Motif 194 (n=262)

Position-wise Probabilities

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uniprot genes site source protein function
A2RUS2 DENND3 S490 ochoa|psp DENN domain-containing protein 3 Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity). {ECO:0000250|UniProtKB:A2RT67, ECO:0000269|PubMed:20937701}.
A6NDE4 RBMY1B S176 ochoa RNA-binding motif protein, Y chromosome, family 1 member B RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis.
A6NEQ0 RBMY1E S176 ochoa RNA-binding motif protein, Y chromosome, family 1 member E RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis.
A6NHQ4 EPOP S36 ochoa Elongin BC and Polycomb repressive complex 2-associated protein (Proline-rich protein 28) Scaffold protein that serves as a bridging partner between the PRC2/EZH2 complex and the elongin BC complex: required to fine-tune the transcriptional status of Polycomb group (PcG) target genes in embryonic stem cells (ESCs). Plays a key role in genomic regions that display both active and repressive chromatin properties in pluripotent stem cells by sustaining low level expression at PcG target genes: acts by recruiting the elongin BC complex, thereby restricting excessive activity of the PRC2/EZH2 complex. Interaction with USP7 promotes deubiquitination of H2B at promoter sites. Acts as a regulator of neuronal differentiation. {ECO:0000250|UniProtKB:Q7TNS8}.
A7KAX9 ARHGAP32 S1630 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}.
K7ELQ4 ATF7-NPFF S188 ochoa ATF7-NPFF readthrough None
O00148 DDX39A Y38 ochoa ATP-dependent RNA helicase DDX39A (EC 3.6.4.13) (DEAD box protein 39) (Nuclear RNA helicase URH49) Helicase that plays an essential role in mRNA export and is involved in multiple steps in RNA metabolism including alternative splicing (PubMed:33941617, PubMed:38801080). Regulates nuclear mRNA export to the cytoplasm through association with ECD (PubMed:33941617). Also involved in spliceosomal uridine-rich small nuclear RNA (U snRNA) export by stimulating the RNA binding of adapter PHAX (PubMed:39011894). Plays a role in the negative regulation of type I IFN production by increasing the nuclear retention of antiviral transcripts and thus reducing their protein expression (PubMed:32393512). Independently of the interferon pathway, plays an antiviral role against alphaviruses by binding to a 5' conserved sequence element in the viral genomic RNA (PubMed:37949067). {ECO:0000269|PubMed:15047853, ECO:0000269|PubMed:17548965, ECO:0000269|PubMed:32393512, ECO:0000269|PubMed:33941617, ECO:0000269|PubMed:37949067, ECO:0000269|PubMed:38801080}.
O00192 ARVCF S332 ochoa Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}.
O14654 IRS4 S1231 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}.
O14686 KMT2D S42 ochoa Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}.
O14686 KMT2D S2239 ochoa Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}.
O14686 KMT2D S3208 ochoa Histone-lysine N-methyltransferase 2D (Lysine N-methyltransferase 2D) (EC 2.1.1.364) (ALL1-related protein) (Myeloid/lymphoid or mixed-lineage leukemia protein 2) Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17500065, PubMed:25561738). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732). {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:25561738}.
O14827 RASGRF2 S793 ochoa Ras-specific guanine nucleotide-releasing factor 2 (Ras-GRF2) (Ras guanine nucleotide exchange factor 2) Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation. {ECO:0000269|PubMed:15128856}.
O14964 HGS S310 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.
O14965 AURKA S66 ochoa Aurora kinase A (EC 2.7.11.1) (Aurora 2) (Aurora/IPL1-related kinase 1) (ARK-1) (Aurora-related kinase 1) (Breast tumor-amplified kinase) (Ipl1- and aurora-related kinase 1) (Serine/threonine-protein kinase 15) (Serine/threonine-protein kinase 6) (Serine/threonine-protein kinase Ayk1) (Serine/threonine-protein kinase aurora-A) Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735). {ECO:0000250|UniProtKB:A0A8I3S724, ECO:0000269|PubMed:11039908, ECO:0000269|PubMed:11551964, ECO:0000269|PubMed:12390251, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:14523000, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15128871, ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:15987997, ECO:0000269|PubMed:17125279, ECO:0000269|PubMed:17360485, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19668197, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:27192185, ECO:0000269|PubMed:27335426, ECO:0000269|PubMed:28218735}.
