0000269|PubMed:12039962, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:21549338, ECO:0000269|PubMed:28781166}. |
| O94913 | PCF11 | S759 | ochoa | Pre-mRNA cleavage complex 2 protein Pcf11 (Pre-mRNA cleavage complex II protein Pcf11) | Component of pre-mRNA cleavage complex II, which promotes transcription termination by RNA polymerase II. {ECO:0000269|PubMed:11060040, ECO:0000269|PubMed:29196535}. |
| O94916 | NFAT5 | S134 | ochoa|psp | 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 | S220 | 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 | S201 | ochoa | E3 ubiquitin-protein ligase UBR5 (EC 2.3.2.26) (E3 ubiquitin-protein ligase, HECT domain-containing 1) (Hyperplastic discs protein homolog) (hHYD) (Progestin-induced protein) | E3 ubiquitin-protein ligase involved in different protein quality control pathways in the cytoplasm and nucleus (PubMed:29033132, PubMed:33208877, PubMed:37478846, PubMed:37478862). Mainly acts as a ubiquitin chain elongator that extends pre-ubiquitinated substrates (PubMed:29033132, PubMed:37409633). Component of the N-end rule pathway: ubiquitinates proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their degradation (By similarity). Recognizes type-1 N-degrons, containing positively charged amino acids (Arg, Lys and His) (By similarity). Together with UBR4, part of a cytoplasm protein quality control pathway that prevents protein aggregation by catalyzing assembly of heterotypic 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on aggregated proteins, leading to substrate recognition by the segregase p97/VCP and degradation by the proteasome: UBR5 is probably branching multiple 'Lys-48'-linked chains of substrates initially modified with mixed conjugates by UBR4 (PubMed:29033132). Together with ITCH, catalyzes 'Lys-48'-/'Lys-63'-branched ubiquitination of TXNIP, leading to its degradation: UBR5 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by ITCH (PubMed:29378950). Catalytic component of a nuclear protein quality control pathway that mediates ubiquitination and degradation of unpaired transcription factors (i.e. transcription factors that are not assembled into functional multiprotein complexes): specifically recognizes and binds degrons that are not accessible when transcription regulators are associated with their coactivators (PubMed:37478846, PubMed:37478862). Ubiquitinates various unpaired transcription regulator (MYC, SUPT4H1, SUPT5H, CDC20 and MCRS1), as well as ligand-bound nuclear receptors (ESR1, NR1H3, NR3C1, PGR, RARA, RXRA AND VDR) that are not associated with their nuclear receptor coactivators (NCOAs) (PubMed:33208877, PubMed:37478846, PubMed:37478862). Involved in maturation and/or transcriptional regulation of mRNA by mediating polyubiquitination and activation of CDK9 (PubMed:21127351). Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes (PubMed:22884692). Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response (PubMed:11714696). Ubiquitinates acetylated PCK1 (PubMed:21726808). Acts as a positive regulator of the canonical Wnt signaling pathway by mediating (1) ubiquitination and stabilization of CTNNB1, and (2) 'Lys-48'-linked ubiquitination and degradation of TLE3 (PubMed:21118991, PubMed:28689657). Promotes disassembly of the mitotic checkpoint complex (MCC) from the APC/C complex by catalyzing ubiquitination of BUB1B, BUB3 and CDC20 (PubMed:35217622). Plays an essential role in extraembryonic development (By similarity). Required for the maintenance of skeletal tissue homeostasis by acting as an inhibitor of hedgehog (HH) signaling (By similarity). {ECO:0000250|UniProtKB:Q80TP3, ECO:0000269|PubMed:11714696, ECO:0000269|PubMed:21118991, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:22884692, ECO:0000269|PubMed:28689657, ECO:0000269|PubMed:29033132, ECO:0000269|PubMed:29378950, ECO:0000269|PubMed:33208877, ECO:0000269|PubMed:35217622, ECO:0000269|PubMed:37409633, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:37478862}. |
| O95071 | UBR5 | S1875 | 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}. |
| O95183 | VAMP5 | S41 | ochoa | Vesicle-associated membrane protein 5 (VAMP-5) (Myobrevin) | May participate in trafficking events that are associated with myogenesis, such as myoblast fusion and/or GLUT4 trafficking. |
| O95210 | STBD1 | S175 | psp | Starch-binding domain-containing protein 1 (Genethonin-1) (Glycophagy cargo receptor STBD1) | Acts as a cargo receptor for glycogen. Delivers its cargo to an autophagic pathway called glycophagy, resulting in the transport of glycogen to lysosomes. {ECO:0000269|PubMed:20810658, ECO:0000269|PubMed:21893048, ECO:0000269|PubMed:24837458}. |
| O95235 | KIF20A | S33 | ochoa | Kinesin-like protein KIF20A (GG10_2) (Mitotic kinesin-like protein 2) (MKlp2) (Rab6-interacting kinesin-like protein) (Rabkinesin-6) | Mitotic kinesin required for chromosome passenger complex (CPC)-mediated cytokinesis. Following phosphorylation by PLK1, involved in recruitment of PLK1 to the central spindle. Interacts with guanosine triphosphate (GTP)-bound forms of RAB6A and RAB6B. May act as a motor required for the retrograde RAB6 regulated transport of Golgi membranes and associated vesicles along microtubules. Has a microtubule plus end-directed motility. {ECO:0000269|PubMed:12939256}. |
| O95271 | TNKS | S218 | ochoa | Poly [ADP-ribose] polymerase tankyrase-1 (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 5) (ARTD5) (Poly [ADP-ribose] polymerase 5A) (Protein poly-ADP-ribosyltransferase tankyrase-1) (EC 2.4.2.-) (TNKS-1) (TRF1-interacting ankyrin-related ADP-ribose polymerase) (Tankyrase I) (Tankyrase-1) (TANK1) | Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379, PubMed:28619731). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245). {ECO:0000269|PubMed:10988299, ECO:0000269|PubMed:11739745, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:19759537, ECO:0000269|PubMed:21478859, ECO:0000269|PubMed:22864114, ECO:0000269|PubMed:23622245, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:28619731}. |
| O95613 | PCNT | S837 | 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}. |
| O95714 | HERC2 | S2010 | 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}. |
| O95757 | HSPA4L | S74 | ochoa | Heat shock 70 kDa protein 4L (Heat shock 70-related protein APG-1) (Heat shock protein family H member 3) (Heat-shock protein family A member 4-like protein) (HSPA4-like protein) (Osmotic stress protein 94) | Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. {ECO:0000250}. |
| O95757 | HSPA4L | S579 | ochoa | Heat shock 70 kDa protein 4L (Heat shock 70-related protein APG-1) (Heat shock protein family H member 3) (Heat-shock protein family A member 4-like protein) (HSPA4-like protein) (Osmotic stress protein 94) | Possesses chaperone activity in vitro where it inhibits aggregation of citrate synthase. {ECO:0000250}. |
| O95801 | TTC4 | S47 | ochoa | Tetratricopeptide repeat protein 4 (TPR repeat protein 4) | May act as a co-chaperone for HSP90AB1 (PubMed:18320024). Promotes Sendai virus (SeV)-induced host cell innate immune responses (PubMed:29251827). {ECO:0000269|PubMed:18320024, ECO:0000269|PubMed:29251827}. |
| O96017 | CHEK2 | S260 | ochoa|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}. |
| P00488 | F13A1 | S128 | ochoa | Coagulation factor XIII A chain (Coagulation factor XIIIa) (EC 2.3.2.13) (Protein-glutamine gamma-glutamyltransferase A chain) (Transglutaminase A chain) | Factor XIII is activated by thrombin and calcium ion to a transglutaminase that catalyzes the formation of gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, thus stabilizing the fibrin clot. Also cross-link alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. {ECO:0000269|PubMed:27363989}. |
| P02671 | FGA | S489 | ochoa | Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain] | Cleaved by the protease thrombin to yield monomers which, together with fibrinogen beta (FGB) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However, subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets via an ITGB3-dependent pathway. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}. |
| P02686 | MBP | S146 | ochoa | Myelin basic protein (MBP) (Myelin A1 protein) (Myelin membrane encephalitogenic protein) | The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}. |
| P04083 | ANXA1 | S143 | ochoa | Annexin A1 (Annexin I) (Annexin-1) (Calpactin II) (Calpactin-2) (Chromobindin-9) (Lipocortin I) (Phospholipase A2 inhibitory protein) (p35) [Cleaved into: Annexin Ac2-26] | Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response (By similarity). Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells (PubMed:17008549). Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (PubMed:17008549). Has no effect on unstimulated T cells (PubMed:17008549). Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton (PubMed:19625660). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (PubMed:2532504, PubMed:8557678). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity). {ECO:0000250|UniProtKB:P10107, ECO:0000250|UniProtKB:P19619, ECO:0000269|PubMed:17008549, ECO:0000269|PubMed:19625660, ECO:0000269|PubMed:2532504, ECO:0000269|PubMed:2936963, ECO:0000269|PubMed:8425544, ECO:0000269|PubMed:8557678}.; FUNCTION: [Annexin Ac2-26]: Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades (PubMed:15187149, PubMed:22879591, PubMed:25664854). Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors (PubMed:15187149). Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration (PubMed:15187149). Promotes resolution of inflammation and wound healing (PubMed:25664854). Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). {ECO:0000269|PubMed:15187149, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:25664854}. |
| P04406 | GAPDH | S293 | 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}. |
| P04626 | ERBB2 | S703 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P04626 | ERBB2 | S819 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P04920 | SLC4A2 | S461 | ochoa | Anion exchange protein 2 (AE 2) (Anion exchanger 2) (Non-erythroid band 3-like protein) (BND3L) (Solute carrier family 4 member 2) | Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15184086, PubMed:34668226). Plays an important role in osteoclast differentiation and function (PubMed:34668226). Regulates bone resorption and calpain-dependent actin cytoskeleton organization in osteoclasts via anion exchange-dependent control of pH (By similarity). Essential for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation, modulating CD8(+) T-cell responses (By similarity). {ECO:0000250|UniProtKB:P13808, ECO:0000269|PubMed:15184086, ECO:0000269|PubMed:34668226}. |
| P05023 | ATP1A1 | S653 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-1 (Na(+)/K(+) ATPase alpha-1 subunit) (EC 7.2.2.13) (Sodium pump subunit alpha-1) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity). {ECO:0000250|UniProtKB:Q8VDN2, ECO:0000269|PubMed:29499166, ECO:0000269|PubMed:30388404}. |
| P05060 | CHGB | S377 | ochoa|psp | Secretogranin-1 (Chromogranin-B) (CgB) (Secretogranin I) (SgI) [Cleaved into: PE-11; GAWK peptide; CCB peptide] | Secretogranin-1 is a neuroendocrine secretory granule protein, which may be the precursor for other biologically active peptides. |
| P05181 | CYP2E1 | S74 | psp | Cytochrome P450 2E1 (EC 1.14.14.1) (4-nitrophenol 2-hydroxylase) (EC 1.14.13.n7) (CYPIIE1) (Cytochrome P450-J) | A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable). {ECO:0000269|PubMed:10553002, ECO:0000269|PubMed:18577768, ECO:0000305|PubMed:9348445}. |
| P05230 | FGF1 | S131 | psp | Fibroblast growth factor 1 (FGF-1) (Acidic fibroblast growth factor) (aFGF) (Endothelial cell growth factor) (ECGF) (Heparin-binding growth factor 1) (HBGF-1) | Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as a potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107). {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:18441324, ECO:0000269|PubMed:20145243, ECO:0000269|PubMed:20422052, ECO:0000269|PubMed:23469107, ECO:0000269|PubMed:8663044}. |
| P05387 | RPLP2 | S29 | ochoa | Large ribosomal subunit protein P2 (60S acidic ribosomal protein P2) (Renal carcinoma antigen NY-REN-44) | Plays an important role in the elongation step of protein synthesis. |
| P05413 | FABP3 | S35 | ochoa | Fatty acid-binding protein, heart (Fatty acid-binding protein 3) (Heart-type fatty acid-binding protein) (H-FABP) (Mammary-derived growth inhibitor) (MDGI) (Muscle fatty acid-binding protein) (M-FABP) | FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. |
| P05455 | SSB | S163 | ochoa | Lupus La protein (La autoantigen) (La ribonucleoprotein) (Sjoegren syndrome type B antigen) (SS-B) | Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation (PubMed:2470590, PubMed:3192525). In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12384597). {ECO:0000269|PubMed:12384597, ECO:0000269|PubMed:2470590, ECO:0000269|PubMed:3192525}. |
| P05783 | KRT18 | S242 | ochoa | Keratin, type I cytoskeletal 18 (Cell proliferation-inducing gene 46 protein) (Cytokeratin-18) (CK-18) (Keratin-18) (K18) | Involved in the uptake of thrombin-antithrombin complexes by hepatic cells (By similarity). When phosphorylated, plays a role in filament reorganization. Involved in the delivery of mutated CFTR to the plasma membrane. Together with KRT8, is involved in interleukin-6 (IL-6)-mediated barrier protection. {ECO:0000250, ECO:0000269|PubMed:15529338, ECO:0000269|PubMed:16424149, ECO:0000269|PubMed:17213200, ECO:0000269|PubMed:7523419, ECO:0000269|PubMed:8522591, ECO:0000269|PubMed:9298992, ECO:0000269|PubMed:9524113}. |
| P07237 | P4HB | S188 | 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}. |
| P07451 | CA3 | S43 | ochoa | Carbonic anhydrase 3 (EC 4.2.1.1) (Carbonate dehydratase III) (Carbonic anhydrase III) (CA-III) | Reversible hydration of carbon dioxide. {ECO:0000269|PubMed:17427958, ECO:0000269|PubMed:18618712}. |
| P07550 | ADRB2 | S364 | psp | Beta-2 adrenergic receptor (Beta-2 adrenoreceptor) (Beta-2 adrenoceptor) | Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. {ECO:0000269|PubMed:2831218, ECO:0000269|PubMed:7915137}. |
| P08151 | GLI1 | S204 | psp | Zinc finger protein GLI1 (Glioma-associated oncogene) (Oncogene GLI) | Acts as a transcriptional activator (PubMed:10806483, PubMed:19706761, PubMed:19878745, PubMed:24076122, PubMed:24217340, PubMed:24311597). Binds to the DNA consensus sequence 5'-GACCACCCA-3' (PubMed:2105456, PubMed:24217340, PubMed:8378770). Regulates the transcription of specific genes during normal development (PubMed:19706761). Plays a role in craniofacial development and digital development, as well as development of the central nervous system and gastrointestinal tract. Mediates SHH signaling (PubMed:19706761, PubMed:28973407). Plays a role in cell proliferation and differentiation via its role in SHH signaling (PubMed:11238441, PubMed:28973407). {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456, ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:28973407, ECO:0000269|PubMed:8378770}.; FUNCTION: [Isoform 2]: Acts as a transcriptional activator, but activates a different set of genes than isoform 1. Activates expression of CD24, unlike isoform 1. Mediates SHH signaling. Promotes cancer cell migration. {ECO:0000269|PubMed:19706761}. |
| P08238 | HSP90AB1 | S48 | 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}. |
| P08684 | CYP3A4 | S139 | ochoa | Cytochrome P450 3A4 (EC 1.14.14.1) (1,4-cineole 2-exo-monooxygenase) (1,8-cineole 2-exo-monooxygenase) (EC 1.14.14.56) (Albendazole monooxygenase (sulfoxide-forming)) (EC 1.14.14.73) (Albendazole sulfoxidase) (CYPIIIA3) (CYPIIIA4) (Cholesterol 25-hydroxylase) (Cytochrome P450 3A3) (Cytochrome P450 HLp) (Cytochrome P450 NF-25) (Cytochrome P450-PCN1) (Nifedipine oxidase) (Quinine 3-monooxygenase) (EC 1.14.14.55) | A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:10759686, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15373842, ECO:0000269|PubMed:15764715, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20702771, ECO:0000269|PubMed:21490593, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:2732228, ECO:0000269|PubMed:29461981, ECO:0000269|PubMed:8968357, ECO:0000269|PubMed:9435160}. |
| P08684 | CYP3A4 | S398 | psp | Cytochrome P450 3A4 (EC 1.14.14.1) (1,4-cineole 2-exo-monooxygenase) (1,8-cineole 2-exo-monooxygenase) (EC 1.14.14.56) (Albendazole monooxygenase (sulfoxide-forming)) (EC 1.14.14.73) (Albendazole sulfoxidase) (CYPIIIA3) (CYPIIIA4) (Cholesterol 25-hydroxylase) (Cytochrome P450 3A3) (Cytochrome P450 HLp) (Cytochrome P450 NF-25) (Cytochrome P450-PCN1) (Nifedipine oxidase) (Quinine 3-monooxygenase) (EC 1.14.14.55) | A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:10759686, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:11159812, ECO:0000269|PubMed:11555828, ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:15373842, ECO:0000269|PubMed:15764715, ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20702771, ECO:0000269|PubMed:21490593, ECO:0000269|PubMed:21576599, ECO:0000269|PubMed:22773874, ECO:0000269|PubMed:2732228, ECO:0000269|PubMed:29461981, ECO:0000269|PubMed:8968357, ECO:0000269|PubMed:9435160}. |
| P08758 | ANXA5 | S295 | 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. |
| P09211 | GSTP1 | S106 | ochoa | Glutathione S-transferase P (EC 2.5.1.18) (GST class-pi) (GSTP1-1) | Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration. {ECO:0000269|PubMed:21046276, ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9084911}. |
| P09497 | CLTB | S205 | psp | Clathrin light chain B (Lcb) | Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. |
| P09629 | HOXB7 | S133 | psp | Homeobox protein Hox-B7 (Homeobox protein HHO.C1) (Homeobox protein Hox-2C) | Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. |
| P0C7T5 | ATXN1L | S346 | 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}. |
| P10244 | MYBL2 | S472 | ochoa | Myb-related protein B (B-Myb) (Myb-like protein 2) | Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene. {ECO:0000269|PubMed:10770937}. |
| P10451 | SPP1 | S228 | 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}. |
| P11166 | SLC2A1 | S465 | ochoa | Solute carrier family 2, facilitated glucose transporter member 1 (Glucose transporter type 1, erythrocyte/brain) (GLUT-1) (HepG2 glucose transporter) | Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:10227690, PubMed:10954735, PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, PubMed:32860739). Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses (PubMed:18245775, PubMed:19449892). Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative transport of glucose into the brain (PubMed:10227690). In association with BSG and NXNL1, promotes retinal cone survival by increasing glucose uptake into photoreceptors (By similarity). Required for mesendoderm differentiation (By similarity). {ECO:0000250|UniProtKB:P17809, ECO:0000250|UniProtKB:P46896, ECO:0000269|PubMed:10227690, ECO:0000269|PubMed:10954735, ECO:0000269|PubMed:18245775, ECO:0000269|PubMed:19449892, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:27078104, ECO:0000269|PubMed:32860739}. |
| P11413 | G6PD | S160 | ochoa | Glucose-6-phosphate 1-dehydrogenase (G6PD) (EC 1.1.1.49) | Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis. The main function of this enzyme is to provide reducing power (NADPH) and pentose phosphates for fatty acid and nucleic acid synthesis. {ECO:0000269|PubMed:15858258, ECO:0000269|PubMed:24769394, ECO:0000269|PubMed:26479991, ECO:0000269|PubMed:35122041, ECO:0000269|PubMed:38066190, ECO:0000269|PubMed:743300}. |
| P12270 | TPR | S1462 | ochoa | Nucleoprotein TPR (Megator) (NPC-associated intranuclear protein) (Translocated promoter region protein) | Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:11952838, PubMed:22253824). Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases. {ECO:0000269|PubMed:11952838, ECO:0000269|PubMed:15654337, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:18981471, ECO:0000269|PubMed:19273613, ECO:0000269|PubMed:20133940, ECO:0000269|PubMed:20407419, ECO:0000269|PubMed:21613532, ECO:0000269|PubMed:22253824, ECO:0000269|PubMed:9864356}. |
| P12694 | BCKDHA | S347 | ochoa|psp | 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial (EC 1.2.4.4) (Branched-chain alpha-keto acid dehydrogenase E1 component alpha chain) (BCKDE1A) (BCKDH E1-alpha) | Together with BCKDHB forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction. {ECO:0000269|PubMed:10745006, ECO:0000269|PubMed:7883996, ECO:0000269|PubMed:9582350}. |
| P13569 | CFTR | S795 | psp | Cystic fibrosis transmembrane conductance regulator (CFTR) (ATP-binding cassette sub-family C member 7) (Channel conductance-controlling ATPase) (EC 5.6.1.6) (cAMP-dependent chloride channel) | Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810, PubMed:29393851). {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016, ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:12727866, ECO:0000269|PubMed:14668433, ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:16645176, ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064, ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428, ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810, ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:29393851, ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:19923167}. |
| P13637 | ATP1A3 | S442 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-3 (Na(+)/K(+) ATPase alpha-3 subunit) (EC 7.2.2.13) (Na(+)/K(+) ATPase alpha(III) subunit) (Sodium pump subunit alpha-3) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P13637 | ATP1A3 | S643 | ochoa | Sodium/potassium-transporting ATPase subunit alpha-3 (Na(+)/K(+) ATPase alpha-3 subunit) (EC 7.2.2.13) (Na(+)/K(+) ATPase alpha(III) subunit) (Sodium pump subunit alpha-3) | This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. {ECO:0000269|PubMed:33880529}. |
| P14625 | HSP90B1 | S109 | 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}. |
| P15036 | ETS2 | S88 | ochoa | Protein C-ets-2 | Transcription factor activating transcription. Binds specifically the DNA GGAA/T core motif (Ets-binding site or EBS) in gene promoters and stimulates transcription. {ECO:0000269|PubMed:11909962}. |
| P16144 | ITGB4 | S1465 | 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}. |
| P16885 | PLCG2 | S1164 | psp | 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (EC 3.1.4.11) (Phosphoinositide phospholipase C-gamma-2) (Phospholipase C-IV) (PLC-IV) (Phospholipase C-gamma-2) (PLC-gamma-2) | The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling. {ECO:0000269|PubMed:23000145}. |
| P16949 | STMN1 | S28 | ochoa | 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}. |
| P17302 | GJA1 | S330 | ochoa|psp | Gap junction alpha-1 protein (Connexin-43) (Cx43) (Gap junction 43 kDa heart protein) | Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity). {ECO:0000250|UniProtKB:P08050, ECO:0000250|UniProtKB:P23242}. |
| 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}. |
| P18887 | XRCC1 | S357 | psp | DNA repair protein XRCC1 (X-ray repair cross-complementing protein 1) | Scaffold protein involved in DNA single-strand break repair by mediating the assembly of DNA break repair protein complexes (PubMed:11163244, PubMed:28002403). Negatively regulates ADP-ribosyltransferase activity of PARP1 during base-excision repair in order to prevent excessive PARP1 activity (PubMed:28002403, PubMed:34102106, PubMed:34811483). Recognizes and binds poly-ADP-ribose chains: specifically binds auto-poly-ADP-ribosylated PARP1, limiting its activity (PubMed:14500814, PubMed:34102106, PubMed:34811483). {ECO:0000269|PubMed:11163244, ECO:0000269|PubMed:14500814, ECO:0000269|PubMed:28002403, ECO:0000269|PubMed:34102106, ECO:0000269|PubMed:34811483}. |
| P19429 | TNNI3 | S150 | psp | Troponin I, cardiac muscle (Cardiac troponin I) | Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. |
| P19838 | NFKB1 | S20 | psp | Nuclear factor NF-kappa-B p105 subunit (DNA-binding factor KBF1) (EBP-1) (Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) [Cleaved into: Nuclear factor NF-kappa-B p50 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 and the heterodimeric p65-p50 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. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. {ECO:0000269|PubMed:15485931, ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:2203531, ECO:0000269|PubMed:2234062, ECO:0000269|PubMed:7830764}.; FUNCTION: [Nuclear factor NF-kappa-B p105 subunit]: P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B (PubMed:1423592). Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105 (PubMed:1423592). {ECO:0000269|PubMed:1423592}.; FUNCTION: [Nuclear factor NF-kappa-B p50 subunit]: Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor (PubMed:1740106, PubMed:7830764). Together with RELA/p65, 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 (PubMed:1740106, PubMed:7830764). {ECO:0000269|PubMed:1740106, ECO:0000269|PubMed:7830764}. |
| 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. |
| P20815 | CYP3A5 | S139 | ochoa | Cytochrome P450 3A5 (EC 1.14.14.1) (CYPIIIA5) (Cytochrome P450-PCN3) | A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228). {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:2732228}. |
| P20963 | CD247 | S58 | ochoa | T-cell surface glycoprotein CD3 zeta chain (T-cell receptor T3 zeta chain) (CD antigen CD247) | Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:1384049, PubMed:1385158, PubMed:2470098, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity). {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:1384049, ECO:0000269|PubMed:1385158, ECO:0000269|PubMed:16027224, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7509083}. |
| P20963 | CD247 | S124 | ochoa | T-cell surface glycoprotein CD3 zeta chain (T-cell receptor T3 zeta chain) (CD antigen CD247) | Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways (PubMed:1384049, PubMed:1385158, PubMed:2470098, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity). {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:1384049, ECO:0000269|PubMed:1385158, ECO:0000269|PubMed:16027224, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7509083}. |
| P21359 | NF1 | S2587 | ochoa | Neurofibromin (Neurofibromatosis-related protein NF-1) [Cleaved into: Neurofibromin truncated] | Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. {ECO:0000269|PubMed:2121371, ECO:0000269|PubMed:8417346}. |
| P21359 | NF1 | S2601 | ochoa | Neurofibromin (Neurofibromatosis-related protein NF-1) [Cleaved into: Neurofibromin truncated] | Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. {ECO:0000269|PubMed:2121371, ECO:0000269|PubMed:8417346}. |
| P22392 | NME2 | S122 | ochoa | Nucleoside diphosphate kinase B (NDK B) (NDP kinase B) (EC 2.7.4.6) (C-myc purine-binding transcription factor PUF) (Histidine protein kinase NDKB) (EC 2.7.13.3) (nm23-H2) | Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate (By similarity). Negatively regulates Rho activity by interacting with AKAP13/LBC (PubMed:15249197). Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:19435876, PubMed:8392752). Binds to both single-stranded guanine- and cytosine-rich strands within the nuclease hypersensitive element (NHE) III(1) region of the MYC gene promoter. Does not bind to duplex NHE III(1) (PubMed:19435876). Has G-quadruplex (G4) DNA-binding activity, which is independent of its nucleotide-binding and kinase activity. Binds both folded and unfolded G4 with similar low nanomolar affinities. Stabilizes folded G4s regardless of whether they are prefolded or not (PubMed:25679041). Exhibits histidine protein kinase activity (PubMed:20946858). {ECO:0000250|UniProtKB:P36010, ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:19435876, ECO:0000269|PubMed:20946858, ECO:0000269|PubMed:25679041, ECO:0000269|PubMed:8392752}. |
| P23467 | PTPRB | S1654 | ochoa | Receptor-type tyrosine-protein phosphatase beta (Protein-tyrosine phosphatase beta) (R-PTP-beta) (EC 3.1.3.48) (Vascular endothelial protein tyrosine phosphatase) (VE-PTP) | Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity). {ECO:0000250, ECO:0000269|PubMed:19116766, ECO:0000269|PubMed:19136612, ECO:0000269|PubMed:22869525}. |
| P24462 | CYP3A7 | S139 | ochoa | Cytochrome P450 3A7 (EC 1.14.14.1) (CYPIIIA7) (Cytochrome P450-HFLA) (P450HLp2) | A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064). {ECO:0000269|PubMed:11093772, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:14559847, ECO:0000269|PubMed:17178770, ECO:0000269|PubMed:9555064}. |
| P24539 | ATP5PB | S226 | ochoa | ATP synthase peripheral stalk subunit b, mitochondrial (ATP synthase F(0) complex subunit B1, mitochondrial) (ATP synthase peripheral stalk-membrane subunit b) (ATP synthase proton-transporting mitochondrial F(0) complex subunit B1) (ATP synthase subunit b) (ATPase subunit b) | Subunit b, 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:P13619, ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P24539 | ATP5PB | S228 | ochoa | ATP synthase peripheral stalk subunit b, mitochondrial (ATP synthase F(0) complex subunit B1, mitochondrial) (ATP synthase peripheral stalk-membrane subunit b) (ATP synthase proton-transporting mitochondrial F(0) complex subunit B1) (ATP synthase subunit b) (ATPase subunit b) | Subunit b, 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:P13619, ECO:0000250|UniProtKB:P19483, ECO:0000269|PubMed:37244256, ECO:0000305|PubMed:37244256}. |
| P25440 | BRD2 | S340 | ochoa | Bromodomain-containing protein 2 (O27.1.1) | Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at 'Lys-5' and 'Lys-12' (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures (PubMed:17148447, PubMed:17848202, PubMed:18406326, PubMed:20048151, PubMed:20709061, PubMed:20871596). Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation (PubMed:28262505). Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation (PubMed:35410381). Also recognizes and binds acetylated non-histone proteins, such as STAT3 (PubMed:28262505). Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at 'Lys-87', promoting STAT3 recruitment to chromatin (PubMed:28262505). In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Specifically binds histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). {ECO:0000269|PubMed:17148447, ECO:0000269|PubMed:17848202, ECO:0000269|PubMed:18406326, ECO:0000269|PubMed:20048151, ECO:0000269|PubMed:20709061, ECO:0000269|PubMed:20871596, ECO:0000269|PubMed:28262505, ECO:0000269|PubMed:35410381, ECO:0000269|PubMed:37731000}. |
| P25815 | S100P | S24 | ochoa | Protein S100-P (Migration-inducing gene 9 protein) (MIG9) (Protein S100-E) (S100 calcium-binding protein P) | May function as calcium sensor and contribute to cellular calcium signaling. In a calcium-dependent manner, functions by interacting with other proteins, such as EZR and PPP5C, and indirectly plays a role in physiological processes like the formation of microvilli in epithelial cells. May stimulate cell proliferation in an autocrine manner via activation of the receptor for activated glycation end products (RAGE). {ECO:0000269|PubMed:14617629, ECO:0000269|PubMed:19111582, ECO:0000269|PubMed:22399290}. |
| P27708 | CAD | S1321 | ochoa | Multifunctional protein CAD (Carbamoyl phosphate synthetase 2-aspartate transcarbamylase-dihydroorotase) [Includes: Glutamine-dependent carbamoyl phosphate synthase (EC 6.3.5.5); Glutamine amidotransferase (GATase) (GLNase) (EC 3.5.1.2); Ammonium-dependent carbamoyl phosphate synthase (CPS) (CPSase) (EC 6.3.4.16); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] | Multifunctional protein that encodes the first 3 enzymatic activities of the de novo pyrimidine pathway: carbamoylphosphate synthetase (CPSase; EC 6.3.5.5), aspartate transcarbamylase (ATCase; EC 2.1.3.2) and dihydroorotase (DHOase; EC 3.5.2.3). The CPSase-function is accomplished in 2 steps, by a glutamine-dependent amidotransferase activity (GATase) that binds and cleaves glutamine to produce ammonia, followed by an ammonium-dependent carbamoyl phosphate synthetase, which reacts with the ammonia, hydrogencarbonate and ATP to form carbamoyl phosphate. The endogenously produced carbamoyl phosphate is sequestered and channeled to the ATCase active site. ATCase then catalyzes the formation of carbamoyl-L-aspartate from L-aspartate and carbamoyl phosphate. In the last step, DHOase catalyzes the cyclization of carbamoyl aspartate to dihydroorotate. {ECO:0000269|PubMed:24332717}. |
| P28290 | ITPRID2 | S944 | ochoa | Protein ITPRID2 (Cleavage signal-1 protein) (CS-1) (ITPR-interacting domain-containing protein 2) (Ki-ras-induced actin-interacting protein) (Sperm-specific antigen 2) | None |
| P28290 | ITPRID2 | S1138 | 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 |
| P29474 | NOS3 | S625 | ochoa | Nitric oxide synthase 3 (EC 1.14.13.39) (Constitutive NOS) (cNOS) (EC-NOS) (NOS type III) (NOSIII) (Nitric oxide synthase, endothelial) (Endothelial NOS) (eNOS) | Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. {ECO:0000269|PubMed:1378832}.; FUNCTION: [Isoform eNOS13C]: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1. |
| P29692 | EEF1D | S44 | ochoa | Elongation factor 1-delta (EF-1-delta) (Antigen NY-CO-4) | [Isoform 1]: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.; FUNCTION: [Isoform 2]: Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE). |
| P29803 | PDHA2 | S310 | ochoa | Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial (EC 1.2.4.1) (PDHE1-A type II) | The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle. {ECO:0000269|PubMed:16436377}. |
| P30874 | SSTR2 | S343 | psp | Somatostatin receptor type 2 (SS-2-R) (SS2-R) (SS2R) (SST2) (SRIF-1) | Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization. {ECO:0000269|PubMed:15231824, ECO:0000269|PubMed:18653781, ECO:0000269|PubMed:19434240, ECO:0000269|PubMed:22495673, ECO:0000269|PubMed:22932785}. |
| P31327 | CPS1 | S468 | 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. |
| P32004 | L1CAM | S1178 | ochoa | Neural cell adhesion molecule L1 (N-CAM-L1) (NCAM-L1) (CD antigen CD171) | Neural cell adhesion molecule involved in the dynamics of cell adhesion and in the generation of transmembrane signals at tyrosine kinase receptors. During brain development, critical in multiple processes, including neuronal migration, axonal growth and fasciculation, and synaptogenesis. In the mature brain, plays a role in the dynamics of neuronal structure and function, including synaptic plasticity. {ECO:0000269|PubMed:20621658, ECO:0000305}. |
| P33176 | KIF5B | S825 | ochoa | Kinesin-1 heavy chain (Conventional kinesin heavy chain) (Ubiquitous kinesin heavy chain) (UKHC) | Microtubule-dependent motor required for normal distribution of mitochondria and lysosomes. Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner (By similarity). Regulates centrosome and nuclear positioning during mitotic entry. During the G2 phase of the cell cycle in a BICD2-dependent manner, antagonizes dynein function and drives the separation of nuclei and centrosomes (PubMed:20386726). Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation (By similarity). Through binding with PLEKHM2 and ARL8B, directs lysosome movement toward microtubule plus ends (Probable). Involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). {ECO:0000250|UniProtKB:Q2PQA9, ECO:0000250|UniProtKB:Q61768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:24088571, ECO:0000305|PubMed:22172677, ECO:0000305|PubMed:24088571}. |
| P33981 | TTK | S49 | ochoa|psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P35240 | NF2 | S518 | ochoa|psp | Merlin (Moesin-ezrin-radixin-like protein) (Neurofibromin-2) (Schwannomerlin) (Schwannomin) | Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with WWC1 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its stimulating activity. Suppresses cell proliferation and tumorigenesis by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase complex. {ECO:0000269|PubMed:20159598, ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}. |
| 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}. |
| P35268 | RPL22 | S66 | ochoa | Large ribosomal subunit protein eL22 (60S ribosomal protein L22) (EBER-associated protein) (EAP) (Epstein-Barr virus small RNA-associated protein) (Heparin-binding protein HBp15) | 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}. |
| P35348 | ADRA1A | S413 | psp | Alpha-1A adrenergic receptor (Alpha-1A adrenoreceptor) (Alpha-1A adrenoceptor) (Alpha-1C adrenergic receptor) (Alpha-adrenergic receptor 1c) | This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. {ECO:0000269|PubMed:18802028, ECO:0000269|PubMed:22120526}. |
| P35462 | DRD3 | S233 | psp | D(3) dopamine receptor (Dopamine D3 receptor) | Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation. {ECO:0000269|PubMed:19520868}. |
| P35523 | CLCN1 | S892 | psp | Chloride channel protein 1 (ClC-1) (Chloride channel protein, skeletal muscle) | Voltage-gated chloride channel involved in skeletal muscle excitability. Generates most of the plasma membrane chloride conductance in skeletal muscle fibers, stabilizes the resting membrane potential and contributes to the repolarization phase during action potential firing (PubMed:12456816, PubMed:16027167, PubMed:22521272, PubMed:22641783, PubMed:26007199, PubMed:26502825, PubMed:26510092, PubMed:7951242, PubMed:8112288, PubMed:8130334, PubMed:9122265, PubMed:9565403, PubMed:9736777). Forms a homodimeric channel where each subunit has its own ion conduction pathway. Conducts double-barreled currents controlled by two types of gates, two fast glutamate gates that control each subunit independently and a slow common gate that opens and shuts off both subunits simultaneously. Has a significant open probability at muscle resting potential and is further activated upon membrane depolarization (PubMed:10051520, PubMed:10962018, PubMed:29809153, PubMed:31022181). Permeable to small monovalent anions with ion selectivity for chloride > thiocyanate > bromide > nitrate > iodide (PubMed:9122265, PubMed:9565403). {ECO:0000269|PubMed:10051520, ECO:0000269|PubMed:10962018, ECO:0000269|PubMed:12456816, ECO:0000269|PubMed:16027167, ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:22641783, ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:29809153, ECO:0000269|PubMed:31022181, ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8130334, ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9565403, ECO:0000269|PubMed:9736777}. |
| P35579 | MYH9 | S751 | 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}. |
| P35579 | MYH9 | S1057 | ochoa | Myosin-9 (Cellular myosin heavy chain, type A) (Myosin heavy chain 9) (Myosin heavy chain, non-muscle IIa) (Non-muscle myosin heavy chain A) (NMMHC-A) (Non-muscle myosin heavy chain IIa) (NMMHC II-a) (NMMHC-IIA) | Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411). {ECO:0000250|UniProtKB:Q8VDD5, ECO:0000269|PubMed:16707441, ECO:0000269|PubMed:20052411}.; FUNCTION: (Microbial infection) Acts as a receptor for herpes simplex virus 1/HHV-1 envelope glycoprotein B. {ECO:0000269|PubMed:20944748, ECO:0000269|PubMed:39048823}. |
| P35606 | COPB2 | S867 | 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}. |
| P35749 | MYH11 | S201 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P35749 | MYH11 | S589 | ochoa | Myosin-11 (Myosin heavy chain 11) (Myosin heavy chain, smooth muscle isoform) (SMMHC) | Muscle contraction. |
| P35869 | AHR | S36 | 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}. |
| P36507 | MAP2K2 | S222 | ochoa|psp | Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2) | Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}. |
| P37198 | NUP62 | S461 | ochoa | Nuclear pore glycoprotein p62 (62 kDa nucleoporin) (Nucleoporin Nup62) | Essential component of the nuclear pore complex (PubMed:1915414). The N-terminal is probably involved in nucleocytoplasmic transport (PubMed:1915414). The C-terminal is involved in protein-protein interaction probably via coiled-coil formation, promotes its association with centrosomes and may function in anchorage of p62 to the pore complex (PubMed:1915414, PubMed:24107630). Plays a role in mitotic cell cycle progression by regulating centrosome segregation, centriole maturation and spindle orientation (PubMed:24107630). It might be involved in protein recruitment to the centrosome after nuclear breakdown (PubMed:24107630). {ECO:0000269|PubMed:1915414, ECO:0000269|PubMed:24107630}. |
| P38398 | BRCA1 | S454 | 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 | S1387 | psp | Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) | E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage (PubMed:10500182, PubMed:12887909, PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340, PubMed:19261748). It is unclear whether it also mediates the formation of other types of polyubiquitin chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability (PubMed:12890688, PubMed:14976165, PubMed:20351172). Regulates centrosomal microtubule nucleation (PubMed:18056443). Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle (PubMed:10724175, PubMed:11836499, PubMed:12183412, PubMed:19261748). Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909). Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation (PubMed:16326698). Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8 (PubMed:16818604). Acts as a transcriptional activator (PubMed:20160719). {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}. |
| P38432 | COIL | S447 | ochoa | Coilin (p80-coilin) | Component of nuclear coiled bodies, also known as Cajal bodies or CBs, which are involved in the modification and assembly of nucleoplasmic snRNPs. {ECO:0000269|PubMed:7679389}. |
| P38606 | ATP6V1A | S418 | ochoa | V-type proton ATPase catalytic subunit A (V-ATPase subunit A) (EC 7.1.2.2) (V-ATPase 69 kDa subunit) (Vacuolar ATPase isoform VA68) (Vacuolar proton pump subunit alpha) | Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:8463241). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in neurite development and synaptic connectivity (PubMed:29668857). {ECO:0000250|UniProtKB:P50516, ECO:0000269|PubMed:28296633, ECO:0000269|PubMed:29668857, ECO:0000269|PubMed:8463241, ECO:0000303|PubMed:32001091}.; FUNCTION: (Microbial infection) Plays an important role in virion uncoating during Rabies virus replication after membrane fusion. Specifically, participates in the dissociation of incoming viral matrix M proteins uncoating through direct interaction. {ECO:0000269|PubMed:33208464}. |
| P39019 | RPS19 | S93 | ochoa | Small ribosomal subunit protein eS19 (40S ribosomal protein S19) | Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399). Required for pre-rRNA processing and maturation of 40S ribosomal subunits (PubMed:16990592). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:16990592, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:34516797}. |
| P39880 | CUX1 | S409 | ochoa | Homeobox protein cut-like 1 (CCAAT displacement protein) (CDP) (CDP/Cux p200) (Homeobox protein cux-1) [Cleaved into: CDP/Cux p110] | Transcription factor involved in the control of neuronal differentiation in the brain. Regulates dendrite development and branching, and dendritic spine formation in cortical layers II-III. Also involved in the control of synaptogenesis. In addition, it has probably a broad role in mammalian development as a repressor of developmentally regulated gene expression. May act by preventing binding of positively-activing CCAAT factors to promoters. Component of nf-munr repressor; binds to the matrix attachment regions (MARs) (5' and 3') of the immunoglobulin heavy chain enhancer. Represses T-cell receptor (TCR) beta enhancer function by binding to MARbeta, an ATC-rich DNA sequence located upstream of the TCR beta enhancer. Binds to the TH enhancer; may require the basic helix-loop-helix protein TCF4 as a coactivator. {ECO:0000250|UniProtKB:P53564}.; FUNCTION: [CDP/Cux p110]: Plays a role in cell cycle progression, in particular at the G1/S transition. As cells progress into S phase, a fraction of CUX1 molecules is proteolytically processed into N-terminally truncated proteins of 110 kDa. While CUX1 only transiently binds to DNA and carries the CCAAT-displacement activity, CDP/Cux p110 makes a stable interaction with DNA and stimulates expression of genes such as POLA1. {ECO:0000269|PubMed:15099520}. |
| P40925 | MDH1 | S141 | ochoa | Malate dehydrogenase, cytoplasmic (EC 1.1.1.37) (Aromatic alpha-keto acid reductase) (KAR) (EC 1.1.1.96) (Cytosolic malate dehydrogenase) | Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation (PubMed:31538237). Catalyzes the reduction of 2-oxoglutarate to 2-hydroxyglutarate, leading to elevated reactive oxygen species (ROS) (PubMed:34012073). {ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244, ECO:0000269|PubMed:31538237}. |
| P41743 | PRKCI | S458 | ochoa | Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) | Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}. |
| P42695 | NCAPD3 | S567 | ochoa | Condensin-2 complex subunit D3 (Non-SMC condensin II complex subunit D3) (hCAP-D3) | Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis (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. Specifically required for decatenation of 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:14532007, ECO:0000269|PubMed:27737959}. |
| P42858 | HTT | S114 | 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}. |
| 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}. |