O15054 KDM6B S802 ochoa Lysine-specific demethylase 6B (EC 1.14.11.68) (JmjC domain-containing protein 3) (Jumonji domain-containing protein 3) (Lysine demethylase 6B) ([histone H3]-trimethyl-L-lysine(27) demethylase 6B) Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17713478, PubMed:17825402, PubMed:17851529, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity). {ECO:0000250|UniProtKB:Q5NCY0, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17825402, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914, ECO:0000269|PubMed:28262558}.
O15240 VGF S65 ochoa Neurosecretory protein VGF [Cleaved into: Neuroendocrine regulatory peptide-1 (NERP-1); Neuroendocrine regulatory peptide-2 (NERP-2); VGF-derived peptide TLQP-21; VGF-derived peptide TLQP-62; Antimicrobial peptide VGF[554-577]] [Neurosecretory protein VGF]: Secreted polyprotein that is packaged and proteolytically processed by prohormone convertases PCSK1 and PCSK2 in a cell-type-specific manner (By similarity). VGF and peptides derived from its processing play many roles in neurogenesis and neuroplasticity associated with learning, memory, depression and chronic pain (By similarity). {ECO:0000250|UniProtKB:P20156, ECO:0000250|UniProtKB:Q0VGU4}.; FUNCTION: [Neuroendocrine regulatory peptide-1]: Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Suppresses presynaptic glutamatergic neurons connected to vasopressin neurons. {ECO:0000250|UniProtKB:P20156}.; FUNCTION: [Neuroendocrine regulatory peptide-2]: Plays a role in the control of body fluid homeostasis by regulating vasopressin release. Activates GABAergic interneurons which are inhibitory neurons of the nervous system and thereby suppresses presynaptic glutamatergic neurons (By similarity). Also stimulates feeding behavior in an orexin-dependent manner in the hypothalamus (By similarity). Functions as a positive regulator for the activation of orexin neurons resulting in elevated gastric acid secretion and gastric emptying (By similarity). {ECO:0000250|UniProtKB:P20156}.; FUNCTION: [VGF-derived peptide TLQP-21]: Secreted multifunctional neuropeptide that binds to different cell receptors and thereby plays multiple physiological roles including modulation of energy expenditure, pain, response to stress, gastric regulation, glucose homeostasis as well as lipolysis (By similarity). Activates the G-protein-coupled receptor C3AR1 via a folding-upon-binding mechanism leading to enhanced lipolysis in adipocytes (By similarity). Interacts with C1QBP receptor in macrophages and microglia causing increased levels of intracellular calcium and hypersensitivity (By similarity). {ECO:0000250|UniProtKB:P20156, ECO:0000250|UniProtKB:Q0VGU4}.; FUNCTION: [VGF-derived peptide TLQP-62]: Plays a role in the regulation of memory formation and depression-related behaviors potentially by influencing synaptic plasticity and neurogenesis. Induces acute and transient activation of the NTRK2/TRKB receptor and subsequent CREB phosphorylation (By similarity). Also induces insulin secretion in insulinoma cells by increasing intracellular calcium mobilization (By similarity). {ECO:0000250|UniProtKB:Q0VGU4}.; FUNCTION: [Antimicrobial peptide VGF[554-577]]: Has bactericidal activity against M.luteus, and antifungal activity against P. Pastoris. {ECO:0000269|PubMed:23250050}.
O15392 BIRC5 S20 psp Baculoviral IAP repeat-containing protein 5 (Apoptosis inhibitor 4) (Apoptosis inhibitor survivin) Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis (PubMed:20627126, PubMed:21364656, PubMed:25778398, PubMed:28218735, PubMed:9859993). Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis (PubMed:16322459). Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules (PubMed:20826784). Involved in the recruitment of CPC to centromeres during early mitosis via association with histone H3 phosphorylated at 'Thr-3' (H3pT3) during mitosis (PubMed:20929775). The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255). May counteract a default induction of apoptosis in G2/M phase (PubMed:9859993). The acetylated form represses STAT3 transactivation of target gene promoters (PubMed:20826784). May play a role in neoplasia (PubMed:10626797). Inhibitor of CASP3 and CASP7 (PubMed:21536684). Essential for the maintenance of mitochondrial integrity and function (PubMed:25778398). Isoform 2 and isoform 3 do not appear to play vital roles in mitosis (PubMed:12773388, PubMed:16291752). Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform (PubMed:10626797). {ECO:0000269|PubMed:10626797, ECO:0000269|PubMed:12773388, ECO:0000269|PubMed:16291752, ECO:0000269|PubMed:16322459, ECO:0000269|PubMed:18591255, ECO:0000269|PubMed:20627126, ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:20929775, ECO:0000269|PubMed:21364656, ECO:0000269|PubMed:21536684, ECO:0000269|PubMed:25778398, ECO:0000269|PubMed:28218735, ECO:0000269|PubMed:9859993}.