| P43243 | MATR3 | S511 | ochoa | Matrin-3 | May play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. In association with the SFPQ-NONO heteromer may play a role in nuclear retention of defective RNAs. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). Binds to N6-methyladenosine (m6A)-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs (PubMed:32245947). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:32245947}. |
| P46013 | MKI67 | S1207 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1815 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S1937 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2299 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2420 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2542 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2599 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2783 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46013 | MKI67 | S2901 | ochoa | Proliferation marker protein Ki-67 (Antigen identified by monoclonal antibody Ki-67) (Antigen KI-67) (Antigen Ki67) | Protein that associates with the surface of mitotic chromosomes and acts both as a chromosome repellent during early mitosis and chromosome attractant during late mitosis (PubMed:27362226, PubMed:32879492, PubMed:35513709, PubMed:39153474). Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). During early mitosis, relocalizes from nucleoli to the chromosome surface where it forms extended brush structures that cover a substantial fraction of the chromosome surface (PubMed:27362226). The MKI67 brush structure prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). During mitotic anaphase, the MKI67 brush structure collapses and MKI67 switches from a chromosome repellent to a chromosome attractant to promote chromosome clustering and facilitate the exclusion of large cytoplasmic particles from the future nuclear space (PubMed:32879492, PubMed:39153474). Mechanistically, dephosphorylation during mitotic exit and simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface, promoting coalescence of neighboring chromosome surfaces and clustering of chromosomes (PubMed:39153474). Binds premature ribosomal RNAs during anaphase; promoting liquid-liquid phase separation (PubMed:28935370, PubMed:39153474). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization; it is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in mitotic chromosome (PubMed:24867636). {ECO:0000250|UniProtKB:E9PVX6, ECO:0000269|PubMed:10878551, ECO:0000269|PubMed:24867636, ECO:0000269|PubMed:27362226, ECO:0000269|PubMed:28935370, ECO:0000269|PubMed:32879492, ECO:0000269|PubMed:35513709, ECO:0000269|PubMed:39153474}. |
| P46531 | NOTCH1 | S1801 | ochoa | Neurogenic locus notch homolog protein 1 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Cleaved into: Notch 1 extracellular truncation (NEXT); Notch 1 intracellular domain (NICD)] | Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis. May enhance HIF1A function by sequestering HIF1AN away from HIF1A. Required for the THBS4 function in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury. Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). {ECO:0000269|PubMed:20616313}. |
| P47985 | UQCRFS1 | S99 | ochoa | Cytochrome b-c1 complex subunit Rieske, mitochondrial (EC 7.1.1.8) (Complex III subunit 5) (Cytochrome b-c1 complex subunit 5) (Rieske iron-sulfur protein) (RISP) (Rieske protein UQCRFS1) (Ubiquinol-cytochrome c reductase iron-sulfur subunit) [Cleaved into: Cytochrome b-c1 complex subunit 9 (Su9) (Subunit 9) (8 kDa subunit 9) (Complex III subunit IX) (Cytochrome b-c1 complex subunit 11) (UQCRFS1 mitochondrial targeting sequence) (UQCRFS1 MTS) (Ubiquinol-cytochrome c reductase 8 kDa protein)] | [Cytochrome b-c1 complex subunit Rieske, mitochondrial]: Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation (PubMed:31883641). The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c. The Rieske protein is a catalytic core subunit containing a [2Fe-2S] iron-sulfur cluster. It cycles between 2 conformational states during catalysis to transfer electrons from the quinol bound in the Q(0) site in cytochrome b to cytochrome c1 (By similarity). Incorporation of UQCRFS1 is the penultimate step in complex III assembly (PubMed:28673544). {ECO:0000250|UniProtKB:P08067, ECO:0000269|PubMed:28673544, ECO:0000269|PubMed:31883641}.; FUNCTION: [Cytochrome b-c1 complex subunit 9]: Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII). UQCRFS1 undergoes proteolytic processing once it is incorporated in the complex III dimer. One of the fragments, called subunit 9, corresponds to its mitochondrial targeting sequence (MTS). The proteolytic processing is necessary for the correct insertion of UQCRFS1 in the complex III dimer, but the persistence of UQCRFS1-derived fragments may prevent newly imported UQCRFS1 to be processed and assembled into complex III and is detrimental for the complex III structure and function. {ECO:0000269|PubMed:28673544}. |
| P48382 | RFX5 | S312 | ochoa | DNA-binding protein RFX5 (Regulatory factor X 5) | Activates transcription from class II MHC promoters. Recognizes X-boxes. Mediates cooperative binding between RFX and NF-Y. RFX binds the X1 box of MHC-II promoters. |
| P48730 | CSNK1D | S191 | psp | Casein kinase I isoform delta (CKI-delta) (CKId) (EC 2.7.11.1) (Tau-protein kinase CSNK1D) (EC 2.7.11.26) | Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (By similarity). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. {ECO:0000250|UniProtKB:Q9DC28, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:16027726, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:19043076, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:20407760, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:20696890, ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:21084295, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092}. |
| P49321 | NASP | S384 | ochoa | Nuclear autoantigenic sperm protein (NASP) | Component of the histone chaperone network (PubMed:22195965). Binds and stabilizes histone H3-H4 not bound to chromatin to maintain a soluble reservoir and modulate degradation by chaperone-mediated autophagy (PubMed:22195965). Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA. {ECO:0000250|UniProtKB:Q99MD9, ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 1]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}.; FUNCTION: [Isoform 2]: Stabilizes soluble histone H3-H4. {ECO:0000269|PubMed:22195965}. |
| P49327 | FASN | S2123 | 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}. |
| P49619 | DGKG | S153 | ochoa | Diacylglycerol kinase gamma (DAG kinase gamma) (EC 2.7.1.107) (Diglyceride kinase gamma) (DGK-gamma) | Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:8034597). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (By similarity). Has no apparent specificity with regard to the acyl compositions of diacylglycerol (PubMed:8034597). Specifically expressed in the cerebellum where it controls the level of diacylglycerol which in turn regulates the activity of protein kinase C gamma. Through protein kinase C gamma, indirectly regulates the dendritic development of Purkinje cells, cerebellar long term depression and ultimately cerebellar motor coordination (By similarity). {ECO:0000250|UniProtKB:Q91WG7, ECO:0000269|PubMed:8034597}. |
| P49736 | MCM2 | S220 | psp | DNA replication licensing factor MCM2 (EC 3.6.4.12) (Minichromosome maintenance protein 2 homolog) (Nuclear protein BM28) | Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (PubMed:8175912). Plays a role in terminally differentiated hair cells development of the cochlea and induces cells apoptosis (PubMed:26196677). {ECO:0000269|PubMed:26196677, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:8175912}. |
| P49759 | CLK1 | S337 | ochoa | Dual specificity protein kinase CLK1 (EC 2.7.12.1) (CDC-like kinase 1) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1 (PubMed:10480872, PubMed:19168442). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (PubMed:19168442). {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442}. |
| P50402 | EMD | S123 | ochoa | Emerin | Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. {ECO:0000269|PubMed:15328537, ECO:0000269|PubMed:16680152, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17785515, ECO:0000269|PubMed:19323649, ECO:0000269|PubMed:32923640}. |
| P50591 | TNFSF10 | S96 | ochoa | Tumor necrosis factor ligand superfamily member 10 (Apo-2 ligand) (Apo-2L) (TNF-related apoptosis-inducing ligand) (Protein TRAIL) (CD antigen CD253) | Cytokine that binds to TNFRSF10A/TRAILR1, TNFRSF10B/TRAILR2, TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and possibly also to TNFRSF11B/OPG (PubMed:10549288, PubMed:26457518). Induces apoptosis. Its activity may be modulated by binding to the decoy receptors TNFRSF10C/TRAILR3, TNFRSF10D/TRAILR4 and TNFRSF11B/OPG that cannot induce apoptosis. {ECO:0000269|PubMed:10549288, ECO:0000269|PubMed:26457518}. |
| P52292 | KPNA2 | S87 | 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}. |
| P53355 | DAPK1 | S366 | ochoa | Death-associated protein kinase 1 (DAP kinase 1) (EC 2.7.11.1) | Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.; FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane blebbing. |
| P53367 | ARFIP1 | S24 | ochoa | Arfaptin-1 (ADP-ribosylation factor-interacting protein 1) | Plays a role in controlling biogenesis of secretory granules at the trans-Golgi network (PubMed:22981988). Mechanistically, binds ARF-GTP at the neck of a growing secretory granule precursor and forms a protective scaffold (PubMed:22981988, PubMed:9038142). Once the granule precursor has been completely loaded, active PRKD1 phosphorylates ARFIP1 and releases it from ARFs (PubMed:22981988). In turn, ARFs induce fission (PubMed:22981988). Through this mechanism, ensures proper secretory granule formation at the Golgi of pancreatic beta cells (PubMed:22981988). {ECO:0000269|PubMed:22981988, ECO:0000269|PubMed:9038142}. |
| P54274 | TERF1 | S367 | 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}. |
| P54296 | MYOM2 | S469 | 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. |
| P55196 | AFDN | S1262 | ochoa | Afadin (ALL1-fused gene from chromosome 6 protein) (Protein AF-6) (Afadin adherens junction formation factor) | Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011). {ECO:0000250|UniProtKB:O35889, ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:30463011}. |
| P55201 | BRPF1 | S577 | ochoa | Peregrin (Bromodomain and PHD finger-containing protein 1) (Protein Br140) | Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:24065767, PubMed:27939640). Plays a key role in HBO1 complex by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac) (PubMed:24065767). Some HAT complexes preferentially mediate histone H3 'Lys-23' (H3K23ac) acetylation (PubMed:27939640). Positively regulates the transcription of RUNX1 and RUNX2 (PubMed:18794358). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:18794358, ECO:0000269|PubMed:24065767, ECO:0000269|PubMed:27939640}. |
| P55210 | CASP7 | S239 | psp | Caspase-7 (CASP-7) (EC 3.4.22.60) (Apoptotic protease Mch-3) (CMH-1) (ICE-like apoptotic protease 3) (ICE-LAP3) [Cleaved into: Caspase-7 subunit p20; Caspase-7 subunit p11] | Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (PubMed:11257230, PubMed:11257231, PubMed:11701129, PubMed:15314233, PubMed:16916640, PubMed:17646170, PubMed:18723680, PubMed:19581639, PubMed:8521391, PubMed:8567622, PubMed:8576161, PubMed:9070923). Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences (PubMed:12824163, PubMed:15314233, PubMed:17697120, PubMed:19581639, PubMed:20566630, PubMed:23650375, PubMed:23897474, PubMed:27032039). Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (By similarity). Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and YY1 (PubMed:10497198, PubMed:16123041, PubMed:16374543, PubMed:16916640, PubMed:18723680, PubMed:20566630, PubMed:21555521, PubMed:22184066, PubMed:22451931, PubMed:27889207, PubMed:28863261, PubMed:31586028, PubMed:34156061, PubMed:35338844, PubMed:35446120). Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins (PubMed:18723680). Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair (PubMed:21157428). Regulates pyroptosis in intestinal epithelial cells: cleaved and activated by CASP1 in response to S.typhimurium infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of gasdermin-D (GSDMD) pores (By similarity). Regulates granzyme-mediated programmed cell death in hepatocytes: cleaved and activated by granzyme B (GZMB) in response to bacterial infection, promoting its secretion to the extracellular milieu, where it catalyzes activation of SMPD1, generating ceramides that repair membranes and counteract the action of perforin (PRF1) pores (By similarity). Following cleavage by CASP1 in response to inflammasome activation, catalyzes processing and inactivation of PARP1, alleviating the transcription repressor activity of PARP1 (PubMed:22464733). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (By similarity). Cleaves and activates sterol regulatory element binding proteins (SREBPs) (PubMed:8643593). Cleaves phospholipid scramblase proteins XKR4, XKR8 and XKR9 (By similarity). In case of infection, catalyzes cleavage of Kaposi sarcoma-associated herpesvirus protein ORF57, thereby preventing expression of viral lytic genes (PubMed:20159985). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106). {ECO:0000250|UniProtKB:P97864, ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:16374543, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17646170, ECO:0000269|PubMed:17697120, ECO:0000269|PubMed:18723680, ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:20159985, ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:21157428, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:22184066, ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23897474, ECO:0000269|PubMed:27032039, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:28863261, ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:36758104, ECO:0000269|PubMed:36758106, ECO:0000269|PubMed:8521391, ECO:0000269|PubMed:8567622, ECO:0000269|PubMed:8576161, ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9070923}.; FUNCTION: [Isoform Beta]: Lacks enzymatic activity. {ECO:0000269|PubMed:8521391}. |
| P57076 | CFAP298 | S236 | ochoa | Cilia- and flagella-associated protein 298 (Protein kurly homolog) | Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly (PubMed:24094744). Seems to be important for initiation rather than maintenance of cilium motility (By similarity). Required for correct positioning of the cilium at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway (By similarity). May suppress canonical Wnt signaling activity (By similarity). {ECO:0000250|UniProtKB:Q6DRC3, ECO:0000269|PubMed:24094744}. |
| 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}. |
| P62195 | PSMC5 | S120 | psp | 26S proteasome regulatory subunit 8 (26S proteasome AAA-ATPase subunit RPT6) (Proteasome 26S subunit ATPase 5) (Proteasome subunit p45) (Thyroid hormone receptor-interacting protein 1) (TRIP1) (p45/SUG) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. {ECO:0000269|PubMed:1317798}. |
| P62851 | RPS25 | S74 | 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}. |
| P62854 | RPS26 | S54 | ochoa | Small ribosomal subunit protein eS26 (40S ribosomal protein S26) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:25957688). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688}. |
| P62857 | RPS28 | S39 | ochoa | Small ribosomal subunit protein eS28 (40S ribosomal protein S28) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:25957688). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:34516797}. |
| P62857 | RPS28 | S41 | ochoa | Small ribosomal subunit protein eS28 (40S ribosomal protein S28) | Component of the small ribosomal subunit (PubMed:23636399, PubMed:25901680, PubMed:25957688). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:25901680, PubMed:25957688). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:25901680, ECO:0000269|PubMed:25957688, ECO:0000269|PubMed:34516797}. |
| P62987 | UBA52 | S65 | ochoa|psp | Ubiquitin-ribosomal protein eL40 fusion protein (CEP52) (Ubiquitin A-52 residue ribosomal protein fusion product 1) [Cleaved into: Ubiquitin; Large ribosomal subunit protein eL40 (60S ribosomal protein L40) (rpL40)] | [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling. {ECO:0000269|PubMed:16543144, ECO:0000269|PubMed:34239127, ECO:0000303|PubMed:19754430}.; FUNCTION: [Large ribosomal subunit protein eL40]: Component of the 60S subunit of the ribosome (PubMed:23169626, PubMed:23636399, PubMed:32669547, PubMed:39048817, PubMed:39103523). Ribosomal protein L40 is essential for translation of a subset of cellular transcripts, and especially for cap-dependent translation of vesicular stomatitis virus mRNAs (PubMed:23169626, PubMed:23636399, PubMed:32669547, PubMed:39048817, PubMed:39103523). {ECO:0000269|PubMed:23169626, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:32669547, ECO:0000269|PubMed:39048817, ECO:0000269|PubMed:39103523}. |
| P68400 | CSNK2A1 | S287 | ochoa | Casein kinase II subunit alpha (CK II alpha) (EC 2.7.11.1) | Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:19188443, PubMed:20545769, PubMed:20625391, PubMed:22017874, PubMed:22406621, PubMed:24962073, PubMed:30898438, PubMed:31439799). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:12631575, PubMed:19387551, PubMed:19387552). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387551, PubMed:19387552). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage (PubMed:11704824, PubMed:19188443). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation (PubMed:11239457). Phosphorylates a number of DNA repair proteins in response to DNA damage, such as MDC1, MRE11, RAD9A, RAD51 and HTATSF1, promoting their recruitment to DNA damage sites (PubMed:18411307, PubMed:18583988, PubMed:18678890, PubMed:20545769, PubMed:21482717, PubMed:22325354, PubMed:26811421, PubMed:28512243, PubMed:30898438, PubMed:35597237). Can also negatively regulate apoptosis (PubMed:16193064, PubMed:22184066). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:16193064). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:16193064). Phosphorylates YY1, protecting YY1 from cleavage by CASP7 during apoptosis (PubMed:22184066). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552, PubMed:23123191). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552, PubMed:23123191). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (PubMed:19387550). Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90 (PubMed:30699359). Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1 (PubMed:19387549). Acts as an ectokinase that phosphorylates several extracellular proteins (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552). During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (PubMed:12631575, PubMed:19387550, PubMed:19387551, PubMed:19387552). Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (PubMed:20625391, PubMed:22406621). Plays an important role in the circadian clock function by phosphorylating BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (By similarity). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073). Phosphorylates FMR1, promoting FMR1-dependent formation of a membraneless compartment (PubMed:30765518, PubMed:31439799). May phosphorylate histone H2A on 'Ser-1' (PubMed:38334665). {ECO:0000250|UniProtKB:P19139, ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:11704824, ECO:0000269|PubMed:16193064, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:19188443, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:20625391, ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22184066, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:23123191, ECO:0000269|PubMed:24962073, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:28512243, ECO:0000269|PubMed:30699359, ECO:0000269|PubMed:30765518, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:31439799, ECO:0000269|PubMed:35597237, ECO:0000269|PubMed:38334665, ECO:0000303|PubMed:12631575, ECO:0000303|PubMed:19387549, ECO:0000303|PubMed:19387550, ECO:0000303|PubMed:19387551, ECO:0000303|PubMed:19387552}. |
| P78332 | RBM6 | S555 | ochoa | RNA-binding protein 6 (Lung cancer antigen NY-LU-12) (Protein G16) (RNA-binding motif protein 6) (RNA-binding protein DEF-3) | Specifically binds poly(G) RNA homopolymers in vitro. |
| Q00534 | CDK6 | S293 | ochoa | Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) | Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}. |
| Q00610 | CLTC | S751 | 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}. |
| Q00872 | MYBPC1 | S422 | 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}. |
| Q02750 | MAP2K1 | S218 | ochoa|psp | Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}. |
| Q02952 | AKAP12 | S353 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q02952 | AKAP12 | S1226 | ochoa | A-kinase anchor protein 12 (AKAP-12) (A-kinase anchor protein 250 kDa) (AKAP 250) (Gravin) (Myasthenia gravis autoantigen) | Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC). |
| Q02978 | SLC25A11 | 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 | S1692 | 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 | S713 | 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}. |
| Q03468 | ERCC6 | S1388 | ochoa | DNA excision repair protein ERCC-6 (EC 3.6.4.-) (ATP-dependent helicase ERCC6) (Cockayne syndrome protein CSB) | Essential factor involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:16246722, PubMed:20541997, PubMed:22483866, PubMed:26620705, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Plays a central role in the initiation of the TC-NER process: specifically recognizes and binds RNA polymerase II stalled at a lesion, and mediates recruitment of ERCC8/CSA, initiating DNA damage excision by TFIIH recruitment (PubMed:32355176, PubMed:34526721, PubMed:38600235, PubMed:38600236). Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA (PubMed:15548521). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (PubMed:16246722, PubMed:9565609). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (PubMed:25820262). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (PubMed:25820262). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs (PubMed:25820262). Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928). Also involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740). {ECO:0000269|PubMed:15548521, ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866, ECO:0000269|PubMed:24874740, ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:38316879, ECO:0000269|PubMed:38600235, ECO:0000269|PubMed:38600236, ECO:0000269|PubMed:9565609}. |
| Q04671 | OCA2 | S195 | ochoa | P protein (Melanocyte-specific transporter protein) (Pink-eyed dilution protein homolog) | Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation (PubMed:11310796, PubMed:15262401, PubMed:22234890, PubMed:25513726). One of the components of the mammalian pigmentary system (PubMed:15262401, PubMed:18252222, PubMed:7601462). May serve as a key control point at which ethnic skin color variation is determined. Major determinant of brown and/or blue eye color (PubMed:15262401, PubMed:18252222, PubMed:7601462). Seems to regulate the post-translational processing of tyrosinase, which catalyzes the limiting reaction in melanin synthesis (By similarity). {ECO:0000250|UniProtKB:Q62052, ECO:0000269|PubMed:11310796, ECO:0000269|PubMed:15262401, ECO:0000269|PubMed:18252222, ECO:0000269|PubMed:22234890, ECO:0000269|PubMed:25513726, ECO:0000269|PubMed:7601462}. |
| Q06187 | BTK | S604 | ochoa | Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) | Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}. |
| Q08117 | TLE5 | S68 | ochoa | TLE family member 5 (Amino-terminal enhancer of split) (Amino enhancer of split) (Gp130-associated protein GAM) (Grg-5) (Groucho-related protein 5) (Protein ESP1) (Protein GRG) (TLE family member 5, transcriptional modulator) | Transcriptional corepressor. Acts as a dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development. {ECO:0000269|PubMed:10660609, ECO:0000269|PubMed:10748198}. |
| Q08211 | DHX9 | S506 | ochoa | ATP-dependent RNA helicase A (EC 3.6.4.13) (DEAH box protein 9) (DExH-box helicase 9) (Leukophysin) (LKP) (Nuclear DNA helicase II) (NDH II) (RNA helicase A) | Multifunctional ATP-dependent nucleic acid helicase that unwinds DNA and RNA in a 3' to 5' direction and that plays important roles in many processes, such as DNA replication, transcriptional activation, post-transcriptional RNA regulation, mRNA translation and RNA-mediated gene silencing (PubMed:11416126, PubMed:12711669, PubMed:15355351, PubMed:16680162, PubMed:17531811, PubMed:20669935, PubMed:21561811, PubMed:24049074, PubMed:24990949, PubMed:25062910, PubMed:28221134, PubMed:9111062, PubMed:37467750). Requires a 3'-single-stranded tail as entry site for acid nuclei unwinding activities as well as the binding and hydrolyzing of any of the four ribo- or deoxyribo-nucleotide triphosphates (NTPs) (PubMed:1537828). Unwinds numerous nucleic acid substrates such as double-stranded (ds) DNA and RNA, DNA:RNA hybrids, DNA and RNA forks composed of either partially complementary DNA duplexes or DNA:RNA hybrids, respectively, and also DNA and RNA displacement loops (D- and R-loops), triplex-helical DNA (H-DNA) structure and DNA and RNA-based G-quadruplexes (PubMed:20669935, PubMed:21561811, PubMed:24049074). Binds dsDNA, single-stranded DNA (ssDNA), dsRNA, ssRNA and poly(A)-containing RNA (PubMed:10198287, PubMed:9111062). Also binds to circular dsDNA or dsRNA of either linear and/or circular forms and stimulates the relaxation of supercoiled DNAs catalyzed by topoisomerase TOP2A (PubMed:12711669). Plays a role in DNA replication at origins of replication and cell cycle progression (PubMed:24990949). Plays a role as a transcriptional coactivator acting as a bridging factor between polymerase II holoenzyme and transcription factors or cofactors, such as BRCA1, CREBBP, RELA and SMN1 (PubMed:11038348, PubMed:11149922, PubMed:11416126, PubMed:15355351, PubMed:28221134, PubMed:9323138, PubMed:9662397). Binds to the CDKN2A promoter (PubMed:11038348). Plays several roles in post-transcriptional regulation of gene expression (PubMed:28221134, PubMed:28355180). In cooperation with NUP98, promotes pre-mRNA alternative splicing activities of a subset of genes (PubMed:11402034, PubMed:16680162, PubMed:28221134, PubMed:28355180). As component of a large PER complex, is involved in the negative regulation of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms (By similarity). Also acts as a nuclear resolvase that is able to bind and neutralize harmful massive secondary double-stranded RNA structures formed by inverted-repeat Alu retrotransposon elements that are inserted and transcribed as parts of genes during the process of gene transposition (PubMed:28355180). Involved in the positive regulation of nuclear export of constitutive transport element (CTE)-containing unspliced mRNA (PubMed:10924507, PubMed:11402034, PubMed:9162007). Component of the coding region determinant (CRD)-mediated complex that promotes cytoplasmic MYC mRNA stability (PubMed:19029303). Plays a role in mRNA translation (PubMed:28355180). Positively regulates translation of selected mRNAs through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Involved with LARP6 in the translation stimulation of type I collagen mRNAs for CO1A1 and CO1A2 through binding of a specific stem-loop structure in their 5'-UTRs (PubMed:22190748). Stimulates LIN28A-dependent mRNA translation probably by facilitating ribonucleoprotein remodeling during the process of translation (PubMed:21247876). Plays also a role as a small interfering (siRNA)-loading factor involved in the RNA-induced silencing complex (RISC) loading complex (RLC) assembly, and hence functions in the RISC-mediated gene silencing process (PubMed:17531811). Binds preferentially to short double-stranded RNA, such as those produced during rotavirus intestinal infection (PubMed:28636595). This interaction may mediate NLRP9 inflammasome activation and trigger inflammatory response, including IL18 release and pyroptosis (PubMed:28636595). Finally, mediates the attachment of heterogeneous nuclear ribonucleoproteins (hnRNPs) to actin filaments in the nucleus (PubMed:11687588). {ECO:0000250|UniProtKB:O70133, ECO:0000269|PubMed:10198287, ECO:0000269|PubMed:10924507, ECO:0000269|PubMed:11038348, ECO:0000269|PubMed:11149922, ECO:0000269|PubMed:11402034, ECO:0000269|PubMed:11416126, ECO:0000269|PubMed:11687588, ECO:0000269|PubMed:12711669, ECO:0000269|PubMed:15355351, ECO:0000269|PubMed:1537828, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:17531811, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:20669935, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:21561811, ECO:0000269|PubMed:22190748, ECO:0000269|PubMed:24049074, ECO:0000269|PubMed:24990949, ECO:0000269|PubMed:25062910, ECO:0000269|PubMed:28221134, ECO:0000269|PubMed:28355180, ECO:0000269|PubMed:28636595, ECO:0000269|PubMed:37467750, ECO:0000269|PubMed:9111062, ECO:0000269|PubMed:9162007, ECO:0000269|PubMed:9323138, ECO:0000269|PubMed:9662397}.; FUNCTION: (Microbial infection) Plays a role in HIV-1 replication and virion infectivity (PubMed:11096080, PubMed:19229320, PubMed:25149208, PubMed:27107641). Enhances HIV-1 transcription by facilitating the binding of RNA polymerase II holoenzyme to the proviral DNA (PubMed:11096080, PubMed:25149208). Binds (via DRBM domain 2) to the HIV-1 TAR RNA and stimulates HIV-1 transcription of transactivation response element (TAR)-containing mRNAs (PubMed:11096080, PubMed:9892698). Involved also in HIV-1 mRNA splicing and transport (PubMed:25149208). Positively regulates HIV-1 gag mRNA translation, through its binding to post-transcriptional control element (PCE) in the 5'-untranslated region (UTR) (PubMed:16680162). Binds (via DRBM domains) to a HIV-1 double-stranded RNA region of the primer binding site (PBS)-segment of the 5'-UTR, and hence stimulates DHX9 incorporation into virions and virion infectivity (PubMed:27107641). Also plays a role as a cytosolic viral MyD88-dependent DNA and RNA sensors in plasmacytoid dendritic cells (pDCs), and hence induce antiviral innate immune responses (PubMed:20696886, PubMed:21957149). Binds (via the OB-fold region) to viral single-stranded DNA unmethylated C-phosphate-G (CpG) oligonucleotide (PubMed:20696886). {ECO:0000269|PubMed:11096080, ECO:0000269|PubMed:16680162, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:20696886, ECO:0000269|PubMed:21957149, ECO:0000269|PubMed:25149208, ECO:0000269|PubMed:27107641, ECO:0000269|PubMed:9892698}. |
| Q08881 | ITK | S565 | ochoa | Tyrosine-protein kinase ITK/TSK (EC 2.7.10.2) (Interleukin-2-inducible T-cell kinase) (IL-2-inducible T-cell kinase) (Kinase EMT) (T-cell-specific kinase) (Tyrosine-protein kinase Lyk) | Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation (PubMed:12186560, PubMed:12682224, PubMed:21725281). Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (By similarity). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity). {ECO:0000250|UniProtKB:Q03526, ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}. |
| Q08AD1 | CAMSAP2 | S453 | 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}. |
| Q12802 | AKAP13 | S1929 | 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}. |
| 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 | S178 | 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}. |
| Q12965 | MYO1E | S980 | ochoa | Unconventional myosin-Ie (Myosin-Ic) (Unconventional myosin 1E) | Actin-based motor molecule with ATPase activity (PubMed:11940582, PubMed:36316095). Unconventional myosins serve in intracellular movements. Their highly divergent tails bind to membranous compartments, which are then moved relative to actin filaments. Binds to membranes containing anionic phospholipids via its tail domain. Involved in clathrin-mediated endocytosis and intracellular movement of clathrin-coated vesicles (PubMed:36316095). Required for normal morphology of the glomerular basement membrane, normal development of foot processes by kidney podocytes and normal kidney function. In dendritic cells, may control the movement of class II-containing cytoplasmic vesicles along the actin cytoskeleton by connecting them with the actin network via ARL14EP and ARL14. {ECO:0000269|PubMed:11940582, ECO:0000269|PubMed:17257598, ECO:0000269|PubMed:20860408, ECO:0000269|PubMed:36316095}. |
| Q12986 | NFX1 | S977 | ochoa | Transcriptional repressor NF-X1 (EC 2.3.2.-) (Nuclear transcription factor, X box-binding protein 1) | Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:15371341, ECO:0000269|PubMed:17267499}. |
| Q13009 | TIAM1 | S329 | psp | Rho guanine nucleotide exchange factor TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1) (TIAM-1) | Guanyl-nucleotide exchange factor that activates RHO-like proteins and connects extracellular signals to cytoskeletal activities. Activates RAC1, CDC42, and to a lesser extent RHOA and their downstream signaling to regulate processes like cell adhesion and cell migration. {ECO:0000269|PubMed:20361982, ECO:0000269|PubMed:25684205}. |
| Q13148 | TARDBP | S92 | ochoa|psp | TAR DNA-binding protein 43 (TDP-43) | RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases (PubMed:21358640, PubMed:29438978). Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts (PubMed:28794432). Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening (PubMed:30520513). In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival (PubMed:19765185, PubMed:23398327). Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins (PubMed:30464263). Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner (PubMed:27123980). Negatively regulates the expression of CDK6 (PubMed:19760257). Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner (PubMed:25678563). {ECO:0000269|PubMed:11285240, ECO:0000269|PubMed:17481916, ECO:0000269|PubMed:19760257, ECO:0000269|PubMed:19765185, ECO:0000269|PubMed:21358640, ECO:0000269|PubMed:23398327, ECO:0000269|PubMed:23519609, ECO:0000269|PubMed:24240615, ECO:0000269|PubMed:24464995, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:27123980, ECO:0000269|PubMed:28794432, ECO:0000269|PubMed:29438978, ECO:0000269|PubMed:30464263, ECO:0000269|PubMed:30520513}. |
| Q13200 | PSMD2 | S46 | ochoa | 26S proteasome non-ATPase regulatory subunit 2 (26S proteasome regulatory subunit RPN1) (26S proteasome regulatory subunit S2) (26S proteasome subunit p97) (Protein 55.11) (Tumor necrosis factor type 1 receptor-associated protein 2) | Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. {ECO:0000269|PubMed:1317798}.; FUNCTION: Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1. |
| Q13228 | SELENBP1 | S286 | ochoa | Methanethiol oxidase (MTO) (EC 1.8.3.4) (56 kDa selenium-binding protein) (SBP56) (SP56) (Selenium-binding protein 1) | Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria (PubMed:29255262). Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity). {ECO:0000250|UniProtKB:Q8VIF7, ECO:0000269|PubMed:29255262}. |
| Q13416 | ORC2 | S255 | 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}. |
| Q13422 | IKZF1 | S364 | ochoa|psp | 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}. |
| 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}. |
| Q13459 | MYO9B | S1045 | ochoa | Unconventional myosin-IXb (Unconventional myosin-9b) | Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}. |
| Q13469 | NFATC2 | S118 | ochoa | Nuclear factor of activated T-cells, cytoplasmic 2 (NF-ATc2) (NFATc2) (NFAT pre-existing subunit) (NF-ATp) (T-cell transcription factor NFAT1) | Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF (PubMed:15790681). Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway (PubMed:21871017). Is involved in the negative regulation of chondrogenesis (PubMed:35789258). Recruited by AKAP5 to ORAI1 pore-forming subunit of CRAC channels in Ca(2+) signaling microdomains where store-operated Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT-dependent transcriptional responses. {ECO:0000250|UniProtKB:Q60591, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:21871017, ECO:0000269|PubMed:35789258}. |
| Q13485 | SMAD4 | S155 | ochoa | Mothers against decapentaplegic homolog 4 (MAD homolog 4) (Mothers against DPP homolog 4) (Deletion target in pancreatic carcinoma 4) (SMAD family member 4) (SMAD 4) (Smad4) (hSMAD4) | In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression. Binds to SMAD binding elements (SBEs) (5'-GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions (By similarity). Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. {ECO:0000250, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:25514493, ECO:0000269|PubMed:9389648}. |
| Q13542 | EIF4EBP2 | S25 | ochoa | Eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2) (eIF4E-binding protein 2) | Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:30765518). Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:25533957, PubMed:30765518). EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity). {ECO:0000250|UniProtKB:P70445, ECO:0000269|PubMed:25533957, ECO:0000269|PubMed:30765518}. |
| Q13546 | RIPK1 | S357 | psp | Receptor-interacting serine/threonine-protein kinase 1 (EC 2.7.11.1) (Cell death protein RIP) (Receptor-interacting protein 1) (RIP-1) | Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:17703191, PubMed:24144979, PubMed:31827280, PubMed:31827281, PubMed:32657447, PubMed:35831301). Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (By similarity). Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (By similarity). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity). In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:15310755, PubMed:17389591). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity). {ECO:0000250|UniProtKB:Q60855, ECO:0000269|PubMed:11101870, ECO:0000269|PubMed:15310755, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:17703191, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513, ECO:0000269|PubMed:24144979, ECO:0000269|PubMed:29440439, ECO:0000269|PubMed:30988283, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32657447, ECO:0000269|PubMed:35831301}. |
| Q13573 | SNW1 | S446 | ochoa | SNW domain-containing protein 1 (Nuclear protein SkiP) (Nuclear receptor coactivator NCoA-62) (Ski-interacting protein) | Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28076346, PubMed:28502770). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. {ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:11278756, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:11514567, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12840015, ECO:0000269|PubMed:14985122, ECO:0000269|PubMed:15194481, ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:18794151, ECO:0000269|PubMed:19818711, ECO:0000269|PubMed:21245387, ECO:0000269|PubMed:21460037, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:9632709, ECO:0000305|PubMed:33509932}.; FUNCTION: (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. {ECO:0000269|PubMed:15905409, ECO:0000269|PubMed:19818711}.; FUNCTION: (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters. {ECO:0000269|PubMed:10644367}. |
| Q13618 | CUL3 | S585 | ochoa | Cullin-3 (CUL-3) | Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21670212, PubMed:21840486, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:27664236). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046). In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400). The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205). By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205). The BCR(KBTBD4) E3 ubiquitin ligase complex targets CoREST corepressor complex components RCOR1, KDM1A/LSD1 and HDAC2 for proteasomal degradation with RCOR1 likely to be the primary target while degradation of KDM1A and HDAC2 is likely due to their association with RCOR1 (PubMed:33417871). It also targets RCOR3, MIER2 and MIER3 for proteasomal degradation as well as associated proteins ZNF217 and RREB1 with degradation being dependent on the presence of an ELM2 domain in the target proteins (PubMed:36997086). The BCR(ARMC5) complex mediates premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation by mediating ubiquitination of Pol II subunit POLR2A (PubMed:35687106, PubMed:38225631, PubMed:39504960, PubMed:39667934). Required for 'Lys-63'-linked ubiquitination of large ribosomal subunit protein MRPL12 (PubMed:37526061). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27664236, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:33417871, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:36997086, ECO:0000269|PubMed:37526061, ECO:0000269|PubMed:38225631, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}. |
| Q13835 | PKP1 | S237 | 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}. |
| Q14004 | CDK13 | S590 | ochoa | Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) | Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}. |
| Q14145 | KEAP1 | S53 | psp | Kelch-like ECH-associated protein 1 (Cytosolic inhibitor of Nrf2) (INrf2) (Kelch-like protein 19) | Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973, PubMed:15379550, PubMed:15572695, PubMed:15601839, PubMed:15983046, PubMed:37339955). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:19489739, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (PubMed:15379550, PubMed:17046835). {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:17127771, ECO:0000269|PubMed:18251510, ECO:0000269|PubMed:19489739, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:29590092, ECO:0000269|PubMed:37339955}. |
| Q14157 | UBAP2L | S836 | ochoa | Ubiquitin-associated protein 2-like (Protein NICE-4) (RNA polymerase II degradation factor UBAP2L) | Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). Plays an important role in the activity of long-term repopulating hematopoietic stem cells (LT-HSCs) (By similarity). Is a regulator of stress granule assembly, required for their efficient formation (PubMed:29395067, PubMed:35977029). Required for proper brain development and neocortex lamination (By similarity). {ECO:0000250|UniProtKB:Q80X50, ECO:0000269|PubMed:29395067, ECO:0000269|PubMed:35633597}. |
| Q14160 | SCRIB | S764 | 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}. |
| Q14517 | FAT1 | S4473 | ochoa | Protocadherin Fat 1 (Cadherin family member 7) (Cadherin-related tumor suppressor homolog) (Protein fat homolog) [Cleaved into: Protocadherin Fat 1, nuclear form] | [Protocadherin Fat 1]: Plays an essential role for cellular polarization, directed cell migration and modulating cell-cell contact. {ECO:0000250}. |
| Q14562 | DHX8 | S129 | 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}. |
| Q14653 | IRF3 | S398 | psp | Interferon regulatory factor 3 (IRF-3) | Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049179, PubMed:25636800, PubMed:27302953, PubMed:31340999, PubMed:36603579, PubMed:8524823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995, PubMed:36603579, PubMed:8524823). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:36603579). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953, PubMed:36603579). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148, PubMed:36603579). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). {ECO:0000269|PubMed:16154084, ECO:0000269|PubMed:22394562, ECO:0000269|PubMed:24049179, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27302953, ECO:0000269|PubMed:31340999, ECO:0000269|PubMed:31413131, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33440148, ECO:0000269|PubMed:36603579, ECO:0000269|PubMed:8524823, ECO:0000303|PubMed:11846977, ECO:0000303|PubMed:16846591, ECO:0000303|PubMed:16979567, ECO:0000303|PubMed:20049431}. |
| Q14766 | LTBP1 | S539 | ochoa | Latent-transforming growth factor beta-binding protein 1 (LTBP-1) (Transforming growth factor beta-1-binding protein 1) (TGF-beta1-BP-1) | Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space (PubMed:2022183, PubMed:8617200, PubMed:8939931). Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (PubMed:15184403, PubMed:8617200, PubMed:8939931). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (PubMed:22278742). {ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}. |
| Q14766 | LTBP1 | S1597 | ochoa | Latent-transforming growth factor beta-binding protein 1 (LTBP-1) (Transforming growth factor beta-1-binding protein 1) (TGF-beta1-BP-1) | Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space (PubMed:2022183, PubMed:8617200, PubMed:8939931). Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta (PubMed:15184403, PubMed:8617200, PubMed:8939931). Outcompeted by LRRC32/GARP for binding to LAP regulatory chain of TGF-beta (PubMed:22278742). {ECO:0000269|PubMed:15184403, ECO:0000269|PubMed:2022183, ECO:0000269|PubMed:22278742, ECO:0000269|PubMed:8617200, ECO:0000269|PubMed:8939931}. |
| Q14789 | GOLGB1 | S1936 | ochoa | Golgin subfamily B member 1 (372 kDa Golgi complex-associated protein) (GCP372) (Giantin) (Macrogolgin) | May participate in forming intercisternal cross-bridges of the Golgi complex. |
| 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}. |
| Q14863 | POU6F1 | S197 | psp | POU domain, class 6, transcription factor 1 (Brain-specific homeobox/POU domain protein 5) (Brain-5) (Brn-5) (mPOU homeobox protein) | Transcription factor that binds preferentially to a variant of the octamer motif (5'-ATGATAAT-3'). {ECO:0000250}. |
| Q14938 | NFIX | S231 | 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. |
| Q14974 | KPNB1 | S683 | ochoa | Importin subunit beta-1 (Importin-90) (Karyopherin subunit beta-1) (Nuclear factor p97) (Pore targeting complex 97 kDa subunit) (PTAC97) | Functions in nuclear protein import, either in association with an adapter protein, like an importin-alpha subunit, which binds to nuclear localization signals (NLS) in cargo substrates, or by acting as autonomous nuclear transport receptor (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). Acting autonomously, serves itself as NLS receptor (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649, PubMed:7615630, PubMed:9687515). The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (PubMed:10228156, PubMed:11682607, PubMed:11891849, PubMed:19386897, PubMed:24699649, PubMed:7615630, PubMed:9687515). Mediates autonomously the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:11682607, PubMed:9687515). In association with IPO7, mediates the nuclear import of H1 histone (PubMed:10228156). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones (By similarity). Imports MRTFA, SNAI1 and PRKCI into the nucleus (PubMed:11891849, PubMed:19386897, PubMed:20818336, PubMed:24699649). {ECO:0000250|UniProtKB:P70168, ECO:0000269|PubMed:10228156, ECO:0000269|PubMed:11682607, ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:19386897, ECO:0000269|PubMed:20818336, ECO:0000269|PubMed:24699649, ECO:0000269|PubMed:7615630, ECO:0000269|PubMed:9687515}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev. {ECO:0000269|PubMed:16704975, ECO:0000269|PubMed:9405152, ECO:0000269|PubMed:9891055}. |
| Q14BN4 | SLMAP | S402 | 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}. |
| Q14BN4 | SLMAP | S459 | 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}. |
| Q14D04 | VEPH1 | S462 | ochoa | Ventricular zone-expressed PH domain-containing protein homolog 1 (Protein melted) | Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling. May also affect FOXO, Hippo and Wnt signaling. {ECO:0000269|PubMed:26039994}. |
| Q15019 | SEPTIN2 | S31 | ochoa | Septin-2 (Neural precursor cell expressed developmentally down-regulated protein 5) (NEDD-5) | Filament-forming cytoskeletal GTPase. Forms a filamentous structure with SEPTIN12, SEPTIN6, SEPTIN2 and probably SEPTIN4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements. In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes: probably acts by regulating the assembly of the tectonic-like complex (also named B9 complex) by localizing TMEM231 protein. May play a role in the internalization of 2 intracellular microbial pathogens, Listeria monocytogenes and Shigella flexneri. {ECO:0000269|PubMed:15774761, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18209106, ECO:0000269|PubMed:19145258, ECO:0000305|PubMed:25588830}. |
| Q15057 | ACAP2 | S453 | ochoa | Arf-GAP with coiled-coil, ANK repeat and PH domain-containing protein 2 (Centaurin-beta-2) (Cnt-b2) | GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6). Doesn't show GAP activity for RAB35 (PubMed:30905672). {ECO:0000269|PubMed:11062263, ECO:0000269|PubMed:30905672}. |
| 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}. |
| Q15080 | NCF4 | S161 | ochoa | Neutrophil cytosol factor 4 (NCF-4) (Neutrophil NADPH oxidase factor 4) (SH3 and PX domain-containing protein 4) (p40-phox) (p40phox) | Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (Probable). In the activated complex, electrons are first transferred from NADPH to flavin adenine dinucleotide (FAD) and subsequently transferred via two heme molecules to molecular oxygen, producing superoxide through an outer-sphere reaction (By similarity). Activation of the NADPH oxidase complex is initiated by the assembly of cytosolic subunits of the NADPH oxidase complex with the core NADPH oxidase complex to form a complex at the plasma membrane or phagosomal membrane (By similarity). This activation process is initiated by phosphorylation dependent binding of the cytosolic NCF1/p47-phox subunit to the C-terminus of CYBA/p22-phox (By similarity). {ECO:0000250|UniProtKB:P04839, ECO:0000250|UniProtKB:P14598, ECO:0000305|PubMed:8280052}. |
| Q15139 | PRKD1 | S738 | ochoa|psp | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q15149 | PLEC | S1446 | 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}. |
| Q15185 | PTGES3 | S72 | 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}. |
| Q15185 | PTGES3 | S82 | 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}. |
| Q15262 | PTPRK | S856 | ochoa | Receptor-type tyrosine-protein phosphatase kappa (Protein-tyrosine phosphatase kappa) (R-PTP-kappa) (EC 3.1.3.48) | Regulation of processes involving cell contact and adhesion such as growth control, tumor invasion, and metastasis. Negative regulator of EGFR signaling pathway. Forms complexes with beta-catenin and gamma-catenin/plakoglobin. Beta-catenin may be a substrate for the catalytic activity of PTPRK/PTP-kappa. {ECO:0000269|PubMed:19836242}. |
| Q15283 | RASA2 | S234 | ochoa | Ras GTPase-activating protein 2 (GTPase-activating protein 1m) (GAP1m) | Inhibitory regulator of the Ras-cyclic AMP pathway. Binds inositol tetrakisphosphate (IP4). |
| Q15699 | ALX1 | S39 | ochoa | ALX homeobox protein 1 (Cartilage homeoprotein 1) (CART-1) | Sequence-specific DNA-binding transcription factor that binds palindromic sequences within promoters and may activate or repress the transcription of a subset of genes (PubMed:8756334, PubMed:9753625). Most probably regulates the expression of genes involved in the development of mesenchyme-derived craniofacial structures. Early on in development, it plays a role in forebrain mesenchyme survival (PubMed:20451171). May also induce epithelial to mesenchymal transition (EMT) through the expression of SNAI1 (PubMed:23288509). {ECO:0000269|PubMed:20451171, ECO:0000269|PubMed:23288509, ECO:0000269|PubMed:8756334, ECO:0000269|PubMed:9753625}. |
| Q15759 | MAPK11 | S272 | psp | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q16473 | TNXA | S142 | ochoa | Putative tenascin-XA (TN-XA) | None |
| Q16595 | FXN | S81 | ochoa | Frataxin, mitochondrial (EC 1.16.3.1) (Friedreich ataxia protein) (Fxn) [Cleaved into: Frataxin intermediate form (i-FXN); Frataxin(56-210) (m56-FXN); Frataxin(78-210) (d-FXN) (m78-FXN); Frataxin mature form (Frataxin(81-210)) (m81-FXN); Extramitochondrial frataxin] | [Frataxin mature form]: Functions as an activator of persulfide transfer to the scaffoding protein ISCU as component of the core iron-sulfur cluster (ISC) assembly complex and participates to the [2Fe-2S] cluster assembly (PubMed:12785837, PubMed:24971490). Accelerates sulfur transfer from NFS1 persulfide intermediate to ISCU and to small thiols such as L-cysteine and glutathione leading to persulfuration of these thiols and ultimately sulfide release (PubMed:24971490). Binds ferrous ion and is released from FXN upon the addition of both L-cysteine and reduced FDX2 during [2Fe-2S] cluster assembly (PubMed:29576242). The core iron-sulfur cluster (ISC) assembly complex is involved in the de novo synthesis of a [2Fe-2S] cluster, the first step of the mitochondrial iron-sulfur protein biogenesis. This process is initiated by the cysteine desulfurase complex (NFS1:LYRM4:NDUFAB1) that produces persulfide which is delivered on the scaffold protein ISCU in a FXN-dependent manner. Then this complex is stabilized by FDX2 which provides reducing equivalents to accomplish the [2Fe-2S] cluster assembly. Finally, the [2Fe-2S] cluster is transferred from ISCU to chaperone proteins, including HSCB, HSPA9 and GLRX5 (By similarity). May play a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+); the oligomeric form but not the monomeric form has in vitro ferroxidase activity (PubMed:15641778). May be able to store large amounts of iron in the form of a ferrihydrite mineral by oligomerization; however, the physiological relevance is unsure as reports are conflicting and the function has only been shown using heterologous overexpression systems (PubMed:11823441, PubMed:12755598). May function as an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation (PubMed:15247478). May play a role as a high affinity iron binding partner for FECH that is capable of both delivering iron to ferrochelatase and mediating the terminal step in mitochondrial heme biosynthesis (PubMed:15123683, PubMed:16239244). {ECO:0000250|UniProtKB:Q9H1K1, ECO:0000269|PubMed:11823441, ECO:0000269|PubMed:12755598, ECO:0000269|PubMed:12785837, ECO:0000269|PubMed:15123683, ECO:0000269|PubMed:15247478, ECO:0000269|PubMed:15641778, ECO:0000269|PubMed:16239244, ECO:0000269|PubMed:24971490, ECO:0000269|PubMed:29576242}.; FUNCTION: [Extramitochondrial frataxin]: Modulates the RNA-binding activity of ACO1 (PubMed:20053667). May be involved in the cytoplasmic iron-sulfur protein biogenesis (PubMed:16091420). May contribute to oxidative stress resistance and overall cell survival (PubMed:16608849). {ECO:0000269|PubMed:16091420, ECO:0000269|PubMed:16608849, ECO:0000269|PubMed:20053667}. |
| Q16665 | HIF1A | S761 | psp | Hypoxia-inducible factor 1-alpha (HIF-1-alpha) (HIF1-alpha) (ARNT-interacting protein) (Basic-helix-loop-helix-PAS protein MOP1) (Class E basic helix-loop-helix protein 78) (bHLHe78) (Member of PAS protein 1) (PAS domain-containing protein 8) | Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:16543236, PubMed:9887100). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}. |
| Q17R91 | DIAPH2 | S196 | psp | Protein diaphanous homolog 2 (Diaphanous-related formin-2) | None |
| Q2KHR3 | QSER1 | S499 | ochoa | Glutamine and serine-rich protein 1 | Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation. {ECO:0000269|PubMed:33833093}. |
| Q2NKX8 | ERCC6L | S807 | ochoa | DNA excision repair protein ERCC-6-like (EC 3.6.4.12) (ATP-dependent helicase ERCC6-like) (PLK1-interacting checkpoint helicase) (Tumor antigen BJ-HCC-15) | DNA helicase that acts as a tension sensor that associates with catenated DNA which is stretched under tension until it is resolved during anaphase (PubMed:17218258, PubMed:23973328). Functions as ATP-dependent DNA translocase (PubMed:23973328, PubMed:28977671). Can promote Holliday junction branch migration (in vitro) (PubMed:23973328). {ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:23973328, ECO:0000269|PubMed:28977671}. |
| Q38SD2 | LRRK1 | S1074 | psp | Leucine-rich repeat serine/threonine-protein kinase 1 (EC 2.7.11.1) | Serine/threonine-protein kinase which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). Phosphorylates RAB7A; this activity is dependent on protein kinase C (PKC) activation (PubMed:36040231, PubMed:37558661, PubMed:37857821). Plays a role in the negative regulation of bone mass, acting through the maturation of osteoclasts (By similarity). {ECO:0000250|UniProtKB:Q3UHC2, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821}. |
| Q3MJ13 | WDR72 | S976 | ochoa | WD repeat-containing protein 72 | Plays a major role in formation of tooth enamel (PubMed:19853237, PubMed:25008349). Specifically required during the maturation phase of amelogenesis for normal formation of the enamel matrix and clearance of enamel proteins. May be involved in localization of the calcium transporter SLC24A4 to the ameloblast cell membrane. {ECO:0000250|UniProtKB:D3YYM4, ECO:0000269|PubMed:19853237, ECO:0000269|PubMed:25008349}. |
| Q4AC94 | C2CD3 | S299 | 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}. |
| Q4KMP7 | TBC1D10B | S316 | ochoa | TBC1 domain family member 10B (Rab27A-GAP-beta) | Acts as a GTPase-activating protein for RAB3A, RAB22A, RAB27A, and RAB35. Does not act on RAB2A and RAB6A. {ECO:0000269|PubMed:16923811, ECO:0000269|PubMed:19077034}. |
| Q53T59 | HS1BP3 | S254 | ochoa | HCLS1-binding protein 3 (HS1-binding protein 3) (HSP1BP-3) | May be a modulator of IL-2 signaling. {ECO:0000250}. |
| Q5BKX6 | SLC45A4 | S307 | ochoa | Solute carrier family 45 member 4 | Proton-associated sucrose transporter. May be able to transport also glucose and fructose. {ECO:0000250|UniProtKB:Q0P5V9}. |
| Q5JSH3 | WDR44 | S411 | 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}. |
| Q5SW79 | CEP170 | S1132 | 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}. |
| Q5T011 | SZT2 | S1199 | 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}. |
| Q5T1M5 | FKBP15 | S1093 | ochoa | FK506-binding protein 15 (FKBP-15) (133 kDa FK506-binding protein) (133 kDa FKBP) (FKBP-133) (WASP- and FKBP-like protein) (WAFL) | May be involved in the cytoskeletal organization of neuronal growth cones. Seems to be inactive as a PPIase (By similarity). Involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement. {ECO:0000250, ECO:0000269|PubMed:19121306}. |
| Q5T200 | ZC3H13 | S1501 | 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}. |
| Q5T5Y3 | CAMSAP1 | S583 | ochoa | Calmodulin-regulated spectrin-associated protein 1 | Key microtubule-organizing protein that specifically binds the minus-end of non-centrosomal microtubules and regulates their dynamics and organization (PubMed:19508979, PubMed:21834987, PubMed:24117850, PubMed:24486153, PubMed:24706919). Specifically recognizes growing microtubule minus-ends and stabilizes microtubules (PubMed:24486153, PubMed:24706919). Acts on free microtubule minus-ends that are not capped by microtubule-nucleating proteins or other factors and protects microtubule minus-ends from depolymerization (PubMed:24486153, PubMed:24706919). In contrast to CAMSAP2 and CAMSAP3, tracks along the growing tips of minus-end microtubules without significantly affecting the polymerization rate: binds at the very tip of the microtubules minus-end and acts as a minus-end tracking protein (-TIP) that dissociates from microtubules after allowing tubulin incorporation (PubMed:24486153, PubMed:24706919). Through interaction with spectrin may regulate neurite outgrowth (PubMed:24117850). {ECO:0000269|PubMed:19508979, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:24117850, ECO:0000269|PubMed:24486153, ECO:0000269|PubMed:24706919}. |
| Q5T7B8 | KIF24 | S1021 | ochoa | Kinesin-like protein KIF24 | Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles. Mediates depolymerization of microtubules of centriolar origin, possibly to suppress aberrant cilia formation (PubMed:21620453). Following activation by NEK2 involved in disassembly of primary cilium during G2/M phase but does not disassemble fully formed ciliary axonemes. As cilium assembly and disassembly is proposed to coexist in a dynamic equilibrium may suppress nascent cilium assembly and, potentially, ciliar re-assembly in cells that have already disassembled their cilia ensuring the completion of cilium removal in the later stages of the cell cycle (PubMed:26290419). Plays an important role in recruiting MPHOSPH9, a negative regulator of cilia formation to the distal end of mother centriole (PubMed:30375385). {ECO:0000269|PubMed:21620453, ECO:0000269|PubMed:26290419, ECO:0000269|PubMed:30375385}. |
| Q5T8I3 | EEIG2 | S276 | ochoa | EEIG family member 2 (EEIG2) | None |
| Q5TCY1 | TTBK1 | S515 | 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}. |
| Q5THJ4 | VPS13D | S1065 | 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}. |
| Q5TKA1 | LIN9 | S95 | ochoa | Protein lin-9 homolog (HuLin-9) (hLin-9) (Beta subunit-associated regulator of apoptosis) (TUDOR gene similar protein) (Type I interferon receptor beta chain-associated protein) (pRB-associated protein) | Acts as a tumor suppressor. Inhibits DNA synthesis. Its ability to inhibit oncogenic transformation is mediated through its association with RB1. Plays a role in the expression of genes required for the G1/S transition. {ECO:0000269|PubMed:15538385, ECO:0000269|PubMed:16730350}. |
| Q5UIP0 | RIF1 | S1666 | ochoa | Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) | Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}. |
| Q5UIP0 | RIF1 | S1810 | 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 | S7395 | 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}. |
| Q5VT06 | CEP350 | S930 | 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}. |
| Q5VUB5 | FAM171A1 | S723 | 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}. |
| Q5VZ89 | DENND4C | S908 | ochoa | DENN domain-containing protein 4C | Guanine nucleotide exchange factor (GEF) activating RAB10. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB10 into its active GTP-bound form. Thereby, stimulates SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane in response to insulin. {ECO:0000269|PubMed:20937701}. |
| Q5W0B1 | OBI1 | S75 | 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}. |
| 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}. |
| Q641Q2 | WASHC2A | S925 | ochoa | WASH complex subunit 2A | Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}. |
| 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}. |
| Q69YH5 | CDCA2 | S24 | 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}. |
| Q69YH5 | CDCA2 | S893 | psp | 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}. |
| Q69YQ0 | SPECC1L | S171 | ochoa | Cytospin-A (Renal carcinoma antigen NY-REN-22) (Sperm antigen with calponin homology and coiled-coil domains 1-like) (SPECC1-like protein) | Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration. {ECO:0000269|PubMed:21703590}. |
| Q6AI12 | ANKRD40 | S202 | ochoa | Ankyrin repeat domain-containing protein 40 | None |
| Q6AWC2 | WWC2 | S851 | ochoa | Protein WWC2 (BH-3-only member B) (WW domain-containing protein 2) | Regulator of the Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway. Enhances phosphorylation of LATS1 and YAP1 and negatively regulates cell proliferation and organ growth due to a suppression of the transcriptional activity of YAP1, the major effector of the Hippo pathway. {ECO:0000269|PubMed:24682284}. |
| Q6B0I6 | KDM4D | S355 | ochoa | Lysine-specific demethylase 4D (EC 1.14.11.66) (JmjC domain-containing histone demethylation protein 3D) (Jumonji domain-containing protein 2D) ([histone H3]-trimethyl-L-lysine(9) demethylase 4D) | Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys-9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:35145029}. |
| Q6DN90 | IQSEC1 | S89 | 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}. |
| Q6ICG6 | KIAA0930 | S358 | ochoa | Uncharacterized protein KIAA0930 | None |
| Q6P0N0 | MIS18BP1 | S172 | 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}. |
| Q6P1L5 | FAM117B | S273 | ochoa | Protein FAM117B (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 13 protein) | None |
| Q6P4Q7 | CNNM4 | S689 | ochoa | Metal transporter CNNM4 (Ancient conserved domain-containing protein 4) (Cyclin-M4) | Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function. {ECO:0000250, ECO:0000269|PubMed:19200525, ECO:0000269|PubMed:19200527}. |
| Q6P995 | FAM171B | S688 | ochoa | Protein FAM171B | None |
| 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}. |
| Q6PL18 | ATAD2 | S421 | 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}. |
| Q6WKZ4 | RAB11FIP1 | S156 | 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 | S266 | 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}. |
| Q6ZNC4 | ZNF704 | S77 | ochoa | Zinc finger protein 704 | Transcription factor which binds to RE2 sequence elements in the MYOD1 enhancer. {ECO:0000250|UniProtKB:Q9ERQ3}. |
| Q6ZU80 | CEP128 | S31 | ochoa | Centrosomal protein of 128 kDa (Cep128) | None |
| Q70CQ2 | USP34 | S2407 | ochoa | Ubiquitin carboxyl-terminal hydrolase 34 (EC 3.4.19.12) (Deubiquitinating enzyme 34) (Ubiquitin thioesterase 34) (Ubiquitin-specific-processing protease 34) | Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. {ECO:0000269|PubMed:21383061}. |
| 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. |
| Q7L2E3 | DHX30 | S260 | ochoa | ATP-dependent RNA helicase DHX30 (EC 3.6.4.13) (DEAH box protein 30) | RNA-dependent helicase (PubMed:29100085). Plays an important role in the assembly of the mitochondrial large ribosomal subunit (PubMed:25683715, PubMed:29100085). Required for optimal function of the zinc-finger antiviral protein ZC3HAV1 (By similarity). Associates with mitochondrial DNA (PubMed:18063578). Involved in nervous system development and differentiation through its involvement in the up-regulation of a number of genes which are required for neurogenesis, including GSC, NCAM1, neurogenin, and NEUROD (By similarity). {ECO:0000250|UniProtKB:Q5BJS0, ECO:0000250|UniProtKB:Q99PU8, ECO:0000269|PubMed:18063578, ECO:0000269|PubMed:25683715, ECO:0000269|PubMed:29100085}. |
| Q7L2Z9 | CENPQ | S248 | ochoa|psp | Centromere protein Q (CENP-Q) | Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex (PubMed:16622420). Plays an important role in chromosome congression and in the recruitment of CENP-O complex (which comprises CENPO, CENPP, CENPQ and CENPU), CENPE and PLK1 to the kinetochores (PubMed:25395579). {ECO:0000269|PubMed:16622420, ECO:0000269|PubMed:25395579}. |
| Q7L804 | RAB11FIP2 | S150 | ochoa | Rab11 family-interacting protein 2 (Rab11-FIP2) (NRip11) | A Rab11 effector binding preferentially phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) and phosphatidic acid (PA) and acting in the regulation of the transport of vesicles from the endosomal recycling compartment (ERC) to the plasma membrane. Involved in insulin granule exocytosis. Also involved in receptor-mediated endocytosis and membrane trafficking of recycling endosomes, probably originating from clathrin-coated vesicles. Required in a complex with MYO5B and RAB11 for the transport of NPC1L1 to the plasma membrane. Also acts as a regulator of cell polarity. Plays an essential role in phagocytosis through a mechanism involving TICAM2, RAC1 and CDC42 Rho GTPases for controlling actin-dynamics. {ECO:0000269|PubMed:12364336, ECO:0000269|PubMed:15304524, ECO:0000269|PubMed:16251358, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:19542231, ECO:0000269|PubMed:30883606}. |
| Q7Z2W4 | ZC3HAV1 | S322 | 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}. |
| Q7Z434 | MAVS | S285 | ochoa | Mitochondrial antiviral-signaling protein (MAVS) (CARD adapter inducing interferon beta) (Cardif) (Interferon beta promoter stimulator protein 1) (IPS-1) (Putative NF-kappa-B-activating protein 031N) (Virus-induced-signaling adapter) (VISA) | Adapter required for innate immune defense against viruses (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:21170385, PubMed:23087404, PubMed:27992402, PubMed:33139700, PubMed:37582970). Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFNB and RANTES (CCL5) (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:20628368, PubMed:21170385, PubMed:23087404, PubMed:25636800, PubMed:27736772, PubMed:33110251). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (PubMed:20451243). Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response (PubMed:20451243). May activate the same pathways following detection of extracellular dsRNA by TLR3 (PubMed:16153868). May protect cells from apoptosis (PubMed:16125763). Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria (PubMed:23582325). {ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20451243, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27736772, ECO:0000269|PubMed:27992402, ECO:0000269|PubMed:33110251, ECO:0000269|PubMed:33139700, ECO:0000269|PubMed:37582970}. |
| Q7Z5L2 | R3HCC1L | S338 | ochoa | Coiled-coil domain-containing protein R3HCC1L (Growth inhibition and differentiation-related protein 88) (Putative mitochondrial space protein 32.1) (R3H and coiled-coil domain-containing protein 1-like) | None |
| Q7Z6J2 | TAMALIN | S235 | ochoa | Protein TAMALIN (General receptor for phosphoinositides 1-associated scaffold protein) (GRP1-associated scaffold protein) | Plays a role in intracellular trafficking and contributes to the macromolecular organization of group 1 metabotropic glutamate receptors (mGluRs) at synapses. {ECO:0000250}. |
| Q7Z6J6 | FRMD5 | S462 | ochoa | FERM domain-containing protein 5 | May be involved in regulation of cell migration (PubMed:22846708, PubMed:25448675). May regulate cell-matrix interactions via its interaction with ITGB5 and modifying ITGB5 cytoplasmic tail interactions such as with FERMT2 and TLN1. May regulate ROCK1 kinase activity possibly involved in regulation of actin stress fiber formation (PubMed:25448675). |
| Q7Z6Z7 | HUWE1 | S927 | psp | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z6Z7 | HUWE1 | S3320 | ochoa | E3 ubiquitin-protein ligase HUWE1 (EC 2.3.2.26) (ARF-binding protein 1) (ARF-BP1) (HECT, UBA and WWE domain-containing protein 1) (HECT-type E3 ubiquitin transferase HUWE1) (Homologous to E6AP carboxyl terminus homologous protein 9) (HectH9) (Large structure of UREB1) (LASU1) (Mcl-1 ubiquitin ligase E3) (Mule) (Upstream regulatory element-binding protein 1) (URE-B1) (URE-binding protein 1) | E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15567145, PubMed:15767685, PubMed:15989957, PubMed:17567951, PubMed:18488021, PubMed:19037095, PubMed:19713937, PubMed:20534529, PubMed:30217973). Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair (PubMed:19713937). Also ubiquitinates the p53/TP53 tumor suppressor and core histones including H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685, PubMed:15989956). Ubiquitinates MFN2 to negatively regulate mitochondrial fusion in response to decreased stearoylation of TFRC (PubMed:26214738). Ubiquitination of MFN2 also takes place following induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated ubiquitination (PubMed:30217973). Regulates neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4 (PubMed:19037095). Acts in concert with MYCBP2 to regulate the circadian clock gene expression by promoting the lithium-induced ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an upstream initiator-like sequence in the preprodynorphin gene (By similarity). Mediates HAPSTR1 degradation, but is also a required cofactor in the pathway by which HAPSTR1 governs stress signaling (PubMed:35776542). Acts as a regulator of the JNK and NF-kappa-B signaling pathways by mediating assembly of heterotypic 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains that are then recognized by TAB2: HUWE1 mediates branching of 'Lys-48'-linked chains of substrates initially modified with 'Lys-63'-linked conjugates by TRAF6 (PubMed:27746020). 'Lys-63'-/'Lys-48'-linked branched ubiquitin chains protect 'Lys-63'-linkages from CYLD deubiquitination (PubMed:27746020). Ubiquitinates PPARA in hepatocytes (By similarity). {ECO:0000250|UniProtKB:P51593, ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685, ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:27746020, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35776542}. |
| Q7Z7G8 | VPS13B | S1815 | 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}. |
| Q86U86 | PBRM1 | S303 | 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}. |
| Q86UE4 | MTDH | S258 | 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}. |
| Q86VR2 | RETREG3 | S313 | ochoa | Reticulophagy regulator 3 | Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress (PubMed:34338405). When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins (PubMed:34338405). Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes (PubMed:33826365). Required for collagen quality control in a LIR motif-dependent manner (By similarity). Mediates NRF1-enhanced neurite outgrowth (PubMed:26040720). {ECO:0000250|UniProtKB:Q9CQV4, ECO:0000269|PubMed:26040720, ECO:0000269|PubMed:33826365, ECO:0000269|PubMed:34338405}. |
| Q86XP1 | DGKH | S695 | ochoa | Diacylglycerol kinase eta (DAG kinase eta) (EC 2.7.1.107) (Diglyceride kinase eta) (DGK-eta) | Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:12810723, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable) (PubMed:12810723, PubMed:23949095). Plays a key role in promoting cell growth (PubMed:19710016). Activates the Ras/B-Raf/C-Raf/MEK/ERK signaling pathway induced by EGF (PubMed:19710016). Regulates the recruitment of RAF1 and BRAF from cytoplasm to membranes and their heterodimerization (PubMed:19710016). {ECO:0000269|PubMed:12810723, ECO:0000269|PubMed:19710016, ECO:0000269|PubMed:23949095, ECO:0000305}. |
| Q86Y01 | DTX1 | S189 | ochoa | E3 ubiquitin-protein ligase DTX1 (EC 2.3.2.27) (Protein deltex-1) (Deltex1) (hDTX1) (RING-type E3 ubiquitin transferase DTX1) | Functions as a ubiquitin ligase protein in vivo, mediating ubiquitination and promoting degradation of MEKK1, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity (By similarity). Regulator of Notch signaling, a signaling pathway involved in cell-cell communications that regulates a broad spectrum of cell-fate determinations. Mainly acts as a positive regulator of Notch, but it also acts as a negative regulator, depending on the developmental and cell context. Mediates the antineural activity of Notch, possibly by inhibiting the transcriptional activation mediated by MATCH1. Involved in neurogenesis, lymphogenesis and myogenesis, and may also be involved in MZB (Marginal zone B) cell differentiation. Promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1. {ECO:0000250, ECO:0000269|PubMed:11564735, ECO:0000269|PubMed:11869684, ECO:0000269|PubMed:9590294}. |
| Q86YT6 | MIB1 | S405 | ochoa | E3 ubiquitin-protein ligase MIB1 (EC 2.3.2.27) (DAPK-interacting protein 1) (DIP-1) (Mind bomb homolog 1) (RING-type E3 ubiquitin transferase MIB1) (Zinc finger ZZ type with ankyrin repeat domain protein 2) | E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors. Probably mediates ubiquitination and subsequent proteasomal degradation of DAPK1, thereby antagonizing anti-apoptotic effects of DAPK1 to promote TNF-induced apoptosis (By similarity). Involved in ubiquitination of centriolar satellite CEP131, CEP290 and PCM1 proteins and hence inhibits primary cilium formation in proliferating cells. Mediates 'Lys-63'-linked polyubiquitination of TBK1, which probably participates in kinase activation. {ECO:0000250, ECO:0000269|PubMed:24121310}.; FUNCTION: (Microbial infection) During adenovirus infection, mediates ubiquitination of Core-capsid bridging protein. This allows viral genome delivery into nucleus for infection. {ECO:0000269|PubMed:31851912}. |
| Q8IVF7 | FMNL3 | S93 | ochoa | Formin-like protein 3 (Formin homology 2 domain-containing protein 3) (WW domain-binding protein 3) (WBP-3) | Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. Required for developmental angiogenesis (By similarity). In this process, required for microtubule reorganization and for efficient endothelial cell elongation. In quiescent endothelial cells, triggers rearrangement of the actin cytoskeleton, but does not alter microtubule alignement. {ECO:0000250|UniProtKB:Q6NXC0, ECO:0000269|PubMed:21834987, ECO:0000269|PubMed:22275430}. |
| Q8IWZ3 | ANKHD1 | S1611 | ochoa | Ankyrin repeat and KH domain-containing protein 1 (HIV-1 Vpr-binding ankyrin repeat protein) (Multiple ankyrin repeats single KH domain) (hMASK) | May play a role as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. Isoform 2 may possess an antiapoptotic effect and protect cells during normal cell survival through its regulation of caspases. {ECO:0000269|PubMed:16098192}. |
| Q8IXK0 | PHC2 | S733 | 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. |
| Q8IY63 | AMOTL1 | S828 | ochoa | Angiomotin-like protein 1 | Inhibits the Wnt/beta-catenin signaling pathway, probably by recruiting CTNNB1 to recycling endosomes and hence preventing its translocation to the nucleus. {ECO:0000269|PubMed:22362771}. |
| Q8IZQ1 | WDFY3 | S2083 | ochoa | WD repeat and FYVE domain-containing protein 3 (Autophagy-linked FYVE protein) (Alfy) | Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (PubMed:27008544). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By similarity). After cytokinetic abscission, involved in midbody remnant degradation (PubMed:24128730). In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400). {ECO:0000250|UniProtKB:Q6VNB8, ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27008544}. |
| Q8N137 | CNTROB | S41 | 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}. |
| Q8N137 | CNTROB | S128 | ochoa | Centrobin (Centrosomal BRCA2-interacting protein) (LYST-interacting protein 8) | Required for centriole duplication. Inhibition of centriole duplication leading to defects in cytokinesis. {ECO:0000269|PubMed:16275750}. |
| Q8N456 | LRRC18 | S82 | ochoa | Leucine-rich repeat-containing protein 18 | May be involved in the regulation of spermatogenesis and sperm maturation. {ECO:0000250}. |
| Q8N5S9 | CAMKK1 | S67 | ochoa | Calcium/calmodulin-dependent protein kinase kinase 1 (CaM-KK 1) (CaM-kinase kinase 1) (CaMKK 1) (EC 2.7.11.17) (CaM-kinase IV kinase) (Calcium/calmodulin-dependent protein kinase kinase alpha) (CaM-KK alpha) (CaM-kinase kinase alpha) (CaMKK alpha) | Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. {ECO:0000269|PubMed:12935886}. |
| Q8NC51 | SERBP1 | S53 | 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}. |
| Q8NEV1 | CSNK2A3 | S287 | ochoa | Casein kinase II subunit alpha 3 (CK II alpha 3) (EC 2.7.11.1) (Casein kinase II alpha 1 polypeptide pseudogene) | Probable catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Amplification-dependent oncogene; promotes cell proliferation and tumorigenesis by down-regulating expression of the tumor suppressor protein, PML. May play a role in the pathogenesis of the lung cancer development and progression. {ECO:0000269|PubMed:20625391}. |
| Q8NEZ4 | KMT2C | S1435 | ochoa | Histone-lysine N-methyltransferase 2C (Lysine N-methyltransferase 2C) (EC 2.1.1.364) (Homologous to ALR protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 3) | Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:22266653, PubMed:24081332, PubMed:25561738). Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements (PubMed:24081332). {ECO:0000269|PubMed:22266653, ECO:0000269|PubMed:24081332, ECO:0000269|PubMed:25561738}. |
| Q8NF50 | DOCK8 | S1279 | ochoa | Dedicator of cytokinesis protein 8 | Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:22461490, PubMed:28028151). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (By similarity). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing (PubMed:25762780). {ECO:0000250|UniProtKB:Q8C147, ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:25762780, ECO:0000269|PubMed:28028151}. |
| 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}. |
| Q8NHQ8 | RASSF8 | S387 | ochoa | Ras association domain-containing protein 8 (Carcinoma-associated protein HOJ-1) | None |
| Q8TAA9 | VANGL1 | S96 | ochoa | Vang-like protein 1 (Loop-tail protein 2 homolog) (LPP2) (Strabismus 2) (Van Gogh-like protein 1) | None |
| Q8TBC3 | SHKBP1 | S161 | ochoa | SH3KBP1-binding protein 1 (SETA-binding protein 1) | Inhibits CBL-SH3KBP1 complex mediated down-regulation of EGFR signaling by sequestration of SH3KBP1. Binds to SH3KBP1 and prevents its interaction with CBL and inhibits translocation of SH3KBP1 to EGFR containing vesicles upon EGF stimulation. {ECO:0000250|UniProtKB:Q6P7W2}. |
| Q8TCT9 | HM13 | S72 | ochoa | Signal peptide peptidase (EC 3.4.23.-) (Intramembrane protease 1) (IMP-1) (IMPAS-1) (hIMP1) (Minor histocompatibility antigen H13) (Presenilin-like protein 3) (Signal peptide peptidase-like 1) | Catalyzes intramembrane proteolysis of signal peptides that have been removed from precursors of secretory and membrane proteins, resulting in the release of the fragment from the ER membrane into the cytoplasm (PubMed:12077416). Required to generate lymphocyte cell surface (HLA-E) epitopes derived from MHC class I signal peptides (PubMed:11714810). May be necessary for the removal of the signal peptide that remains attached to the hepatitis C virus core protein after the initial proteolytic processing of the polyprotein (PubMed:12145199). Involved in the intramembrane cleavage of the integral membrane protein PSEN1 (PubMed:11714810, PubMed:12077416, PubMed:14741365). Cleaves the integral membrane protein XBP1 isoform 1 in a DERL1/RNF139-dependent manner (PubMed:25239945). May play a role in graft rejection (By similarity). {ECO:0000250|UniProtKB:Q9D8V0, ECO:0000269|PubMed:11714810, ECO:0000269|PubMed:12077416, ECO:0000269|PubMed:12145199, ECO:0000269|PubMed:14741365, ECO:0000269|PubMed:25239945}. |
| Q8TD43 | TRPM4 | S1145 | psp | Transient receptor potential cation channel subfamily M member 4 (hTRPM4) (Calcium-activated non-selective cation channel 1) (Long transient receptor potential channel 4) (LTrpC-4) (LTrpC4) (Melastatin-4) | Calcium-activated selective cation channel that mediates membrane depolarization (PubMed:12015988, PubMed:12842017, PubMed:29211723, PubMed:30528822). While it is activated by increase in intracellular Ca(2+), it is impermeable to it (PubMed:12015988). Mediates transport of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to depolarize the membrane (PubMed:12015988). It thereby plays a central role in cadiomyocytes, neurons from entorhinal cortex, dorsal root and vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells, cochlea hair cells etc. Participates in T-cell activation by modulating Ca(2+) oscillations after T lymphocyte activation, which is required for NFAT-dependent IL2 production. Involved in myogenic constriction of cerebral arteries. Controls insulin secretion in pancreatic beta-cells. May also be involved in pacemaking or could cause irregular electrical activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1) and T-helper 2 (Th2) cell motility and cytokine production through differential regulation of calcium signaling and NFATC1 localization. Enhances cell proliferation through up-regulation of the beta-catenin signaling pathway. Plays a role in keratinocyte differentiation (PubMed:30528822). {ECO:0000269|PubMed:11535825, ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:12799367, ECO:0000269|PubMed:12842017, ECO:0000269|PubMed:14758478, ECO:0000269|PubMed:15121803, ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15472118, ECO:0000269|PubMed:15550671, ECO:0000269|PubMed:15590641, ECO:0000269|PubMed:15845551, ECO:0000269|PubMed:16186107, ECO:0000269|PubMed:16407466, ECO:0000269|PubMed:16424899, ECO:0000269|PubMed:16806463, ECO:0000269|PubMed:20625999, ECO:0000269|PubMed:20656926, ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:30528822}.; FUNCTION: [Isoform 2]: Lacks channel activity. {ECO:0000269|PubMed:12842017}. |
| Q8TDJ6 | DMXL2 | S1151 | 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}. |
| Q8TEA7 | TBCK | S409 | 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}. |
| Q8TEV9 | SMCR8 | S467 | ochoa | Guanine nucleotide exchange protein SMCR8 (Smith-Magenis syndrome chromosomal region candidate gene 8 protein) | Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27103069, PubMed:27193190, PubMed:27559131, PubMed:27617292, PubMed:28195531, PubMed:32303654). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro (PubMed:32303654). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531). {ECO:0000269|PubMed:20562859, ECO:0000269|PubMed:27103069, ECO:0000269|PubMed:27193190, ECO:0000269|PubMed:27559131, ECO:0000269|PubMed:27617292, ECO:0000269|PubMed:28195531, ECO:0000269|PubMed:32303654}. |
| Q8WUM0 | NUP133 | S594 | 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 | S423 | 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}. |
| Q8WXE9 | STON2 | S368 | ochoa | Stonin-2 (Stoned B) | Adapter protein involved in endocytic machinery. Involved in the synaptic vesicle recycling. May facilitate clathrin-coated vesicle uncoating. {ECO:0000269|PubMed:11381094, ECO:0000269|PubMed:11454741, ECO:0000269|PubMed:21102408}. |
| Q8WXE9 | STON2 | S762 | ochoa | Stonin-2 (Stoned B) | Adapter protein involved in endocytic machinery. Involved in the synaptic vesicle recycling. May facilitate clathrin-coated vesicle uncoating. {ECO:0000269|PubMed:11381094, ECO:0000269|PubMed:11454741, ECO:0000269|PubMed:21102408}. |
| Q8WYL5 | SSH1 | S812 | ochoa | Protein phosphatase Slingshot homolog 1 (EC 3.1.3.16) (EC 3.1.3.48) (SSH-like protein 1) (SSH-1L) (hSSH-1L) | Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. {ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12684437, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:14531860, ECO:0000269|PubMed:14645219, ECO:0000269|PubMed:15056216, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:16230460}. |
| 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}. |
| Q92574 | TSC1 | S303 | ochoa | Hamartin (Tuberous sclerosis 1 protein) | Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155). {ECO:0000250|UniProtKB:Q9Z136, ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:16464865, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:33215753, ECO:0000269|PubMed:9242607}. |
| Q92616 | GCN1 | S937 | 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}. |
| Q92752 | TNR | S724 | ochoa | Tenascin-R (TN-R) (Janusin) (Restrictin) | Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. These interactions can influence cellular behavior by either evoking a stable adhesion and differentiation, or repulsion and inhibition of neurite growth. Binding to cell surface gangliosides inhibits RGD-dependent integrin-mediated cell adhesion and results in an inhibition of PTK2/FAK1 (FAK) phosphorylation and cell detachment. Binding to membrane surface sulfatides results in a oligodendrocyte adhesion and differentiation. Interaction with CNTN1 induces a repulsion of neurons and an inhibition of neurite outgrowth. Interacts with SCN2B may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier. TNR-linked chondroitin sulfate glycosaminoglycans are involved in the interaction with FN1 and mediate inhibition of cell adhesion and neurite outgrowth. The highly regulated addition of sulfated carbohydrate structure may modulate the adhesive properties of TNR over the course of development and during synapse maintenance (By similarity). {ECO:0000250}. |
| Q92754 | TFAP2C | S22 | ochoa | Transcription factor AP-2 gamma (AP2-gamma) (Activating enhancer-binding protein 2 gamma) (Transcription factor ERF-1) | Sequence-specific DNA-binding transcription factor that interacts with cellular enhancer elements to regulate transcription of selected genes, and which plays a key role in early embryonic development (PubMed:11694877, PubMed:24413532). AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions (PubMed:11694877, PubMed:24413532). TFAP2C plays a key role in early embryonic development by regulating both inner cell mass (ICM) and trophectoderm differentiation (By similarity). At the 8-cell stage, during morula development, controls expression of cell-polarity genes (By similarity). Upon trophoblast commitment, binds to late trophectoderm genes in blastocysts together with CDX2, and later to extra-embryonic ectoderm genes together with SOX2 (By similarity). Binds to both closed and open chromatin with other transcription factors (By similarity). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532). {ECO:0000250|UniProtKB:Q61312, ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:24413532}. |
| Q92766 | RREB1 | S1388 | ochoa | Ras-responsive element-binding protein 1 (RREB-1) (Finger protein in nuclear bodies) (Raf-responsive zinc finger protein LZ321) (Zinc finger motif enhancer-binding protein 1) (Zep-1) | Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters (PubMed:10390538, PubMed:15067362, PubMed:17550981, PubMed:8816445, PubMed:9305772). Represses the angiotensinogen gene (PubMed:15067362). Negatively regulates the transcriptional activity of AR (PubMed:17550981). Potentiates the transcriptional activity of NEUROD1 (PubMed:12482979). Promotes brown adipocyte differentiation (By similarity). May be involved in Ras/Raf-mediated cell differentiation by enhancing calcitonin expression (PubMed:8816445). {ECO:0000250|UniProtKB:Q3UH06, ECO:0000269|PubMed:10390538, ECO:0000269|PubMed:12482979, ECO:0000269|PubMed:15067362, ECO:0000269|PubMed:17550981, ECO:0000269|PubMed:8816445, ECO:0000269|PubMed:9305772}. |
| Q92859 | NEO1 | S1434 | ochoa | Neogenin (Immunoglobulin superfamily DCC subclass member 2) | Multi-functional cell surface receptor regulating cell adhesion in many diverse developmental processes, including neural tube and mammary gland formation, myogenesis and angiogenesis. Receptor for members of the BMP, netrin, and repulsive guidance molecule (RGM) families. Netrin-Neogenin interactions result in a chemoattractive axon guidance response and cell-cell adhesion, the interaction between NEO1/Neogenin and RGMa and RGMb induces a chemorepulsive response. {ECO:0000269|PubMed:21149453}. |
| Q92896 | GLG1 | S509 | ochoa | 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}. |
| Q93073 | SECISBP2L | S934 | ochoa | Selenocysteine insertion sequence-binding protein 2-like (SECIS-binding protein 2-like) | Binds SECIS (Sec insertion sequence) elements present on selenocysteine (Sec) protein mRNAs, but does not promote Sec incorporation into selenoproteins in vitro. |
| Q93084 | ATP2A3 | S362 | ochoa | Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (SERCA3) (SR Ca(2+)-ATPase 3) (EC 7.2.2.10) (Calcium pump 3) | This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction. {ECO:0000269|PubMed:11956212, ECO:0000269|PubMed:15028735}. |