O43237 DYNC1LI2 S203 ochoa Cytoplasmic dynein 1 light intermediate chain 2 (Dynein light intermediate chain 2, cytosolic) (LIC-2) (LIC53/55) Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. {ECO:0000305|PubMed:36071160}.
O43294 TGFB1I1 S82 ochoa Transforming growth factor beta-1-induced transcript 1 protein (Androgen receptor coactivator 55 kDa protein) (Androgen receptor-associated protein of 55 kDa) (Hydrogen peroxide-inducible clone 5 protein) (Hic-5) Functions as a molecular adapter coordinating multiple protein-protein interactions at the focal adhesion complex and in the nucleus. Links various intracellular signaling modules to plasma membrane receptors and regulates the Wnt and TGFB signaling pathways. May also regulate SLC6A3 and SLC6A4 targeting to the plasma membrane hence regulating their activity. In the nucleus, functions as a nuclear receptor coactivator regulating glucocorticoid, androgen, mineralocorticoid and progesterone receptor transcriptional activity. May play a role in the processes of cell growth, proliferation, migration, differentiation and senescence. May have a zinc-dependent DNA-binding activity. {ECO:0000269|PubMed:10075738, ECO:0000269|PubMed:11463817, ECO:0000269|PubMed:11856738, ECO:0000269|PubMed:12177201, ECO:0000269|PubMed:12445807, ECO:0000269|PubMed:12700349, ECO:0000269|PubMed:15211577, ECO:0000269|PubMed:15561701, ECO:0000269|PubMed:16141357, ECO:0000269|PubMed:16624805, ECO:0000269|PubMed:16803896, ECO:0000269|PubMed:16849583, ECO:0000269|PubMed:17166536, ECO:0000269|PubMed:17233630, ECO:0000269|PubMed:9032249}.
O43426 SYNJ1 S1292 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 S1156 ochoa|psp 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}.
O43639 NCK2 S275 ochoa Cytoplasmic protein NCK2 (Growth factor receptor-bound protein 4) (NCK adaptor protein 2) (Nck-2) (SH2/SH3 adaptor protein NCK-beta) Adapter protein which associates with tyrosine-phosphorylated growth factor receptors or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16835242}.
O60269 GPRIN2 S24 ochoa G protein-regulated inducer of neurite outgrowth 2 (GRIN2) May be involved in neurite outgrowth. {ECO:0000269|PubMed:10480904}.
O60346 PHLPP1 S336 ochoa|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}.