| Q96BD0 | SLCO4A1 | S361 | ochoa | Solute carrier organic anion transporter family member 4A1 (OATP4A1) (Colon organic anion transporter) (Organic anion transporter polypeptide-related protein 1) (OATP-RP1) (OATPRP1) (POAT) (Organic anion-transporting polypeptide E) (OATP-E) (Sodium-independent organic anion transporter E) (Solute carrier family 21 member 12) | Organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormones 3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4) and 3,3',5'-triiodo-L-thyronine (rT3), conjugated steroids such as estrone 3-sulfate and estradiol 17-beta glucuronide, bile acids such as taurocholate and prostanoids such as prostaglandin E2, likely operating in a tissue-specific manner (PubMed:10873595, PubMed:19129463, PubMed:30343886). May be involved in uptake of metabolites from the circulation into organs such as kidney, liver or placenta. Possibly drives the selective transport of thyroid hormones and estrogens coupled to an outward glutamate gradient across the microvillous membrane of the placenta (PubMed:30343886). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable). {ECO:0000269|PubMed:10873595, ECO:0000269|PubMed:19129463, ECO:0000269|PubMed:30343886, ECO:0000305}. |
| Q96CC6 | RHBDF1 | S133 | 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}. |
| Q96CC6 | RHBDF1 | S346 | 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}. |
| Q96D96 | HVCN1 | S97 | psp | Voltage-gated hydrogen channel 1 (Hydrogen voltage-gated channel 1) (HV1) (Voltage sensor domain-only protein) | Voltage-gated proton-selective channel that conducts outward proton currents in response to intracellular acidification. Lacks a canonical ion-channel pore domain and mediates proton permeability via its voltage sensor domain (PubMed:16554753, PubMed:20037153, PubMed:20548053, PubMed:22020278, PubMed:27859356, PubMed:30478045, PubMed:37669933). Appears to play a dominant role in regulation of CO2/HCO3(-)/H(+) equilibrium in sperm flagellum. Prevents the acidification resulting from HCO3(-) synthesis and thus sustains high HCO3(-) levels inside sperm for capacitation (PubMed:20144758, PubMed:30478045, PubMed:37669933). Provides for proton efflux that compensates for electron charge generated by NADPH oxidase activity either in the extracellular or phagosomal compartments, thus enabling the production of high levels of bactericidal reactive oxygen species during the respiratory burst (PubMed:20037153, PubMed:30478045). Opens when the pH of airway surface liquid exceeds 7 and contributes to respiratory epithelial acid secretion to maintain pH in the mucosa (PubMed:20548053). {ECO:0000269|PubMed:16554753, ECO:0000269|PubMed:20037153, ECO:0000269|PubMed:20144758, ECO:0000269|PubMed:20548053, ECO:0000269|PubMed:22020278, ECO:0000269|PubMed:27859356, ECO:0000269|PubMed:30478045, ECO:0000269|PubMed:37669933}. |
| Q96F07 | CYFIP2 | S927 | ochoa | Cytoplasmic FMR1-interacting protein 2 (p53-inducible protein 121) | Involved in T-cell adhesion and p53/TP53-dependent induction of apoptosis. Does not bind RNA. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). {ECO:0000250|UniProtKB:Q5SQX6, ECO:0000269|PubMed:10449408, ECO:0000269|PubMed:15048733, ECO:0000269|PubMed:17245118}. |
| Q96I25 | RBM17 | S291 | ochoa|psp | Splicing factor 45 (45 kDa-splicing factor) (RNA-binding motif protein 17) | Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia. {ECO:0000269|PubMed:12015979, ECO:0000269|PubMed:17589525}. |
| Q96ID5 | IGSF21 | S389 | ochoa | Immunoglobulin superfamily member 21 (IgSF21) | Involved in synaptic inhibition in the brain. Selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic NRXN2. {ECO:0000250|UniProtKB:Q7TNR6}. |
| Q96IF1 | AJUBA | S263 | ochoa | LIM domain-containing protein ajuba | Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. {ECO:0000269|PubMed:12417594, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:15870274, ECO:0000269|PubMed:16413547, ECO:0000269|PubMed:17909014, ECO:0000269|PubMed:18805794, ECO:0000269|PubMed:20303269, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:22286099}. |
| Q96JH7 | VCPIP1 | S1064 | 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}. |
| Q96JK2 | DCAF5 | S496 | ochoa | DDB1- and CUL4-associated factor 5 (Breakpoint cluster region protein 2) (BCRP2) (WD repeat-containing protein 22) | Is a substrate receptor for the CUL4-DDB1 E3 ubiquitin-protein ligase complex (CRL4) (PubMed:29691401, PubMed:30442713). The complex CRL4-DCAF5 is involved in the ubiquitination of a set of methylated non-histone proteins, including SOX2, DNMT1 and E2F1 (PubMed:29691401, PubMed:30442713). {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:29691401, ECO:0000269|PubMed:30442713}. |
| Q96K58 | ZNF668 | S176 | ochoa | Zinc finger protein 668 | May be involved in transcriptional regulation. May play a role in DNA repair process. {ECO:0000269|PubMed:34313816}. |
| Q96N11 | INTS15 | S362 | ochoa | Integrator complex subunit 15 | Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:36920904, PubMed:38570683, PubMed:38823386). 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:38570683). INTS15 is part of the integrator tail module that acts as a platform for the recruitment of transcription factors at promoters (PubMed:38823386). Within the integrator complex, INTS15 is required to bridge different integrator modules (PubMed:36920904). {ECO:0000269|PubMed:36920904, ECO:0000269|PubMed:38570683, ECO:0000269|PubMed:38823386}. |
| Q96PY5 | FMNL2 | S677 | 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}. |
| Q96QE3 | ATAD5 | S821 | ochoa | ATPase family AAA domain-containing protein 5 (Chromosome fragility-associated gene 1 protein) | Has an important role in DNA replication and in maintaining genome integrity during replication stress (PubMed:15983387, PubMed:19755857). Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis (PubMed:15983387). Modulates the RAD9A interaction with BCL2 and thereby induces DNA damage-induced apoptosis (PubMed:15983387). Promotes PCNA deubiquitination by recruiting the ubiquitin-specific protease 1 (USP1) and WDR48 thereby down-regulating the error-prone damage bypass pathway (PubMed:20147293). As component of the ATAD5 RFC-like complex, regulates the function of the DNA polymerase processivity factor PCNA by unloading the ring-shaped PCNA homotrimer from DNA after replication during the S phase of the cell cycle (PubMed:23277426, PubMed:23937667). This seems to be dependent on its ATPase activity (PubMed:23277426). Plays important roles in restarting stalled replication forks under replication stress, by unloading the PCNA homotrimer from DNA and recruiting RAD51 possibly through an ATR-dependent manner (PubMed:31844045). Ultimately this enables replication fork regression, breakage, and eventual fork restart (PubMed:31844045). Both the PCNA unloading activity and the interaction with WDR48 are required to efficiently recruit RAD51 to stalled replication forks (PubMed:31844045). Promotes the generation of MUS81-mediated single-stranded DNA-associated breaks in response to replication stress, which is an alternative pathway to restart stalled/regressed replication forks (PubMed:31844045). {ECO:0000269|PubMed:15983387, ECO:0000269|PubMed:19755857, ECO:0000269|PubMed:20147293, ECO:0000269|PubMed:23277426, ECO:0000269|PubMed:23937667, ECO:0000269|PubMed:31844045}. |
| Q96R06 | SPAG5 | S401 | 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}. |
| Q96RE7 | NACC1 | S330 | ochoa | Nucleus accumbens-associated protein 1 (NAC-1) (BTB/POZ domain-containing protein 14B) | Functions as a transcriptional repressor. Seems to function as a transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell proliferation and survival. This may be mediated at least in part through repressing transcriptional activity of GADD45GIP1. Required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines. {ECO:0000269|PubMed:17130457, ECO:0000269|PubMed:17804717}. |
| Q96RG2 | PASK | S953 | ochoa|psp | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q96RL1 | UIMC1 | S241 | ochoa | BRCA1-A complex subunit RAP80 (Receptor-associated protein 80) (Retinoid X receptor-interacting protein 110) (Ubiquitin interaction motif-containing protein 1) | Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1. {ECO:0000269|PubMed:12080054, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17525341, ECO:0000269|PubMed:17525342, ECO:0000269|PubMed:17621610, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19328070, ECO:0000269|PubMed:24627472, ECO:0000269|Ref.38}. |
| Q96S38 | RPS6KC1 | S872 | ochoa | Ribosomal protein S6 kinase delta-1 (S6K-delta-1) (EC 2.7.11.1) (52 kDa ribosomal protein S6 kinase) (Ribosomal S6 kinase-like protein with two PSK domains 118 kDa protein) (SPHK1-binding protein) | May be involved in transmitting sphingosine-1 phosphate (SPP)-mediated signaling into the cell (PubMed:12077123). Plays a role in the recruitment of PRDX3 to early endosomes (PubMed:15750338). {ECO:0000269|PubMed:12077123, ECO:0000269|PubMed:15750338}. |
| Q99081 | TCF12 | S116 | ochoa | Transcription factor 12 (TCF-12) (Class B basic helix-loop-helix protein 20) (bHLHb20) (DNA-binding protein HTF4) (E-box-binding protein) (Transcription factor HTF-4) | Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3') (By similarity). May be involved in the functional network that regulates the development of the GnRH axis (PubMed:32620954). {ECO:0000250|UniProtKB:Q61286, ECO:0000269|PubMed:32620954}. |
| Q99623 | PHB2 | S151 | 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}. |
| Q99798 | ACO2 | S562 | 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}. |
| Q9BPX3 | NCAPG | S390 | 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}. |
| 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}. |
| Q9BXS6 | NUSAP1 | S247 | 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}. |
| Q9BYM8 | RBCK1 | S272 | 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}. |
| Q9BZL6 | PRKD2 | S706 | ochoa|psp | Serine/threonine-protein kinase D2 (EC 2.7.11.13) (nPKC-D2) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}. |
| Q9BZZ2 | SIGLEC1 | S654 | ochoa | Sialoadhesin (Sialic acid-binding Ig-like lectin 1) (Siglec-1) (CD antigen CD169) | Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, including granulocytes, monocytes, natural killer cells, B-cells and CD8 T-cells. Plays a crucial role in limiting bacterial dissemination by engaging sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response (PubMed:12940982, PubMed:33489013). Mediates the uptake of various enveloped viruses via sialic acid recognition and subsequently induces the formation of intracellular compartments filled with virions (VCCs) (PubMed:28129379). In turn, enhances macrophage-to-T-cell transmission of several viruses including HIV-1 or SARS-CoV-2 (PubMed:28129379, PubMed:34782760). Acts as an endocytic receptor mediating clathrin dependent endocytosis. Preferentially binds to alpha-2,3-linked sialic acid (PubMed:12940982). Binds to SPN/CD43 on T-cells (By similarity). May play a role in hemopoiesis. Plays a role in the inhibition of antiviral innate immune by promoting TBK1 degradation via TYROBP and TRIM27-mediated ubiquitination (PubMed:26358190). {ECO:0000250|UniProtKB:Q62230, ECO:0000269|PubMed:12940982, ECO:0000269|PubMed:26358190, ECO:0000269|PubMed:28129379, ECO:0000269|PubMed:33489013, ECO:0000269|PubMed:34782760}.; FUNCTION: (Microbial infection) Facilitates viral cytoplasmic entry into activated dendritic cells via recognition of sialylated gangliosides pesent on viral membrane. {ECO:0000269|PubMed:31160823}. |
| Q9C0C2 | TNKS1BP1 | S877 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9C0C2 | TNKS1BP1 | S920 | ochoa | 182 kDa tankyrase-1-binding protein | None |
| Q9GZV1 | ANKRD2 | S83 | ochoa | Ankyrin repeat domain-containing protein 2 (Skeletal muscle ankyrin repeat protein) (hArpp) | Functions as a negative regulator of myocyte differentiation. May interact with both sarcoplasmic structural proteins and nuclear proteins to regulate gene expression during muscle development and in response to muscle stress. {ECO:0000269|PubMed:21737686, ECO:0000269|PubMed:22016770}. |
| Q9GZV9 | FGF23 | S207 | psp | Fibroblast growth factor 23 (FGF-23) (Phosphatonin) (Tumor-derived hypophosphatemia-inducing factor) [Cleaved into: Fibroblast growth factor 23 N-terminal peptide; Fibroblast growth factor 23 C-terminal peptide] | Regulator of phosphate homeostasis (PubMed:11062477). Inhibits renal tubular phosphate transport by reducing SLC34A1 levels (PubMed:11409890). Up-regulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism (PubMed:15040831). Negatively regulates osteoblast differentiation and matrix mineralization (PubMed:18282132). {ECO:0000250|UniProtKB:Q8VI82, ECO:0000269|PubMed:11062477, ECO:0000269|PubMed:11409890, ECO:0000269|PubMed:15040831, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:18282132}. |
| 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}. |
| 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}. |
| Q9H0A0 | NAT10 | S674 | 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}. |
| Q9H0K1 | SIK2 | S512 | psp | 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}. |
| Q9H2U1 | DHX36 | S167 | ochoa | ATP-dependent DNA/RNA helicase DHX36 (EC 3.6.4.12) (EC 3.6.4.13) (DEAD/H box polypeptide 36) (DEAH-box protein 36) (G4-resolvase-1) (G4R1) (MLE-like protein 1) (RNA helicase associated with AU-rich element protein) | Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:16150737, PubMed:18854321, PubMed:20472641, PubMed:21586581). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:14731398, PubMed:18279852, PubMed:21993297, PubMed:22238380, PubMed:25579584). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-DNA and G4-RNA) (PubMed:16150737, PubMed:18842585, PubMed:20472641, PubMed:21586581, PubMed:24369427, PubMed:26195789). Plays a role in genomic integrity (PubMed:22238380). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (PubMed:20472641, PubMed:21149580, PubMed:21846770, PubMed:22238380, PubMed:24151078, PubMed:25579584). Plays a role in transcriptional regulation (PubMed:21586581, PubMed:21993297). Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:21993297). Plays a role in post-transcriptional regulation (PubMed:27940037). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (PubMed:27940037). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (PubMed:24369427, PubMed:26489465). Binds to both G4-RNA structures and alternative non-quadruplex-forming sequence within the 3'-UTR of the PITX1 mRNA regulating negatively PITX1 protein expression (PubMed:24369427). Binds to both G4-RNA structure in the 5'-UTR and AU-rich elements (AREs) localized in the 3'-UTR of NKX2-5 mRNA to either stimulate protein translation or induce mRNA decay in an ELAVL1-dependent manner, respectively (PubMed:26489465). Also binds to ARE sequences present in several mRNAs mediating exosome-mediated 3'-5' mRNA degradation (PubMed:14731398, PubMed:18279852). Involved in cytoplasmic urokinase-type plasminogen activator (uPA) mRNA decay (PubMed:14731398). 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). Required for early embryonic development and hematopoiesis. Involved in the regulation of cardioblast differentiation and proliferation during heart development. Involved in spermatogonia differentiation. May play a role in ossification (By similarity). {ECO:0000250|UniProtKB:D4A2Z8, ECO:0000250|UniProtKB:Q05B79, ECO:0000250|UniProtKB:Q8VHK9, ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:16150737, ECO:0000269|PubMed:18279852, ECO:0000269|PubMed:18842585, ECO:0000269|PubMed:18854321, ECO:0000269|PubMed:20472641, ECO:0000269|PubMed:21149580, ECO:0000269|PubMed:21586581, ECO:0000269|PubMed:21846770, ECO:0000269|PubMed:21993297, ECO:0000269|PubMed:22238380, ECO:0000269|PubMed:24151078, ECO:0000269|PubMed:24369427, ECO:0000269|PubMed:25579584, ECO:0000269|PubMed:26195789, ECO:0000269|PubMed:26489465, ECO:0000269|PubMed:27940037}. |
| 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}. |
| 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. |
| Q9H400 | LIME1 | S201 | ochoa | Lck-interacting transmembrane adapter 1 (Lck-interacting membrane protein) (Lck-interacting molecule) | Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and TCR (T-cell antigen receptor)-mediated T-cell signaling in T-cells. In absence of TCR signaling, may be involved in CD4-mediated inhibition of T-cell activation. Couples activation of these receptors and their associated kinases with distal intracellular events such as calcium mobilization or MAPK activation through the recruitment of PLCG2, GRB2, GRAP2, and other signaling molecules. {ECO:0000269|PubMed:14610046}. |
| 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}. |
| Q9H8T0 | AKTIP | S237 | psp | AKT-interacting protein (Ft1) (Fused toes protein homolog) | Component of the FTS/Hook/FHIP complex (FHF complex) (PubMed:32073997). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Regulates apoptosis by enhancing phosphorylation and activation of AKT1. Increases release of TNFSF6 via the AKT1/GSK3B/NFATC1 signaling cascade. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). {ECO:0000269|PubMed:14749367, ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}. |
| Q9H8V3 | ECT2 | S38 | 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}. |
| Q9HAZ1 | CLK4 | S335 | ochoa | Dual specificity protein kinase CLK4 (EC 2.7.12.1) (CDC-like kinase 4) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:11170754, ECO:0000269|PubMed:19168442}. |
| 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. |
| Q9HCD6 | TANC2 | S294 | 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}. |
| Q9HD26 | GOPC | S439 | 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}. |
| Q9NP62 | GCM1 | S326 | psp | Chorion-specific transcription factor GCMa (hGCMa) (GCM motif protein 1) (Glial cells missing homolog 1) | Transcription factor involved in the control of expression of placental growth factor (PGF) and other placenta-specific genes (PubMed:10542267, PubMed:18160678). Binds to the trophoblast-specific element 2 (TSE2) of the aromatase gene enhancer (PubMed:10542267). Binds to the SYDE1 promoter (PubMed:27917469). Has a central role in mediating the differentiation of trophoblast cells along both the villous and extravillous pathways in placental development (PubMed:19219068). {ECO:0000269|PubMed:10542267, ECO:0000269|PubMed:18160678, ECO:0000269|PubMed:19219068, ECO:0000269|PubMed:27917469}. |
| Q9NQW6 | ANLN | S252 | 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}. |
| Q9NR16 | CD163L1 | S1426 | ochoa | Scavenger receptor cysteine-rich type 1 protein M160 (CD163 antigen-like 1) (CD antigen CD163b) | None |
| Q9NR45 | NANS | S251 | 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}. |
| Q9NS87 | KIF15 | S560 | ochoa | Kinesin-like protein KIF15 (Kinesin-like protein 2) (hKLP2) (Kinesin-like protein 7) (Serologically defined breast cancer antigen NY-BR-62) | Plus-end directed kinesin-like motor enzyme involved in mitotic spindle assembly. {ECO:0000250}. |
| Q9NSA2 | KCND1 | S568 | psp | A-type voltage-gated potassium channel KCND1 (Potassium voltage-gated channel subfamily D member 1) (Shal-type potassium channel KCND1) (Voltage-gated potassium channel subunit Kv4.1) | A-type voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes in the brain (PubMed:15454437). Mediates A-type current I(SA) in suprachiasmatic nucleus (SCN) neurons. Exhibits a low-threshold A-type current with a hyperpolarized steady-state inactivation midpoint and the recovery process was steeply voltage-dependent, with recovery being markedly faster at more negative potentials. May regulates repetitive firing rates in the suprachiasmatic nucleus (SCN) neurons and circadian rhythms in neuronal excitability and behavior. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity. The regulatory subunit KCNIP1 modulates the kinetics of channel inactivation, increases the current amplitudes and accelerates recovery from inactivation, shifts activation in a depolarizing direction (By similarity). The regulatory subunit DPP10 decreases the voltage sensitivity of the inactivation channel gating (PubMed:15454437). {ECO:0000250|UniProtKB:Q03719, ECO:0000269|PubMed:15454437}. |
| Q9NSC2 | SALL1 | S1106 | ochoa | Sal-like protein 1 (Spalt-like transcription factor 1) (Zinc finger protein 794) (Zinc finger protein SALL1) (Zinc finger protein Spalt-1) (HSal1) (Sal-1) | Transcriptional repressor involved in organogenesis. Plays an essential role in ureteric bud invasion during kidney development. {ECO:0000250|UniProtKB:Q9ER74}. |
| Q9NSK0 | KLC4 | S598 | ochoa | Kinesin light chain 4 (KLC 4) (Kinesin-like protein 8) | Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (By similarity). {ECO:0000250}. |
| Q9NUL5 | SHFL | S247 | ochoa | Shiftless antiviral inhibitor of ribosomal frameshifting protein (SFL) (SHFL) (Interferon-regulated antiviral protein) (IRAV) (Repressor of yield of DENV protein) (RyDEN) | Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses, such as HIV1, and cellular genes, such as PEG10. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site (PubMed:30682371). Regulates HIV1 GAG-POL expression by inhibiting -1PRF (PubMed:30682371). Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Also interrupts Zika virus replication by promoting viral NS3 degradation via a lysosome-dependent pathway (PubMed:32150556). Can also limit the replication of hepatitis C virus (HCV) by restricting formation of viral replication organelle, West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes virus type 8 (HHV-8) and human adenovirus (PubMed:26735137, PubMed:27974568, PubMed:30944177, PubMed:32294532). Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA (PubMed:27974568). {ECO:0000269|PubMed:26735137, ECO:0000269|PubMed:27974568, ECO:0000269|PubMed:30682371, ECO:0000269|PubMed:30944177, ECO:0000269|PubMed:32150556, ECO:0000269|PubMed:32294532}.; FUNCTION: Isoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes. {ECO:0000269|PubMed:30682371}. |
| Q9NVI1 | FANCI | S972 | psp | Fanconi anemia group I protein (Protein FACI) | Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites (PubMed:17412408, PubMed:17460694, PubMed:17452773, PubMed:19111657, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (PubMed:19589784). Participates in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:25862789). {ECO:0000250|UniProtKB:B0I564, ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17452773, ECO:0000269|PubMed:17460694, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784, ECO:0000269|PubMed:25862789, ECO:0000269|PubMed:36385258}. |
| Q9NVI1 | FANCI | S1121 | ochoa|psp | Fanconi anemia group I protein (Protein FACI) | Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites (PubMed:17412408, PubMed:17460694, PubMed:17452773, PubMed:19111657, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (PubMed:19589784). Participates in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:25862789). {ECO:0000250|UniProtKB:B0I564, ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17452773, ECO:0000269|PubMed:17460694, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784, ECO:0000269|PubMed:25862789, ECO:0000269|PubMed:36385258}. |
| Q9NWQ8 | PAG1 | S229 | ochoa | Phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (Csk-binding protein) (Transmembrane adapter protein PAG) (Transmembrane phosphoprotein Cbp) | Negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. Inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins. May be involved in cell adhesion signaling. {ECO:0000269|PubMed:10790433}. |
| Q9NWS0 | PIH1D1 | S173 | ochoa | PIH1 domain-containing protein 1 (Nucleolar protein 17 homolog) | Involved in the assembly of C/D box small nucleolar ribonucleoprotein (snoRNP) particles (PubMed:17636026). Recruits the SWI/SNF complex to the core promoter of rRNA genes and enhances pre-rRNA transcription (PubMed:22368283, PubMed:24036451). Mediates interaction of TELO2 with the R2TP complex which is necessary for the stability of MTOR and SMG1 (PubMed:20864032). Positively regulates the assembly and activity of the mTORC1 complex (PubMed:24036451). {ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:20864032, ECO:0000269|PubMed:22368283, ECO:0000269|PubMed:24036451}. |
| Q9NY57 | STK32B | S378 | ochoa | Serine/threonine-protein kinase 32B (EC 2.7.11.1) (Yet another novel kinase 2) | None |
| Q9NYB0 | TERF2IP | S28 | 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}. |
| Q9NYF3 | FAM53C | S299 | ochoa | Protein FAM53C | None |
| Q9NYQ7 | CELSR3 | S3058 | ochoa | Cadherin EGF LAG seven-pass G-type receptor 3 (Cadherin family member 11) (Epidermal growth factor-like protein 1) (EGF-like protein 1) (Flamingo homolog 1) (hFmi1) (Multiple epidermal growth factor-like domains protein 2) (Multiple EGF-like domains protein 2) | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| Q9NYV4 | CDK12 | S1200 | 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}. |
| Q9NZU5 | LMCD1 | S42 | ochoa | LIM and cysteine-rich domains protein 1 (Dyxin) | Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue-specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter (By similarity). Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway. {ECO:0000250, ECO:0000269|PubMed:20026769}. |
| 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}. |
| Q9P0L0 | VAPA | S214 | ochoa | Vesicle-associated membrane protein-associated protein A (VAMP-A) (VAMP-associated protein A) (VAP-A) (33 kDa VAMP-associated protein) (VAP-33) | Endoplasmic reticulum (ER)-anchored protein that mediates the formation of contact sites between the ER and endosomes via interaction with FFAT motif-containing proteins such as STARD3 or WDR44 (PubMed:32344433, PubMed:33124732). STARD3-VAPA interaction enables cholesterol transfer from the ER to endosomes (PubMed:33124732). Via interaction with WDR44 participates in neosynthesized protein export (PubMed:32344433). In addition, recruited to the plasma membrane through OSBPL3 binding (PubMed:25447204). The OSBPL3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER morphology (PubMed:16143324). May play a role in vesicle trafficking (PubMed:11511104, PubMed:19289470). {ECO:0000269|PubMed:11511104, ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:25447204, ECO:0000269|PubMed:32344433, ECO:0000269|PubMed:33124732}. |
| 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}. |
| 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. |
| Q9P2B7 | CFAP97 | S329 | ochoa | Cilia- and flagella-associated protein 97 | None |
| Q9UBI6 | GNG12 | S36 | ochoa | Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 | Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. |
| Q9UBP0 | SPAST | S243 | ochoa | Spastin (EC 5.6.1.1) (Spastic paraplegia 4 protein) | ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:20530212, PubMed:22637577, PubMed:26875866). Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Severing activity is not dependent on tubulin acetylation or detyrosination (PubMed:26875866). Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. It is critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles and cilia. SPAST is involved in abscission step of cytokinesis and nuclear envelope reassembly during anaphase in cooperation with the ESCRT-III complex (PubMed:19000169, PubMed:21310966, PubMed:26040712). Recruited at the midbody, probably by IST1, and participates in membrane fission during abscission together with the ESCRT-III complex (PubMed:21310966). Recruited to the nuclear membrane by IST1 and mediates microtubule severing, promoting nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and endosome recycling (PubMed:23897888). Recruited by IST1 to endosomes and regulates early endosomal tubulation and recycling by mediating microtubule severing (PubMed:23897888). Probably plays a role in axon growth and the formation of axonal branches (PubMed:15716377). {ECO:0000255|HAMAP-Rule:MF_03021, ECO:0000269|PubMed:11809724, ECO:0000269|PubMed:15716377, ECO:0000269|PubMed:16219033, ECO:0000269|PubMed:17389232, ECO:0000269|PubMed:19000169, ECO:0000269|PubMed:20530212, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22637577, ECO:0000269|PubMed:23897888, ECO:0000269|PubMed:26040712, ECO:0000269|PubMed:26875866}.; FUNCTION: [Isoform 1]: Involved in lipid metabolism by regulating the size and distribution of lipid droplets. {ECO:0000269|PubMed:25875445}. |
| Q9UBU8 | MORF4L1 | S47 | ochoa | Mortality factor 4-like protein 1 (MORF-related gene 15 protein) (MRG15) (Protein MSL3-1) (Transcription factor-like protein MRG15) | Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. 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:12391155, PubMed:14966270, 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). Required for homologous recombination repair (HRR) and resistance to mitomycin C (MMC). Involved in the localization of PALB2, BRCA2 and RAD51, but not BRCA1, to DNA-damage foci. {ECO:0000269|PubMed:12391155, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:20332121, ECO:0000269|PubMed:21041482, ECO:0000269|PubMed:37137925}. |
| Q9UGI8 | TES | S105 | ochoa | Testin (TESS) | Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Plays a role in the regulation of cell proliferation. May act as a tumor suppressor. Inhibits tumor cell growth. {ECO:0000269|PubMed:11420696, ECO:0000269|PubMed:12571287, ECO:0000269|PubMed:12695497}. |
| Q9UHD1 | CHORDC1 | S20 | ochoa | Cysteine and histidine-rich domain-containing protein 1 (CHORD domain-containing protein 1) (CHORD-containing protein 1) (CHP-1) (Protein morgana) | Regulates centrosome duplication, probably by inhibiting the kinase activity of ROCK2 (PubMed:20230755). Proposed to act as co-chaperone for HSP90 (PubMed:20230755). May play a role in the regulation of NOD1 via a HSP90 chaperone complex (PubMed:20230755). In vitro, has intrinsic chaperone activity (PubMed:20230755). This function may be achieved by inhibiting association of ROCK2 with NPM1 (PubMed:20230755). Plays a role in ensuring the localization of the tyrosine kinase receptor EGFR to the plasma membrane, and thus ensures the subsequent regulation of EGFR activity and EGF-induced actin cytoskeleton remodeling (PubMed:32053105). Involved in stress response (PubMed:20230755). Prevents tumorigenesis (PubMed:20230755). {ECO:0000269|PubMed:20230755, ECO:0000269|PubMed:32053105}. |
| Q9UHF7 | TRPS1 | S810 | 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}. |
| Q9UI36 | DACH1 | S735 | psp | Dachshund homolog 1 (Dach1) | Transcription factor that is involved in regulation of organogenesis. Seems to be a regulator of SIX1, SIX6 and probably SIX5. Corepression of precursor cell proliferation in myoblasts by SIX1 is switched to coactivation through recruitment of EYA3 to the SIX1-DACH1 complex. Transcriptional activation also seems to involve association of CREBBP. Seems to act as a corepressor of SIX6 in regulating proliferation by directly repressing cyclin-dependent kinase inhibitors, including the p27Kip1 promoter (By similarity). Inhibits TGF-beta signaling through interaction with SMAD4 and NCOR1. Binds to chromatin DNA via its DACHbox-N domain (By similarity). {ECO:0000250, ECO:0000269|PubMed:14525983}. |
| Q9UJF2 | RASAL2 | S692 | ochoa | Ras GTPase-activating protein nGAP (RAS protein activator-like 2) | Inhibitory regulator of the Ras-cyclic AMP pathway. |
| Q9UKA4 | AKAP11 | S20 | 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 | S239 | ochoa | A-kinase anchor protein 11 (AKAP-11) (A-kinase anchor protein 220 kDa) (AKAP 220) (hAKAP220) (Protein kinase A-anchoring protein 11) (PRKA11) | Binds to type II regulatory subunits of protein kinase A and anchors/targets them. |
| Q9UKE5 | TNIK | S1034 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
| Q9UKK3 | PARP4 | S1491 | 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}. |
| Q9UKL3 | CASP8AP2 | S1745 | ochoa | CASP8-associated protein 2 (FLICE-associated huge protein) | Participates in TNF-alpha-induced blockade of glucocorticoid receptor (GR) transactivation at the nuclear receptor coactivator level, upstream and independently of NF-kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of GR transactivation. Involved in TNF-alpha-induced activation of NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream mediator for CASP8-induced activation of NF-kappa-B. Required for the activation of CASP8 in FAS-mediated apoptosis. Required for histone gene transcription and progression through S phase. {ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:15698540, ECO:0000269|PubMed:17003125, ECO:0000269|PubMed:17245429}. |
| Q9UKM9 | RALY | S63 | ochoa | RNA-binding protein Raly (Autoantigen p542) (Heterogeneous nuclear ribonucleoprotein C-like 2) (hnRNP core protein C-like 2) (hnRNP associated with lethal yellow protein homolog) | RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver. Binds the lipid-responsive non-coding RNA LeXis and is required for LeXis-mediated effect on cholesterogenesis (By similarity). May be a heterogeneous nuclear ribonucleoprotein (hnRNP) (PubMed:9376072). {ECO:0000250|UniProtKB:Q64012, ECO:0000269|PubMed:9376072}. |
| Q9UKY1 | ZHX1 | S590 | ochoa | Zinc fingers and homeoboxes protein 1 | Acts as a transcriptional repressor. Increases DNMT3B-mediated repressive transcriptional activity when DNMT3B is tethered to DNA. May link molecule between DNMT3B and other co-repressor proteins. {ECO:0000269|PubMed:12237128}. |
| Q9ULJ7 | ANKRD50 | S1352 | ochoa | Ankyrin repeat domain-containing protein 50 | Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1 (PubMed:25278552). |
| Q9UMS6 | SYNPO2 | S264 | 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}. |
| Q9UPN4 | CEP131 | S447 | ochoa | Centrosomal protein of 131 kDa (5-azacytidine-induced protein 1) (Pre-acrosome localization protein 1) | Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Also acts as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208). {ECO:0000250|UniProtKB:Q62036, ECO:0000269|PubMed:17954613, ECO:0000269|PubMed:22797915, ECO:0000269|PubMed:24121310, ECO:0000269|PubMed:24185901, ECO:0000269|PubMed:24550735, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:30804208}. |
| Q9UPQ9 | TNRC6B | S1504 | ochoa | Trinucleotide repeat-containing gene 6B protein | Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs) (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). Required for miRNA-dependent translational repression and siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins (PubMed:16289642, PubMed:19167051, PubMed:19304925, PubMed:32354837). As scaffolding protein associates with argonaute proteins bound to partially complementary mRNAs and simultaneously can recruit CCR4-NOT and PAN deadenylase complexes (PubMed:21981923). {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:19167051, ECO:0000269|PubMed:19304925, ECO:0000269|PubMed:21981923, ECO:0000269|PubMed:32354837}. |
| Q9UPZ3 | HPS5 | S679 | ochoa | BLOC-2 complex member HPS5 (Alpha-integrin-binding protein 63) (Hermansky-Pudlak syndrome 5 protein) (Ruby-eye protein 2 homolog) (Ru2) | May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules. Regulates intracellular vesicular trafficking in fibroblasts. May be involved in the regulation of general functions of integrins. {ECO:0000269|PubMed:15296495, ECO:0000269|PubMed:17301833}. |
| Q9UQ26 | RIMS2 | S1212 | ochoa | Regulating synaptic membrane exocytosis protein 2 (Rab-3-interacting molecule 2) (RIM 2) (Rab-3-interacting protein 3) | Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (PubMed:23999003). {ECO:0000269|PubMed:23999003}. |
| Q9UQ35 | SRRM2 | S1300 | ochoa | Serine/arginine repetitive matrix protein 2 (300 kDa nuclear matrix antigen) (Serine/arginine-rich splicing factor-related nuclear matrix protein of 300 kDa) (SR-related nuclear matrix protein of 300 kDa) (Ser/Arg-related nuclear matrix protein of 300 kDa) (Splicing coactivator subunit SRm300) (Tax-responsive enhancer element-binding protein 803) (TaxREB803) | Required for pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). {ECO:0000269|PubMed:19854871, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:9531537, ECO:0000305|PubMed:33509932}. |
| Q9UQM7 | CAMK2A | S404 | ochoa | Calcium/calmodulin-dependent protein kinase type II subunit alpha (CaM kinase II subunit alpha) (CaMK-II subunit alpha) (EC 2.7.11.17) | Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in various processes, such as synaptic plasticity, neurotransmitter release and long-term potentiation (PubMed:14722083). Member of the NMDAR signaling complex in excitatory synapses, it regulates NMDAR-dependent potentiation of the AMPAR and therefore excitatory synaptic transmission (By similarity). Regulates dendritic spine development (PubMed:28130356). Also regulates the migration of developing neurons (PubMed:29100089). Phosphorylates the transcription factor FOXO3 to activate its transcriptional activity (PubMed:23805378). Phosphorylates the transcription factor ETS1 in response to calcium signaling, thereby decreasing ETS1 affinity for DNA (By similarity). In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (PubMed:11972023). In response to interferon-beta (IFN-beta) stimulation, stimulates the JAK-STAT signaling pathway (PubMed:35568036). Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated synaptic signaling via modulation of DAGLA activity (By similarity). {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798, ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28130356, ECO:0000269|PubMed:29100089}. |
| Q9Y243 | AKT3 | S34 | ochoa | RAC-gamma serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-3) (Protein kinase B gamma) (PKB gamma) (RAC-PK-gamma) (STK-2) | AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. {ECO:0000269|PubMed:18524868, ECO:0000269|PubMed:21191416}. |
| 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}. |
| Q9Y2G3 | ATP11B | S445 | ochoa | Phospholipid-transporting ATPase IF (EC 7.6.2.1) (ATPase IR) (ATPase class VI type 11B) (P4-ATPase flippase complex alpha subunit ATP11B) | 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 intracellular membranes (PubMed:30018401). May contribute to the maintenance of membrane lipid asymmetry in endosome compartment (PubMed:30018401). {ECO:0000269|PubMed:30018401}. |
| Q9Y2U8 | LEMD3 | S881 | ochoa | Inner nuclear membrane protein Man1 (LEM domain-containing protein 3) | Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest. {ECO:0000269|PubMed:15601644, ECO:0000269|PubMed:15647271}. |
| Q9Y320 | TMX2 | S243 | 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}. |
| Q9Y333 | LSM2 | S65 | ochoa | U6 snRNA-associated Sm-like protein LSm2 (Protein G7b) (Small nuclear ribonuclear protein D homolog) (snRNP core Sm-like protein Sm-x5) | Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320). {ECO:0000269|PubMed:10523320, ECO:0000269|PubMed:28781166}. |
| Q9Y3M8 | STARD13 | S457 | ochoa | StAR-related lipid transfer protein 13 (46H23.2) (Deleted in liver cancer 2 protein) (DLC-2) (Rho GTPase-activating protein) (START domain-containing protein 13) (StARD13) | GTPase-activating protein for RhoA, and perhaps for Cdc42. May be involved in regulation of cytoskeletal reorganization, cell proliferation and cell motility. Acts a tumor suppressor in hepatocellular carcinoma cells. {ECO:0000269|PubMed:14697242, ECO:0000269|PubMed:16217026}. |
| Q9Y3Z3 | SAMHD1 | S603 | 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}. |
| Q9Y478 | PRKAB1 | S101 | ochoa | 5'-AMP-activated protein kinase subunit beta-1 (AMPK subunit beta-1) (AMPKb) | Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3). |
| Q9Y490 | TLN1 | S45 | 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}. |
| Q9Y4F5 | CEP170B | S907 | ochoa | Centrosomal protein of 170 kDa protein B (Centrosomal protein 170B) (Cep170B) | Plays a role in microtubule organization. {ECO:0000250|UniProtKB:Q5SW79}. |
| Q9Y5K6 | CD2AP | S469 | 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}. |
| Q9Y5M8 | SRPRB | S112 | 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}. |
| Q9Y5X5 | NPFFR2 | S478 | psp | Neuropeptide FF receptor 2 (G-protein coupled receptor 74) (G-protein coupled receptor HLWAR77) (Neuropeptide G-protein coupled receptor) | Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. {ECO:0000269|PubMed:11024015}. |
| Q9Y617 | PSAT1 | S46 | ochoa | Phosphoserine aminotransferase (EC 2.6.1.52) (Phosphohydroxythreonine aminotransferase) (PSAT) | Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine. Catalyzes the second step, that is the pyridoxal 5'-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and alpha-ketoglutarate. {ECO:0000269|PubMed:36851825, ECO:0000269|PubMed:37627284}. |
| Q9Y617 | PSAT1 | S47 | ochoa | Phosphoserine aminotransferase (EC 2.6.1.52) (Phosphohydroxythreonine aminotransferase) (PSAT) | Involved in L-serine biosynthesis via the phosphorylated pathway, a three-step pathway converting the glycolytic intermediate 3-phospho-D-glycerate into L-serine. Catalyzes the second step, that is the pyridoxal 5'-phosphate-dependent transamination of 3-phosphohydroxypyruvate and L-glutamate to O-phosphoserine (OPS) and alpha-ketoglutarate. {ECO:0000269|PubMed:36851825, ECO:0000269|PubMed:37627284}. |
| Q9Y6A5 | TACC3 | S524 | 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}. |
| Q9Y6E2 | BZW2 | S202 | 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}. |
| Q9Y6N9 | USH1C | S287 | ochoa | Harmonin (Antigen NY-CO-38/NY-CO-37) (Autoimmune enteropathy-related antigen AIE-75) (Protein PDZ-73) (Renal carcinoma antigen NY-REN-3) (Usher syndrome type-1C protein) | Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (By similarity). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018). {ECO:0000250|UniProtKB:Q9ES64, ECO:0000269|PubMed:24725409, ECO:0000269|PubMed:26812018}. |
| Q9Y6Q9 | NCOA3 | S101 | 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. |
| O00141 | SGK1 | S252 | Sugiyama | Serine/threonine-protein kinase Sgk1 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 1) | Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}. |
| P28066 | PSMA5 | S174 | Sugiyama | Proteasome subunit alpha type-5 (Macropain zeta chain) (Multicatalytic endopeptidase complex zeta chain) (Proteasome subunit alpha-5) (alpha-5) (Proteasome zeta chain) | Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). {ECO:0000269|PubMed:15244466, ECO:0000269|PubMed:27176742, ECO:0000269|PubMed:8610016}. |
| P78371 | CCT2 | S150 | Sugiyama | T-complex protein 1 subunit beta (TCP-1-beta) (EC 3.6.1.-) (CCT-beta) (Chaperonin containing T-complex polypeptide 1 subunit 2) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q04637 | EIF4G1 | S1430 | Sugiyama | Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}. |
| Q96GM8 | TOE1 | S420 | Sugiyama | Target of EGR1 protein 1 | Inhibits cell growth rate and cell cycle. Induces CDKN1A expression as well as TGF-beta expression. Mediates the inhibitory growth effect of EGR1. Involved in the maturation of snRNAs and snRNA 3'-tail processing (PubMed:28092684). {ECO:0000269|PubMed:12562764, ECO:0000269|PubMed:28092684}. |
| O14757 | CHEK1 | S147 | Sugiyama | Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.; FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. {ECO:0000269|PubMed:22184239}. |
| P53350 | PLK1 | S529 | SIGNOR | Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13) | Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250|UniProtKB:P70032, ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080, ECO:0000269|PubMed:8991084}. |
| Q99613 | EIF3C | S638 | 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}. |
| O00116 | AGPS | S174 | Sugiyama | Alkyldihydroxyacetonephosphate synthase, peroxisomal (Alkyl-DHAP synthase) (EC 2.5.1.26) (Aging-associated gene 5 protein) (Alkylglycerone-phosphate synthase) | Catalyzes the exchange of the acyl chain in acyl-dihydroxyacetonephosphate (acyl-DHAP) for a long chain fatty alcohol, yielding the first ether linked intermediate, i.e. alkyl-dihydroxyacetonephosphate (alkyl-DHAP), in the pathway of ether lipid biosynthesis. {ECO:0000269|PubMed:8399344, ECO:0000269|PubMed:9553082}. |
| O14744 | PRMT5 | S463 | Sugiyama | Protein arginine N-methyltransferase 5 (PRMT5) (EC 2.1.1.320) (72 kDa ICln-binding protein) (Histone-arginine N-methyltransferase PRMT5) (Jak-binding protein 1) (Shk1 kinase-binding protein 1 homolog) (SKB1 homolog) (SKB1Hs) [Cleaved into: Protein arginine N-methyltransferase 5, N-terminally processed] | Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21081503, PubMed:21258366, PubMed:21917714, PubMed:22269951). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:11747828, PubMed:12411503, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). May methylate the N-terminal region of MBD2 (PubMed:16428440). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity). Methylates histone H3 'Arg-8', which may repress transcription (By similarity). Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21258366, PubMed:21917714). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically methylates NCL (PubMed:21081503). Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (PubMed:19011621). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (By similarity). {ECO:0000250|UniProtKB:Q8CIG8, ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:11152681, ECO:0000269|PubMed:11747828, ECO:0000269|PubMed:12411503, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:19011621, ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20421892, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805}. |
| Q14152 | EIF3A | S513 | Sugiyama | Eukaryotic translation initiation factor 3 subunit A (eIF3a) (Eukaryotic translation initiation factor 3 subunit 10) (eIF-3-theta) (eIF3 p167) (eIF3 p180) (eIF3 p185) | RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:11169732, PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773, PubMed:27462815). {ECO:0000255|HAMAP-Rule:MF_03000, ECO:0000269|PubMed:11169732, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634). {ECO:0000269|PubMed:23766293, ECO:0000269|PubMed:24357634}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}. |
| Q92621 | NUP205 | S1857 | Sugiyama | Nuclear pore complex protein Nup205 (205 kDa nucleoporin) (Nucleoporin Nup205) | Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:9348540). May anchor NUP62 and other nucleoporins, but not NUP153 and TPR, to the NPC (PubMed:15229283). In association with TMEM209, may be involved in nuclear transport of various nuclear proteins in addition to MYC (PubMed:22719065). {ECO:0000269|PubMed:15229283, ECO:0000269|PubMed:22719065, ECO:0000269|PubMed:9348540}. |
| P20290 | BTF3 | S126 | Sugiyama | Transcription factor BTF3 (Nascent polypeptide-associated complex subunit beta) (NAC-beta) (RNA polymerase B transcription factor 3) | When associated with NACA, prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. BTF3 is also a general transcription factor that can form a stable complex with RNA polymerase II. Required for the initiation of transcription. {ECO:0000269|PubMed:10982809}. |
| O15111 | CHUK | S369 | 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}. |
| O15146 | MUSK | S531 | 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}. |
| P32929 | CTH | S61 | Sugiyama | Cystathionine gamma-lyase (CGL) (CSE) (EC 4.4.1.1) (Cysteine desulfhydrase) (Cysteine-protein sulfhydrase) (Gamma-cystathionase) (Homocysteine desulfhydrase) (EC 4.4.1.2) | Catalyzes the last step in the trans-sulfuration pathway from L-methionine to L-cysteine in a pyridoxal-5'-phosphate (PLP)-dependent manner, which consists on cleaving the L,L-cystathionine molecule into L-cysteine, ammonia and 2-oxobutanoate (PubMed:10212249, PubMed:18476726, PubMed:19261609, PubMed:19961860). Part of the L-cysteine derived from the trans-sulfuration pathway is utilized for biosynthesis of the ubiquitous antioxidant glutathione (PubMed:18476726). Besides its role in the conversion of L-cystathionine into L-cysteine, it utilizes L-cysteine and L-homocysteine as substrates (at much lower rates than L,L-cystathionine) to produce the endogenous gaseous signaling molecule hydrogen sulfide (H2S) (PubMed:10212249, PubMed:19019829, PubMed:19261609, PubMed:19961860). In vitro, it converts two L-cysteine molecules into lanthionine and H2S, also two L-homocysteine molecules to homolanthionine and H2S, which can be particularly relevant under conditions of severe hyperhomocysteinemia (which is a risk factor for cardiovascular disease, diabetes, and Alzheimer's disease) (PubMed:19261609). Lanthionine and homolanthionine are structural homologs of L,L-cystathionine that differ by the absence or presence of an extra methylene group, respectively (PubMed:19261609). Acts as a cysteine-protein sulfhydrase by mediating sulfhydration of target proteins: sulfhydration consists of converting -SH groups into -SSH on specific cysteine residues of target proteins such as GAPDH, PTPN1 and NF-kappa-B subunit RELA, thereby regulating their function (PubMed:22169477). By generating the gasotransmitter H2S, it participates in a number of physiological processes such as vasodilation, bone protection, and inflammation (Probable) (PubMed:29254196). Plays an essential role in myogenesis by contributing to the biogenesis of H2S in skeletal muscle tissue (By similarity). Can also accept homoserine as substrate (By similarity). Catalyzes the elimination of selenocystathionine (which can be derived from the diet) to yield selenocysteine, ammonia and 2-oxobutanoate (By similarity). {ECO:0000250|UniProtKB:P18757, ECO:0000250|UniProtKB:Q8VCN5, ECO:0000269|PubMed:10212249, ECO:0000269|PubMed:18476726, ECO:0000269|PubMed:19019829, ECO:0000269|PubMed:19261609, ECO:0000269|PubMed:19961860, ECO:0000269|PubMed:22169477, ECO:0000269|PubMed:29254196, ECO:0000303|PubMed:18476726, ECO:0000305|PubMed:18476726, ECO:0000305|PubMed:19019829}. |
| Q9UHL4 | DPP7 | S213 | Sugiyama | Dipeptidyl peptidase 2 (EC 3.4.14.2) (Dipeptidyl aminopeptidase II) (Dipeptidyl peptidase 7) (Dipeptidyl peptidase II) (DPP II) (Quiescent cell proline dipeptidase) | Plays an important role in the degradation of some oligopeptides. {ECO:0000269|PubMed:15487984}. |
| O60763 | USO1 | S32 | 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}. |
| P13667 | PDIA4 | S126 | 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 |
| P29401 | TKT | S443 | 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}. |
| Q8N129 | CNPY4 | S45 | Sugiyama | Protein canopy homolog 4 | Plays a role in the regulation of the cell surface expression of TLR4. {ECO:0000269|PubMed:16338228}. |
| Q14028 | CNGB1 | S958 | Sugiyama | Cyclic nucleotide-gated channel beta-1 (CNG channel beta-1) (Cyclic nucleotide-gated cation channel 4) (CNG channel 4) (CNG-4) (CNG4) (Cyclic nucleotide-gated cation channel gamma) (Cyclic nucleotide-gated cation channel modulatory subunit) (Glutamic acid-rich protein) (GARP) | Pore-forming subunit of the rod cyclic nucleotide-gated channel. Mediates rod photoresponses at dim light converting transient changes in intracellular cGMP levels into electrical signals. In the dark, cGMP levels are high and keep the channel open enabling a steady inward current carried by Na(+) and Ca(2+) ions that leads to membrane depolarization and neurotransmitter release from synaptic terminals. Upon photon absorption cGMP levels decline leading to channel closure and membrane hyperpolarization that ultimately slows neurotransmitter release and signals the presence of light, the end point of the phototransduction cascade (By similarity) (PubMed:34699778). Pore-forming subunit of the olfactory cyclic nucleotide-gated channel. Operates in the cilia of olfactory sensory neurons where chemical stimulation of the odorant is converted to an electrical signal. Mediates odorant-induced cAMP-dependent Ca(2+) influx triggering neuron depolarization. The rise of intracellular Ca(2+) levels potentiates the olfactory response by activating Ca(2+)-dependent Cl(-) channels, but it also serves as a negative feedback signal to desensitize the channel for rapid adaptation to odorants (By similarity). Conducts cGMP- and cAMP-gated ion currents, with permeability for monovalent and divalent cations. The selectivity for Ca(2+) over Na(+) increases with cGMP concentrations, whereas the selectivity among monovalent ions is independent of the cGMP levels (By similarity) (PubMed:34699778). {ECO:0000250|UniProtKB:A0A8I5ZN27, ECO:0000250|UniProtKB:Q28181, ECO:0000250|UniProtKB:Q9NQW8, ECO:0000269|PubMed:34699778}.; FUNCTION: [Isoform GARP2]: High affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties: it is a regulator of spontaneous activation of rod PDE6, thereby serving to lower rod photoreceptor 'dark noise' and allowing these sensory cells to operate at the single photon detection limit. {ECO:0000269|PubMed:16407240}. |
| P26641 | EEF1G | S286 | Sugiyama | Elongation factor 1-gamma (EF-1-gamma) (eEF-1B gamma) | Probably plays a role in anchoring the complex to other cellular components. |
| P19367 | HK1 | S733 | Sugiyama | Hexokinase-1 (EC 2.7.1.1) (Brain form hexokinase) (Hexokinase type I) (HK I) (Hexokinase-A) | Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively) (PubMed:1637300, PubMed:25316723, PubMed:27374331). Does not phosphorylate N-acetyl-D-glucosamine (PubMed:27374331). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity). Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan (PubMed:27374331). When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331). {ECO:0000250|UniProtKB:P05708, ECO:0000269|PubMed:1637300, ECO:0000269|PubMed:25316723, ECO:0000269|PubMed:27374331}. |
| O43707 | ACTN4 | S488 | Sugiyama | Alpha-actinin-4 (Non-muscle alpha-actinin 4) | F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778). Association with IGSF8 regulates the immune synapse formation and is required for efficient T-cell activation (PubMed:22689882). {ECO:0000250|UniProtKB:P57780, ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:22351778, ECO:0000269|PubMed:22689882, ECO:0000305|PubMed:9508771}. |
| Q92626 | PXDN | S918 | Sugiyama | Peroxidasin homolog (EC 1.11.2.-) (Melanoma-associated antigen MG50) (Peroxidasin 1) (hsPxd01) (Vascular peroxidase 1) (p53-responsive gene 2 protein) [Cleaved into: PXDN active fragment] | Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncross-linked collagen IV/COL4A1 NC1 hexamer (PubMed:18929642, PubMed:19590037, PubMed:22842973, PubMed:25708780, PubMed:25713063, PubMed:27697841, PubMed:28154175, PubMed:34679700). In turns, directly contributes to the collagen IV network-dependent fibronectin/FN and laminin assembly, which is required for full extracellular matrix (ECM)-mediated signaling (PubMed:19590037, PubMed:32543734, PubMed:34679700). Thus, sulfilimine cross-links are essential for growth factor-induced cell proliferation and survival in endothelial cells, an event essential to basement membrane integrity (PubMed:32543734). In addition, through the bromide oxidation, may promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and FAK pathways (PubMed:25713063). Moreover brominates alpha2 collagen IV chain/COL4A2 at 'Tyr-1485' and leads to bromine enrichment of the basement membranes (PubMed:32571911). In vitro, can also catalyze the two-electron oxidation of thiocyanate and iodide and these two substrates could effectively compete with bromide and thus inhibit the formation of sulfilimine bonds (PubMed:28154175). Binds laminins (PubMed:32485152). May play a role in the organization of eyeball structure and lens development during eye development (By similarity). {ECO:0000250|UniProtKB:Q3UQ28, ECO:0000269|PubMed:18929642, ECO:0000269|PubMed:19590037, ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:25713063, ECO:0000269|PubMed:27697841, ECO:0000269|PubMed:28154175, ECO:0000269|PubMed:32485152, ECO:0000269|PubMed:32543734, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:34679700}. |
| O60479 | DLX3 | S137 | 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}. |
| P17948 | FLT1 | S1205 | Sugiyama | Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor) | Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275). {ECO:0000250|UniProtKB:P35969, ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537, ECO:0000269|Ref.11}.; FUNCTION: [Isoform 1]: Phosphorylates PLCG. {ECO:0000269|PubMed:9299537}.; FUNCTION: [Isoform 2]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 3]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 4]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:20512933}. |
| P19525 | EIF2AK2 | S461 | Sugiyama | Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) | IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. |
| Q9NZV7 | ZIM2 | S158 | Sugiyama | Zinc finger imprinted 2 (Zinc finger protein 656) | May be involved in transcriptional regulation. |
| O60941 | DTNB | S465 | Sugiyama | Dystrobrevin beta (DTN-B) (Beta-dystrobrevin) | Scaffolding protein that assembles DMD and SNTA1 molecules to the basal membrane of kidney cells and liver sinusoids (By similarity). May function as a repressor of the SYN1 promoter through the binding of repressor element-1 (RE-1), in turn regulates SYN1 expression and may be involved in cell proliferation regulation during the early phase of neural differentiation (PubMed:27223470). May be required for proper maturation and function of a subset of inhibitory synapses (By similarity). {ECO:0000250|UniProtKB:O70585, ECO:0000269|PubMed:27223470}. |
| Q9Y4J8 | DTNA | S501 | Sugiyama | Dystrobrevin alpha (DTN-A) (Alpha-dystrobrevin) (Dystrophin-related protein 3) | May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors. |
| P41235 | HNF4A | S262 | 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}. |
| Q04637 | EIF4G1 | S198 | Sugiyama | Eukaryotic translation initiation factor 4 gamma 1 (eIF-4-gamma 1) (eIF-4G 1) (eIF-4G1) (p220) | Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139). {ECO:0000269|PubMed:29062139, ECO:0000269|PubMed:29987188}. |
| P62258 | YWHAE | S156 | Sugiyama | 14-3-3 protein epsilon (14-3-3E) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}. |
| Q8N9F7 | GDPD1 | S119 | Sugiyama | Lysophospholipase D GDPD1 (EC 3.1.4.-) (Glycerophosphodiester phosphodiesterase 4) (Glycerophosphodiester phosphodiesterase domain-containing protein 1) | Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines (PubMed:25596343, PubMed:27637550). Shows a preference for 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF), lysophosphatidylethanolamine (lyso-PE) and lysophosphatidylcholine (lyso-PC) (PubMed:25596343, PubMed:27637550). May be involved in bioactive N-acylethanolamine biosynthesis from both N-acyl-lysoplasmenylethanolamin (N-acyl-lysoPlsEt) and N-acyl-lysophosphatidylethanolamin (N-acyl-lysoPE) (PubMed:25596343, PubMed:27637550). In addition, hydrolyzes glycerophospho-N-acylethanolamine to N-acylethanolamine (PubMed:27637550). Does not display glycerophosphodiester phosphodiesterase activity, since it cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine (By similarity). {ECO:0000250|UniProtKB:Q9CRY7, ECO:0000269|PubMed:25596343, ECO:0000269|PubMed:27637550}. |
| P42681 | TXK | S422 | Sugiyama | Tyrosine-protein kinase TXK (EC 2.7.10.2) (Protein-tyrosine kinase 4) (Resting lymphocyte kinase) | Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation leads to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Also contributes to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with PARP1 and EEF1A1 (PubMed:11859127, PubMed:17177976). Within the complex, phosphorylates both PARP1 and EEF1A1 (PubMed:17177976). Also phosphorylates key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor. {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:11564877, ECO:0000269|PubMed:11859127, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:9813138}. |
| Q8TF05 | PPP4R1 | S57 | Sugiyama | 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}. |
| P53992 | SEC24C | S378 | Sugiyama | Protein transport protein Sec24C (SEC24-related protein C) | Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex (PubMed:10214955, PubMed:17499046, PubMed:18843296, PubMed:20427317). Plays a central role in cargo selection within the COPII complex and together with SEC24D may have a different specificity compared to SEC24A and SEC24B (PubMed:17499046, PubMed:18843296, PubMed:20427317). May more specifically package GPI-anchored proteins through the cargo receptor TMED10 (PubMed:20427317). May also be specific for IxM motif-containing cargos like the SNAREs GOSR2 and STX5 (PubMed:18843296). {ECO:0000269|PubMed:10214955, ECO:0000269|PubMed:17499046, ECO:0000269|PubMed:18843296, ECO:0000269|PubMed:20427317}. |
| Q16644 | MAPKAPK3 | S337 | 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}. |
| P56645 | PER3 | S633 | SIGNOR|iPTMNet | Period circadian protein homolog 3 (hPER3) (Cell growth-inhibiting gene 13 protein) (Circadian clock protein PERIOD 3) | Originally described as 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, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance. In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters. Can bind heme. {ECO:0000269|PubMed:17346965, ECO:0000269|PubMed:19716732, ECO:0000269|PubMed:24439663, ECO:0000269|PubMed:24577121, ECO:0000269|PubMed:26903630}. |
| P51813 | BMX | S619 | Sugiyama | Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) | Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}. |
| O75663 | TIPRL | S124 | Sugiyama | TIP41-like protein (Putative MAPK-activating protein PM10) (Type 2A-interacting protein) (TIP) | May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as a negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AX phosphorylated on Ser-140 (gamma-H2AX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair. {ECO:0000269|PubMed:17384681, ECO:0000269|PubMed:26717153}. |
| P11586 | MTHFD1 | S323 | 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}. |
| O95786 | RIGI | S764 | EPSD|PSP | Antiviral innate immune response receptor RIG-I (ATP-dependent RNA helicase DDX58) (EC 3.6.4.13) (DEAD box protein 58) (RIG-I-like receptor 1) (RLR-1) (RNA sensor RIG-I) (Retinoic acid-inducible gene 1 protein) (RIG-1) (Retinoic acid-inducible gene I protein) (RIG-I) | Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines (PubMed:15208624, PubMed:15708988, PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988). The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms (PubMed:28469175, PubMed:31006531). Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons (PubMed:28469175, PubMed:31006531). Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.74). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration. {ECO:0000269|PubMed:15208624, ECO:0000269|PubMed:15708988, ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:17190814, ECO:0000269|PubMed:18636086, ECO:0000269|PubMed:19122199, ECO:0000269|PubMed:19211564, ECO:0000269|PubMed:19576794, ECO:0000269|PubMed:19609254, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:21742966, ECO:0000269|PubMed:24366338, ECO:0000269|PubMed:28469175, ECO:0000269|PubMed:29117565, ECO:0000269|PubMed:31006531, ECO:0000269|PubMed:34935440, ECO:0000269|PubMed:35263596, ECO:0000269|PubMed:36793726, ECO:0000269|Ref.74, ECO:0000303|PubMed:21616437, ECO:0000303|PubMed:21884169}. |
| P52597 | HNRNPF | S279 | Sugiyama | Heterogeneous nuclear ribonucleoprotein F (hnRNP F) (Nucleolin-like protein mcs94-1) [Cleaved into: Heterogeneous nuclear ribonucleoprotein F, N-terminally processed] | Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes which provide the substrate for the processing events that pre-mRNAs undergo before becoming functional, translatable mRNAs in the cytoplasm. Plays a role in the regulation of alternative splicing events. Binds G-rich sequences in pre-mRNAs and keeps target RNA in an unfolded state. {ECO:0000269|PubMed:20526337}. |
| P55769 | SNU13 | S29 | Sugiyama | NHP2-like protein 1 (High mobility group-like nuclear protein 2 homolog 1) (OTK27) (SNU13 homolog) (hSNU13) (U4/U6.U5 small nuclear ribonucleoprotein SNU13) (U4/U6.U5 tri-snRNP 15.5 kDa protein) [Cleaved into: NHP2-like protein 1, N-terminally processed] | Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28781166). Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly (PubMed:10545122, PubMed:17412961). The protein undergoes a conformational change upon RNA-binding (PubMed:10545122, PubMed:17412961, PubMed:28781166). Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that function in methylation of multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) (PubMed:39570315). {ECO:0000269|PubMed:10545122, ECO:0000269|PubMed:17412961, ECO:0000269|PubMed:28781166, ECO:0000269|PubMed:34516797, ECO:0000269|PubMed:39570315}. |
| Q01082 | SPTBN1 | S1666 | Sugiyama | Spectrin beta chain, non-erythrocytic 1 (Beta-II spectrin) (Fodrin beta chain) (Spectrin, non-erythroid beta chain 1) | Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function. {ECO:0000269|PubMed:34211179}. |
| Q15078 | CDK5R1 | S135 | Sugiyama | Cyclin-dependent kinase 5 activator 1 (CDK5 activator 1) (Cyclin-dependent kinase 5 regulatory subunit 1) (TPKII regulatory subunit) [Cleaved into: Cyclin-dependent kinase 5 activator 1, p35 (p35); Cyclin-dependent kinase 5 activator 1, p25 (p25) (Tau protein kinase II 23 kDa subunit) (p23)] | p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-BMAL1 heterodimer in association with altered stability and subcellular distribution. {ECO:0000269|PubMed:24235147}. |
| P61927 | RPL37 | S50 | Sugiyama | Large ribosomal subunit protein eL37 (60S ribosomal protein L37) (G1.16) | 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}. |
| Q08881 | ITK | S71 | Sugiyama | Tyrosine-protein kinase ITK/TSK (EC 2.7.10.2) (Interleukin-2-inducible T-cell kinase) (IL-2-inducible T-cell kinase) (Kinase EMT) (T-cell-specific kinase) (Tyrosine-protein kinase Lyk) | Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation (PubMed:12186560, PubMed:12682224, PubMed:21725281). Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (By similarity). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity). {ECO:0000250|UniProtKB:Q03526, ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}. |
| P50991 | CCT4 | S166 | Sugiyama | T-complex protein 1 subunit delta (TCP-1-delta) (EC 3.6.1.-) (CCT-delta) (Chaperonin containing T-complex polypeptide 1 subunit 4) (Stimulator of TAR RNA-binding) | Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:36493755, PubMed:35449234, PubMed:37193829). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). {ECO:0000269|PubMed:20080638, ECO:0000269|PubMed:25467444, ECO:0000269|PubMed:35449234, ECO:0000269|PubMed:36493755, ECO:0000269|PubMed:37193829}. |
| Q13237 | PRKG2 | S285 | Sugiyama | 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}. |
| P29475 | NOS1 | S746 | iPTMNet | Nitric oxide synthase 1 (EC 1.14.13.39) (Constitutive NOS) (NC-NOS) (NOS type I) (Neuronal NOS) (N-NOS) (nNOS) (Nitric oxide synthase, brain) (bNOS) (Peptidyl-cysteine S-nitrosylase NOS1) | Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. {ECO:0000269|PubMed:35772285}. |
| P50416 | CPT1A | S747 | Sugiyama | Carnitine O-palmitoyltransferase 1, liver isoform (CPT1-L) (EC 2.3.1.21) (Carnitine O-palmitoyltransferase I, liver isoform) (CPT I) (CPTI-L) (Carnitine palmitoyltransferase 1A) (Succinyltransferase CPT1A) (EC 2.3.1.-) | Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion (PubMed:11350182, PubMed:14517221, PubMed:16651524, PubMed:9691089). Also possesses a lysine succinyltransferase activity that can regulate enzymatic activity of substrate proteins such as ENO1 and metabolism independent of its classical carnitine O-palmitoyltransferase activity (PubMed:29425493). Plays an important role in hepatic triglyceride metabolism (By similarity). Also plays a role in inducible regulatory T-cell (iTreg) differentiation once activated by butyryl-CoA that antagonizes malonyl-CoA-mediated CPT1A repression (By similarity). Sustains the IFN-I response by recruiting ZDHCC4 to palmitoylate MAVS at the mitochondria leading to MAVS stabilization and activation (PubMed:38016475). Promotes ROS-induced oxidative stress in liver injury via modulation of NFE2L2 and NLRP3-mediated signaling pathways (By similarity). {ECO:0000250|UniProtKB:P32198, ECO:0000269|PubMed:11350182, ECO:0000269|PubMed:14517221, ECO:0000269|PubMed:16651524, ECO:0000269|PubMed:29425493, ECO:0000269|PubMed:38016475, ECO:0000269|PubMed:9691089}. |
| Q12906 | ILF3 | S317 | 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}. |
| 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 | 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}. |
| Q99962 | SH3GL2 | S75 | SIGNOR | Endophilin-A1 (EEN-B1) (Endophilin-1) (SH3 domain protein 2A) (SH3 domain-containing GRB2-like protein 2) | Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes. {ECO:0000250|UniProtKB:Q62420}. |
| P49327 | FASN | S324 | Sugiyama | Fatty acid synthase (EC 2.3.1.85) (Type I fatty acid synthase) [Includes: [Acyl-carrier-protein] S-acetyltransferase (EC 2.3.1.38); [Acyl-carrier-protein] S-malonyltransferase (EC 2.3.1.39); 3-oxoacyl-[acyl-carrier-protein] synthase (EC 2.3.1.41); 3-oxoacyl-[acyl-carrier-protein] reductase (EC 1.1.1.100); 3-hydroxyacyl-[acyl-carrier-protein] dehydratase (EC 4.2.1.59); Enoyl-[acyl-carrier-protein] reductase (EC 1.3.1.39); Acyl-[acyl-carrier-protein] hydrolase (EC 3.1.2.14)] | Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. {ECO:0000269|PubMed:16215233, ECO:0000269|PubMed:16969344, ECO:0000269|PubMed:26851298, ECO:0000269|PubMed:7567999, ECO:0000269|PubMed:8962082, ECO:0000269|PubMed:9356448}.; FUNCTION: (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}. |
| P51452 | DUSP3 | S43 | Sugiyama | Dual specificity protein phosphatase 3 (EC 3.1.3.16) (EC 3.1.3.48) (Dual specificity protein phosphatase VHR) (Vaccinia H1-related phosphatase) (VHR) | Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines (PubMed:10224087, PubMed:11863439). Specifically dephosphorylates and inactivates ERK1 and ERK2 (PubMed:10224087, PubMed:11863439). {ECO:0000269|PubMed:10224087, ECO:0000269|PubMed:11863439}. |
| Q5JSH3 | WDR44 | S667 | Sugiyama | WD repeat-containing protein 44 (Rab11-binding protein) (Rab11BP) (Rabphilin-11) | Downstream effector for Rab11 which regulates Rab11 intracellular membrane trafficking functions such as endocytic recycling, intracellular ciliogenesis and protein export (PubMed:31204173, PubMed:32344433). ATK1-mediated phosphorylation of WDR44 induces binding to Rab11 which activates endocytic recycling of transferrin receptor back to the plasma membrane (PubMed:31204173). When bound to Rab11, prevents the formation of the ciliogenic Rab11-Rabin8/RAB3IP-RAB11FIP3 complex, therefore inhibiting preciliary trafficking and ciliogenesis (PubMed:31204173). Participates in neo-synthesized protein export by connecting the endoplasmic reticulum (ER) with the endosomal tubule via direct interactions with the integral ER proteins VAPA or VAPB and the endosomal protein GRAFs (GRAF1/ARHGAP26 or GRAF2/ARHGAP10), which facilitates the transfer of proteins such as E-cadherin, MPP14 and CFTR into a Rab8-Rab10-Rab11-dependent export route (PubMed:32344433). {ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:32344433}. |
| Q96BY7 | ATG2B | S1395 | Sugiyama | Autophagy-related protein 2 homolog B | Lipid transfer protein required for both autophagosome formation and regulation of lipid droplet morphology and dispersion (PubMed:22219374, PubMed:31721365). Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion (PubMed:22219374, PubMed:31721365). Binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, and extracts phospholipids from the membrane source and transfers them to ATG9 (ATG9A or ATG9B) to the IM for membrane expansion (By similarity). Lipid transfer activity is enhanced by WDR45/WIPI4, which promotes ATG2B-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31721365). {ECO:0000250|UniProtKB:Q2TAZ0, ECO:0000269|PubMed:22219374, ECO:0000269|PubMed:31721365}. |
| Q9NQE9 | HINT3 | S46 | Sugiyama | Adenosine 5'-monophosphoramidase HINT3 (EC 3.9.1.-) (Histidine triad nucleotide-binding protein 3) (HINT-3) | Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:17870088). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase (PubMed:17870088). Hydrolyzes 3-indolepropionic acyl-adenylate and fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17870088). {ECO:0000269|PubMed:17870088}. |
| P46109 | CRKL | S20 | Sugiyama | Crk-like protein | May mediate the transduction of intracellular signals. |
| O60879 | DIAPH2 | S196 | SIGNOR | Protein diaphanous homolog 2 (Diaphanous-related formin-2) (DRF2) | Could be involved in oogenesis. Involved in the regulation of endosome dynamics. Implicated in a novel signal transduction pathway, in which isoform 3 and CSK are sequentially activated by RHOD to regulate the motility of early endosomes through interactions with the actin cytoskeleton. {ECO:0000269|PubMed:12577064}. |
| Q99759 | MAP3K3 | S399 | Sugiyama | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q9Y2U5 | MAP3K2 | S393 | 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}. |
| Q9BQI3 | EIF2AK1 | S409 | Sugiyama | Eukaryotic translation initiation factor 2-alpha kinase 1 (EC 2.7.11.1) (Heme-controlled repressor) (HCR) (Heme-regulated eukaryotic initiation factor eIF-2-alpha kinase) (Heme-regulated inhibitor) (hHRI) (Hemin-sensitive initiation factor 2-alpha kinase) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress conditions (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:38340717). Key activator of the integrated stress response (ISR) required for adaptation to various stress, such as heme deficiency, oxidative stress, osmotic shock, mitochondrial dysfunction and heat shock (PubMed:32132706, PubMed:32132707, PubMed:37327776, PubMed:37550454, PubMed:38340717). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707, PubMed:37327776). Acts as a key sensor of heme-deficiency: in normal conditions, binds hemin via a cysteine thiolate and histidine nitrogenous coordination, leading to inhibit the protein kinase activity (By similarity). This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell: heme depletion relieves inhibition and stimulates kinase activity, activating the ISR (By similarity). Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions (By similarity). In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties (By similarity). It thereby plays an essential protective role for RBC survival in anemias of iron deficiency (By similarity). Iron deficiency also triggers activation by full-length DELE1 (PubMed:37327776). Also activates the ISR in response to mitochondrial dysfunction: HRI/EIF2AK1 protein kinase activity is activated upon binding to the processed form of DELE1 (S-DELE1), thereby promoting the ATF4-mediated reprogramming (PubMed:32132706, PubMed:32132707). Also acts as an activator of mitophagy in response to mitochondrial damage: catalyzes phosphorylation of eIF-2-alpha (EIF2S1) following activation by S-DELE1, thereby promoting mitochondrial localization of EIF2S1, triggering PRKN-independent mitophagy (PubMed:38340717). {ECO:0000250|UniProtKB:Q9Z2R9, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:32197074, ECO:0000269|PubMed:37550454, ECO:0000269|PubMed:38340717}. |
| Q6UB35 | MTHFD1L | S366 | Sugiyama | Monofunctional C1-tetrahydrofolate synthase, mitochondrial (EC 6.3.4.3) (Formyltetrahydrofolate synthetase) | May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2. {ECO:0000250, ECO:0000269|PubMed:16171773}. |
| Q9NSV4 | DIAPH3 | S1119 | Sugiyama | Protein diaphanous homolog 3 (Diaphanous-related formin-3) (DRF3) (MDia2) | Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers. Required for cytokinesis, stress fiber formation and transcriptional activation of the serum response factor. Binds to GTP-bound form of Rho and to profilin: acts in a Rho-dependent manner to recruit profilin to the membrane, where it promotes actin polymerization. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity. {ECO:0000250|UniProtKB:Q9Z207}. |
| P05388 | RPLP0 | S37 | Sugiyama | Large ribosomal subunit protein uL10 (60S acidic ribosomal protein P0) (60S ribosomal protein L10E) | Ribosomal protein P0 is the functional equivalent of E.coli protein L10. |
| Q8NHW5 | RPLP0P6 | S37 | Sugiyama | Putative ribosomal protein uL10-like (60S acidic ribosomal protein P0-like) (Large ribosomal subunit protein uL10-like) | Ribosomal protein P0 is the functional equivalent of E.coli protein L10. {ECO:0000250}. |
| Q9H1R3 | MYLK2 | S577 | Sugiyama | Myosin light chain kinase 2, skeletal/cardiac muscle (MLCK2) (EC 2.7.11.18) | Implicated in the level of global muscle contraction and cardiac function. Phosphorylates a specific serine in the N-terminus of a myosin light chain. {ECO:0000269|PubMed:11733062}. |
| Q9H3Y6 | SRMS | S293 | Sugiyama | Tyrosine-protein kinase Srms (EC 2.7.10.2) | Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues (PubMed:23822091). Also phosphorylates KHDRBS1/SAM68 and VIM on tyrosine residues (PubMed:29496907). Phosphorylation of KHDRBS1 is EGF-dependent (PubMed:29496907). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). {ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907, ECO:0000269|PubMed:35927303}. |
| Q8N584 | TTC39C | S472 | Sugiyama | Tetratricopeptide repeat protein 39C (TPR repeat protein 39C) | None |
| Q9C0D5 | TANC1 | S1830 | Sugiyama | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9P2K8 | EIF2AK4 | S467 | Sugiyama | eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}. |
| Q6GYQ0 | RALGAPA1 | S1280 | Sugiyama | 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}. |
| Q9UM73 | ALK | S1538 | Sugiyama | ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) | Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}. |
| Q9Y4K4 | MAP4K5 | S28 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 5 (EC 2.7.11.1) (Kinase homologous to SPS1/STE20) (KHS) (MAPK/ERK kinase kinase kinase 5) (MEK kinase kinase 5) (MEKKK 5) | May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. {ECO:0000269|PubMed:9038372}. |
| Q9Y5S2 | CDC42BPB | S421 | Sugiyama | Serine/threonine-protein kinase MRCK beta (EC 2.7.11.1) (CDC42-binding protein kinase beta) (CDC42BP-beta) (DMPK-like beta) (Myotonic dystrophy kinase-related CDC42-binding kinase beta) (MRCK beta) (Myotonic dystrophy protein kinase-like beta) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). {ECO:0000250|UniProtKB:Q7TT50, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:21949762}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-1640170 | Cell Cycle | 2.573497e-13 | 12.589 |
| R-HSA-69278 | Cell Cycle, Mitotic | 3.831340e-10 | 9.417 |
| R-HSA-68886 | M Phase | 2.217670e-07 | 6.654 |
| R-HSA-913531 | Interferon Signaling | 1.957403e-06 | 5.708 |
| R-HSA-69275 | G2/M Transition | 2.634593e-06 | 5.579 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 3.303875e-06 | 5.481 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 4.511900e-06 | 5.346 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 7.167523e-06 | 5.145 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 7.237851e-06 | 5.140 |
| R-HSA-5633007 | Regulation of TP53 Activity | 9.228161e-06 | 5.035 |
| R-HSA-68877 | Mitotic Prometaphase | 1.302318e-05 | 4.885 |
| R-HSA-8953897 | Cellular responses to stimuli | 1.502121e-05 | 4.823 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 1.627098e-05 | 4.789 |
| R-HSA-2262752 | Cellular responses to stress | 2.340744e-05 | 4.631 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 2.647796e-05 | 4.577 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 2.892609e-05 | 4.539 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 2.923995e-05 | 4.534 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 3.534391e-05 | 4.452 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 3.676349e-05 | 4.435 |
| R-HSA-3134963 | DEx/H-box helicases activate type I IFN and inflammatory cytokines production | 3.878527e-05 | 4.411 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 3.998858e-05 | 4.398 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 4.106207e-05 | 4.387 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 5.147312e-05 | 4.288 |
| R-HSA-193639 | p75NTR signals via NF-kB | 5.147312e-05 | 4.288 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 5.538573e-05 | 4.257 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 6.562428e-05 | 4.183 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 6.562428e-05 | 4.183 |
| R-HSA-162582 | Signal Transduction | 6.944080e-05 | 4.158 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 7.201910e-05 | 4.143 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 7.403035e-05 | 4.131 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 8.038596e-05 | 4.095 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 8.276349e-05 | 4.082 |
| R-HSA-5617833 | Cilium Assembly | 1.004589e-04 | 3.998 |
| R-HSA-918233 | TRAF3-dependent IRF activation pathway | 1.089454e-04 | 3.963 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 1.335598e-04 | 3.874 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 1.892792e-04 | 3.723 |
| R-HSA-68882 | Mitotic Anaphase | 2.453333e-04 | 3.610 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 3.200426e-04 | 3.495 |
| R-HSA-9833482 | PKR-mediated signaling | 3.147291e-04 | 3.502 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 2.959031e-04 | 3.529 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.138903e-04 | 3.503 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 3.081662e-04 | 3.511 |
| R-HSA-209560 | NF-kB is activated and signals survival | 3.771494e-04 | 3.423 |
| R-HSA-380287 | Centrosome maturation | 4.242762e-04 | 3.372 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 4.492098e-04 | 3.348 |
| R-HSA-69620 | Cell Cycle Checkpoints | 4.337421e-04 | 3.363 |
| R-HSA-9825895 | Regulation of MITF-M-dependent genes involved in DNA replication, damage repair ... | 4.375215e-04 | 3.359 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 4.417459e-04 | 3.355 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 4.244506e-04 | 3.372 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 4.797338e-04 | 3.319 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 5.721904e-04 | 3.242 |
| R-HSA-73887 | Death Receptor Signaling | 6.287920e-04 | 3.201 |
| R-HSA-199992 | trans-Golgi Network Vesicle Budding | 7.525427e-04 | 3.123 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 7.525427e-04 | 3.123 |
| R-HSA-9931509 | Expression of BMAL (ARNTL), CLOCK, and NPAS2 | 8.017456e-04 | 3.096 |
| R-HSA-69481 | G2/M Checkpoints | 7.987429e-04 | 3.098 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 8.017456e-04 | 3.096 |
| R-HSA-9711123 | Cellular response to chemical stress | 8.543867e-04 | 3.068 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 8.792291e-04 | 3.056 |
| R-HSA-9663891 | Selective autophagy | 9.862827e-04 | 3.006 |
| R-HSA-9613829 | Chaperone Mediated Autophagy | 9.984334e-04 | 3.001 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 1.026987e-03 | 2.988 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 1.113130e-03 | 2.953 |
| R-HSA-437239 | Recycling pathway of L1 | 1.200377e-03 | 2.921 |
| R-HSA-9031628 | NGF-stimulated transcription | 1.405002e-03 | 2.852 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 1.472887e-03 | 2.832 |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1.813652e-03 | 2.741 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 1.868307e-03 | 2.729 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 1.899920e-03 | 2.721 |
| R-HSA-5693579 | Homologous DNA Pairing and Strand Exchange | 2.144831e-03 | 2.669 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 2.463683e-03 | 2.608 |
| R-HSA-4839726 | Chromatin organization | 2.496737e-03 | 2.603 |
| R-HSA-109581 | Apoptosis | 2.428606e-03 | 2.615 |
| R-HSA-9692916 | SARS-CoV-1 activates/modulates innate immune responses | 2.534801e-03 | 2.596 |
| R-HSA-5357801 | Programmed Cell Death | 2.647749e-03 | 2.577 |
| R-HSA-9909396 | Circadian clock | 2.865695e-03 | 2.543 |
| R-HSA-983189 | Kinesins | 2.789115e-03 | 2.555 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 2.896059e-03 | 2.538 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 3.103264e-03 | 2.508 |
| R-HSA-166520 | Signaling by NTRKs | 3.103264e-03 | 2.508 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 3.304573e-03 | 2.481 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 3.486126e-03 | 2.458 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 3.533374e-03 | 2.452 |
| R-HSA-9707616 | Heme signaling | 3.588735e-03 | 2.445 |
| R-HSA-9709570 | Impaired BRCA2 binding to RAD51 | 3.789618e-03 | 2.421 |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes | 3.880100e-03 | 2.411 |
| R-HSA-5693616 | Presynaptic phase of homologous DNA pairing and strand exchange | 4.005124e-03 | 2.397 |
| R-HSA-2559585 | Oncogene Induced Senescence | 4.005124e-03 | 2.397 |
| R-HSA-9700206 | Signaling by ALK in cancer | 4.183731e-03 | 2.378 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 4.183731e-03 | 2.378 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 4.195371e-03 | 2.377 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 4.518767e-03 | 2.345 |
| R-HSA-2132295 | MHC class II antigen presentation | 4.661878e-03 | 2.331 |
| R-HSA-432720 | Lysosome Vesicle Biogenesis | 4.701890e-03 | 2.328 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 5.123803e-03 | 2.290 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 4.993305e-03 | 2.302 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 5.128879e-03 | 2.290 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 5.129738e-03 | 2.290 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 5.262986e-03 | 2.279 |
| R-HSA-3247509 | Chromatin modifying enzymes | 5.220236e-03 | 2.282 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 5.444115e-03 | 2.264 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 5.444115e-03 | 2.264 |
| R-HSA-373760 | L1CAM interactions | 5.258182e-03 | 2.279 |
| R-HSA-9612973 | Autophagy | 5.602642e-03 | 2.252 |
| R-HSA-5688426 | Deubiquitination | 6.006918e-03 | 2.221 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 6.032708e-03 | 2.219 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 6.032708e-03 | 2.219 |
| R-HSA-9679506 | SARS-CoV Infections | 6.137072e-03 | 2.212 |
| R-HSA-186712 | Regulation of beta-cell development | 6.232511e-03 | 2.205 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 6.561064e-03 | 2.183 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 6.507963e-03 | 2.187 |
| R-HSA-199991 | Membrane Trafficking | 6.716949e-03 | 2.173 |
| R-HSA-877300 | Interferon gamma signaling | 6.894532e-03 | 2.161 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 7.050681e-03 | 2.152 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 7.375033e-03 | 2.132 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 7.460753e-03 | 2.127 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 7.853871e-03 | 2.105 |
| R-HSA-9818749 | Regulation of NFE2L2 gene expression | 8.039382e-03 | 2.095 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 7.853871e-03 | 2.105 |
| R-HSA-9675135 | Diseases of DNA repair | 8.079373e-03 | 2.093 |
| R-HSA-75153 | Apoptotic execution phase | 8.079373e-03 | 2.093 |
| R-HSA-163765 | ChREBP activates metabolic gene expression | 7.753534e-03 | 2.111 |
| R-HSA-210744 | Regulation of gene expression in late stage (branching morphogenesis) pancreatic... | 8.315257e-03 | 2.080 |
| R-HSA-9646399 | Aggrephagy | 8.487227e-03 | 2.071 |
| R-HSA-5260271 | Diseases of Immune System | 8.487227e-03 | 2.071 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 8.487227e-03 | 2.071 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 8.765711e-03 | 2.057 |
| R-HSA-2995383 | Initiation of Nuclear Envelope (NE) Reformation | 9.656221e-03 | 2.015 |
| R-HSA-72706 | GTP hydrolysis and joining of the 60S ribosomal subunit | 9.317216e-03 | 2.031 |
| R-HSA-909733 | Interferon alpha/beta signaling | 9.622733e-03 | 2.017 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 9.069944e-03 | 2.042 |
| R-HSA-3214841 | PKMTs methylate histone lysines | 9.723810e-03 | 2.012 |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) | 9.769308e-03 | 2.010 |
| R-HSA-9675136 | Diseases of DNA Double-Strand Break Repair | 1.009482e-02 | 1.996 |
| R-HSA-9701190 | Defective homologous recombination repair (HRR) due to BRCA2 loss of function | 1.009482e-02 | 1.996 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 1.014401e-02 | 1.994 |
| R-HSA-5689880 | Ub-specific processing proteases | 1.017294e-02 | 1.993 |
| R-HSA-9013973 | TICAM1-dependent activation of IRF3/IRF7 | 1.021785e-02 | 1.991 |
| R-HSA-9818028 | NFE2L2 regulates pentose phosphate pathway genes | 1.021785e-02 | 1.991 |
| R-HSA-438064 | Post NMDA receptor activation events | 1.040236e-02 | 1.983 |
| R-HSA-8849473 | PTK6 Expression | 1.146492e-02 | 1.941 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 1.169586e-02 | 1.932 |
| R-HSA-1632852 | Macroautophagy | 1.162370e-02 | 1.935 |
| R-HSA-69206 | G1/S Transition | 1.140717e-02 | 1.943 |
| R-HSA-9615710 | Late endosomal microautophagy | 1.189233e-02 | 1.925 |
| R-HSA-9673013 | Diseases of Telomere Maintenance | 1.314161e-02 | 1.881 |
| R-HSA-9670621 | Defective Inhibition of DNA Recombination at Telomere | 1.314161e-02 | 1.881 |
| R-HSA-9006821 | Alternative Lengthening of Telomeres (ALT) | 1.314161e-02 | 1.881 |
| R-HSA-9670615 | Defective Inhibition of DNA Recombination at Telomere Due to ATRX Mutations | 1.314161e-02 | 1.881 |
| R-HSA-9699150 | Defective DNA double strand break response due to BARD1 loss of function | 1.314161e-02 | 1.881 |
| R-HSA-9663199 | Defective DNA double strand break response due to BRCA1 loss of function | 1.314161e-02 | 1.881 |
| R-HSA-9670613 | Defective Inhibition of DNA Recombination at Telomere Due to DAXX Mutations | 1.314161e-02 | 1.881 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 1.379287e-02 | 1.860 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 1.279102e-02 | 1.893 |
| R-HSA-68875 | Mitotic Prophase | 1.395169e-02 | 1.855 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 1.296939e-02 | 1.887 |
| R-HSA-69205 | G1/S-Specific Transcription | 1.337409e-02 | 1.874 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 1.406468e-02 | 1.852 |
| R-HSA-165181 | Inhibition of TSC complex formation by PKB | 1.552349e-02 | 1.809 |
| R-HSA-196025 | Formation of annular gap junctions | 1.570929e-02 | 1.804 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 1.627806e-02 | 1.788 |
| R-HSA-936440 | Negative regulators of DDX58/IFIH1 signaling | 1.603854e-02 | 1.795 |
| R-HSA-933541 | TRAF6 mediated IRF7 activation | 1.528220e-02 | 1.816 |
| R-HSA-194441 | Metabolism of non-coding RNA | 1.482772e-02 | 1.829 |
| R-HSA-191859 | snRNP Assembly | 1.482772e-02 | 1.829 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 1.556567e-02 | 1.808 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 1.603854e-02 | 1.795 |
| R-HSA-5685942 | HDR through Homologous Recombination (HRR) | 1.470753e-02 | 1.832 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.523096e-02 | 1.817 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.523096e-02 | 1.817 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.523096e-02 | 1.817 |