O60356 NUPR1 S22 ochoa Nuclear protein 1 (Candidate of metastasis 1) (Protein p8) Transcription regulator that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Thereby participates in the regulation of many processes namely cell-cycle, apoptosis, autophagy and DNA repair responses (PubMed:11056169, PubMed:11940591, PubMed:16300740, PubMed:16478804, PubMed:18690848, PubMed:19650074, PubMed:19723804, PubMed:20181828, PubMed:22565310, PubMed:22858377, PubMed:30451898). Controls cell cycle progression and protects cells from genotoxic stress induced by doxorubicin through the complex formation with TP53 and EP300 that binds CDKN1A promoter leading to transcriptional induction of CDKN1A (PubMed:18690848). Protects pancreatic cancer cells from stress-induced cell death by binding the RELB promoter and activating its transcription, leading to IER3 transactivation (PubMed:22565310). Negatively regulates apoptosis through interaction with PTMA (PubMed:16478804). Inhibits autophagy-induced apoptosis in cardiac cells through FOXO3 interaction, inducing cytoplasmic translocation of FOXO3 thereby preventing the FOXO3 association with the pro-autophagic BNIP3 promoter (PubMed:20181828). Inhibits cell growth and facilitates programmed cell death by apoptosis after adriamycin-induced DNA damage through transactivation of TP53 (By similarity). Regulates methamphetamine-induced apoptosis and autophagy through DDIT3-mediated endoplasmic reticulum stress pathway (By similarity). Participates in DNA repair following gamma-irradiation by facilitating DNA access of the transcription machinery through interaction with MSL1 leading to inhibition of histone H4' Lys-16' acetylation (H4K16ac) (PubMed:19650074). Coactivator of PAX2 transcription factor activity, both by recruiting EP300 to increase PAX2 transcription factor activity and by binding PAXIP1 to suppress PAXIP1-induced inhibition on PAX2 (PubMed:11940591). Positively regulates cell cycle progression through interaction with COPS5 inducing cytoplasmic translocation of CDKN1B leading to the CDKN1B degradation (PubMed:16300740). Coordinates, through its interaction with EP300, the assiociation of MYOD1, EP300 and DDX5 to the MYOG promoter, leading to inhibition of cell-cycle progression and myogenic differentiation promotion (PubMed:19723804). Negatively regulates beta cell proliferation via inhibition of cell-cycle regulatory genes expression through the suppression of their promoter activities (By similarity). Also required for LHB expression and ovarian maturation (By similarity). Exacerbates CNS inflammation and demyelination upon cuprizone treatment (By similarity). {ECO:0000250|UniProtKB:O54842, ECO:0000250|UniProtKB:Q9WTK0, ECO:0000269|PubMed:11056169, ECO:0000269|PubMed:11940591, ECO:0000269|PubMed:16300740, ECO:0000269|PubMed:16478804, ECO:0000269|PubMed:18690848, ECO:0000269|PubMed:19650074, ECO:0000269|PubMed:19723804, ECO:0000269|PubMed:20181828, ECO:0000269|PubMed:22565310, ECO:0000269|PubMed:22858377, ECO:0000269|PubMed:30451898}.
O60732 MAGEC1 S58 ochoa Melanoma-associated antigen C1 (Cancer/testis antigen 7.1) (CT7.1) (MAGE-C1 antigen) None
O75061 DNAJC6 S625 ochoa Auxilin (EC 3.1.3.-) (DnaJ homolog subfamily C member 6) May act as a protein phosphatase and/or a lipid phosphatase. Co-chaperone that recruits HSPA8/HSC70 to clathrin-coated vesicles (CCVs) and promotes the ATP-dependent dissociation of clathrin from CCVs and participates in clathrin-mediated endocytosis of synaptic vesicles and their recycling and also in intracellular trafficking (PubMed:18489706). Firstly, binds tightly to the clathrin cages, at a ratio of one DNAJC6 per clathrin triskelion. The HSPA8:ATP complex then binds to the clathrin-auxilin cage, initially at a ratio of one HSPA8 per triskelion leading to ATP hydrolysis stimulation and causing a conformational change in the HSPA8. This cycle is repeated three times to drive to a complex containing the clathrin-auxilin cage associated to three HSPA8:ADP complex. The ATP hydrolysis of the third HSPA8:ATP complex leads to a concerted dismantling of the cage into component triskelia. Then, dissociates from the released triskelia and be recycled to initiate another cycle of HSPA8's recruitment. Also acts during the early steps of clathrin-coated vesicle (CCV) formation through its interaction with the GTP bound form of DNM1 (By similarity). {ECO:0000250|UniProtKB:Q27974, ECO:0000269|PubMed:18489706}.