| R-HSA-190828 | Gap junction trafficking | 1.608296e-02 | 1.794 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 1.556567e-02 | 1.808 |
| R-HSA-190873 | Gap junction degradation | 2.082684e-02 | 1.681 |
| R-HSA-9700645 | ALK mutants bind TKIs | 2.082684e-02 | 1.681 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 2.069472e-02 | 1.684 |
| R-HSA-9709603 | Impaired BRCA2 binding to PALB2 | 1.873117e-02 | 1.727 |
| R-HSA-5693554 | Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SD... | 1.906454e-02 | 1.720 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 2.113916e-02 | 1.675 |
| R-HSA-72695 | Formation of the ternary complex, and subsequently, the 43S complex | 2.022774e-02 | 1.694 |
| R-HSA-72649 | Translation initiation complex formation | 2.028884e-02 | 1.693 |
| R-HSA-72737 | Cap-dependent Translation Initiation | 1.963749e-02 | 1.707 |
| R-HSA-72613 | Eukaryotic Translation Initiation | 1.963749e-02 | 1.707 |
| R-HSA-5675482 | Regulation of necroptotic cell death | 2.113916e-02 | 1.675 |
| R-HSA-432722 | Golgi Associated Vesicle Biogenesis | 1.827983e-02 | 1.738 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 1.827983e-02 | 1.738 |
| R-HSA-416482 | G alpha (12/13) signalling events | 1.886695e-02 | 1.724 |
| R-HSA-2467813 | Separation of Sister Chromatids | 1.679255e-02 | 1.775 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 1.906454e-02 | 1.720 |
| R-HSA-168898 | Toll-like Receptor Cascades | 1.692344e-02 | 1.772 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 1.947557e-02 | 1.711 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 2.113916e-02 | 1.675 |
| R-HSA-156827 | L13a-mediated translational silencing of Ceruloplasmin expression | 1.811786e-02 | 1.742 |
| R-HSA-448424 | Interleukin-17 signaling | 1.951827e-02 | 1.710 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 1.951827e-02 | 1.710 |
| R-HSA-450294 | MAP kinase activation | 1.815671e-02 | 1.741 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 2.135879e-02 | 1.670 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 2.082684e-02 | 1.681 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.846314e-02 | 1.734 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 2.096473e-02 | 1.679 |
| R-HSA-525793 | Myogenesis | 2.216871e-02 | 1.654 |
| R-HSA-9615933 | Postmitotic nuclear pore complex (NPC) reformation | 2.216871e-02 | 1.654 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 2.220427e-02 | 1.654 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 2.231001e-02 | 1.652 |
| R-HSA-9701193 | Defective homologous recombination repair (HRR) due to PALB2 loss of function | 2.231001e-02 | 1.652 |
| R-HSA-9701192 | Defective homologous recombination repair (HRR) due to BRCA1 loss of function | 2.231001e-02 | 1.652 |
| R-HSA-9704331 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 2.231001e-02 | 1.652 |
| R-HSA-9704646 | Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of... | 2.231001e-02 | 1.652 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 2.231001e-02 | 1.652 |
| R-HSA-5693538 | Homology Directed Repair | 2.248789e-02 | 1.648 |
| R-HSA-9931529 | Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK | 2.316009e-02 | 1.635 |
| R-HSA-8849472 | PTK6 Down-Regulation | 2.316009e-02 | 1.635 |
| R-HSA-72689 | Formation of a pool of free 40S subunits | 2.358388e-02 | 1.627 |
| R-HSA-72702 | Ribosomal scanning and start codon recognition | 2.478803e-02 | 1.606 |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) | 2.510271e-02 | 1.600 |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment | 2.532915e-02 | 1.596 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 2.532915e-02 | 1.596 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 2.539095e-02 | 1.595 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 2.542394e-02 | 1.595 |
| R-HSA-5545619 | XAV939 stabilizes AXIN | 2.795538e-02 | 1.554 |
| R-HSA-5603027 | IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... | 2.795538e-02 | 1.554 |
| R-HSA-3315487 | SMAD2/3 MH2 Domain Mutants in Cancer | 2.795538e-02 | 1.554 |
| R-HSA-3311021 | SMAD4 MH2 Domain Mutants in Cancer | 2.795538e-02 | 1.554 |
| R-HSA-3304347 | Loss of Function of SMAD4 in Cancer | 2.795538e-02 | 1.554 |
| R-HSA-5602636 | IKBKB deficiency causes SCID | 2.795538e-02 | 1.554 |
| R-HSA-9664873 | Pexophagy | 2.685862e-02 | 1.571 |
| R-HSA-180746 | Nuclear import of Rev protein | 2.729338e-02 | 1.564 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 2.791469e-02 | 1.554 |
| R-HSA-72662 | Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... | 2.997097e-02 | 1.523 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 2.747073e-02 | 1.561 |
| R-HSA-157858 | Gap junction trafficking and regulation | 2.783319e-02 | 1.555 |
| R-HSA-3371556 | Cellular response to heat stress | 2.734335e-02 | 1.563 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 2.570220e-02 | 1.590 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 2.685862e-02 | 1.571 |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription | 2.685862e-02 | 1.571 |
| R-HSA-1362300 | Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... | 3.058009e-02 | 1.515 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 3.079382e-02 | 1.512 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 3.127975e-02 | 1.505 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 3.131008e-02 | 1.504 |
| R-HSA-5693606 | DNA Double Strand Break Response | 3.150314e-02 | 1.502 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 3.240377e-02 | 1.489 |
| R-HSA-5635851 | GLI proteins bind promoters of Hh responsive genes to promote transcription | 3.249054e-02 | 1.488 |
| R-HSA-176417 | Phosphorylation of Emi1 | 3.249054e-02 | 1.488 |
| R-HSA-8941855 | RUNX3 regulates CDKN1A transcription | 3.249054e-02 | 1.488 |
| R-HSA-8937144 | Aryl hydrocarbon receptor signalling | 3.249054e-02 | 1.488 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 3.249054e-02 | 1.488 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 3.283388e-02 | 1.484 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 3.321138e-02 | 1.479 |
| R-HSA-74160 | Gene expression (Transcription) | 3.339754e-02 | 1.476 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 3.353502e-02 | 1.475 |
| R-HSA-156842 | Eukaryotic Translation Elongation | 3.356295e-02 | 1.474 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 3.357507e-02 | 1.474 |
| R-HSA-5610787 | Hedgehog 'off' state | 3.366762e-02 | 1.473 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 3.391584e-02 | 1.470 |
| R-HSA-9024446 | NR1H2 and NR1H3-mediated signaling | 3.521828e-02 | 1.453 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 3.577184e-02 | 1.446 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 3.577184e-02 | 1.446 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 4.176400e-02 | 1.379 |
| R-HSA-936964 | Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) | 3.646728e-02 | 1.438 |
| R-HSA-9931521 | The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... | 3.646728e-02 | 1.438 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 3.805109e-02 | 1.420 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 4.294856e-02 | 1.367 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 4.294856e-02 | 1.367 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 4.294856e-02 | 1.367 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 3.869098e-02 | 1.412 |
| R-HSA-5213460 | RIPK1-mediated regulated necrosis | 4.310482e-02 | 1.365 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 3.646728e-02 | 1.438 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 4.250097e-02 | 1.372 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 4.250097e-02 | 1.372 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 4.310482e-02 | 1.365 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 4.348978e-02 | 1.362 |
| R-HSA-9933387 | RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression | 3.805109e-02 | 1.420 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 3.869098e-02 | 1.412 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 3.857800e-02 | 1.414 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 4.113110e-02 | 1.386 |
| R-HSA-168255 | Influenza Infection | 3.951084e-02 | 1.403 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 4.376326e-02 | 1.359 |
| R-HSA-73894 | DNA Repair | 4.436888e-02 | 1.353 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 4.552627e-02 | 1.342 |
| R-HSA-373755 | Semaphorin interactions | 4.622107e-02 | 1.335 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 4.652446e-02 | 1.332 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 4.652446e-02 | 1.332 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 4.652446e-02 | 1.332 |
| R-HSA-6802949 | Signaling by RAS mutants | 4.652446e-02 | 1.332 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 4.700664e-02 | 1.328 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 4.700664e-02 | 1.328 |
| R-HSA-194306 | Neurophilin interactions with VEGF and VEGFR | 4.700664e-02 | 1.328 |
| R-HSA-8951911 | RUNX3 regulates RUNX1-mediated transcription | 4.700664e-02 | 1.328 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 4.700664e-02 | 1.328 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 4.700664e-02 | 1.328 |
| R-HSA-68881 | Mitotic Metaphase/Anaphase Transition | 4.700664e-02 | 1.328 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 4.700664e-02 | 1.328 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 4.700664e-02 | 1.328 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 4.700664e-02 | 1.328 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 4.700664e-02 | 1.328 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 4.700664e-02 | 1.328 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 4.700664e-02 | 1.328 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 4.700664e-02 | 1.328 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 4.708893e-02 | 1.327 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 4.712573e-02 | 1.327 |
| R-HSA-69541 | Stabilization of p53 | 4.783863e-02 | 1.320 |
| R-HSA-9031528 | NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipo... | 5.610041e-02 | 1.251 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 5.610041e-02 | 1.251 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 5.065645e-02 | 1.295 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 5.065645e-02 | 1.295 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 5.065645e-02 | 1.295 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 | 5.806561e-02 | 1.236 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 5.391937e-02 | 1.268 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 5.391937e-02 | 1.268 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 6.000441e-02 | 1.222 |
| R-HSA-975956 | Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) | 5.776317e-02 | 1.238 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 5.065645e-02 | 1.295 |
| R-HSA-9839394 | TGFBR3 expression | 5.343561e-02 | 1.272 |
| R-HSA-156711 | Polo-like kinase mediated events | 5.020326e-02 | 1.299 |
| R-HSA-3214847 | HATs acetylate histones | 5.689962e-02 | 1.245 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 5.828917e-02 | 1.234 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 5.048802e-02 | 1.297 |
| R-HSA-8941856 | RUNX3 regulates NOTCH signaling | 5.065645e-02 | 1.295 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 5.048802e-02 | 1.297 |
| R-HSA-170968 | Frs2-mediated activation | 6.050245e-02 | 1.218 |
| R-HSA-5693537 | Resolution of D-Loop Structures | 6.000441e-02 | 1.222 |
| R-HSA-5693568 | Resolution of D-loop Structures through Holliday Junction Intermediates | 5.391937e-02 | 1.268 |
| R-HSA-8849932 | Synaptic adhesion-like molecules | 5.020326e-02 | 1.299 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 6.050245e-02 | 1.218 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 4.869176e-02 | 1.313 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 6.050245e-02 | 1.218 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 6.000441e-02 | 1.222 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 5.007550e-02 | 1.300 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 6.034025e-02 | 1.219 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 5.391937e-02 | 1.268 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 5.997528e-02 | 1.222 |
| R-HSA-5674135 | MAP2K and MAPK activation | 6.401467e-02 | 1.194 |
| R-HSA-5658442 | Regulation of RAS by GAPs | 6.629696e-02 | 1.179 |
| R-HSA-202403 | TCR signaling | 6.630146e-02 | 1.178 |
| R-HSA-1368108 | BMAL1:CLOCK,NPAS2 activates circadian expression | 6.649418e-02 | 1.177 |
| R-HSA-190861 | Gap junction assembly | 6.649418e-02 | 1.177 |
| R-HSA-6807004 | Negative regulation of MET activity | 6.659156e-02 | 1.177 |
| R-HSA-373753 | Nephrin family interactions | 6.659156e-02 | 1.177 |
| R-HSA-9675108 | Nervous system development | 6.714075e-02 | 1.173 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 6.720518e-02 | 1.173 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 6.763787e-02 | 1.170 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 6.775018e-02 | 1.169 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 6.775018e-02 | 1.169 |
| R-HSA-5423599 | Diseases of Mismatch Repair (MMR) | 6.949914e-02 | 1.158 |
| R-HSA-446107 | Type I hemidesmosome assembly | 7.024020e-02 | 1.153 |
| R-HSA-3371378 | Regulation by c-FLIP | 7.024020e-02 | 1.153 |
| R-HSA-9828211 | Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation | 7.024020e-02 | 1.153 |
| R-HSA-69416 | Dimerization of procaspase-8 | 7.024020e-02 | 1.153 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 7.024020e-02 | 1.153 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 7.024020e-02 | 1.153 |
| R-HSA-390696 | Adrenoceptors | 7.024020e-02 | 1.153 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 7.024020e-02 | 1.153 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 7.128463e-02 | 1.147 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 7.231048e-02 | 1.141 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 7.339030e-02 | 1.134 |
| R-HSA-9772755 | Formation of WDR5-containing histone-modifying complexes | 7.339030e-02 | 1.134 |
| R-HSA-1989781 | PPARA activates gene expression | 7.564509e-02 | 1.121 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 7.577564e-02 | 1.120 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 7.611348e-02 | 1.119 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 7.774276e-02 | 1.109 |
| R-HSA-6794361 | Neurexins and neuroligins | 7.790239e-02 | 1.108 |
| R-HSA-9700649 | Drug resistance of ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9717326 | crizotinib-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9717264 | ASP-3026-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9717316 | alectinib-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9717301 | NVP-TAE684-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9717323 | ceritinib-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9717319 | brigatinib-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9661070 | Defective translocation of RB1 mutants to the nucleus | 8.224534e-02 | 1.085 |
| R-HSA-9717329 | lorlatinib-resistant ALK mutants | 8.224534e-02 | 1.085 |
| R-HSA-9692913 | SARS-CoV-1-mediated effects on programmed cell death | 9.473881e-02 | 1.023 |
| R-HSA-9013957 | TLR3-mediated TICAM1-dependent programmed cell death | 9.473881e-02 | 1.023 |
| R-HSA-8952158 | RUNX3 regulates BCL2L11 (BIM) transcription | 9.473881e-02 | 1.023 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 9.473881e-02 | 1.023 |
| R-HSA-9613354 | Lipophagy | 8.580846e-02 | 1.066 |
| R-HSA-5218900 | CASP8 activity is inhibited | 8.580846e-02 | 1.066 |
| R-HSA-110312 | Translesion synthesis by REV1 | 8.297674e-02 | 1.081 |
| R-HSA-140534 | Caspase activation via Death Receptors in the presence of ligand | 9.554478e-02 | 1.020 |
| R-HSA-5656121 | Translesion synthesis by POLI | 9.554478e-02 | 1.020 |
| R-HSA-5576886 | Phase 4 - resting membrane potential | 9.554478e-02 | 1.020 |
| R-HSA-5696397 | Gap-filling DNA repair synthesis and ligation in GG-NER | 8.560794e-02 | 1.067 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 9.607434e-02 | 1.017 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 1.050119e-01 | 0.979 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 9.030087e-02 | 1.044 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 9.030087e-02 | 1.044 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 1.027461e-01 | 0.988 |
| R-HSA-1799339 | SRP-dependent cotranslational protein targeting to membrane | 9.422407e-02 | 1.026 |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha | 8.262146e-02 | 1.083 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1.045973e-01 | 0.980 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 9.299240e-02 | 1.032 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 8.839962e-02 | 1.054 |
| R-HSA-140342 | Apoptosis induced DNA fragmentation | 1.026913e-01 | 0.988 |
| R-HSA-8848021 | Signaling by PTK6 | 9.004077e-02 | 1.046 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 9.004077e-02 | 1.046 |
| R-HSA-3214858 | RMTs methylate histone arginines | 8.322091e-02 | 1.080 |
| R-HSA-205025 | NADE modulates death signalling | 9.473881e-02 | 1.023 |
| R-HSA-2025928 | Calcineurin activates NFAT | 8.580846e-02 | 1.066 |
| R-HSA-1592230 | Mitochondrial biogenesis | 1.052361e-01 | 0.978 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 8.297674e-02 | 1.081 |
| R-HSA-169893 | Prolonged ERK activation events | 9.554478e-02 | 1.020 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 9.004077e-02 | 1.046 |
| R-HSA-5358351 | Signaling by Hedgehog | 8.154057e-02 | 1.089 |
| R-HSA-446652 | Interleukin-1 family signaling | 1.020110e-01 | 0.991 |
| R-HSA-111933 | Calmodulin induced events | 8.069270e-02 | 1.093 |
| R-HSA-211163 | AKT-mediated inactivation of FOXO1A | 9.473881e-02 | 1.023 |
| R-HSA-9840373 | Cellular response to mitochondrial stress | 8.580846e-02 | 1.066 |
| R-HSA-1296346 | Tandem pore domain potassium channels | 1.026913e-01 | 0.988 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 8.297674e-02 | 1.081 |
| R-HSA-111997 | CaM pathway | 8.069270e-02 | 1.093 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 8.839962e-02 | 1.054 |
| R-HSA-2559583 | Cellular Senescence | 9.736159e-02 | 1.012 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 1.050119e-01 | 0.979 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 8.874725e-02 | 1.052 |
| R-HSA-9013508 | NOTCH3 Intracellular Domain Regulates Transcription | 9.299240e-02 | 1.032 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 9.771757e-02 | 1.010 |
| R-HSA-9008059 | Interleukin-37 signaling | 9.299240e-02 | 1.032 |
| R-HSA-9012852 | Signaling by NOTCH3 | 9.748987e-02 | 1.011 |
| R-HSA-448706 | Interleukin-1 processing | 8.580846e-02 | 1.066 |
| R-HSA-193648 | NRAGE signals death through JNK | 1.045973e-01 | 0.980 |
| R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 1.028915e-01 | 0.988 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 1.054680e-01 | 0.977 |
| R-HSA-391251 | Protein folding | 1.063708e-01 | 0.973 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 1.071569e-01 | 0.970 |
| R-HSA-9020702 | Interleukin-1 signaling | 1.081656e-01 | 0.966 |
| R-HSA-5655862 | Translesion synthesis by POLK | 1.089480e-01 | 0.963 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 1.089480e-01 | 0.963 |
| R-HSA-9909649 | Regulation of PD-L1(CD274) transcription | 1.096951e-01 | 0.960 |
| R-HSA-212436 | Generic Transcription Pathway | 1.116570e-01 | 0.952 |
| R-HSA-1538133 | G0 and Early G1 | 1.122673e-01 | 0.950 |
| R-HSA-9020591 | Interleukin-12 signaling | 1.134604e-01 | 0.945 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 1.137530e-01 | 0.944 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 1.139058e-01 | 0.943 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 1.139058e-01 | 0.943 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 1.152425e-01 | 0.938 |
| R-HSA-8863678 | Neurodegenerative Diseases | 1.188342e-01 | 0.925 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 1.188342e-01 | 0.925 |
| R-HSA-9029569 | NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... | 1.196657e-01 | 0.922 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 1.207662e-01 | 0.918 |
| R-HSA-9706019 | RHOBTB3 ATPase cycle | 1.207662e-01 | 0.918 |
| R-HSA-73893 | DNA Damage Bypass | 1.219527e-01 | 0.914 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 1.219527e-01 | 0.914 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 1.219527e-01 | 0.914 |
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN | 1.221223e-01 | 0.913 |
| R-HSA-165158 | Activation of AKT2 | 1.221223e-01 | 0.913 |
| R-HSA-447038 | NrCAM interactions | 1.221223e-01 | 0.913 |
| R-HSA-3134973 | LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production | 1.221223e-01 | 0.913 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 1.223060e-01 | 0.913 |
| R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 1.577309e-01 | 0.802 |
| R-HSA-1299344 | TWIK-related spinal cord K+ channel (TRESK) | 1.577309e-01 | 0.802 |
| R-HSA-5632927 | Defective Mismatch Repair Associated With MSH3 | 1.577309e-01 | 0.802 |
| R-HSA-5632968 | Defective Mismatch Repair Associated With MSH6 | 1.577309e-01 | 0.802 |
| R-HSA-9763198 | Impaired BRCA2 binding to SEM1 (DSS1) | 1.577309e-01 | 0.802 |
| R-HSA-5602566 | TICAM1 deficiency - HSE | 1.577309e-01 | 0.802 |
| R-HSA-5545483 | Defective Mismatch Repair Associated With MLH1 | 1.577309e-01 | 0.802 |
| R-HSA-9709275 | Impaired BRCA2 translocation to the nucleus | 1.577309e-01 | 0.802 |
| R-HSA-5619043 | Defective SLC2A1 causes GLUT1 deficiency syndrome 1 (GLUT1DS1) | 1.577309e-01 | 0.802 |
| R-HSA-1299287 | Tandem pore domain halothane-inhibited K+ channel (THIK) | 1.577309e-01 | 0.802 |
| R-HSA-5632987 | Defective Mismatch Repair Associated With PMS2 | 1.577309e-01 | 0.802 |
| R-HSA-5657560 | Hereditary fructose intolerance | 1.577309e-01 | 0.802 |
| R-HSA-165160 | PDE3B signalling | 1.511269e-01 | 0.821 |
| R-HSA-109703 | PKB-mediated events | 1.511269e-01 | 0.821 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 1.511269e-01 | 0.821 |
| R-HSA-5576894 | Phase 1 - inactivation of fast Na+ channels | 1.511269e-01 | 0.821 |
| R-HSA-113507 | E2F-enabled inhibition of pre-replication complex formation | 1.813011e-01 | 0.742 |
| R-HSA-1234158 | Regulation of gene expression by Hypoxia-inducible Factor | 1.399056e-01 | 0.854 |
| R-HSA-2514853 | Condensation of Prometaphase Chromosomes | 1.399056e-01 | 0.854 |
| R-HSA-9824878 | Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 | 1.399056e-01 | 0.854 |
| R-HSA-9931512 | Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters | 1.399056e-01 | 0.854 |
| R-HSA-8951936 | RUNX3 regulates p14-ARF | 1.599795e-01 | 0.796 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 1.599795e-01 | 0.796 |
| R-HSA-2691232 | Constitutive Signaling by NOTCH1 HD Domain Mutants | 1.599795e-01 | 0.796 |
| R-HSA-2691230 | Signaling by NOTCH1 HD Domain Mutants in Cancer | 1.599795e-01 | 0.796 |
| R-HSA-9029558 | NR1H2 & NR1H3 regulate gene expression linked to lipogenesis | 1.808589e-01 | 0.743 |
| R-HSA-1362277 | Transcription of E2F targets under negative control by DREAM complex | 1.699237e-01 | 0.770 |
| R-HSA-5620916 | VxPx cargo-targeting to cilium | 1.699237e-01 | 0.770 |
| R-HSA-2122948 | Activated NOTCH1 Transmits Signal to the Nucleus | 1.438717e-01 | 0.842 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 1.438717e-01 | 0.842 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1.226073e-01 | 0.911 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 1.231815e-01 | 0.909 |
| R-HSA-174113 | SCF-beta-TrCP mediated degradation of Emi1 | 1.562563e-01 | 0.806 |
| R-HSA-68949 | Orc1 removal from chromatin | 1.490471e-01 | 0.827 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 1.586786e-01 | 0.799 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 1.586786e-01 | 0.799 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 1.271525e-01 | 0.896 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 1.292924e-01 | 0.888 |
| R-HSA-9954716 | ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... | 1.243406e-01 | 0.905 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 1.641156e-01 | 0.785 |
| R-HSA-9954714 | PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA | 1.577798e-01 | 0.802 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 1.431803e-01 | 0.844 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 1.665753e-01 | 0.778 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 1.231815e-01 | 0.909 |
| R-HSA-1227986 | Signaling by ERBB2 | 1.358458e-01 | 0.867 |
| R-HSA-5358508 | Mismatch Repair | 1.380704e-01 | 0.860 |
| R-HSA-69231 | Cyclin D associated events in G1 | 1.638946e-01 | 0.785 |
| R-HSA-69236 | G1 Phase | 1.638946e-01 | 0.785 |
| R-HSA-5358565 | Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) | 1.231402e-01 | 0.910 |
| R-HSA-5358606 | Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) | 1.231402e-01 | 0.910 |
| R-HSA-110320 | Translesion Synthesis by POLH | 1.536840e-01 | 0.813 |
| R-HSA-4641257 | Degradation of AXIN | 1.806944e-01 | 0.743 |
| R-HSA-202424 | Downstream TCR signaling | 1.503750e-01 | 0.823 |
| R-HSA-397795 | G-protein beta:gamma signalling | 1.226073e-01 | 0.911 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 1.503045e-01 | 0.823 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 1.808589e-01 | 0.743 |
| R-HSA-5689901 | Metalloprotease DUBs | 1.438717e-01 | 0.842 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 1.574725e-01 | 0.803 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 1.473937e-01 | 0.832 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 1.473937e-01 | 0.832 |
| R-HSA-3214842 | HDMs demethylate histones | 1.310815e-01 | 0.882 |
| R-HSA-194138 | Signaling by VEGF | 1.557351e-01 | 0.808 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 1.231815e-01 | 0.909 |
| R-HSA-156902 | Peptide chain elongation | 1.361282e-01 | 0.866 |
| R-HSA-8866427 | VLDLR internalisation and degradation | 1.599795e-01 | 0.796 |
| R-HSA-9931530 | Phosphorylation and nuclear translocation of the CRY:PER:kinase complex | 1.599795e-01 | 0.796 |
| R-HSA-450408 | AUF1 (hnRNP D0) binds and destabilizes mRNA | 1.682884e-01 | 0.774 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 1.446846e-01 | 0.840 |
| R-HSA-6807070 | PTEN Regulation | 1.310690e-01 | 0.883 |
| R-HSA-445144 | Signal transduction by L1 | 1.699237e-01 | 0.770 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 1.439264e-01 | 0.842 |
| R-HSA-9711097 | Cellular response to starvation | 1.294754e-01 | 0.888 |
| R-HSA-1500620 | Meiosis | 1.817032e-01 | 0.741 |
| R-HSA-195399 | VEGF binds to VEGFR leading to receptor dimerization | 1.511269e-01 | 0.821 |
| R-HSA-5673000 | RAF activation | 1.446192e-01 | 0.840 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 1.837617e-01 | 0.736 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 1.749134e-01 | 0.757 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 1.749134e-01 | 0.757 |
| R-HSA-9827857 | Specification of primordial germ cells | 1.231402e-01 | 0.910 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 1.571748e-01 | 0.804 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 1.427971e-01 | 0.845 |
| R-HSA-5357769 | Caspase activation via extrinsic apoptotic signalling pathway | 1.438717e-01 | 0.842 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 1.486371e-01 | 0.828 |
| R-HSA-5653656 | Vesicle-mediated transport | 1.546390e-01 | 0.811 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 1.372213e-01 | 0.863 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 1.813011e-01 | 0.742 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 1.226073e-01 | 0.911 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 1.231815e-01 | 0.909 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 1.638946e-01 | 0.785 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 1.493069e-01 | 0.826 |
| R-HSA-5218859 | Regulated Necrosis | 1.240485e-01 | 0.906 |
| R-HSA-5632684 | Hedgehog 'on' state | 1.473937e-01 | 0.832 |
| R-HSA-73857 | RNA Polymerase II Transcription | 1.617942e-01 | 0.791 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 1.328294e-01 | 0.877 |
| R-HSA-1834941 | STING mediated induction of host immune responses | 1.536840e-01 | 0.813 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 1.531985e-01 | 0.815 |
| R-HSA-77042 | Formation of editosomes by ADAR proteins | 1.577309e-01 | 0.802 |
| R-HSA-169131 | Inhibition of PKR | 1.577309e-01 | 0.802 |
| R-HSA-194313 | VEGF ligand-receptor interactions | 1.511269e-01 | 0.821 |
| R-HSA-68689 | CDC6 association with the ORC:origin complex | 1.511269e-01 | 0.821 |
| R-HSA-69242 | S Phase | 1.303507e-01 | 0.885 |
| R-HSA-1489509 | DAG and IP3 signaling | 1.749134e-01 | 0.757 |
| R-HSA-111996 | Ca-dependent events | 1.428390e-01 | 0.845 |
| R-HSA-187687 | Signalling to ERKs | 1.562563e-01 | 0.806 |
| R-HSA-211000 | Gene Silencing by RNA | 1.507448e-01 | 0.822 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 1.446192e-01 | 0.840 |
| R-HSA-422475 | Axon guidance | 1.248314e-01 | 0.904 |
| R-HSA-8869496 | TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... | 1.813011e-01 | 0.742 |
| R-HSA-844456 | The NLRP3 inflammasome | 1.536840e-01 | 0.813 |
| R-HSA-449147 | Signaling by Interleukins | 1.661468e-01 | 0.780 |
| R-HSA-9682385 | FLT3 signaling in disease | 1.682884e-01 | 0.774 |
| R-HSA-5660668 | CLEC7A/inflammasome pathway | 1.511269e-01 | 0.821 |
| R-HSA-9013694 | Signaling by NOTCH4 | 1.728075e-01 | 0.762 |
| R-HSA-9619665 | EGR2 and SOX10-mediated initiation of Schwann cell myelination | 1.333968e-01 | 0.875 |
| R-HSA-447115 | Interleukin-12 family signaling | 1.292924e-01 | 0.888 |
| R-HSA-622312 | Inflammasomes | 1.709592e-01 | 0.767 |
| R-HSA-9860276 | SLC15A4:TASL-dependent IRF5 activation | 1.511269e-01 | 0.821 |
| R-HSA-8983711 | OAS antiviral response | 1.599795e-01 | 0.796 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 1.851912e-01 | 0.732 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 1.851912e-01 | 0.732 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 1.851912e-01 | 0.732 |
| R-HSA-927802 | Nonsense-Mediated Decay (NMD) | 1.859021e-01 | 0.731 |
| R-HSA-975957 | Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) | 1.859021e-01 | 0.731 |
| R-HSA-9948299 | Ribosome-associated quality control | 1.859927e-01 | 0.731 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 1.862399e-01 | 0.730 |
| R-HSA-5357786 | TNFR1-induced proapoptotic signaling | 1.867303e-01 | 0.729 |
| R-HSA-198753 | ERK/MAPK targets | 1.867303e-01 | 0.729 |
| R-HSA-1500931 | Cell-Cell communication | 1.879894e-01 | 0.726 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 1.892369e-01 | 0.723 |
| R-HSA-1980143 | Signaling by NOTCH1 | 1.908210e-01 | 0.719 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 1.917919e-01 | 0.717 |
| R-HSA-1474165 | Reproduction | 1.954969e-01 | 0.709 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 1.978583e-01 | 0.704 |
| R-HSA-114452 | Activation of BH3-only proteins | 1.998360e-01 | 0.699 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 1.999403e-01 | 0.699 |
| R-HSA-5632928 | Defective Mismatch Repair Associated With MSH2 | 2.270118e-01 | 0.644 |
| R-HSA-5619081 | Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | 2.270118e-01 | 0.644 |
| R-HSA-5602571 | TRAF3 deficiency - HSE | 2.270118e-01 | 0.644 |
| R-HSA-9630794 | Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... | 2.270118e-01 | 0.644 |
| R-HSA-5660724 | Defective SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS) | 2.270118e-01 | 0.644 |
| R-HSA-5602680 | MyD88 deficiency (TLR5) | 2.270118e-01 | 0.644 |
| R-HSA-9632700 | Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... | 2.270118e-01 | 0.644 |
| R-HSA-5619056 | Defective HK1 causes hexokinase deficiency (HK deficiency) | 2.270118e-01 | 0.644 |
| R-HSA-3560796 | Defective PAPSS2 causes SEMD-PA | 2.905979e-01 | 0.537 |
| R-HSA-1299503 | TWIK related potassium channel (TREK) | 2.905979e-01 | 0.537 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 2.122567e-01 | 0.673 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 2.122567e-01 | 0.673 |
| R-HSA-203641 | NOSTRIN mediated eNOS trafficking | 2.122567e-01 | 0.673 |
| R-HSA-2562578 | TRIF-mediated programmed cell death | 2.122567e-01 | 0.673 |
| R-HSA-2470946 | Cohesin Loading onto Chromatin | 2.122567e-01 | 0.673 |
| R-HSA-75157 | FasL/ CD95L signaling | 3.489568e-01 | 0.457 |
| R-HSA-209563 | Axonal growth stimulation | 3.489568e-01 | 0.457 |
| R-HSA-8866906 | TFAP2 (AP-2) family regulates transcription of other transcription factors | 3.489568e-01 | 0.457 |
| R-HSA-1296053 | Classical Kir channels | 3.489568e-01 | 0.457 |
| R-HSA-5682113 | Defective ABCA1 causes TGD | 3.489568e-01 | 0.457 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 3.489568e-01 | 0.457 |
| R-HSA-5660862 | Defective SLC7A7 causes lysinuric protein intolerance (LPI) | 3.489568e-01 | 0.457 |
| R-HSA-5579006 | Defective GSS causes GSS deficiency | 3.489568e-01 | 0.457 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 2.436614e-01 | 0.613 |
| R-HSA-444257 | RSK activation | 2.436614e-01 | 0.613 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 2.024165e-01 | 0.694 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 2.024165e-01 | 0.694 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 2.752322e-01 | 0.560 |
| R-HSA-191650 | Regulation of gap junction activity | 4.025180e-01 | 0.395 |
| R-HSA-9818035 | NFE2L2 regulating ER-stress associated genes | 4.025180e-01 | 0.395 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 4.025180e-01 | 0.395 |
| R-HSA-5083630 | Defective LFNG causes SCDO3 | 4.025180e-01 | 0.395 |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... | 4.025180e-01 | 0.395 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 4.025180e-01 | 0.395 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 4.025180e-01 | 0.395 |
| R-HSA-2644607 | Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling | 4.025180e-01 | 0.395 |
| R-HSA-2644605 | FBXW7 Mutants and NOTCH1 in Cancer | 4.025180e-01 | 0.395 |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN | 2.245292e-01 | 0.649 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 3.067295e-01 | 0.513 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 3.067295e-01 | 0.513 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 3.067295e-01 | 0.513 |
| R-HSA-451308 | Activation of Ca-permeable Kainate Receptor | 3.067295e-01 | 0.513 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 3.067295e-01 | 0.513 |
| R-HSA-438066 | Unblocking of NMDA receptors, glutamate binding and activation | 2.040434e-01 | 0.690 |
| R-HSA-442982 | Ras activation upon Ca2+ influx through NMDA receptor | 2.040434e-01 | 0.690 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 2.699530e-01 | 0.569 |
| R-HSA-430039 | mRNA decay by 5' to 3' exoribonuclease | 2.699530e-01 | 0.569 |
| R-HSA-429947 | Deadenylation of mRNA | 2.584134e-01 | 0.588 |
| R-HSA-9623433 | NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis | 3.687318e-01 | 0.433 |
| R-HSA-5651801 | PCNA-Dependent Long Patch Base Excision Repair | 3.162592e-01 | 0.500 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 2.960888e-01 | 0.529 |
| R-HSA-1912420 | Pre-NOTCH Processing in Golgi | 3.395008e-01 | 0.469 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 3.989307e-01 | 0.399 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 2.475254e-01 | 0.606 |
| R-HSA-6814122 | Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding | 2.779786e-01 | 0.556 |
| R-HSA-174414 | Processive synthesis on the C-strand of the telomere | 3.151831e-01 | 0.501 |
| R-HSA-9609523 | Insertion of tail-anchored proteins into the endoplasmic reticulum membrane | 3.626866e-01 | 0.440 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 3.857394e-01 | 0.414 |
| R-HSA-1221632 | Meiotic synapsis | 2.727275e-01 | 0.564 |
| R-HSA-9006335 | Signaling by Erythropoietin | 3.536176e-01 | 0.451 |
| R-HSA-917729 | Endosomal Sorting Complex Required For Transport (ESCRT) | 3.536176e-01 | 0.451 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 2.532260e-01 | 0.596 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 2.493511e-01 | 0.603 |
| R-HSA-72165 | mRNA Splicing - Minor Pathway | 3.200802e-01 | 0.495 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 3.126492e-01 | 0.505 |
| R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 3.920522e-01 | 0.407 |
| R-HSA-192823 | Viral mRNA Translation | 2.784343e-01 | 0.555 |
| R-HSA-9954709 | Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide | 3.052381e-01 | 0.515 |
| R-HSA-109704 | PI3K Cascade | 3.801203e-01 | 0.420 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 3.811040e-01 | 0.419 |
| R-HSA-8957275 | Post-translational protein phosphorylation | 3.365273e-01 | 0.473 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 2.910296e-01 | 0.536 |
| R-HSA-72172 | mRNA Splicing | 2.912663e-01 | 0.536 |
| R-HSA-6798695 | Neutrophil degranulation | 2.351287e-01 | 0.629 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 2.302201e-01 | 0.638 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.913907e-01 | 0.536 |
| R-HSA-1234174 | Cellular response to hypoxia | 2.930056e-01 | 0.533 |
| R-HSA-2122947 | NOTCH1 Intracellular Domain Regulates Transcription | 2.219034e-01 | 0.654 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 3.126492e-01 | 0.505 |
| R-HSA-1234176 | Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha | 2.469088e-01 | 0.607 |
| R-HSA-68867 | Assembly of the pre-replicative complex | 3.914158e-01 | 0.407 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 2.285603e-01 | 0.641 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 2.285603e-01 | 0.641 |
| R-HSA-73886 | Chromosome Maintenance | 3.766065e-01 | 0.424 |
| R-HSA-174417 | Telomere C-strand (Lagging Strand) Synthesis | 2.475254e-01 | 0.606 |
| R-HSA-68962 | Activation of the pre-replicative complex | 3.728582e-01 | 0.428 |
| R-HSA-8866652 | Synthesis of active ubiquitin: roles of E1 and E2 enzymes | 3.151831e-01 | 0.501 |
| R-HSA-1660517 | Synthesis of PIPs at the late endosome membrane | 2.930461e-01 | 0.533 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 3.684600e-01 | 0.434 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 2.285603e-01 | 0.641 |
| R-HSA-110314 | Recognition of DNA damage by PCNA-containing replication complex | 2.584134e-01 | 0.588 |
| R-HSA-174411 | Polymerase switching on the C-strand of the telomere | 2.771471e-01 | 0.557 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 2.616802e-01 | 0.582 |
| R-HSA-9831926 | Nephron development | 3.162592e-01 | 0.500 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 2.040434e-01 | 0.690 |
| R-HSA-429914 | Deadenylation-dependent mRNA decay | 2.220489e-01 | 0.654 |
| R-HSA-169911 | Regulation of Apoptosis | 2.943320e-01 | 0.531 |
| R-HSA-3371568 | Attenuation phase | 3.777480e-01 | 0.423 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 3.121225e-01 | 0.506 |
| R-HSA-75893 | TNF signaling | 3.126492e-01 | 0.505 |
| R-HSA-8866907 | Activation of the TFAP2 (AP-2) family of transcription factors | 2.752322e-01 | 0.560 |
| R-HSA-8866911 | TFAP2 (AP-2) family regulates transcription of cell cycle factors | 4.025180e-01 | 0.395 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 2.218020e-01 | 0.654 |
| R-HSA-113510 | E2F mediated regulation of DNA replication | 3.395008e-01 | 0.469 |
| R-HSA-69091 | Polymerase switching | 3.989307e-01 | 0.399 |
| R-HSA-69109 | Leading Strand Synthesis | 3.989307e-01 | 0.399 |
| R-HSA-877312 | Regulation of IFNG signaling | 3.989307e-01 | 0.399 |
| R-HSA-5205685 | PINK1-PRKN Mediated Mitophagy | 3.343764e-01 | 0.476 |
| R-HSA-162588 | Budding and maturation of HIV virion | 3.920522e-01 | 0.407 |
| R-HSA-9764561 | Regulation of CDH1 Function | 3.261984e-01 | 0.487 |
| R-HSA-3371571 | HSF1-dependent transactivation | 3.952053e-01 | 0.403 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 3.037514e-01 | 0.517 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 3.410691e-01 | 0.467 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 3.881501e-01 | 0.411 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 4.025180e-01 | 0.395 |
| R-HSA-9620244 | Long-term potentiation | 2.771471e-01 | 0.557 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 2.567654e-01 | 0.590 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 3.536176e-01 | 0.451 |
| R-HSA-4641258 | Degradation of DVL | 3.274723e-01 | 0.485 |
| R-HSA-201556 | Signaling by ALK | 3.609584e-01 | 0.443 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 3.940599e-01 | 0.404 |
| R-HSA-204005 | COPII-mediated vesicle transport | 3.557079e-01 | 0.449 |
| R-HSA-182971 | EGFR downregulation | 2.148579e-01 | 0.668 |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA | 2.699530e-01 | 0.569 |
| R-HSA-5620924 | Intraflagellar transport | 2.097518e-01 | 0.678 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 2.335999e-01 | 0.632 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 3.575622e-01 | 0.447 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 3.773134e-01 | 0.423 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 2.470788e-01 | 0.607 |
| R-HSA-9843745 | Adipogenesis | 2.856835e-01 | 0.544 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 2.554612e-01 | 0.593 |
| R-HSA-193697 | p75NTR regulates axonogenesis | 2.752322e-01 | 0.560 |
| R-HSA-9636249 | Inhibition of nitric oxide production | 3.489568e-01 | 0.457 |
| R-HSA-349425 | Autodegradation of the E3 ubiquitin ligase COP1 | 2.779786e-01 | 0.556 |
| R-HSA-5620922 | BBSome-mediated cargo-targeting to cilium | 3.626866e-01 | 0.440 |
| R-HSA-72764 | Eukaryotic Translation Termination | 2.058976e-01 | 0.686 |
| R-HSA-9766229 | Degradation of CDH1 | 3.650421e-01 | 0.438 |
| R-HSA-1181150 | Signaling by NODAL | 3.626866e-01 | 0.440 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 2.458857e-01 | 0.609 |
| R-HSA-912631 | Regulation of signaling by CBL | 3.395008e-01 | 0.469 |
| R-HSA-379716 | Cytosolic tRNA aminoacylation | 2.616802e-01 | 0.582 |
| R-HSA-5205647 | Mitophagy | 2.779786e-01 | 0.556 |
| R-HSA-157118 | Signaling by NOTCH | 3.108628e-01 | 0.507 |
| R-HSA-8939211 | ESR-mediated signaling | 2.250359e-01 | 0.648 |
| R-HSA-5693548 | Sensing of DNA Double Strand Breaks | 3.687318e-01 | 0.433 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 2.218020e-01 | 0.654 |
| R-HSA-9759475 | Regulation of CDH11 Expression and Function | 3.536176e-01 | 0.451 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 4.005902e-01 | 0.397 |
| R-HSA-162587 | HIV Life Cycle | 2.518258e-01 | 0.599 |
| R-HSA-190827 | Transport of connexins along the secretory pathway | 2.270118e-01 | 0.644 |
| R-HSA-163282 | Mitochondrial transcription initiation | 2.270118e-01 | 0.644 |
| R-HSA-9630750 | Evasion of Oncogene Induced Senescence Due to p16INK4A Defects | 2.270118e-01 | 0.644 |
| R-HSA-9632693 | Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects | 2.270118e-01 | 0.644 |
| R-HSA-75064 | mRNA Editing: A to I Conversion | 2.905979e-01 | 0.537 |
| R-HSA-75102 | C6 deamination of adenosine | 2.905979e-01 | 0.537 |
| R-HSA-3249367 | STAT6-mediated induction of chemokines | 3.489568e-01 | 0.457 |
| R-HSA-193634 | Axonal growth inhibition (RHOA activation) | 2.436614e-01 | 0.613 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 2.752322e-01 | 0.560 |
| R-HSA-176974 | Unwinding of DNA | 2.752322e-01 | 0.560 |
| R-HSA-8941333 | RUNX2 regulates genes involved in differentiation of myeloid cells | 4.025180e-01 | 0.395 |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity | 4.025180e-01 | 0.395 |
| R-HSA-5140745 | WNT5A-dependent internalization of FZD2, FZD5 and ROR2 | 3.067295e-01 | 0.513 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 2.040434e-01 | 0.690 |
| R-HSA-451306 | Ionotropic activity of kainate receptors | 3.379520e-01 | 0.471 |
| R-HSA-1839122 | Signaling by activated point mutants of FGFR1 | 3.687318e-01 | 0.433 |
| R-HSA-202670 | ERKs are inactivated | 3.687318e-01 | 0.433 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 3.343764e-01 | 0.476 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 3.536176e-01 | 0.451 |
| R-HSA-9725554 | Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin | 3.609584e-01 | 0.443 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 3.777480e-01 | 0.423 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.689351e-01 | 0.570 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 3.691097e-01 | 0.433 |
| R-HSA-162906 | HIV Infection | 2.980071e-01 | 0.526 |
| R-HSA-389356 | Co-stimulation by CD28 | 3.499936e-01 | 0.456 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 2.708046e-01 | 0.567 |
| R-HSA-5683057 | MAPK family signaling cascades | 2.310060e-01 | 0.636 |
| R-HSA-1236974 | ER-Phagosome pathway | 3.352163e-01 | 0.475 |
| R-HSA-73933 | Resolution of Abasic Sites (AP sites) | 3.945266e-01 | 0.404 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 3.892404e-01 | 0.410 |
| R-HSA-446728 | Cell junction organization | 2.726146e-01 | 0.564 |
| R-HSA-9856872 | Malate-aspartate shuttle | 2.024165e-01 | 0.694 |
| R-HSA-9762293 | Regulation of CDH11 gene transcription | 2.752322e-01 | 0.560 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 2.976195e-01 | 0.526 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 2.976195e-01 | 0.526 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 3.454936e-01 | 0.462 |
| R-HSA-397014 | Muscle contraction | 2.050998e-01 | 0.688 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 2.450046e-01 | 0.611 |
| R-HSA-162909 | Host Interactions of HIV factors | 2.131843e-01 | 0.671 |
| R-HSA-111453 | BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members | 2.436614e-01 | 0.613 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 2.752322e-01 | 0.560 |
| R-HSA-69190 | DNA strand elongation | 2.302201e-01 | 0.638 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 3.812487e-01 | 0.419 |
| R-HSA-168256 | Immune System | 2.644394e-01 | 0.578 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 2.245292e-01 | 0.649 |
| R-HSA-112043 | PLC beta mediated events | 3.811040e-01 | 0.419 |
| R-HSA-9617828 | FOXO-mediated transcription of cell cycle genes | 2.040434e-01 | 0.690 |
| R-HSA-69186 | Lagging Strand Synthesis | 3.857394e-01 | 0.414 |
| R-HSA-9861718 | Regulation of pyruvate metabolism | 3.200802e-01 | 0.495 |
| R-HSA-163560 | Triglyceride catabolism | 3.108418e-01 | 0.507 |
| R-HSA-5578775 | Ion homeostasis | 3.126492e-01 | 0.505 |
| R-HSA-165159 | MTOR signalling | 2.616802e-01 | 0.582 |
| R-HSA-177929 | Signaling by EGFR | 3.126492e-01 | 0.505 |
| R-HSA-1483249 | Inositol phosphate metabolism | 2.722855e-01 | 0.565 |
| R-HSA-190704 | Oligomerization of connexins into connexons | 2.270118e-01 | 0.644 |
| R-HSA-352238 | Breakdown of the nuclear lamina | 2.270118e-01 | 0.644 |
| R-HSA-9635644 | Inhibition of membrane repair | 2.270118e-01 | 0.644 |
| R-HSA-75944 | Transcription from mitochondrial promoters | 2.905979e-01 | 0.537 |
| R-HSA-9675132 | Diseases of cellular response to stress | 2.905979e-01 | 0.537 |
| R-HSA-9630747 | Diseases of Cellular Senescence | 2.905979e-01 | 0.537 |
| R-HSA-5607763 | CLEC7A (Dectin-1) induces NFAT activation | 2.024165e-01 | 0.694 |
| R-HSA-1483226 | Synthesis of PI | 3.379520e-01 | 0.471 |
| R-HSA-418359 | Reduction of cytosolic Ca++ levels | 3.687318e-01 | 0.433 |
| R-HSA-9735869 | SARS-CoV-1 modulates host translation machinery | 2.779786e-01 | 0.556 |
| R-HSA-9754678 | SARS-CoV-2 modulates host translation machinery | 2.858947e-01 | 0.544 |
| R-HSA-5576891 | Cardiac conduction | 2.025594e-01 | 0.693 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 3.777480e-01 | 0.423 |
| R-HSA-379724 | tRNA Aminoacylation | 3.673080e-01 | 0.435 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 3.811040e-01 | 0.419 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 3.474256e-01 | 0.459 |
| R-HSA-9945266 | Differentiation of T cells | 2.470788e-01 | 0.607 |
| R-HSA-9942503 | Differentiation of naive CD+ T cells to T helper 1 cells (Th1 cells) | 2.470788e-01 | 0.607 |
| R-HSA-9839373 | Signaling by TGFBR3 | 3.200802e-01 | 0.495 |
| R-HSA-264870 | Caspase-mediated cleavage of cytoskeletal proteins | 2.752322e-01 | 0.560 |
| R-HSA-6803207 | TP53 Regulates Transcription of Caspase Activators and Caspases | 2.470788e-01 | 0.607 |
| R-HSA-6803211 | TP53 Regulates Transcription of Death Receptors and Ligands | 2.024165e-01 | 0.694 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 2.992083e-01 | 0.524 |
| R-HSA-2408557 | Selenocysteine synthesis | 2.595462e-01 | 0.586 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 2.914202e-01 | 0.535 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 3.557079e-01 | 0.449 |
| R-HSA-9701898 | STAT3 nuclear events downstream of ALK signaling | 2.245292e-01 | 0.649 |
| R-HSA-9824446 | Viral Infection Pathways | 3.343492e-01 | 0.476 |
| R-HSA-9007101 | Rab regulation of trafficking | 2.409712e-01 | 0.618 |
| R-HSA-844455 | The NLRP1 inflammasome | 3.489568e-01 | 0.457 |
| R-HSA-390651 | Dopamine receptors | 4.025180e-01 | 0.395 |
| R-HSA-9707587 | Regulation of HMOX1 expression and activity | 4.025180e-01 | 0.395 |
| R-HSA-9705677 | SARS-CoV-2 targets PDZ proteins in cell-cell junction | 4.025180e-01 | 0.395 |
| R-HSA-9820962 | Assembly and release of respiratory syncytial virus (RSV) virions | 3.067295e-01 | 0.513 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 3.151831e-01 | 0.501 |
| R-HSA-9010553 | Regulation of expression of SLITs and ROBOs | 3.897503e-01 | 0.409 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 2.423283e-01 | 0.616 |
| R-HSA-2408522 | Selenoamino acid metabolism | 3.049037e-01 | 0.516 |
| R-HSA-9857377 | Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autopha... | 2.218020e-01 | 0.654 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 3.441890e-01 | 0.463 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 2.024165e-01 | 0.694 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 3.052642e-01 | 0.515 |
| R-HSA-8949275 | RUNX3 Regulates Immune Response and Cell Migration | 2.122567e-01 | 0.673 |
| R-HSA-5336415 | Uptake and function of diphtheria toxin | 2.122567e-01 | 0.673 |
| R-HSA-9834752 | Respiratory syncytial virus genome replication | 2.752322e-01 | 0.560 |
| R-HSA-193692 | Regulated proteolysis of p75NTR | 2.752322e-01 | 0.560 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 2.930461e-01 | 0.533 |
| R-HSA-381183 | ATF6 (ATF6-alpha) activates chaperone genes | 3.687318e-01 | 0.433 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 2.550879e-01 | 0.593 |
| R-HSA-5578768 | Physiological factors | 2.024165e-01 | 0.694 |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 3.379520e-01 | 0.471 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 3.151831e-01 | 0.501 |
| R-HSA-6784531 | tRNA processing in the nucleus | 3.949165e-01 | 0.403 |
| R-HSA-8851680 | Butyrophilin (BTN) family interactions | 2.752322e-01 | 0.560 |
| R-HSA-9820965 | Respiratory syncytial virus (RSV) genome replication, transcription and translat... | 2.065384e-01 | 0.685 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 4.085897e-01 | 0.389 |
| R-HSA-6790901 | rRNA modification in the nucleus and cytosol | 4.087285e-01 | 0.389 |
| R-HSA-174184 | Cdc20:Phospho-APC/C mediated degradation of Cyclin A | 4.102750e-01 | 0.387 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 4.111566e-01 | 0.386 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 4.112647e-01 | 0.386 |
| R-HSA-9932298 | Degradation of CRY and PER proteins | 4.112647e-01 | 0.386 |
| R-HSA-6811438 | Intra-Golgi traffic | 4.112647e-01 | 0.386 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 4.189686e-01 | 0.378 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 4.203948e-01 | 0.376 |
| R-HSA-2428924 | IGF1R signaling cascade | 4.225232e-01 | 0.374 |
| R-HSA-936837 | Ion transport by P-type ATPases | 4.225232e-01 | 0.374 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 4.253082e-01 | 0.371 |
| R-HSA-445355 | Smooth Muscle Contraction | 4.253082e-01 | 0.371 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 4.279336e-01 | 0.369 |
| R-HSA-8877330 | RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs) | 4.284360e-01 | 0.368 |
| R-HSA-190375 | FGFR2c ligand binding and activation | 4.284360e-01 | 0.368 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 4.284360e-01 | 0.368 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 4.284360e-01 | 0.368 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 4.284360e-01 | 0.368 |
| R-HSA-174490 | Membrane binding and targetting of GAG proteins | 4.284360e-01 | 0.368 |
| R-HSA-190373 | FGFR1c ligand binding and activation | 4.284360e-01 | 0.368 |
| R-HSA-1482883 | Acyl chain remodeling of DAG and TAG | 4.284360e-01 | 0.368 |
| R-HSA-190322 | FGFR4 ligand binding and activation | 4.284360e-01 | 0.368 |
| R-HSA-5685939 | HDR through MMEJ (alt-NHEJ) | 4.284360e-01 | 0.368 |
| R-HSA-1839130 | Signaling by activated point mutants of FGFR3 | 4.284360e-01 | 0.368 |
| R-HSA-1059683 | Interleukin-6 signaling | 4.284360e-01 | 0.368 |
| R-HSA-2033514 | FGFR3 mutant receptor activation | 4.284360e-01 | 0.368 |
| R-HSA-381033 | ATF6 (ATF6-alpha) activates chaperones | 4.284360e-01 | 0.368 |
| R-HSA-68616 | Assembly of the ORC complex at the origin of replication | 4.301311e-01 | 0.366 |
| R-HSA-354192 | Integrin signaling | 4.301311e-01 | 0.366 |
| R-HSA-9764260 | Regulation of Expression and Function of Type II Classical Cadherins | 4.301311e-01 | 0.366 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 4.301311e-01 | 0.366 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 4.301311e-01 | 0.366 |
| R-HSA-9733709 | Cardiogenesis | 4.301311e-01 | 0.366 |
| R-HSA-350054 | Notch-HLH transcription pathway | 4.311744e-01 | 0.365 |
| R-HSA-212676 | Dopamine Neurotransmitter Release Cycle | 4.311744e-01 | 0.365 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 4.311744e-01 | 0.365 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 4.311744e-01 | 0.365 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 4.311744e-01 | 0.365 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 4.329267e-01 | 0.364 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 4.362842e-01 | 0.360 |
| R-HSA-70268 | Pyruvate metabolism | 4.408686e-01 | 0.356 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 4.414054e-01 | 0.355 |
| R-HSA-69239 | Synthesis of DNA | 4.436719e-01 | 0.353 |
| R-HSA-376176 | Signaling by ROBO receptors | 4.442174e-01 | 0.352 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 4.479799e-01 | 0.349 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 4.489386e-01 | 0.348 |
| R-HSA-9768727 | Regulation of CDH1 posttranslational processing and trafficking to plasma membra... | 4.489386e-01 | 0.348 |
| R-HSA-180534 | Vpu mediated degradation of CD4 | 4.489386e-01 | 0.348 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 4.489386e-01 | 0.348 |
| R-HSA-8939247 | RUNX1 regulates transcription of genes involved in interleukin signaling | 4.516756e-01 | 0.345 |
| R-HSA-8939245 | RUNX1 regulates transcription of genes involved in BCR signaling | 4.516756e-01 | 0.345 |
| R-HSA-74713 | IRS activation | 4.516756e-01 | 0.345 |
| R-HSA-9818026 | NFE2L2 regulating inflammation associated genes | 4.516756e-01 | 0.345 |
| R-HSA-190374 | FGFR1c and Klotho ligand binding and activation | 4.516756e-01 | 0.345 |
| R-HSA-203754 | NOSIP mediated eNOS trafficking | 4.516756e-01 | 0.345 |
| R-HSA-9673768 | Signaling by membrane-tethered fusions of PDGFRA or PDGFRB | 4.516756e-01 | 0.345 |
| R-HSA-9706377 | FLT3 signaling by CBL mutants | 4.516756e-01 | 0.345 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 4.516756e-01 | 0.345 |
| R-HSA-8849468 | PTK6 Regulates Proteins Involved in RNA Processing | 4.516756e-01 | 0.345 |
| R-HSA-110381 | Resolution of AP sites via the single-nucleotide replacement pathway | 4.516756e-01 | 0.345 |
| R-HSA-426496 | Post-transcriptional silencing by small RNAs | 4.516756e-01 | 0.345 |
| R-HSA-8849474 | PTK6 Activates STAT3 | 4.516756e-01 | 0.345 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 4.516756e-01 | 0.345 |
| R-HSA-111464 | SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes | 4.516756e-01 | 0.345 |
| R-HSA-71737 | Pyrophosphate hydrolysis | 4.516756e-01 | 0.345 |
| R-HSA-111463 | SMAC (DIABLO) binds to IAPs | 4.516756e-01 | 0.345 |
| R-HSA-8941284 | RUNX2 regulates chondrocyte maturation | 4.516756e-01 | 0.345 |
| R-HSA-435368 | Zinc efflux and compartmentalization by the SLC30 family | 4.516756e-01 | 0.345 |
| R-HSA-1855167 | Synthesis of pyrophosphates in the cytosol | 4.534376e-01 | 0.343 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 4.534376e-01 | 0.343 |
| R-HSA-982772 | Growth hormone receptor signaling | 4.534376e-01 | 0.343 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 4.544150e-01 | 0.343 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 4.551837e-01 | 0.342 |
| R-HSA-190372 | FGFR3c ligand binding and activation | 4.571575e-01 | 0.340 |
| R-HSA-418457 | cGMP effects | 4.571575e-01 | 0.340 |
| R-HSA-5654227 | Phospholipase C-mediated cascade; FGFR3 | 4.571575e-01 | 0.340 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 4.571575e-01 | 0.340 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 4.571575e-01 | 0.340 |
| R-HSA-8963896 | HDL assembly | 4.571575e-01 | 0.340 |
| R-HSA-174495 | Synthesis And Processing Of GAG, GAGPOL Polyproteins | 4.571575e-01 | 0.340 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 4.571575e-01 | 0.340 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 4.609583e-01 | 0.336 |
| R-HSA-112040 | G-protein mediated events | 4.636438e-01 | 0.334 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 4.675443e-01 | 0.330 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 4.675443e-01 | 0.330 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 4.675443e-01 | 0.330 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 4.675443e-01 | 0.330 |
| R-HSA-3299685 | Detoxification of Reactive Oxygen Species | 4.699878e-01 | 0.328 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 4.699878e-01 | 0.328 |
| R-HSA-9679191 | Potential therapeutics for SARS | 4.740260e-01 | 0.324 |
| R-HSA-9865881 | Complex III assembly | 4.753297e-01 | 0.323 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 4.753297e-01 | 0.323 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 4.753297e-01 | 0.323 |
| R-HSA-6783589 | Interleukin-6 family signaling | 4.753297e-01 | 0.323 |
| R-HSA-1266738 | Developmental Biology | 4.761975e-01 | 0.322 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 4.772127e-01 | 0.321 |
| R-HSA-5678895 | Defective CFTR causes cystic fibrosis | 4.772649e-01 | 0.321 |
| R-HSA-606279 | Deposition of new CENPA-containing nucleosomes at the centromere | 4.772649e-01 | 0.321 |
| R-HSA-774815 | Nucleosome assembly | 4.772649e-01 | 0.321 |
| R-HSA-4608870 | Asymmetric localization of PCP proteins | 4.772649e-01 | 0.321 |
| R-HSA-9824272 | Somitogenesis | 4.772649e-01 | 0.321 |
| R-HSA-418990 | Adherens junctions interactions | 4.789532e-01 | 0.320 |
| R-HSA-70171 | Glycolysis | 4.818268e-01 | 0.317 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 4.832415e-01 | 0.316 |
| R-HSA-112399 | IRS-mediated signalling | 4.846789e-01 | 0.315 |
| R-HSA-8948700 | Competing endogenous RNAs (ceRNAs) regulate PTEN translation | 4.850246e-01 | 0.314 |
| R-HSA-9027284 | Erythropoietin activates RAS | 4.850246e-01 | 0.314 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 4.850246e-01 | 0.314 |
| R-HSA-190239 | FGFR3 ligand binding and activation | 4.850246e-01 | 0.314 |
| R-HSA-5654228 | Phospholipase C-mediated cascade; FGFR4 | 4.850246e-01 | 0.314 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 4.850246e-01 | 0.314 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 4.850246e-01 | 0.314 |
| R-HSA-174430 | Telomere C-strand synthesis initiation | 4.850246e-01 | 0.314 |
| R-HSA-1502540 | Signaling by Activin | 4.850246e-01 | 0.314 |
| R-HSA-171007 | p38MAPK events | 4.850246e-01 | 0.314 |
| R-HSA-174362 | Transport and metabolism of PAPS | 4.850246e-01 | 0.314 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 4.850246e-01 | 0.314 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 4.850246e-01 | 0.314 |
| R-HSA-196780 | Biotin transport and metabolism | 4.850246e-01 | 0.314 |
| R-HSA-8854050 | FBXL7 down-regulates AURKA during mitotic entry and in early mitosis | 4.859169e-01 | 0.313 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 4.934041e-01 | 0.307 |
| R-HSA-8935964 | RUNX1 regulates expression of components of tight junctions | 4.967915e-01 | 0.304 |
| R-HSA-2660826 | Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 4.967915e-01 | 0.304 |
| R-HSA-2660825 | Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant | 4.967915e-01 | 0.304 |
| R-HSA-9833576 | CDH11 homotypic and heterotypic interactions | 4.967915e-01 | 0.304 |
| R-HSA-111957 | Cam-PDE 1 activation | 4.967915e-01 | 0.304 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 4.967915e-01 | 0.304 |
| R-HSA-8985586 | SLIT2:ROBO1 increases RHOA activity | 4.967915e-01 | 0.304 |
| R-HSA-9865113 | Loss-of-function mutations in DBT cause MSUD2 | 4.967915e-01 | 0.304 |
| R-HSA-9652817 | Signaling by MAPK mutants | 4.967915e-01 | 0.304 |
| R-HSA-9907570 | Loss-of-function mutations in DLD cause MSUD3/DLDD | 4.967915e-01 | 0.304 |
| R-HSA-75158 | TRAIL signaling | 4.967915e-01 | 0.304 |
| R-HSA-111459 | Activation of caspases through apoptosome-mediated cleavage | 4.967915e-01 | 0.304 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 4.967915e-01 | 0.304 |
| R-HSA-187706 | Signalling to p38 via RIT and RIN | 4.967915e-01 | 0.304 |
| R-HSA-111469 | SMAC, XIAP-regulated apoptotic response | 4.967915e-01 | 0.304 |
| R-HSA-444821 | Relaxin receptors | 4.967915e-01 | 0.304 |
| R-HSA-389397 | Orexin and neuropeptides FF and QRFP bind to their respective receptors | 4.967915e-01 | 0.304 |
| R-HSA-9764302 | Regulation of CDH19 Expression and Function | 4.967915e-01 | 0.304 |
| R-HSA-9694493 | Maturation of protein E | 4.967915e-01 | 0.304 |
| R-HSA-9683683 | Maturation of protein E | 4.967915e-01 | 0.304 |
| R-HSA-9033500 | TYSND1 cleaves peroxisomal proteins | 4.967915e-01 | 0.304 |
| R-HSA-203927 | MicroRNA (miRNA) biogenesis | 4.968074e-01 | 0.304 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 4.968074e-01 | 0.304 |
| R-HSA-1660516 | Synthesis of PIPs at the early endosome membrane | 4.968074e-01 | 0.304 |
| R-HSA-72312 | rRNA processing | 4.969640e-01 | 0.304 |
| R-HSA-3371511 | HSF1 activation | 5.040276e-01 | 0.298 |
| R-HSA-180585 | Vif-mediated degradation of APOBEC3G | 5.040276e-01 | 0.298 |
| R-HSA-174154 | APC/C:Cdc20 mediated degradation of Securin | 5.093553e-01 | 0.293 |
| R-HSA-74752 | Signaling by Insulin receptor | 5.118313e-01 | 0.291 |
| R-HSA-2682334 | EPH-Ephrin signaling | 5.118313e-01 | 0.291 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 5.119833e-01 | 0.291 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 5.119833e-01 | 0.291 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 5.119833e-01 | 0.291 |
| R-HSA-9706369 | Negative regulation of FLT3 | 5.119833e-01 | 0.291 |
| R-HSA-389948 | Co-inhibition by PD-1 | 5.122542e-01 | 0.291 |
| R-HSA-180786 | Extension of Telomeres | 5.136562e-01 | 0.289 |
| R-HSA-8979227 | Triglyceride metabolism | 5.136562e-01 | 0.289 |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins | 5.178330e-01 | 0.286 |
| R-HSA-110373 | Resolution of AP sites via the multiple-nucleotide patch replacement pathway | 5.178330e-01 | 0.286 |
| R-HSA-9637687 | Suppression of phagosomal maturation | 5.178330e-01 | 0.286 |
| R-HSA-70635 | Urea cycle | 5.178330e-01 | 0.286 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 5.205242e-01 | 0.284 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 5.218503e-01 | 0.282 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 5.218503e-01 | 0.282 |
| R-HSA-2644603 | Signaling by NOTCH1 in Cancer | 5.279119e-01 | 0.277 |
| R-HSA-2644602 | Signaling by NOTCH1 PEST Domain Mutants in Cancer | 5.279119e-01 | 0.277 |
| R-HSA-2894862 | Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants | 5.279119e-01 | 0.277 |
| R-HSA-2894858 | Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer | 5.279119e-01 | 0.277 |
| R-HSA-2644606 | Constitutive Signaling by NOTCH1 PEST Domain Mutants | 5.279119e-01 | 0.277 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 5.279119e-01 | 0.277 |
| R-HSA-381426 | Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... | 5.284847e-01 | 0.277 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 5.327467e-01 | 0.273 |
| R-HSA-9833110 | RSV-host interactions | 5.369138e-01 | 0.270 |
| R-HSA-141405 | Inhibition of the proteolytic activity of APC/C required for the onset of anapha... | 5.379946e-01 | 0.269 |
| R-HSA-141430 | Inactivation of APC/C via direct inhibition of the APC/C complex | 5.379946e-01 | 0.269 |
| R-HSA-9027307 | Biosynthesis of maresin-like SPMs | 5.379946e-01 | 0.269 |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants | 5.379946e-01 | 0.269 |
| R-HSA-2892247 | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | 5.379946e-01 | 0.269 |
| R-HSA-8939256 | RUNX1 regulates transcription of genes involved in WNT signaling | 5.381978e-01 | 0.269 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 5.381978e-01 | 0.269 |
| R-HSA-6802953 | RAS signaling downstream of NF1 loss-of-function variants | 5.381978e-01 | 0.269 |
| R-HSA-9865125 | Loss-of-function mutations in BCKDHA or BCKDHB cause MSUD | 5.381978e-01 | 0.269 |
| R-HSA-9912529 | H139Hfs13* PPM1K causes a mild variant of MSUD | 5.381978e-01 | 0.269 |
| R-HSA-9912481 | Branched-chain ketoacid dehydrogenase kinase deficiency | 5.381978e-01 | 0.269 |
| R-HSA-426486 | Small interfering RNA (siRNA) biogenesis | 5.381978e-01 | 0.269 |
| R-HSA-5653890 | Lactose synthesis | 5.381978e-01 | 0.269 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 5.381978e-01 | 0.269 |
| R-HSA-164944 | Nef and signal transduction | 5.381978e-01 | 0.269 |
| R-HSA-8866423 | VLDL assembly | 5.381978e-01 | 0.269 |
| R-HSA-447043 | Neurofascin interactions | 5.381978e-01 | 0.269 |
| R-HSA-8949613 | Cristae formation | 5.383746e-01 | 0.269 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 5.383746e-01 | 0.269 |
| R-HSA-264876 | Insulin processing | 5.383746e-01 | 0.269 |
| R-HSA-9828806 | Maturation of hRSV A proteins | 5.383746e-01 | 0.269 |
| R-HSA-8953854 | Metabolism of RNA | 5.389942e-01 | 0.268 |
| R-HSA-1280218 | Adaptive Immune System | 5.400332e-01 | 0.268 |
| R-HSA-4086398 | Ca2+ pathway | 5.434162e-01 | 0.265 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 5.565412e-01 | 0.255 |
| R-HSA-9648002 | RAS processing | 5.565412e-01 | 0.255 |
| R-HSA-451326 | Activation of kainate receptors upon glutamate binding | 5.584051e-01 | 0.253 |
| R-HSA-77387 | Insulin receptor recycling | 5.584051e-01 | 0.253 |
| R-HSA-174437 | Removal of the Flap Intermediate from the C-strand | 5.630319e-01 | 0.249 |
| R-HSA-5654219 | Phospholipase C-mediated cascade: FGFR1 | 5.630319e-01 | 0.249 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 5.630319e-01 | 0.249 |
| R-HSA-2408550 | Metabolism of ingested H2SeO4 and H2SeO3 into H2Se | 5.630319e-01 | 0.249 |
| R-HSA-2028269 | Signaling by Hippo | 5.630319e-01 | 0.249 |
| R-HSA-9006936 | Signaling by TGFB family members | 5.630917e-01 | 0.249 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 5.689147e-01 | 0.245 |
| R-HSA-912446 | Meiotic recombination | 5.709203e-01 | 0.243 |
| R-HSA-5358346 | Hedgehog ligand biogenesis | 5.709203e-01 | 0.243 |
| R-HSA-9670095 | Inhibition of DNA recombination at telomere | 5.733704e-01 | 0.242 |
| R-HSA-9844594 | Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 | 5.733704e-01 | 0.242 |
| R-HSA-9843743 | Transcriptional regulation of brown and beige adipocyte differentiation | 5.733704e-01 | 0.242 |
| R-HSA-202433 | Generation of second messenger molecules | 5.733704e-01 | 0.242 |
| R-HSA-112412 | SOS-mediated signalling | 5.761992e-01 | 0.239 |
| R-HSA-72731 | Recycling of eIF2:GDP | 5.761992e-01 | 0.239 |
| R-HSA-9031525 | NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake | 5.761992e-01 | 0.239 |
| R-HSA-190371 | FGFR3b ligand binding and activation | 5.761992e-01 | 0.239 |
| R-HSA-1912399 | Pre-NOTCH Processing in the Endoplasmic Reticulum | 5.761992e-01 | 0.239 |
| R-HSA-8931987 | RUNX1 regulates estrogen receptor mediated transcription | 5.761992e-01 | 0.239 |
| R-HSA-163754 | Insulin effects increased synthesis of Xylulose-5-Phosphate | 5.761992e-01 | 0.239 |
| R-HSA-8948747 | Regulation of PTEN localization | 5.761992e-01 | 0.239 |
| R-HSA-1614603 | Cysteine formation from homocysteine | 5.761992e-01 | 0.239 |
| R-HSA-9686347 | Microbial modulation of RIPK1-mediated regulated necrosis | 5.761992e-01 | 0.239 |
| R-HSA-139915 | Activation of PUMA and translocation to mitochondria | 5.761992e-01 | 0.239 |
| R-HSA-8964041 | LDL remodeling | 5.761992e-01 | 0.239 |
| R-HSA-3371599 | Defective HLCS causes multiple carboxylase deficiency | 5.761992e-01 | 0.239 |
| R-HSA-447041 | CHL1 interactions | 5.761992e-01 | 0.239 |
| R-HSA-110357 | Displacement of DNA glycosylase by APEX1 | 5.761992e-01 | 0.239 |
| R-HSA-418360 | Platelet calcium homeostasis | 5.779025e-01 | 0.238 |
| R-HSA-5689603 | UCH proteinases | 5.814129e-01 | 0.236 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 5.814129e-01 | 0.236 |
| R-HSA-112316 | Neuronal System | 5.818201e-01 | 0.235 |
| R-HSA-74751 | Insulin receptor signalling cascade | 5.830723e-01 | 0.234 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 5.856752e-01 | 0.232 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 5.856752e-01 | 0.232 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 5.856752e-01 | 0.232 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 5.856752e-01 | 0.232 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 5.870793e-01 | 0.231 |
| R-HSA-190242 | FGFR1 ligand binding and activation | 5.870793e-01 | 0.231 |
| R-HSA-2033519 | Activated point mutants of FGFR2 | 5.870793e-01 | 0.231 |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants | 5.870793e-01 | 0.231 |
| R-HSA-73980 | RNA Polymerase III Transcription Termination | 5.870793e-01 | 0.231 |
| R-HSA-9926550 | Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adh... | 5.870793e-01 | 0.231 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 5.888769e-01 | 0.230 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 5.892194e-01 | 0.230 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 5.897884e-01 | 0.229 |
| R-HSA-5362768 | Hh mutants are degraded by ERAD | 5.898337e-01 | 0.229 |
| R-HSA-9607240 | FLT3 Signaling | 5.898337e-01 | 0.229 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 5.968487e-01 | 0.224 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 5.968487e-01 | 0.224 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 5.968487e-01 | 0.224 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 5.968487e-01 | 0.224 |
| R-HSA-73864 | RNA Polymerase I Transcription | 6.058655e-01 | 0.218 |
| R-HSA-4086400 | PCP/CE pathway | 6.058655e-01 | 0.218 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 6.059175e-01 | 0.218 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 6.059175e-01 | 0.218 |
| R-HSA-69306 | DNA Replication | 6.060158e-01 | 0.218 |
| R-HSA-174048 | APC/C:Cdc20 mediated degradation of Cyclin B | 6.101302e-01 | 0.215 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 6.101302e-01 | 0.215 |
| R-HSA-9754189 | Germ layer formation at gastrulation | 6.101302e-01 | 0.215 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 6.101302e-01 | 0.215 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 6.110756e-01 | 0.214 |
| R-HSA-112126 | ALKBH3 mediated reversal of alkylation damage | 6.110756e-01 | 0.214 |
| R-HSA-190370 | FGFR1b ligand binding and activation | 6.110756e-01 | 0.214 |
| R-HSA-8875656 | MET receptor recycling | 6.110756e-01 | 0.214 |
| R-HSA-9768778 | Regulation of NPAS4 mRNA translation | 6.110756e-01 | 0.214 |
| R-HSA-8939242 | RUNX1 regulates transcription of genes involved in differentiation of keratinocy... | 6.110756e-01 | 0.214 |
| R-HSA-164940 | Nef mediated downregulation of MHC class I complex cell surface expression | 6.110756e-01 | 0.214 |
| R-HSA-8866904 | Negative regulation of activity of TFAP2 (AP-2) family transcription factors | 6.110756e-01 | 0.214 |
| R-HSA-444473 | Formyl peptide receptors bind formyl peptides and many other ligands | 6.110756e-01 | 0.214 |
| R-HSA-9927354 | Co-stimulation by ICOS | 6.110756e-01 | 0.214 |
| R-HSA-3785653 | Myoclonic epilepsy of Lafora | 6.110756e-01 | 0.214 |
| R-HSA-8985947 | Interleukin-9 signaling | 6.110756e-01 | 0.214 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 6.110756e-01 | 0.214 |
| R-HSA-9637628 | Modulation by Mtb of host immune system | 6.110756e-01 | 0.214 |
| R-HSA-351906 | Apoptotic cleavage of cell adhesion proteins | 6.110756e-01 | 0.214 |
| R-HSA-9020933 | Interleukin-23 signaling | 6.110756e-01 | 0.214 |
| R-HSA-983712 | Ion channel transport | 6.127612e-01 | 0.213 |
| R-HSA-5694530 | Cargo concentration in the ER | 6.152303e-01 | 0.211 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 6.152303e-01 | 0.211 |
| R-HSA-9659379 | Sensory processing of sound | 6.178050e-01 | 0.209 |
| R-HSA-72766 | Translation | 6.267102e-01 | 0.203 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 6.273919e-01 | 0.202 |
| R-HSA-9734767 | Developmental Cell Lineages | 6.319450e-01 | 0.199 |
| R-HSA-5654221 | Phospholipase C-mediated cascade; FGFR2 | 6.321858e-01 | 0.199 |
| R-HSA-9823730 | Formation of definitive endoderm | 6.321858e-01 | 0.199 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 6.321858e-01 | 0.199 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 6.321858e-01 | 0.199 |
| R-HSA-140875 | Common Pathway of Fibrin Clot Formation | 6.321858e-01 | 0.199 |
| R-HSA-9629569 | Protein hydroxylation | 6.321858e-01 | 0.199 |
| R-HSA-421270 | Cell-cell junction organization | 6.323156e-01 | 0.199 |
| R-HSA-9937080 | Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 6.330370e-01 | 0.199 |
| R-HSA-110330 | Recognition and association of DNA glycosylase with site containing an affected ... | 6.330370e-01 | 0.199 |
| R-HSA-350562 | Regulation of ornithine decarboxylase (ODC) | 6.330370e-01 | 0.199 |
| R-HSA-5654743 | Signaling by FGFR4 | 6.369030e-01 | 0.196 |
| R-HSA-5387390 | Hh mutants abrogate ligand secretion | 6.369030e-01 | 0.196 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 6.369030e-01 | 0.196 |
| R-HSA-8854214 | TBC/RABGAPs | 6.369030e-01 | 0.196 |
| R-HSA-9818032 | NFE2L2 regulating MDR associated enzymes | 6.430838e-01 | 0.192 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 6.430838e-01 | 0.192 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 6.430838e-01 | 0.192 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 6.430838e-01 | 0.192 |
| R-HSA-5649702 | APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement P... | 6.430838e-01 | 0.192 |
| R-HSA-9020958 | Interleukin-21 signaling | 6.430838e-01 | 0.192 |
| R-HSA-75072 | mRNA Editing | 6.430838e-01 | 0.192 |
| R-HSA-170984 | ARMS-mediated activation | 6.430838e-01 | 0.192 |
| R-HSA-1433617 | Regulation of signaling by NODAL | 6.430838e-01 | 0.192 |
| R-HSA-201688 | WNT mediated activation of DVL | 6.430838e-01 | 0.192 |
| R-HSA-3323169 | Defects in biotin (Btn) metabolism | 6.430838e-01 | 0.192 |
| R-HSA-418889 | Caspase activation via Dependence Receptors in the absence of ligand | 6.430838e-01 | 0.192 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 6.430838e-01 | 0.192 |
| R-HSA-9925563 | Developmental Lineage of Pancreatic Ductal Cells | 6.470552e-01 | 0.189 |
| R-HSA-1855204 | Synthesis of IP3 and IP4 in the cytosol | 6.502623e-01 | 0.187 |
| R-HSA-375280 | Amine ligand-binding receptors | 6.517880e-01 | 0.186 |
| R-HSA-111885 | Opioid Signalling | 6.530807e-01 | 0.185 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 6.532536e-01 | 0.185 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 6.532536e-01 | 0.185 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 6.532536e-01 | 0.185 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 6.532536e-01 | 0.185 |
| R-HSA-202040 | G-protein activation | 6.532536e-01 | 0.185 |
| R-HSA-190241 | FGFR2 ligand binding and activation | 6.532536e-01 | 0.185 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 6.532536e-01 | 0.185 |
| R-HSA-9636383 | Prevention of phagosomal-lysosomal fusion | 6.532536e-01 | 0.185 |
| R-HSA-167044 | Signalling to RAS | 6.532536e-01 | 0.185 |
| R-HSA-210991 | Basigin interactions | 6.532536e-01 | 0.185 |
| R-HSA-2979096 | NOTCH2 Activation and Transmission of Signal to the Nucleus | 6.532536e-01 | 0.185 |
| R-HSA-162594 | Early Phase of HIV Life Cycle | 6.532536e-01 | 0.185 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 6.635098e-01 | 0.178 |
| R-HSA-5654741 | Signaling by FGFR3 | 6.662598e-01 | 0.176 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 6.662598e-01 | 0.176 |
| R-HSA-390522 | Striated Muscle Contraction | 6.669026e-01 | 0.176 |
| R-HSA-6782135 | Dual incision in TC-NER | 6.680097e-01 | 0.175 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 6.724594e-01 | 0.172 |
| R-HSA-2468052 | Establishment of Sister Chromatid Cohesion | 6.724594e-01 | 0.172 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 6.724594e-01 | 0.172 |
| R-HSA-198203 | PI3K/AKT activation | 6.724594e-01 | 0.172 |
| R-HSA-164843 | 2-LTR circle formation | 6.724594e-01 | 0.172 |
| R-HSA-9693928 | Defective RIPK1-mediated regulated necrosis | 6.724594e-01 | 0.172 |
| R-HSA-9762292 | Regulation of CDH11 function | 6.724594e-01 | 0.172 |
| R-HSA-5689877 | Josephin domain DUBs | 6.724594e-01 | 0.172 |
| R-HSA-74749 | Signal attenuation | 6.724594e-01 | 0.172 |
| R-HSA-1236973 | Cross-presentation of particulate exogenous antigens (phagosomes) | 6.724594e-01 | 0.172 |
| R-HSA-426048 | Arachidonate production from DAG | 6.724594e-01 | 0.172 |
| R-HSA-9020956 | Interleukin-27 signaling | 6.724594e-01 | 0.172 |
| R-HSA-1300642 | Sperm Motility And Taxes | 6.724594e-01 | 0.172 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 6.724594e-01 | 0.172 |
| R-HSA-2586552 | Signaling by Leptin | 6.724594e-01 | 0.172 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 6.733470e-01 | 0.172 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 6.733470e-01 | 0.172 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 6.733470e-01 | 0.172 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 6.733470e-01 | 0.172 |
| R-HSA-8949215 | Mitochondrial calcium ion transport | 6.733470e-01 | 0.172 |
| R-HSA-175474 | Assembly Of The HIV Virion | 6.733470e-01 | 0.172 |
| R-HSA-977347 | Serine metabolism | 6.733470e-01 | 0.172 |
| R-HSA-9671555 | Signaling by PDGFR in disease | 6.733470e-01 | 0.172 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 6.733470e-01 | 0.172 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 6.743985e-01 | 0.171 |
| R-HSA-174084 | Autodegradation of Cdh1 by Cdh1:APC/C | 6.803145e-01 | 0.167 |
| R-HSA-9660826 | Purinergic signaling in leishmaniasis infection | 6.803145e-01 | 0.167 |
| R-HSA-9664424 | Cell recruitment (pro-inflammatory response) | 6.803145e-01 | 0.167 |
| R-HSA-5696400 | Dual Incision in GG-NER | 6.829571e-01 | 0.166 |
| R-HSA-983170 | Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 6.829571e-01 | 0.166 |
| R-HSA-1980145 | Signaling by NOTCH2 | 6.829571e-01 | 0.166 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 6.850645e-01 | 0.164 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 6.861343e-01 | 0.164 |
| R-HSA-70326 | Glucose metabolism | 6.861922e-01 | 0.164 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 6.924835e-01 | 0.160 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 6.924835e-01 | 0.160 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 6.924835e-01 | 0.160 |
| R-HSA-166208 | mTORC1-mediated signalling | 6.924835e-01 | 0.160 |
| R-HSA-9669938 | Signaling by KIT in disease | 6.924835e-01 | 0.160 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 6.929308e-01 | 0.159 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 6.929308e-01 | 0.159 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 6.955051e-01 | 0.158 |
| R-HSA-195721 | Signaling by WNT | 6.975817e-01 | 0.156 |
| R-HSA-1296071 | Potassium Channels | 6.979138e-01 | 0.156 |
| R-HSA-917977 | Transferrin endocytosis and recycling | 6.984274e-01 | 0.156 |
| R-HSA-381042 | PERK regulates gene expression | 6.984274e-01 | 0.156 |
| R-HSA-9759811 | Regulation of CDH11 mRNA translation by microRNAs | 6.994190e-01 | 0.155 |
| R-HSA-190377 | FGFR2b ligand binding and activation | 6.994190e-01 | 0.155 |
| R-HSA-5658623 | FGFRL1 modulation of FGFR1 signaling | 6.994190e-01 | 0.155 |
| R-HSA-192905 | vRNP Assembly | 6.994190e-01 | 0.155 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 6.994190e-01 | 0.155 |
| R-HSA-8963888 | Chylomicron assembly | 6.994190e-01 | 0.155 |
| R-HSA-210747 | Regulation of gene expression in early pancreatic precursor cells | 6.994190e-01 | 0.155 |
| R-HSA-425381 | Bicarbonate transporters | 6.994190e-01 | 0.155 |
| R-HSA-427601 | Inorganic anion exchange by SLC26 transporters | 6.994190e-01 | 0.155 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 6.994190e-01 | 0.155 |
| R-HSA-9635465 | Suppression of apoptosis | 6.994190e-01 | 0.155 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 6.994190e-01 | 0.155 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 7.006515e-01 | 0.154 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 7.047058e-01 | 0.152 |
| R-HSA-1222556 | ROS and RNS production in phagocytes | 7.047058e-01 | 0.152 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 7.049002e-01 | 0.152 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 7.057179e-01 | 0.151 |
| R-HSA-157579 | Telomere Maintenance | 7.074746e-01 | 0.150 |
| R-HSA-8943723 | Regulation of PTEN mRNA translation | 7.106845e-01 | 0.148 |
| R-HSA-9648895 | Response of EIF2AK1 (HRI) to heme deficiency | 7.106845e-01 | 0.148 |
| R-HSA-9018682 | Biosynthesis of maresins | 7.106845e-01 | 0.148 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 7.106845e-01 | 0.148 |
| R-HSA-200425 | Carnitine shuttle | 7.106845e-01 | 0.148 |
| R-HSA-9830674 | Formation of the ureteric bud | 7.106845e-01 | 0.148 |
| R-HSA-8941326 | RUNX2 regulates bone development | 7.133174e-01 | 0.147 |
| R-HSA-114604 | GPVI-mediated activation cascade | 7.133174e-01 | 0.147 |
| R-HSA-8852135 | Protein ubiquitination | 7.154332e-01 | 0.145 |
| R-HSA-917937 | Iron uptake and transport | 7.154332e-01 | 0.145 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 7.154332e-01 | 0.145 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 7.165402e-01 | 0.145 |
| R-HSA-113501 | Inhibition of replication initiation of damaged DNA by RB1/E2F1 | 7.241609e-01 | 0.140 |
| R-HSA-75896 | Plasmalogen biosynthesis | 7.241609e-01 | 0.140 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 7.241609e-01 | 0.140 |
| R-HSA-110362 | POLB-Dependent Long Patch Base Excision Repair | 7.241609e-01 | 0.140 |
| R-HSA-162592 | Integration of provirus | 7.241609e-01 | 0.140 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 7.241609e-01 | 0.140 |
| R-HSA-9645723 | Diseases of programmed cell death | 7.254535e-01 | 0.139 |
| R-HSA-9614085 | FOXO-mediated transcription | 7.259963e-01 | 0.139 |
| R-HSA-1296072 | Voltage gated Potassium channels | 7.276329e-01 | 0.138 |
| R-HSA-110331 | Cleavage of the damaged purine | 7.276329e-01 | 0.138 |
| R-HSA-196757 | Metabolism of folate and pterines | 7.276329e-01 | 0.138 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 7.279744e-01 | 0.138 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 7.279744e-01 | 0.138 |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants | 7.279744e-01 | 0.138 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 7.368891e-01 | 0.133 |
| R-HSA-211981 | Xenobiotics | 7.388313e-01 | 0.131 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 7.413814e-01 | 0.130 |
| R-HSA-73927 | Depurination | 7.413814e-01 | 0.130 |
| R-HSA-73884 | Base Excision Repair | 7.442626e-01 | 0.128 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 7.443797e-01 | 0.128 |
| R-HSA-1296041 | Activation of G protein gated Potassium channels | 7.443797e-01 | 0.128 |
| R-HSA-1296059 | G protein gated Potassium channels | 7.443797e-01 | 0.128 |
| R-HSA-997272 | Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits | 7.443797e-01 | 0.128 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 7.443797e-01 | 0.128 |
| R-HSA-5601884 | PIWI-interacting RNA (piRNA) biogenesis | 7.443797e-01 | 0.128 |
| R-HSA-1266695 | Interleukin-7 signaling | 7.443797e-01 | 0.128 |
| R-HSA-983168 | Antigen processing: Ubiquitination & Proteasome degradation | 7.455573e-01 | 0.128 |
| R-HSA-5619084 | ABC transporter disorders | 7.459842e-01 | 0.127 |
| R-HSA-9865114 | Maple Syrup Urine Disease | 7.468677e-01 | 0.127 |
| R-HSA-9820865 | Z-decay: degradation of maternal mRNAs by zygotically expressed factors | 7.468677e-01 | 0.127 |
| R-HSA-3000484 | Scavenging by Class F Receptors | 7.468677e-01 | 0.127 |
| R-HSA-77285 | Beta oxidation of myristoyl-CoA to lauroyl-CoA | 7.468677e-01 | 0.127 |
| R-HSA-77305 | Beta oxidation of palmitoyl-CoA to myristoyl-CoA | 7.468677e-01 | 0.127 |
| R-HSA-380615 | Serotonin clearance from the synaptic cleft | 7.468677e-01 | 0.127 |
| R-HSA-8984722 | Interleukin-35 Signalling | 7.468677e-01 | 0.127 |
| R-HSA-73943 | Reversal of alkylation damage by DNA dioxygenases | 7.468677e-01 | 0.127 |
| R-HSA-9617629 | Regulation of FOXO transcriptional activity by acetylation | 7.468677e-01 | 0.127 |
| R-HSA-1679131 | Trafficking and processing of endosomal TLR | 7.468677e-01 | 0.127 |
| R-HSA-446205 | Synthesis of GDP-mannose | 7.468677e-01 | 0.127 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 7.468677e-01 | 0.127 |
| R-HSA-2197563 | NOTCH2 intracellular domain regulates transcription | 7.468677e-01 | 0.127 |
| R-HSA-1247673 | Erythrocytes take up oxygen and release carbon dioxide | 7.468677e-01 | 0.127 |
| R-HSA-4641265 | Repression of WNT target genes | 7.468677e-01 | 0.127 |
| R-HSA-9842663 | Signaling by LTK | 7.468677e-01 | 0.127 |
| R-HSA-9609690 | HCMV Early Events | 7.491783e-01 | 0.125 |
| R-HSA-1483255 | PI Metabolism | 7.522648e-01 | 0.124 |
| R-HSA-1236978 | Cross-presentation of soluble exogenous antigens (endosomes) | 7.545721e-01 | 0.122 |
| R-HSA-8964043 | Plasma lipoprotein clearance | 7.545721e-01 | 0.122 |
| R-HSA-72187 | mRNA 3'-end processing | 7.558460e-01 | 0.122 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 7.558460e-01 | 0.122 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 7.599289e-01 | 0.119 |
| R-HSA-3295583 | TRP channels | 7.599289e-01 | 0.119 |
| R-HSA-1660514 | Synthesis of PIPs at the Golgi membrane | 7.599289e-01 | 0.119 |
| R-HSA-9845614 | Sphingolipid catabolism | 7.599289e-01 | 0.119 |
| R-HSA-381070 | IRE1alpha activates chaperones | 7.621437e-01 | 0.118 |
| R-HSA-6806834 | Signaling by MET | 7.649942e-01 | 0.116 |
| R-HSA-9639288 | Amino acids regulate mTORC1 | 7.669880e-01 | 0.115 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 7.669880e-01 | 0.115 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 7.672152e-01 | 0.115 |
| R-HSA-9861559 | PDH complex synthesizes acetyl-CoA from PYR | 7.677065e-01 | 0.115 |
| R-HSA-8949664 | Processing of SMDT1 | 7.677065e-01 | 0.115 |
| R-HSA-9796292 | Formation of axial mesoderm | 7.677065e-01 | 0.115 |
| R-HSA-2559584 | Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 7.677065e-01 | 0.115 |
| R-HSA-5676594 | TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway | 7.677065e-01 | 0.115 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 7.677065e-01 | 0.115 |
| R-HSA-1475029 | Reversible hydration of carbon dioxide | 7.677065e-01 | 0.115 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 7.677065e-01 | 0.115 |
| R-HSA-9683610 | Maturation of nucleoprotein | 7.677065e-01 | 0.115 |
| R-HSA-9682706 | Replication of the SARS-CoV-1 genome | 7.677065e-01 | 0.115 |
| R-HSA-9830369 | Kidney development | 7.698135e-01 | 0.114 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 7.704794e-01 | 0.113 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 7.746518e-01 | 0.111 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 7.746518e-01 | 0.111 |
| R-HSA-171306 | Packaging Of Telomere Ends | 7.746518e-01 | 0.111 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 7.746518e-01 | 0.111 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 7.746518e-01 | 0.111 |
| R-HSA-1483213 | Synthesis of PE | 7.746518e-01 | 0.111 |
| R-HSA-6803204 | TP53 Regulates Transcription of Genes Involved in Cytochrome C Release | 7.746518e-01 | 0.111 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 7.746518e-01 | 0.111 |
| R-HSA-193807 | Synthesis of bile acids and bile salts via 27-hydroxycholesterol | 7.746518e-01 | 0.111 |
| R-HSA-114608 | Platelet degranulation | 7.747217e-01 | 0.111 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 7.777283e-01 | 0.109 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 7.793222e-01 | 0.108 |
| R-HSA-8853884 | Transcriptional Regulation by VENTX | 7.793222e-01 | 0.108 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 7.794958e-01 | 0.108 |
| R-HSA-5696398 | Nucleotide Excision Repair | 7.844570e-01 | 0.105 |
| R-HSA-9859138 | BCKDH synthesizes BCAA-CoA from KIC, KMVA, KIV | 7.868309e-01 | 0.104 |
| R-HSA-9764562 | Regulation of CDH1 mRNA translation by microRNAs | 7.868309e-01 | 0.104 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 7.868309e-01 | 0.104 |
| R-HSA-1855191 | Synthesis of IPs in the nucleus | 7.868309e-01 | 0.104 |
| R-HSA-77350 | Beta oxidation of hexanoyl-CoA to butanoyl-CoA | 7.868309e-01 | 0.104 |
| R-HSA-77310 | Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA | 7.868309e-01 | 0.104 |
| R-HSA-77348 | Beta oxidation of octanoyl-CoA to hexanoyl-CoA | 7.868309e-01 | 0.104 |
| R-HSA-196843 | Vitamin B2 (riboflavin) metabolism | 7.868309e-01 | 0.104 |
| R-HSA-173599 | Formation of the active cofactor, UDP-glucuronate | 7.868309e-01 | 0.104 |
| R-HSA-6814848 | Glycerophospholipid catabolism | 7.868309e-01 | 0.104 |
| R-HSA-9828642 | Respiratory syncytial virus genome transcription | 7.868309e-01 | 0.104 |
| R-HSA-1482798 | Acyl chain remodeling of CL | 7.868309e-01 | 0.104 |
| R-HSA-435354 | Zinc transporters | 7.868309e-01 | 0.104 |
| R-HSA-9679514 | SARS-CoV-1 Genome Replication and Transcription | 7.868309e-01 | 0.104 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 7.872369e-01 | 0.104 |
| R-HSA-1474290 | Collagen formation | 7.872369e-01 | 0.104 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 7.885789e-01 | 0.103 |
| R-HSA-171319 | Telomere Extension By Telomerase | 7.885789e-01 | 0.103 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 7.885789e-01 | 0.103 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 7.885789e-01 | 0.103 |