O75154 RAB11FIP3 S52 ochoa Rab11 family-interacting protein 3 (FIP3) (FIP3-Rab11) (Rab11-FIP3) (Arfophilin-1) (EF hands-containing Rab-interacting protein) (Eferin) (MU-MB-17.148) Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery (PubMed:15601896, PubMed:16148947, PubMed:17394487, PubMed:17628206, PubMed:18511905, PubMed:19327867, PubMed:20026645, PubMed:25673879, PubMed:26258637, PubMed:31204173). Recruited by Rab11 to endosomes where it links Rab11 to dynein motor complex (PubMed:20026645). The functional Rab11-RAB11FIP3-dynein complex regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endocytic recycling compartment (ERC) during interphase of cell cycle (PubMed:17394487, PubMed:20026645). Facilitates the interaction between dynein and dynactin and activates dynein processivity (PubMed:25035494). Binding with ASAP1 is needed to regulate the pericentrosomal localization of recycling endosomes (By similarity). The Rab11-RAB11FIP3 complex is also implicated in the transport during telophase of vesicles derived from recycling endosomes to the cleavage furrow via centrosome-anchored microtubules, where the vesicles function to deliver membrane during late cytokinesis and abscission (PubMed:15601896, PubMed:16148947). The recruitment of Rab11-RAB11FIP3-containing endosomes to the cleavage furrow and tethering to the midbody is co-mediated by RAB11FIP3 interaction with ARF6-exocyst and RACGAP1-MKLP1 tethering complexes (PubMed:17628206, PubMed:18511905). Also involved in the Rab11-Rabin8-Rab8 ciliogenesis cascade by facilitating the orderly assembly of a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which directs preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:26258637, PubMed:31204173). Also promotes the activity of Rab11 and ASAP1 in the ARF4-dependent Golgi-to-cilia transport of the sensory receptor rhodopsin (PubMed:25673879). Competes with WDR44 for binding to Rab11, which controls intracellular ciliogenesis pathway (PubMed:31204173). May play a role in breast cancer cell motility by regulating actin cytoskeleton (PubMed:19327867). {ECO:0000250|UniProtKB:Q8CHD8, ECO:0000269|PubMed:15601896, ECO:0000269|PubMed:16148947, ECO:0000269|PubMed:17394487, ECO:0000269|PubMed:17628206, ECO:0000269|PubMed:18511905, ECO:0000269|PubMed:19327867, ECO:0000269|PubMed:20026645, ECO:0000269|PubMed:25035494, ECO:0000269|PubMed:25673879, ECO:0000269|PubMed:26258637, ECO:0000269|PubMed:31204173}.
O75781 PALM S356 ochoa Paralemmin-1 (Paralemmin) Involved in plasma membrane dynamics and cell process formation. Isoform 1 and isoform 2 are necessary for axonal and dendritic filopodia induction, for dendritic spine maturation and synapse formation in a palmitoylation-dependent manner. {ECO:0000269|PubMed:14978216}.
O75962 TRIO S2426 ochoa Triple functional domain protein (EC 2.7.11.1) (PTPRF-interacting protein) Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity). {ECO:0000250|UniProtKB:F1M0Z1, ECO:0000269|PubMed:10341202, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:27418539, ECO:0000269|PubMed:32109419, ECO:0000269|PubMed:8643598}.
O75995 SASH3 S349 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}.
O94804 STK10 S488 ochoa Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}.
O94826 TOMM70 S110 ochoa Mitochondrial import receptor subunit TOM70 (Mitochondrial precursor proteins import receptor) (Translocase of outer membrane 70 kDa subunit) (Translocase of outer mitochondrial membrane protein 70) Acts as a receptor of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex) (PubMed:12526792). Recognizes and mediates the translocation of mitochondrial preproteins from the cytosol into the mitochondria in a chaperone dependent manner (PubMed:12526792, PubMed:35025629). Mediates TBK1 and IRF3 activation induced by MAVS in response to Sendai virus infection and promotes host antiviral responses during virus infection (PubMed:20628368, PubMed:25609812, PubMed:32728199). Upon Sendai virus infection, recruits HSP90AA1:IRF3:BAX in mitochondrion and the complex induces apoptosis (PubMed:25609812). {ECO:0000269|PubMed:12526792, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:25609812, ECO:0000269|PubMed:32728199, ECO:0000269|PubMed:35025629}.
O94880 PHF14 S572 ochoa PHD finger protein 14 Histone-binding protein (PubMed:23688586). Binds preferentially to unmodified histone H3 but can also bind to a lesser extent to histone H3 trimethylated at 'Lys-9' (H3K9me3) as well as to histone H3 monomethylated at 'Lys-27' (H3K27ac) and trimethylated at 'Lys-27' (H3K27me3) (By similarity). Represses PDGFRA expression, thus playing a role in regulation of mesenchymal cell proliferation (By similarity). Suppresses the expression of CDKN1A/p21 by reducing the level of trimethylation of histone H3 'Lys-4', leading to enhanced proliferation of germinal center B cells (By similarity). {ECO:0000250|UniProtKB:A0A286Y9D1, ECO:0000250|UniProtKB:Q9D4H9, ECO:0000269|PubMed:23688586}.