| R-HSA-5620971 | Pyroptosis | 7.885789e-01 | 0.103 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 7.909055e-01 | 0.102 |
| R-HSA-167161 | HIV Transcription Initiation | 7.909055e-01 | 0.102 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 7.909055e-01 | 0.102 |
| R-HSA-442660 | SLC-mediated transport of neurotransmitters | 7.909055e-01 | 0.102 |
| R-HSA-418346 | Platelet homeostasis | 7.920033e-01 | 0.101 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 7.946047e-01 | 0.100 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 7.979136e-01 | 0.098 |
| R-HSA-5654736 | Signaling by FGFR1 | 7.980296e-01 | 0.098 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 8.017415e-01 | 0.096 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 8.017415e-01 | 0.096 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 8.017415e-01 | 0.096 |
| R-HSA-204174 | Regulation of pyruvate dehydrogenase (PDH) complex | 8.017415e-01 | 0.096 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 8.019783e-01 | 0.096 |
| R-HSA-73942 | DNA Damage Reversal | 8.043818e-01 | 0.095 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 8.043818e-01 | 0.095 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 8.043818e-01 | 0.095 |
| R-HSA-379401 | Dopamine clearance from the synaptic cleft | 8.043818e-01 | 0.095 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 8.043818e-01 | 0.095 |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 8.043818e-01 | 0.095 |
| R-HSA-69183 | Processive synthesis on the lagging strand | 8.043818e-01 | 0.095 |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants | 8.043818e-01 | 0.095 |
| R-HSA-8876725 | Protein methylation | 8.043818e-01 | 0.095 |
| R-HSA-2672351 | Stimuli-sensing channels | 8.065024e-01 | 0.093 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 8.066579e-01 | 0.093 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 8.125544e-01 | 0.090 |
| R-HSA-1433557 | Signaling by SCF-KIT | 8.125544e-01 | 0.090 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 8.141710e-01 | 0.089 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 8.141710e-01 | 0.089 |
| R-HSA-2424491 | DAP12 signaling | 8.141710e-01 | 0.089 |
| R-HSA-112311 | Neurotransmitter clearance | 8.141710e-01 | 0.089 |
| R-HSA-888590 | GABA synthesis, release, reuptake and degradation | 8.141710e-01 | 0.089 |
| R-HSA-168249 | Innate Immune System | 8.176222e-01 | 0.087 |
| R-HSA-112315 | Transmission across Chemical Synapses | 8.201928e-01 | 0.086 |
| R-HSA-168275 | Entry of Influenza Virion into Host Cell via Endocytosis | 8.204887e-01 | 0.086 |
| R-HSA-9687136 | Aberrant regulation of mitotic exit in cancer due to RB1 defects | 8.204887e-01 | 0.086 |
| R-HSA-176412 | Phosphorylation of the APC/C | 8.204887e-01 | 0.086 |
| R-HSA-9754706 | Atorvastatin ADME | 8.204887e-01 | 0.086 |
| R-HSA-2485179 | Activation of the phototransduction cascade | 8.204887e-01 | 0.086 |
| R-HSA-70350 | Fructose catabolism | 8.204887e-01 | 0.086 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 8.204887e-01 | 0.086 |
| R-HSA-399955 | SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 8.204887e-01 | 0.086 |
| R-HSA-9708530 | Regulation of BACH1 activity | 8.204887e-01 | 0.086 |
| R-HSA-5635838 | Activation of SMO | 8.204887e-01 | 0.086 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 8.209313e-01 | 0.086 |
| R-HSA-8951664 | Neddylation | 8.220017e-01 | 0.085 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 8.220510e-01 | 0.085 |
| R-HSA-9907900 | Proteasome assembly | 8.226480e-01 | 0.085 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 8.226480e-01 | 0.085 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 8.231983e-01 | 0.084 |
| R-HSA-2022090 | Assembly of collagen fibrils and other multimeric structures | 8.256435e-01 | 0.083 |
| R-HSA-2129379 | Molecules associated with elastic fibres | 8.258989e-01 | 0.083 |
| R-HSA-399719 | Trafficking of AMPA receptors | 8.258989e-01 | 0.083 |
| R-HSA-186763 | Downstream signal transduction | 8.258989e-01 | 0.083 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 8.322739e-01 | 0.080 |
| R-HSA-6783310 | Fanconi Anemia Pathway | 8.322739e-01 | 0.080 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 8.341242e-01 | 0.079 |
| R-HSA-351202 | Metabolism of polyamines | 8.341242e-01 | 0.079 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 8.352703e-01 | 0.078 |
| R-HSA-9912633 | Antigen processing: Ub, ATP-independent proteasomal degradation | 8.352703e-01 | 0.078 |
| R-HSA-8964616 | G beta:gamma signalling through CDC42 | 8.352703e-01 | 0.078 |
| R-HSA-77595 | Processing of Intronless Pre-mRNAs | 8.352703e-01 | 0.078 |
| R-HSA-9927020 | Heme assimilation | 8.352703e-01 | 0.078 |
| R-HSA-77288 | mitochondrial fatty acid beta-oxidation of unsaturated fatty acids | 8.352703e-01 | 0.078 |
| R-HSA-196783 | Coenzyme A biosynthesis | 8.352703e-01 | 0.078 |
| R-HSA-1483148 | Synthesis of PG | 8.352703e-01 | 0.078 |
| R-HSA-77346 | Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA | 8.352703e-01 | 0.078 |
| R-HSA-9609646 | HCMV Infection | 8.361984e-01 | 0.078 |
| R-HSA-1296065 | Inwardly rectifying K+ channels | 8.369563e-01 | 0.077 |
| R-HSA-4791275 | Signaling by WNT in cancer | 8.369563e-01 | 0.077 |
| R-HSA-5633008 | TP53 Regulates Transcription of Cell Death Genes | 8.386570e-01 | 0.076 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 8.414471e-01 | 0.075 |
| R-HSA-73856 | RNA Polymerase II Transcription Termination | 8.422576e-01 | 0.075 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 8.443665e-01 | 0.073 |
| R-HSA-9758941 | Gastrulation | 8.466712e-01 | 0.072 |
| R-HSA-159418 | Recycling of bile acids and salts | 8.473742e-01 | 0.072 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 8.473742e-01 | 0.072 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 8.488355e-01 | 0.071 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 8.488355e-01 | 0.071 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 8.488355e-01 | 0.071 |
| R-HSA-4641263 | Regulation of FZD by ubiquitination | 8.488355e-01 | 0.071 |
| R-HSA-176407 | Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase | 8.488355e-01 | 0.071 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 8.488355e-01 | 0.071 |
| R-HSA-139853 | Elevation of cytosolic Ca2+ levels | 8.488355e-01 | 0.071 |
| R-HSA-9768759 | Regulation of NPAS4 gene expression | 8.488355e-01 | 0.071 |
| R-HSA-3229121 | Glycogen storage diseases | 8.488355e-01 | 0.071 |
| R-HSA-9694686 | Replication of the SARS-CoV-2 genome | 8.488355e-01 | 0.071 |
| R-HSA-1268020 | Mitochondrial protein import | 8.500528e-01 | 0.071 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 8.500528e-01 | 0.071 |
| R-HSA-186797 | Signaling by PDGF | 8.500528e-01 | 0.071 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 8.501826e-01 | 0.070 |
| R-HSA-1483191 | Synthesis of PC | 8.501826e-01 | 0.070 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 8.571829e-01 | 0.067 |
| R-HSA-9818027 | NFE2L2 regulating anti-oxidant/detoxification enzymes | 8.571829e-01 | 0.067 |
| R-HSA-199220 | Vitamin B5 (pantothenate) metabolism | 8.571829e-01 | 0.067 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 8.584958e-01 | 0.066 |
| R-HSA-418217 | G beta:gamma signalling through PLC beta | 8.612843e-01 | 0.065 |
| R-HSA-2564830 | Cytosolic iron-sulfur cluster assembly | 8.612843e-01 | 0.065 |
| R-HSA-181429 | Serotonin Neurotransmitter Release Cycle | 8.612843e-01 | 0.065 |
| R-HSA-500657 | Presynaptic function of Kainate receptors | 8.612843e-01 | 0.065 |
| R-HSA-163615 | PKA activation | 8.612843e-01 | 0.065 |
| R-HSA-9614657 | FOXO-mediated transcription of cell death genes | 8.612843e-01 | 0.065 |
| R-HSA-111471 | Apoptotic factor-mediated response | 8.612843e-01 | 0.065 |
| R-HSA-428643 | Organic anion transport by SLC5/17/25 transporters | 8.612843e-01 | 0.065 |
| R-HSA-2142700 | Biosynthesis of Lipoxins (LX) | 8.612843e-01 | 0.065 |
| R-HSA-3928664 | Ephrin signaling | 8.612843e-01 | 0.065 |
| R-HSA-180292 | GAB1 signalosome | 8.612843e-01 | 0.065 |
| R-HSA-9679504 | Translation of Replicase and Assembly of the Replication Transcription Complex | 8.612843e-01 | 0.065 |
| R-HSA-9927426 | Developmental Lineage of Mammary Gland Alveolar Cells | 8.664120e-01 | 0.062 |
| R-HSA-203615 | eNOS activation | 8.664120e-01 | 0.062 |
| R-HSA-901042 | Calnexin/calreticulin cycle | 8.664120e-01 | 0.062 |
| R-HSA-110328 | Recognition and association of DNA glycosylase with site containing an affected ... | 8.664120e-01 | 0.062 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 8.693320e-01 | 0.061 |
| R-HSA-5654738 | Signaling by FGFR2 | 8.724028e-01 | 0.059 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 8.724028e-01 | 0.059 |
| R-HSA-167242 | Abortive elongation of HIV-1 transcript in the absence of Tat | 8.727087e-01 | 0.059 |
| R-HSA-392851 | Prostacyclin signalling through prostacyclin receptor | 8.727087e-01 | 0.059 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 8.727087e-01 | 0.059 |
| R-HSA-500753 | Pyrimidine biosynthesis | 8.727087e-01 | 0.059 |
| R-HSA-9834899 | Specification of the neural plate border | 8.727087e-01 | 0.059 |
| R-HSA-429958 | mRNA decay by 3' to 5' exoribonuclease | 8.727087e-01 | 0.059 |
| R-HSA-1237044 | Erythrocytes take up carbon dioxide and release oxygen | 8.727087e-01 | 0.059 |
| R-HSA-1480926 | O2/CO2 exchange in erythrocytes | 8.727087e-01 | 0.059 |
| R-HSA-9913635 | Strand-asynchronous mitochondrial DNA replication | 8.727087e-01 | 0.059 |
| R-HSA-392517 | Rap1 signalling | 8.727087e-01 | 0.059 |
| R-HSA-2243919 | Crosslinking of collagen fibrils | 8.727087e-01 | 0.059 |
| R-HSA-9694631 | Maturation of nucleoprotein | 8.727087e-01 | 0.059 |
| R-HSA-9694682 | SARS-CoV-2 Genome Replication and Transcription | 8.727087e-01 | 0.059 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 8.750905e-01 | 0.058 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 8.750905e-01 | 0.058 |
| R-HSA-9909620 | Regulation of PD-L1(CD274) translation | 8.831928e-01 | 0.054 |
| R-HSA-163210 | Formation of ATP by chemiosmotic coupling | 8.831928e-01 | 0.054 |
| R-HSA-1362409 | Mitochondrial iron-sulfur cluster biogenesis | 8.831928e-01 | 0.054 |
| R-HSA-8848584 | Wax and plasmalogen biosynthesis | 8.831928e-01 | 0.054 |
| R-HSA-3322077 | Glycogen synthesis | 8.831928e-01 | 0.054 |
| R-HSA-5662702 | Melanin biosynthesis | 8.831928e-01 | 0.054 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 8.832463e-01 | 0.054 |
| R-HSA-140877 | Formation of Fibrin Clot (Clotting Cascade) | 8.832463e-01 | 0.054 |
| R-HSA-749476 | RNA Polymerase III Abortive And Retractive Initiation | 8.832463e-01 | 0.054 |
| R-HSA-74158 | RNA Polymerase III Transcription | 8.832463e-01 | 0.054 |
| R-HSA-9610379 | HCMV Late Events | 8.837748e-01 | 0.054 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 8.841228e-01 | 0.053 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 8.871520e-01 | 0.052 |
| R-HSA-8866654 | E3 ubiquitin ligases ubiquitinate target proteins | 8.878281e-01 | 0.052 |
| R-HSA-167172 | Transcription of the HIV genome | 8.902558e-01 | 0.050 |
| R-HSA-392170 | ADP signalling through P2Y purinoceptor 12 | 8.928139e-01 | 0.049 |
| R-HSA-264642 | Acetylcholine Neurotransmitter Release Cycle | 8.928139e-01 | 0.049 |
| R-HSA-9824594 | Regulation of MITF-M-dependent genes involved in apoptosis | 8.928139e-01 | 0.049 |
| R-HSA-111931 | PKA-mediated phosphorylation of CREB | 8.928139e-01 | 0.049 |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane | 8.928139e-01 | 0.049 |
| R-HSA-9819196 | Zygotic genome activation (ZGA) | 8.928139e-01 | 0.049 |
| R-HSA-196836 | Vitamin C (ascorbate) metabolism | 8.928139e-01 | 0.049 |
| R-HSA-8956320 | Nucleotide biosynthesis | 8.942560e-01 | 0.049 |
| R-HSA-1566948 | Elastic fibre formation | 8.980980e-01 | 0.047 |
| R-HSA-9958790 | SLC-mediated transport of inorganic anions | 8.980980e-01 | 0.047 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 9.003417e-01 | 0.046 |
| R-HSA-73929 | Base-Excision Repair, AP Site Formation | 9.003511e-01 | 0.046 |
| R-HSA-174403 | Glutathione synthesis and recycling | 9.016431e-01 | 0.045 |
| R-HSA-9755088 | Ribavirin ADME | 9.016431e-01 | 0.045 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 9.048454e-01 | 0.043 |
| R-HSA-71336 | Pentose phosphate pathway | 9.048454e-01 | 0.043 |
| R-HSA-163685 | Integration of energy metabolism | 9.071383e-01 | 0.042 |
| R-HSA-6803529 | FGFR2 alternative splicing | 9.097455e-01 | 0.041 |
| R-HSA-6803205 | TP53 regulates transcription of several additional cell death genes whose specif... | 9.097455e-01 | 0.041 |
| R-HSA-189200 | Cellular hexose transport | 9.097455e-01 | 0.041 |
| R-HSA-8964038 | LDL clearance | 9.097455e-01 | 0.041 |
| R-HSA-5652084 | Fructose metabolism | 9.097455e-01 | 0.041 |
| R-HSA-6807062 | Cholesterol biosynthesis via lathosterol | 9.097455e-01 | 0.041 |
| R-HSA-9694676 | Translation of Replicase and Assembly of the Replication Transcription Complex | 9.097455e-01 | 0.041 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 9.111732e-01 | 0.040 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 9.111732e-01 | 0.040 |
| R-HSA-167169 | HIV Transcription Elongation | 9.111732e-01 | 0.040 |
| R-HSA-427389 | ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 9.111732e-01 | 0.040 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 9.111732e-01 | 0.040 |
| R-HSA-9854311 | Maturation of TCA enzymes and regulation of TCA cycle | 9.111732e-01 | 0.040 |
| R-HSA-379726 | Mitochondrial tRNA aminoacylation | 9.111732e-01 | 0.040 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 9.111732e-01 | 0.040 |
| R-HSA-382556 | ABC-family proteins mediated transport | 9.134774e-01 | 0.039 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 9.170007e-01 | 0.038 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 9.170964e-01 | 0.038 |
| R-HSA-9821002 | Chromatin modifications during the maternal to zygotic transition (MZT) | 9.171047e-01 | 0.038 |
| R-HSA-73817 | Purine ribonucleoside monophosphate biosynthesis | 9.171047e-01 | 0.038 |
| R-HSA-5423646 | Aflatoxin activation and detoxification | 9.171047e-01 | 0.038 |
| R-HSA-9694548 | Maturation of spike protein | 9.171047e-01 | 0.038 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 9.171809e-01 | 0.038 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 9.171809e-01 | 0.038 |
| R-HSA-8854691 | Interleukin-20 family signaling | 9.171809e-01 | 0.038 |
| R-HSA-446210 | Synthesis of UDP-N-acetyl-glucosamine | 9.171809e-01 | 0.038 |
| R-HSA-879518 | Organic anion transport by SLCO transporters | 9.171809e-01 | 0.038 |
| R-HSA-3000170 | Syndecan interactions | 9.171809e-01 | 0.038 |
| R-HSA-5619102 | SLC transporter disorders | 9.195253e-01 | 0.036 |
| R-HSA-1226099 | Signaling by FGFR in disease | 9.206907e-01 | 0.036 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 9.213123e-01 | 0.036 |
| R-HSA-201722 | Formation of the beta-catenin:TCF transactivating complex | 9.216808e-01 | 0.035 |
| R-HSA-9615017 | FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes | 9.226623e-01 | 0.035 |
| R-HSA-9683701 | Translation of Structural Proteins | 9.226623e-01 | 0.035 |
| R-HSA-211999 | CYP2E1 reactions | 9.240042e-01 | 0.034 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 9.240042e-01 | 0.034 |
| R-HSA-428930 | Thromboxane signalling through TP receptor | 9.240042e-01 | 0.034 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 9.240042e-01 | 0.034 |
| R-HSA-181430 | Norepinephrine Neurotransmitter Release Cycle | 9.240042e-01 | 0.034 |
| R-HSA-75067 | Processing of Capped Intronless Pre-mRNA | 9.240042e-01 | 0.034 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 9.240042e-01 | 0.034 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 9.250696e-01 | 0.034 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 9.278673e-01 | 0.033 |
| R-HSA-991365 | Activation of GABAB receptors | 9.278673e-01 | 0.033 |
| R-HSA-977444 | GABA B receptor activation | 9.278673e-01 | 0.033 |
| R-HSA-110329 | Cleavage of the damaged pyrimidine | 9.278673e-01 | 0.033 |
| R-HSA-73928 | Depyrimidination | 9.278673e-01 | 0.033 |
| R-HSA-420029 | Tight junction interactions | 9.302656e-01 | 0.031 |
| R-HSA-1187000 | Fertilization | 9.302656e-01 | 0.031 |
| R-HSA-3000157 | Laminin interactions | 9.302656e-01 | 0.031 |
| R-HSA-9694635 | Translation of Structural Proteins | 9.328690e-01 | 0.030 |
| R-HSA-211976 | Endogenous sterols | 9.348425e-01 | 0.029 |
| R-HSA-400042 | Adrenaline,noradrenaline inhibits insulin secretion | 9.360116e-01 | 0.029 |
| R-HSA-9865118 | Diseases of branched-chain amino acid catabolism | 9.360116e-01 | 0.029 |
| R-HSA-210500 | Glutamate Neurotransmitter Release Cycle | 9.360116e-01 | 0.029 |
| R-HSA-1855183 | Synthesis of IP2, IP, and Ins in the cytosol | 9.360116e-01 | 0.029 |
| R-HSA-216083 | Integrin cell surface interactions | 9.365357e-01 | 0.028 |
| R-HSA-191273 | Cholesterol biosynthesis | 9.365357e-01 | 0.028 |
| R-HSA-2172127 | DAP12 interactions | 9.372999e-01 | 0.028 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 9.387551e-01 | 0.027 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 9.400197e-01 | 0.027 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 9.412844e-01 | 0.026 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 9.412844e-01 | 0.026 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 9.412844e-01 | 0.026 |
| R-HSA-83936 | Transport of nucleosides and free purine and pyrimidine bases across the plasma ... | 9.412844e-01 | 0.026 |
| R-HSA-201451 | Signaling by BMP | 9.412844e-01 | 0.026 |
| R-HSA-901032 | ER Quality Control Compartment (ERQC) | 9.412844e-01 | 0.026 |
| R-HSA-75109 | Triglyceride biosynthesis | 9.412844e-01 | 0.026 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 9.415654e-01 | 0.026 |
| R-HSA-167287 | HIV elongation arrest and recovery | 9.461229e-01 | 0.024 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 9.461229e-01 | 0.024 |
| R-HSA-5576892 | Phase 0 - rapid depolarisation | 9.461229e-01 | 0.024 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 9.461229e-01 | 0.024 |
| R-HSA-380994 | ATF4 activates genes in response to endoplasmic reticulum stress | 9.461229e-01 | 0.024 |
| R-HSA-73614 | Pyrimidine salvage | 9.461229e-01 | 0.024 |
| R-HSA-9757110 | Prednisone ADME | 9.461229e-01 | 0.024 |
| R-HSA-6811440 | Retrograde transport at the Trans-Golgi-Network | 9.492825e-01 | 0.023 |
| R-HSA-5334118 | DNA methylation | 9.505631e-01 | 0.022 |
| R-HSA-72086 | mRNA Capping | 9.505631e-01 | 0.022 |
| R-HSA-209968 | Thyroxine biosynthesis | 9.505631e-01 | 0.022 |
| R-HSA-420092 | Glucagon-type ligand receptors | 9.505631e-01 | 0.022 |
| R-HSA-6809371 | Formation of the cornified envelope | 9.507201e-01 | 0.022 |
| R-HSA-70263 | Gluconeogenesis | 9.527664e-01 | 0.021 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 9.545890e-01 | 0.020 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 9.546375e-01 | 0.020 |
| R-HSA-532668 | N-glycan trimming in the ER and Calnexin/Calreticulin cycle | 9.560209e-01 | 0.020 |
| R-HSA-190236 | Signaling by FGFR | 9.563862e-01 | 0.019 |
| R-HSA-9609507 | Protein localization | 9.565487e-01 | 0.019 |
| R-HSA-1650814 | Collagen biosynthesis and modifying enzymes | 9.580070e-01 | 0.019 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 9.586481e-01 | 0.018 |
| R-HSA-9664407 | Parasite infection | 9.586481e-01 | 0.018 |
| R-HSA-9664417 | Leishmania phagocytosis | 9.586481e-01 | 0.018 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 9.590601e-01 | 0.018 |
| R-HSA-2162123 | Synthesis of Prostaglandins (PG) and Thromboxanes (TX) | 9.590601e-01 | 0.018 |
| R-HSA-9930044 | Nuclear RNA decay | 9.649555e-01 | 0.015 |
| R-HSA-8978934 | Metabolism of cofactors | 9.653488e-01 | 0.015 |
| R-HSA-499943 | Interconversion of nucleotide di- and triphosphates | 9.675145e-01 | 0.014 |
| R-HSA-109582 | Hemostasis | 9.676486e-01 | 0.014 |
| R-HSA-1474244 | Extracellular matrix organization | 9.677558e-01 | 0.014 |
| R-HSA-597592 | Post-translational protein modification | 9.677709e-01 | 0.014 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 9.678445e-01 | 0.014 |
| R-HSA-112310 | Neurotransmitter release cycle | 9.701687e-01 | 0.013 |
| R-HSA-5617472 | Activation of anterior HOX genes in hindbrain development during early embryogen... | 9.703086e-01 | 0.013 |
| R-HSA-5619507 | Activation of HOX genes during differentiation | 9.703086e-01 | 0.013 |
| R-HSA-392518 | Signal amplification | 9.704954e-01 | 0.013 |
| R-HSA-9843970 | Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex | 9.704954e-01 | 0.013 |
| R-HSA-5686938 | Regulation of TLR by endogenous ligand | 9.704954e-01 | 0.013 |
| R-HSA-1236394 | Signaling by ERBB4 | 9.714680e-01 | 0.013 |
| R-HSA-3214815 | HDACs deacetylate histones | 9.714686e-01 | 0.013 |
| R-HSA-418597 | G alpha (z) signalling events | 9.714686e-01 | 0.013 |
| R-HSA-9753281 | Paracetamol ADME | 9.714686e-01 | 0.013 |
| R-HSA-2408508 | Metabolism of ingested SeMet, Sec, MeSec into H2Se | 9.729280e-01 | 0.012 |
| R-HSA-3296482 | Defects in vitamin and cofactor metabolism | 9.729280e-01 | 0.012 |
| R-HSA-71403 | Citric acid cycle (TCA cycle) | 9.732695e-01 | 0.012 |
| R-HSA-8957322 | Metabolism of steroids | 9.746576e-01 | 0.011 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 9.750860e-01 | 0.011 |
| R-HSA-212300 | PRC2 methylates histones and DNA | 9.751601e-01 | 0.011 |
| R-HSA-8853659 | RET signaling | 9.751601e-01 | 0.011 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 9.758125e-01 | 0.011 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 9.765484e-01 | 0.010 |
| R-HSA-9772572 | Early SARS-CoV-2 Infection Events | 9.770783e-01 | 0.010 |
| R-HSA-427359 | SIRT1 negatively regulates rRNA expression | 9.772083e-01 | 0.010 |
| R-HSA-549127 | SLC-mediated transport of organic cations | 9.772083e-01 | 0.010 |
| R-HSA-9033241 | Peroxisomal protein import | 9.786988e-01 | 0.009 |
| R-HSA-352230 | Amino acid transport across the plasma membrane | 9.786988e-01 | 0.009 |
| R-HSA-8875878 | MET promotes cell motility | 9.790877e-01 | 0.009 |
| R-HSA-8873719 | RAB geranylgeranylation | 9.802081e-01 | 0.009 |
| R-HSA-977443 | GABA receptor activation | 9.802081e-01 | 0.009 |
| R-HSA-156590 | Glutathione conjugation | 9.802081e-01 | 0.009 |
| R-HSA-445717 | Aquaporin-mediated transport | 9.816134e-01 | 0.008 |
| R-HSA-418555 | G alpha (s) signalling events | 9.819165e-01 | 0.008 |
| R-HSA-977225 | Amyloid fiber formation | 9.820060e-01 | 0.008 |
| R-HSA-451927 | Interleukin-2 family signaling | 9.823947e-01 | 0.008 |
| R-HSA-71240 | Tryptophan catabolism | 9.823947e-01 | 0.008 |
| R-HSA-8982491 | Glycogen metabolism | 9.823947e-01 | 0.008 |
| R-HSA-1483257 | Phospholipid metabolism | 9.849897e-01 | 0.007 |
| R-HSA-3000480 | Scavenging by Class A Receptors | 9.851791e-01 | 0.006 |
| R-HSA-9710421 | Defective pyroptosis | 9.875233e-01 | 0.005 |
| R-HSA-73621 | Pyrimidine catabolism | 9.875233e-01 | 0.005 |
| R-HSA-9958863 | SLC-mediated transport of amino acids | 9.882189e-01 | 0.005 |
| R-HSA-193368 | Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol | 9.882189e-01 | 0.005 |
| R-HSA-373752 | Netrin-1 signaling | 9.885526e-01 | 0.005 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 9.885526e-01 | 0.005 |
| R-HSA-5683826 | Surfactant metabolism | 9.885526e-01 | 0.005 |
| R-HSA-77286 | mitochondrial fatty acid beta-oxidation of saturated fatty acids | 9.894970e-01 | 0.005 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 9.894970e-01 | 0.005 |
| R-HSA-1614558 | Degradation of cysteine and homocysteine | 9.894970e-01 | 0.005 |
| R-HSA-3560782 | Diseases associated with glycosaminoglycan metabolism | 9.894970e-01 | 0.005 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 9.903636e-01 | 0.004 |
| R-HSA-75105 | Fatty acyl-CoA biosynthesis | 9.905877e-01 | 0.004 |
| R-HSA-3000178 | ECM proteoglycans | 9.912685e-01 | 0.004 |
| R-HSA-72306 | tRNA processing | 9.915269e-01 | 0.004 |
| R-HSA-9634597 | GPER1 signaling | 9.918882e-01 | 0.004 |
| R-HSA-425410 | Metal ion SLC transporters | 9.918882e-01 | 0.004 |
| R-HSA-8963899 | Plasma lipoprotein remodeling | 9.918882e-01 | 0.004 |
| R-HSA-9749641 | Aspirin ADME | 9.924890e-01 | 0.003 |
| R-HSA-5663084 | Diseases of carbohydrate metabolism | 9.924890e-01 | 0.003 |
| R-HSA-9748787 | Azathioprine ADME | 9.931718e-01 | 0.003 |
| R-HSA-9837999 | Mitochondrial protein degradation | 9.935026e-01 | 0.003 |
| R-HSA-70895 | Branched-chain amino acid catabolism | 9.937353e-01 | 0.003 |
| R-HSA-2514856 | The phototransduction cascade | 9.937353e-01 | 0.003 |
| R-HSA-9864848 | Complex IV assembly | 9.937353e-01 | 0.003 |
| R-HSA-9955298 | SLC-mediated transport of organic anions | 9.948557e-01 | 0.002 |
| R-HSA-156588 | Glucuronidation | 9.951621e-01 | 0.002 |
| R-HSA-422356 | Regulation of insulin secretion | 9.954100e-01 | 0.002 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 9.954539e-01 | 0.002 |
| R-HSA-192105 | Synthesis of bile acids and bile salts | 9.957200e-01 | 0.002 |
| R-HSA-1428517 | Aerobic respiration and respiratory electron transport | 9.957778e-01 | 0.002 |
| R-HSA-211897 | Cytochrome P450 - arranged by substrate type | 9.958182e-01 | 0.002 |
| R-HSA-416476 | G alpha (q) signalling events | 9.958342e-01 | 0.002 |
| R-HSA-9018677 | Biosynthesis of DHA-derived SPMs | 9.959062e-01 | 0.002 |
| R-HSA-209776 | Metabolism of amine-derived hormones | 9.959279e-01 | 0.002 |
| R-HSA-9658195 | Leishmania infection | 9.960695e-01 | 0.002 |
| R-HSA-9824443 | Parasitic Infection Pathways | 9.960695e-01 | 0.002 |
| R-HSA-5621480 | Dectin-2 family | 9.962640e-01 | 0.002 |
| R-HSA-1483166 | Synthesis of PA | 9.962640e-01 | 0.002 |
| R-HSA-375276 | Peptide ligand-binding receptors | 9.964115e-01 | 0.002 |
| R-HSA-1483206 | Glycerophospholipid biosynthesis | 9.964211e-01 | 0.002 |
| R-HSA-4085001 | Sialic acid metabolism | 9.968555e-01 | 0.001 |
| R-HSA-5663205 | Infectious disease | 9.968559e-01 | 0.001 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 9.969359e-01 | 0.001 |
| R-HSA-5362517 | Signaling by Retinoic Acid | 9.971152e-01 | 0.001 |
| R-HSA-8956321 | Nucleotide salvage | 9.973534e-01 | 0.001 |
| R-HSA-163841 | Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation | 9.974147e-01 | 0.001 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 9.975720e-01 | 0.001 |
| R-HSA-6799198 | Complex I biogenesis | 9.977725e-01 | 0.001 |
| R-HSA-611105 | Respiratory electron transport | 9.979016e-01 | 0.001 |
| R-HSA-196849 | Metabolism of water-soluble vitamins and cofactors | 9.980211e-01 | 0.001 |
| R-HSA-194068 | Bile acid and bile salt metabolism | 9.981693e-01 | 0.001 |
| R-HSA-6782315 | tRNA modification in the nucleus and cytosol | 9.982801e-01 | 0.001 |
| R-HSA-392499 | Metabolism of proteins | 9.982951e-01 | 0.001 |
| R-HSA-196807 | Nicotinate metabolism | 9.984222e-01 | 0.001 |
| R-HSA-9843940 | Regulation of endogenous retroelements by KRAB-ZFP proteins | 9.987818e-01 | 0.001 |
| R-HSA-3906995 | Diseases associated with O-glycosylation of proteins | 9.988825e-01 | 0.000 |
| R-HSA-9638482 | Metal ion assimilation from the host | 9.988825e-01 | 0.000 |
| R-HSA-975634 | Retinoid metabolism and transport | 9.988825e-01 | 0.000 |
| R-HSA-2980736 | Peptide hormone metabolism | 9.990424e-01 | 0.000 |
| R-HSA-425397 | Transport of vitamins, nucleosides, and related molecules | 9.991373e-01 | 0.000 |
| R-HSA-5579029 | Metabolic disorders of biological oxidation enzymes | 9.994396e-01 | 0.000 |
| R-HSA-388396 | GPCR downstream signalling | 9.994433e-01 | 0.000 |
| R-HSA-428157 | Sphingolipid metabolism | 9.994692e-01 | 0.000 |
| R-HSA-6806667 | Metabolism of fat-soluble vitamins | 9.995284e-01 | 0.000 |
| R-HSA-6805567 | Keratinization | 9.996329e-01 | 0.000 |
| R-HSA-446219 | Synthesis of substrates in N-glycan biosythesis | 9.997033e-01 | 0.000 |
| R-HSA-1614635 | Sulfur amino acid metabolism | 9.997190e-01 | 0.000 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 9.997312e-01 | 0.000 |
| R-HSA-373080 | Class B/2 (Secretin family receptors) | 9.998011e-01 | 0.000 |
| R-HSA-15869 | Metabolism of nucleotides | 9.998149e-01 | 0.000 |
| R-HSA-1643685 | Disease | 9.998256e-01 | 0.000 |
| R-HSA-71291 | Metabolism of amino acids and derivatives | 9.998574e-01 | 0.000 |
| R-HSA-2029481 | FCGR activation | 9.998592e-01 | 0.000 |
| R-HSA-211945 | Phase I - Functionalization of compounds | 9.998636e-01 | 0.000 |
| R-HSA-77289 | Mitochondrial Fatty Acid Beta-Oxidation | 9.998815e-01 | 0.000 |
| R-HSA-2168880 | Scavenging of heme from plasma | 9.998913e-01 | 0.000 |
| R-HSA-9018678 | Biosynthesis of specialized proresolving mediators (SPMs) | 9.998955e-01 | 0.000 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 9.999003e-01 | 0.000 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 9.999304e-01 | 0.000 |
| R-HSA-2173782 | Binding and Uptake of Ligands by Scavenger Receptors | 9.999383e-01 | 0.000 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 9.999414e-01 | 0.000 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 9.999414e-01 | 0.000 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 9.999416e-01 | 0.000 |
| R-HSA-8956319 | Nucleotide catabolism | 9.999453e-01 | 0.000 |
| R-HSA-2142753 | Arachidonate metabolism | 9.999469e-01 | 0.000 |
| R-HSA-372790 | Signaling by GPCR | 9.999565e-01 | 0.000 |
| R-HSA-1474228 | Degradation of the extracellular matrix | 9.999603e-01 | 0.000 |
| R-HSA-446193 | Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... | 9.999637e-01 | 0.000 |
| R-HSA-418594 | G alpha (i) signalling events | 9.999649e-01 | 0.000 |
| R-HSA-6803157 | Antimicrobial peptides | 9.999750e-01 | 0.000 |
| R-HSA-373076 | Class A/1 (Rhodopsin-like receptors) | 9.999897e-01 | 0.000 |
| R-HSA-2187338 | Visual phototransduction | 9.999899e-01 | 0.000 |
| R-HSA-9717207 | Sensory perception of sweet, bitter, and umami (glutamate) taste | 9.999926e-01 | 0.000 |
| R-HSA-198933 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 9.999950e-01 | 0.000 |
| R-HSA-9717189 | Sensory perception of taste | 9.999969e-01 | 0.000 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 9.999975e-01 | 0.000 |
| R-HSA-9748784 | Drug ADME | 9.999980e-01 | 0.000 |
| R-HSA-425407 | SLC-mediated transmembrane transport | 9.999991e-01 | 0.000 |
| R-HSA-382551 | Transport of small molecules | 9.999991e-01 | 0.000 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 9.999995e-01 | 0.000 |
| R-HSA-3781865 | Diseases of glycosylation | 9.999995e-01 | 0.000 |
| R-HSA-9824439 | Bacterial Infection Pathways | 9.999996e-01 | 0.000 |
| R-HSA-1630316 | Glycosaminoglycan metabolism | 9.999998e-01 | 0.000 |
| R-HSA-156580 | Phase II - Conjugation of compounds | 9.999999e-01 | 0.000 |
| R-HSA-9640148 | Infection with Enterobacteria | 1.000000e+00 | 0.000 |
| R-HSA-211859 | Biological oxidations | 1.000000e+00 | 0.000 |
| R-HSA-8978868 | Fatty acid metabolism | 1.000000e+00 | 0.000 |
| R-HSA-556833 | Metabolism of lipids | 1.000000e+00 | 0.000 |
| R-HSA-500792 | GPCR ligand binding | 1.000000e+00 | 0.000 |
| R-HSA-5668914 | Diseases of metabolism | 1.000000e+00 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | -0.000 |
| R-HSA-381753 | Olfactory Signaling Pathway | 1.000000e+00 | -0.000 |
| R-HSA-9709957 | Sensory Perception | 1.000000e+00 | -0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
NLK |
0.911 | 0.552 | 1 | 0.942 |
CLK3 |
0.907 | 0.392 | 1 | 0.927 |
COT |
0.903 | 0.024 | 2 | 0.916 |
ERK5 |
0.901 | 0.325 | 1 | 0.883 |
KIS |
0.901 | 0.435 | 1 | 0.911 |
CDK8 |
0.900 | 0.471 | 1 | 0.893 |
HIPK4 |
0.899 | 0.332 | 1 | 0.908 |
CDC7 |
0.898 | 0.011 | 1 | 0.804 |
SRPK1 |
0.897 | 0.281 | -3 | 0.793 |
MTOR |
0.897 | 0.078 | 1 | 0.833 |
CDK7 |
0.897 | 0.475 | 1 | 0.902 |
CDKL1 |
0.896 | 0.173 | -3 | 0.849 |
CDK19 |
0.896 | 0.469 | 1 | 0.869 |
DYRK2 |
0.895 | 0.477 | 1 | 0.901 |
CDKL5 |
0.895 | 0.193 | -3 | 0.841 |
PRPK |
0.894 | -0.115 | -1 | 0.839 |
CDK18 |
0.893 | 0.508 | 1 | 0.853 |
JNK2 |
0.892 | 0.548 | 1 | 0.865 |
PIM3 |
0.892 | 0.058 | -3 | 0.870 |
CDK5 |
0.892 | 0.491 | 1 | 0.908 |
CAMK1B |
0.892 | 0.052 | -3 | 0.909 |
CDK13 |
0.892 | 0.469 | 1 | 0.886 |
MOS |
0.891 | -0.007 | 1 | 0.843 |
ICK |
0.891 | 0.263 | -3 | 0.879 |
GCN2 |
0.891 | -0.145 | 2 | 0.855 |
P38A |
0.890 | 0.508 | 1 | 0.907 |
RAF1 |
0.890 | -0.121 | 1 | 0.799 |
SRPK2 |
0.889 | 0.239 | -3 | 0.720 |
NDR2 |
0.889 | 0.018 | -3 | 0.871 |
ATR |
0.889 | 0.029 | 1 | 0.821 |
CLK1 |
0.889 | 0.358 | -3 | 0.794 |
DSTYK |
0.889 | -0.054 | 2 | 0.926 |
NUAK2 |
0.888 | 0.088 | -3 | 0.883 |
RSK2 |
0.888 | 0.115 | -3 | 0.817 |
WNK1 |
0.888 | 0.051 | -2 | 0.920 |
ERK1 |
0.888 | 0.499 | 1 | 0.864 |
PKN3 |
0.888 | 0.048 | -3 | 0.875 |
JNK3 |
0.888 | 0.513 | 1 | 0.889 |
BMPR2 |
0.888 | -0.112 | -2 | 0.925 |
PDHK4 |
0.888 | -0.240 | 1 | 0.834 |
TBK1 |
0.888 | -0.114 | 1 | 0.706 |
CLK4 |
0.888 | 0.329 | -3 | 0.814 |
P38B |
0.888 | 0.516 | 1 | 0.865 |
CDK1 |
0.888 | 0.477 | 1 | 0.866 |
MST4 |
0.888 | 0.077 | 2 | 0.905 |
CDK17 |
0.887 | 0.498 | 1 | 0.813 |
PRKD1 |
0.887 | 0.066 | -3 | 0.857 |
CAMLCK |
0.887 | 0.119 | -2 | 0.913 |
HIPK2 |
0.887 | 0.484 | 1 | 0.855 |
P38G |
0.887 | 0.518 | 1 | 0.810 |
HIPK1 |
0.887 | 0.466 | 1 | 0.911 |
ULK2 |
0.887 | -0.155 | 2 | 0.845 |
PRKD2 |
0.886 | 0.113 | -3 | 0.810 |
NEK6 |
0.886 | -0.025 | -2 | 0.903 |
NIK |
0.886 | 0.040 | -3 | 0.922 |
P90RSK |
0.886 | 0.087 | -3 | 0.820 |
NDR1 |
0.886 | 0.036 | -3 | 0.872 |
CDK12 |
0.886 | 0.471 | 1 | 0.868 |
TGFBR2 |
0.886 | 0.005 | -2 | 0.834 |
CDK14 |
0.885 | 0.519 | 1 | 0.879 |
IKKB |
0.885 | -0.158 | -2 | 0.795 |
RSK3 |
0.885 | 0.087 | -3 | 0.813 |
ERK2 |
0.884 | 0.487 | 1 | 0.889 |
RIPK3 |
0.884 | -0.017 | 3 | 0.819 |
PIM1 |
0.884 | 0.116 | -3 | 0.821 |
CDK9 |
0.884 | 0.450 | 1 | 0.890 |
DAPK2 |
0.884 | 0.089 | -3 | 0.913 |
PDHK1 |
0.884 | -0.205 | 1 | 0.815 |
SKMLCK |
0.884 | 0.069 | -2 | 0.911 |
PKCD |
0.883 | 0.095 | 2 | 0.853 |
IKKE |
0.883 | -0.142 | 1 | 0.700 |
NEK7 |
0.883 | -0.115 | -3 | 0.875 |
AMPKA1 |
0.882 | 0.043 | -3 | 0.892 |
DYRK1A |
0.882 | 0.400 | 1 | 0.926 |
CAMK2G |
0.882 | -0.117 | 2 | 0.846 |
PKN2 |
0.882 | 0.044 | -3 | 0.881 |
CDK3 |
0.882 | 0.471 | 1 | 0.828 |
SRPK3 |
0.882 | 0.201 | -3 | 0.768 |
HIPK3 |
0.881 | 0.440 | 1 | 0.904 |
CDK16 |
0.881 | 0.508 | 1 | 0.827 |
MARK4 |
0.881 | -0.000 | 4 | 0.896 |
P70S6KB |
0.881 | 0.078 | -3 | 0.844 |
WNK3 |
0.881 | -0.105 | 1 | 0.781 |
CDK2 |
0.881 | 0.375 | 1 | 0.893 |
P38D |
0.880 | 0.522 | 1 | 0.835 |
AURC |
0.880 | 0.135 | -2 | 0.728 |
MLK1 |
0.879 | -0.092 | 2 | 0.872 |
MAPKAPK3 |
0.879 | 0.032 | -3 | 0.815 |
DYRK4 |
0.878 | 0.469 | 1 | 0.867 |
CDK10 |
0.878 | 0.489 | 1 | 0.871 |
CLK2 |
0.878 | 0.347 | -3 | 0.791 |
AMPKA2 |
0.878 | 0.057 | -3 | 0.861 |
NIM1 |
0.878 | -0.005 | 3 | 0.834 |
DYRK1B |
0.878 | 0.452 | 1 | 0.878 |
NEK9 |
0.878 | -0.073 | 2 | 0.898 |
PKACG |
0.877 | 0.058 | -2 | 0.803 |
CHAK2 |
0.877 | -0.077 | -1 | 0.801 |
TSSK1 |
0.876 | 0.046 | -3 | 0.909 |
DYRK3 |
0.876 | 0.398 | 1 | 0.901 |
LATS2 |
0.876 | -0.020 | -5 | 0.801 |
TSSK2 |
0.876 | 0.011 | -5 | 0.879 |
HUNK |
0.876 | -0.172 | 2 | 0.851 |
CAMK2D |
0.876 | -0.051 | -3 | 0.885 |
BCKDK |
0.875 | -0.183 | -1 | 0.797 |
GRK5 |
0.875 | -0.198 | -3 | 0.889 |
ATM |
0.875 | 0.014 | 1 | 0.763 |
PRKD3 |
0.875 | 0.084 | -3 | 0.789 |
PAK6 |
0.875 | 0.138 | -2 | 0.784 |
ULK1 |
0.875 | -0.211 | -3 | 0.860 |
IRE1 |
0.874 | -0.054 | 1 | 0.757 |
MNK2 |
0.874 | 0.066 | -2 | 0.858 |
NUAK1 |
0.874 | 0.024 | -3 | 0.837 |
SMG1 |
0.873 | 0.138 | 1 | 0.777 |
PAK3 |
0.873 | 0.029 | -2 | 0.849 |
MELK |
0.873 | 0.035 | -3 | 0.849 |
AURB |
0.873 | 0.122 | -2 | 0.728 |
MASTL |
0.872 | -0.252 | -2 | 0.857 |
PAK1 |
0.872 | 0.042 | -2 | 0.849 |
MLK2 |
0.872 | -0.106 | 2 | 0.876 |
CAMK4 |
0.872 | -0.034 | -3 | 0.864 |
PKR |
0.872 | 0.026 | 1 | 0.803 |
PRP4 |
0.871 | 0.303 | -3 | 0.811 |
MAPKAPK2 |
0.871 | 0.031 | -3 | 0.766 |
IRE2 |
0.871 | -0.015 | 2 | 0.820 |
ANKRD3 |
0.871 | -0.145 | 1 | 0.816 |
RIPK1 |
0.871 | -0.170 | 1 | 0.773 |
PKCA |
0.871 | 0.066 | 2 | 0.800 |
GRK6 |
0.870 | -0.112 | 1 | 0.785 |
IKKA |
0.870 | -0.128 | -2 | 0.779 |
MLK3 |
0.870 | -0.013 | 2 | 0.809 |
QIK |
0.870 | -0.028 | -3 | 0.880 |
ALK4 |
0.870 | -0.009 | -2 | 0.863 |
PKCB |
0.870 | 0.047 | 2 | 0.807 |
MSK2 |
0.869 | 0.021 | -3 | 0.781 |
QSK |
0.869 | 0.032 | 4 | 0.874 |
CDK4 |
0.869 | 0.490 | 1 | 0.859 |
CDK6 |
0.869 | 0.476 | 1 | 0.870 |
PKG2 |
0.869 | 0.107 | -2 | 0.742 |
MYLK4 |
0.869 | 0.090 | -2 | 0.836 |
PHKG1 |
0.868 | -0.005 | -3 | 0.863 |
RSK4 |
0.868 | 0.087 | -3 | 0.781 |
SGK3 |
0.868 | 0.102 | -3 | 0.807 |
PKCG |
0.868 | 0.024 | 2 | 0.805 |
PIM2 |
0.868 | 0.118 | -3 | 0.795 |
AKT2 |
0.868 | 0.119 | -3 | 0.736 |
SIK |
0.868 | 0.030 | -3 | 0.806 |
LATS1 |
0.868 | 0.015 | -3 | 0.884 |
PKACB |
0.868 | 0.119 | -2 | 0.744 |
VRK2 |
0.867 | -0.022 | 1 | 0.863 |
GRK1 |
0.867 | -0.064 | -2 | 0.811 |
NEK2 |
0.867 | -0.057 | 2 | 0.876 |
BMPR1B |
0.867 | 0.042 | 1 | 0.738 |
DLK |
0.867 | -0.259 | 1 | 0.790 |
MNK1 |
0.867 | 0.053 | -2 | 0.865 |
DNAPK |
0.867 | 0.035 | 1 | 0.719 |
TGFBR1 |
0.866 | -0.007 | -2 | 0.831 |
PAK2 |
0.866 | 0.019 | -2 | 0.836 |
PKCH |
0.866 | 0.019 | 2 | 0.794 |
PKCZ |
0.865 | -0.008 | 2 | 0.847 |
MSK1 |
0.865 | 0.071 | -3 | 0.789 |
PLK1 |
0.865 | -0.102 | -2 | 0.860 |
CAMK2B |
0.865 | -0.024 | 2 | 0.807 |
FAM20C |
0.865 | 0.010 | 2 | 0.618 |
TTBK2 |
0.864 | -0.219 | 2 | 0.762 |
MEK1 |
0.864 | -0.146 | 2 | 0.876 |
ERK7 |
0.863 | 0.223 | 2 | 0.603 |
GRK4 |
0.863 | -0.216 | -2 | 0.852 |
YSK4 |
0.863 | -0.127 | 1 | 0.739 |
JNK1 |
0.863 | 0.437 | 1 | 0.851 |
CHK1 |
0.862 | -0.019 | -3 | 0.863 |
CAMK2A |
0.862 | -0.021 | 2 | 0.822 |
CHAK1 |
0.862 | -0.123 | 2 | 0.832 |
AURA |
0.861 | 0.079 | -2 | 0.702 |
MAK |
0.861 | 0.367 | -2 | 0.784 |
BRSK2 |
0.861 | -0.056 | -3 | 0.860 |
PINK1 |
0.861 | 0.014 | 1 | 0.872 |
BRSK1 |
0.860 | -0.030 | -3 | 0.835 |
MARK2 |
0.860 | -0.005 | 4 | 0.800 |
PRKX |
0.860 | 0.124 | -3 | 0.717 |
ACVR2A |
0.860 | -0.039 | -2 | 0.825 |
ALK2 |
0.860 | -0.009 | -2 | 0.841 |
MARK3 |
0.860 | 0.002 | 4 | 0.838 |
AKT1 |
0.860 | 0.127 | -3 | 0.752 |
WNK4 |
0.860 | -0.044 | -2 | 0.913 |
HRI |
0.860 | -0.114 | -2 | 0.890 |
ACVR2B |
0.859 | -0.035 | -2 | 0.835 |
MLK4 |
0.859 | -0.109 | 2 | 0.784 |
CAMK1G |
0.858 | -0.004 | -3 | 0.812 |
MOK |
0.858 | 0.351 | 1 | 0.883 |
PERK |
0.858 | -0.106 | -2 | 0.871 |
DCAMKL1 |
0.858 | 0.014 | -3 | 0.824 |
IRAK4 |
0.858 | -0.045 | 1 | 0.759 |
GRK7 |
0.858 | -0.029 | 1 | 0.745 |
SMMLCK |
0.857 | 0.062 | -3 | 0.868 |
SNRK |
0.857 | -0.142 | 2 | 0.733 |
MPSK1 |
0.857 | 0.076 | 1 | 0.784 |
MAPKAPK5 |
0.857 | -0.075 | -3 | 0.768 |
PKCT |
0.856 | 0.031 | 2 | 0.804 |
NEK5 |
0.856 | -0.045 | 1 | 0.792 |
P70S6K |
0.856 | 0.048 | -3 | 0.760 |
MEKK1 |
0.856 | -0.135 | 1 | 0.779 |
PHKG2 |
0.856 | 0.004 | -3 | 0.848 |
MST3 |
0.855 | 0.027 | 2 | 0.891 |
BRAF |
0.855 | -0.126 | -4 | 0.855 |
PLK3 |
0.855 | -0.129 | 2 | 0.799 |
TLK2 |
0.855 | -0.156 | 1 | 0.763 |
MARK1 |
0.855 | -0.042 | 4 | 0.858 |
PKACA |
0.855 | 0.104 | -2 | 0.692 |
PLK4 |
0.854 | -0.127 | 2 | 0.680 |
MEK5 |
0.854 | -0.215 | 2 | 0.873 |
DRAK1 |
0.853 | -0.116 | 1 | 0.710 |
MEKK2 |
0.853 | -0.107 | 2 | 0.861 |
PKCI |
0.853 | 0.034 | 2 | 0.814 |
ZAK |
0.852 | -0.165 | 1 | 0.745 |
PAK5 |
0.851 | 0.066 | -2 | 0.715 |
SSTK |
0.851 | -0.006 | 4 | 0.865 |
DCAMKL2 |
0.851 | -0.025 | -3 | 0.852 |
TAO3 |
0.851 | -0.035 | 1 | 0.774 |
MEKK3 |
0.850 | -0.210 | 1 | 0.766 |
BMPR1A |
0.850 | 0.015 | 1 | 0.719 |
TAO2 |
0.849 | -0.008 | 2 | 0.908 |
PKCE |
0.849 | 0.081 | 2 | 0.792 |
CAMK1D |
0.849 | 0.033 | -3 | 0.730 |
PAK4 |
0.849 | 0.075 | -2 | 0.722 |
DAPK3 |
0.847 | 0.080 | -3 | 0.841 |
NEK8 |
0.847 | -0.107 | 2 | 0.878 |
PKN1 |
0.847 | 0.050 | -3 | 0.776 |
GSK3A |
0.847 | 0.097 | 4 | 0.477 |
GAK |
0.846 | 0.004 | 1 | 0.821 |
TLK1 |
0.846 | -0.177 | -2 | 0.856 |
GRK2 |
0.846 | -0.142 | -2 | 0.740 |
AKT3 |
0.846 | 0.115 | -3 | 0.666 |
LKB1 |
0.846 | -0.049 | -3 | 0.875 |
MRCKB |
0.846 | 0.126 | -3 | 0.787 |
GSK3B |
0.845 | 0.007 | 4 | 0.469 |
SGK1 |
0.845 | 0.113 | -3 | 0.652 |
NEK4 |
0.845 | -0.063 | 1 | 0.753 |
CAMKK1 |
0.845 | -0.151 | -2 | 0.814 |
IRAK1 |
0.844 | -0.230 | -1 | 0.754 |
PDK1 |
0.844 | -0.061 | 1 | 0.781 |
NEK11 |
0.843 | -0.170 | 1 | 0.767 |
MRCKA |
0.843 | 0.111 | -3 | 0.801 |
TNIK |
0.843 | 0.034 | 3 | 0.908 |
HGK |
0.843 | -0.008 | 3 | 0.907 |
TTBK1 |
0.842 | -0.175 | 2 | 0.675 |
CHK2 |
0.842 | 0.054 | -3 | 0.682 |
MEKK6 |
0.842 | -0.067 | 1 | 0.766 |
PASK |
0.842 | -0.090 | -3 | 0.883 |
ROCK2 |
0.842 | 0.114 | -3 | 0.828 |
EEF2K |
0.841 | -0.017 | 3 | 0.873 |
NEK1 |
0.841 | -0.018 | 1 | 0.761 |
CK1E |
0.841 | -0.094 | -3 | 0.542 |
MINK |
0.840 | -0.041 | 1 | 0.751 |
CAMK1A |
0.840 | 0.060 | -3 | 0.697 |
GCK |
0.840 | -0.048 | 1 | 0.762 |
CAMKK2 |
0.840 | -0.146 | -2 | 0.808 |
LOK |
0.840 | -0.002 | -2 | 0.819 |
SBK |
0.839 | 0.117 | -3 | 0.615 |
LRRK2 |
0.839 | -0.078 | 2 | 0.903 |
DAPK1 |
0.839 | 0.052 | -3 | 0.825 |
BUB1 |
0.839 | 0.102 | -5 | 0.825 |
MAP3K15 |
0.838 | -0.104 | 1 | 0.742 |
TAK1 |
0.838 | -0.069 | 1 | 0.785 |
HPK1 |
0.838 | -0.011 | 1 | 0.749 |
MST2 |
0.838 | -0.117 | 1 | 0.766 |
KHS1 |
0.836 | 0.021 | 1 | 0.747 |
VRK1 |
0.835 | -0.107 | 2 | 0.889 |
DMPK1 |
0.835 | 0.138 | -3 | 0.805 |
KHS2 |
0.835 | 0.051 | 1 | 0.759 |
PBK |
0.834 | 0.017 | 1 | 0.752 |
YSK1 |
0.833 | -0.040 | 2 | 0.873 |
CK1G1 |
0.833 | -0.118 | -3 | 0.536 |
CK1D |
0.833 | -0.076 | -3 | 0.489 |
PKG1 |
0.832 | 0.063 | -2 | 0.659 |
RIPK2 |
0.831 | -0.211 | 1 | 0.709 |
MST1 |
0.831 | -0.127 | 1 | 0.747 |
MEK2 |
0.830 | -0.186 | 2 | 0.858 |
ROCK1 |
0.830 | 0.106 | -3 | 0.799 |
NEK3 |
0.830 | -0.087 | 1 | 0.740 |
CK1A2 |
0.829 | -0.092 | -3 | 0.489 |
GRK3 |
0.828 | -0.148 | -2 | 0.690 |
SLK |
0.828 | -0.100 | -2 | 0.753 |
CRIK |
0.828 | 0.098 | -3 | 0.747 |
CK2A2 |
0.828 | -0.055 | 1 | 0.649 |
PDHK3_TYR |
0.827 | 0.127 | 4 | 0.938 |
TTK |
0.825 | -0.004 | -2 | 0.863 |
STK33 |
0.825 | -0.199 | 2 | 0.660 |
BIKE |
0.824 | 0.052 | 1 | 0.717 |
PLK2 |
0.824 | -0.102 | -3 | 0.819 |
HASPIN |
0.823 | -0.012 | -1 | 0.659 |
MYO3B |
0.822 | 0.001 | 2 | 0.885 |
TESK1_TYR |
0.820 | -0.023 | 3 | 0.920 |
LIMK2_TYR |
0.819 | 0.110 | -3 | 0.928 |
PKMYT1_TYR |
0.819 | 0.014 | 3 | 0.895 |
TAO1 |
0.818 | -0.052 | 1 | 0.707 |
MAP2K4_TYR |
0.818 | -0.064 | -1 | 0.859 |
OSR1 |
0.818 | -0.108 | 2 | 0.851 |
CK2A1 |
0.816 | -0.074 | 1 | 0.624 |
MYO3A |
0.816 | -0.049 | 1 | 0.748 |
ASK1 |
0.816 | -0.147 | 1 | 0.732 |
MAP2K7_TYR |
0.816 | -0.173 | 2 | 0.900 |
PDHK4_TYR |
0.815 | -0.043 | 2 | 0.909 |
MAP2K6_TYR |
0.814 | -0.107 | -1 | 0.848 |
PINK1_TYR |
0.813 | -0.174 | 1 | 0.820 |
BMPR2_TYR |
0.811 | -0.104 | -1 | 0.821 |
EPHA6 |
0.810 | -0.009 | -1 | 0.823 |
LIMK1_TYR |
0.810 | -0.090 | 2 | 0.906 |
RET |
0.810 | -0.089 | 1 | 0.781 |
TYRO3 |
0.810 | -0.012 | 3 | 0.858 |
AAK1 |
0.809 | 0.088 | 1 | 0.631 |
ROS1 |
0.809 | -0.038 | 3 | 0.838 |
TYK2 |
0.809 | -0.131 | 1 | 0.776 |
MST1R |
0.809 | -0.068 | 3 | 0.869 |
EPHB4 |
0.808 | -0.006 | -1 | 0.835 |
PDHK1_TYR |
0.808 | -0.186 | -1 | 0.851 |
ALPHAK3 |
0.808 | -0.135 | -1 | 0.736 |
JAK2 |
0.807 | -0.104 | 1 | 0.781 |
CSF1R |
0.806 | -0.057 | 3 | 0.856 |
ABL2 |
0.805 | -0.009 | -1 | 0.812 |
DDR1 |
0.804 | -0.125 | 4 | 0.862 |
TNK2 |
0.804 | 0.028 | 3 | 0.820 |
YES1 |
0.804 | -0.008 | -1 | 0.846 |
TXK |
0.804 | 0.071 | 1 | 0.765 |
ABL1 |
0.802 | -0.028 | -1 | 0.809 |
TNNI3K_TYR |
0.801 | -0.008 | 1 | 0.785 |
JAK1 |
0.800 | -0.008 | 1 | 0.724 |
HCK |
0.800 | -0.033 | -1 | 0.828 |
NEK10_TYR |
0.800 | -0.061 | 1 | 0.681 |
TNK1 |
0.800 | -0.049 | 3 | 0.837 |
LCK |
0.799 | 0.013 | -1 | 0.815 |
JAK3 |
0.799 | -0.162 | 1 | 0.765 |
YANK3 |
0.798 | -0.126 | 2 | 0.425 |
STLK3 |
0.798 | -0.233 | 1 | 0.714 |
BLK |
0.798 | 0.043 | -1 | 0.820 |
FGR |
0.798 | -0.156 | 1 | 0.792 |
TEK |
0.798 | -0.029 | 3 | 0.796 |
FER |
0.797 | -0.167 | 1 | 0.811 |
INSRR |
0.797 | -0.142 | 3 | 0.809 |
AXL |
0.797 | -0.032 | 3 | 0.838 |
ITK |
0.797 | -0.043 | -1 | 0.814 |
EPHB1 |
0.797 | -0.070 | 1 | 0.784 |
TEC |
0.796 | 0.025 | -1 | 0.790 |
PDGFRB |
0.796 | -0.172 | 3 | 0.865 |
SRMS |
0.796 | -0.076 | 1 | 0.785 |
EPHB3 |
0.796 | -0.066 | -1 | 0.825 |
MERTK |
0.796 | 0.002 | 3 | 0.832 |
FGFR2 |
0.795 | -0.135 | 3 | 0.845 |
EPHA4 |
0.795 | -0.086 | 2 | 0.792 |
KDR |
0.795 | -0.099 | 3 | 0.823 |
FLT3 |
0.794 | -0.151 | 3 | 0.854 |
EPHB2 |
0.794 | -0.061 | -1 | 0.816 |
FGFR1 |
0.794 | -0.122 | 3 | 0.823 |
BTK |
0.794 | -0.053 | -1 | 0.813 |
WEE1_TYR |
0.793 | -0.065 | -1 | 0.752 |
KIT |
0.793 | -0.167 | 3 | 0.852 |
BMX |
0.791 | -0.033 | -1 | 0.749 |
PDGFRA |
0.791 | -0.193 | 3 | 0.863 |
ALK |
0.790 | -0.118 | 3 | 0.778 |
LTK |
0.790 | -0.090 | 3 | 0.796 |
EPHA1 |
0.789 | -0.032 | 3 | 0.826 |
EPHA7 |
0.787 | -0.067 | 2 | 0.803 |
FRK |
0.787 | -0.057 | -1 | 0.848 |
DDR2 |
0.787 | -0.025 | 3 | 0.795 |
MET |
0.786 | -0.167 | 3 | 0.844 |
CK1A |
0.786 | -0.142 | -3 | 0.392 |
PTK6 |
0.785 | -0.211 | -1 | 0.744 |
FYN |
0.784 | -0.058 | -1 | 0.779 |
LYN |
0.783 | -0.082 | 3 | 0.775 |
PTK2B |
0.783 | -0.047 | -1 | 0.804 |
NTRK1 |
0.783 | -0.245 | -1 | 0.806 |
NTRK2 |
0.783 | -0.204 | 3 | 0.815 |
EPHA3 |
0.783 | -0.151 | 2 | 0.773 |
FGFR3 |
0.782 | -0.167 | 3 | 0.820 |
INSR |
0.781 | -0.205 | 3 | 0.788 |
FLT4 |
0.780 | -0.225 | 3 | 0.808 |
ERBB2 |
0.780 | -0.233 | 1 | 0.726 |
FLT1 |
0.779 | -0.218 | -1 | 0.777 |
NTRK3 |
0.778 | -0.193 | -1 | 0.761 |
EPHA5 |
0.777 | -0.110 | 2 | 0.778 |
MATK |
0.775 | -0.176 | -1 | 0.719 |
SRC |
0.774 | -0.122 | -1 | 0.789 |
EPHA8 |
0.773 | -0.144 | -1 | 0.781 |
MUSK |
0.771 | -0.151 | 1 | 0.629 |
CSK |
0.770 | -0.219 | 2 | 0.807 |
EGFR |
0.769 | -0.171 | 1 | 0.639 |
CK1G3 |
0.768 | -0.127 | -3 | 0.342 |
FGFR4 |
0.766 | -0.181 | -1 | 0.749 |
PTK2 |
0.764 | -0.123 | -1 | 0.716 |
EPHA2 |
0.764 | -0.145 | -1 | 0.752 |
YANK2 |
0.762 | -0.164 | 2 | 0.441 |
IGF1R |
0.762 | -0.230 | 3 | 0.723 |
SYK |
0.759 | -0.156 | -1 | 0.713 |
ERBB4 |
0.755 | -0.160 | 1 | 0.647 |
FES |
0.751 | -0.180 | -1 | 0.716 |
CK1G2 |
0.740 | -0.167 | -3 | 0.446 |
ZAP70 |
0.737 | -0.161 | -1 | 0.645 |