O95049 TJP3 S845 ochoa Tight junction protein ZO-3 (Tight junction protein 3) (Zona occludens protein 3) (Zonula occludens protein 3) TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}.
O95382 MAP3K6 S964 ochoa|psp Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2) Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways. {ECO:0000269|PubMed:17210579, ECO:0000269|PubMed:9875215}.
P03372 ESR1 S341 psp Estrogen receptor (ER) (ER-alpha) (Estradiol receptor) (Nuclear receptor subfamily 3 group A member 1) Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.; FUNCTION: [Isoform 3]: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861). {ECO:0000269|PubMed:10970861, ECO:0000269|PubMed:21937726}.
P05412 JUN S249 ochoa|psp Transcription factor Jun (Activator protein 1) (AP1) (Proto-oncogene c-Jun) (Transcription factor AP-1 subunit Jun) (V-jun avian sarcoma virus 17 oncogene homolog) (p39) Transcription factor that recognizes and binds to the AP-1 consensus motif 5'-TGA[GC]TCA-3' (PubMed:10995748, PubMed:22083952). Heterodimerizes with proteins of the FOS family to form an AP-1 transcription complex, thereby enhancing its DNA binding activity to the AP-1 consensus sequence 5'-TGA[GC]TCA-3' and enhancing its transcriptional activity (By similarity). Together with FOSB, plays a role in activation-induced cell death of T cells by binding to the AP-1 promoter site of FASLG/CD95L, and inducing its transcription in response to activation of the TCR/CD3 signaling pathway (PubMed:12618758). Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation (PubMed:17210646). Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306). {ECO:0000250|UniProtKB:P05627, ECO:0000269|PubMed:10995748, ECO:0000269|PubMed:12618758, ECO:0000269|PubMed:17210646, ECO:0000269|PubMed:22083952, ECO:0000269|PubMed:24623306}.; FUNCTION: (Microbial infection) Upon Epstein-Barr virus (EBV) infection, binds to viral BZLF1 Z promoter and activates viral BZLF1 expression. {ECO:0000269|PubMed:31341047}.
P05549 TFAP2A S223 ochoa Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2) Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region. {ECO:0000269|PubMed:11694877, ECO:0000269|PubMed:12586840}.
P08651 NFIC S487 ochoa Nuclear factor 1 C-type (NF1-C) (Nuclear factor 1/C) (CCAAT-box-binding transcription factor) (CTF) (Nuclear factor I/C) (NF-I/C) (NFI-C) (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.
P09874 PARP1 S385 ochoa Poly [ADP-ribose] polymerase 1 (PARP-1) (EC 2.4.2.30) (ADP-ribosyltransferase diphtheria toxin-like 1) (ARTD1) (DNA ADP-ribosyltransferase PARP1) (EC 2.4.2.-) (NAD(+) ADP-ribosyltransferase 1) (ADPRT 1) (Poly[ADP-ribose] synthase 1) (Protein poly-ADP-ribosyltransferase PARP1) (EC 2.4.2.-) [Cleaved into: Poly [ADP-ribose] polymerase 1, processed C-terminus (Poly [ADP-ribose] polymerase 1, 89-kDa form); Poly [ADP-ribose] polymerase 1, processed N-terminus (NT-PARP-1) (Poly [ADP-ribose] polymerase 1, 24-kDa form) (Poly [ADP-ribose] polymerase 1, 28-kDa form)] Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18055453, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:20388712, PubMed:21680843, PubMed:22582261, PubMed:23230272, PubMed:25043379, PubMed:26344098, PubMed:26626479, PubMed:26626480, PubMed:30104678, PubMed:31796734, PubMed:32028527, PubMed:32241924, PubMed:32358582, PubMed:33186521, PubMed:34465625, PubMed:34737271). Mediates glutamate, aspartate, serine, histidine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836, PubMed:35393539, PubMed:7852410, PubMed:9315851). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521, PubMed:34874266). Specificity for the different amino acids is conferred by interacting factors, such as HPF1 and NMNAT1 (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 confers serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:32028527, PubMed:33186521, PubMed:33589610, PubMed:34625544, PubMed:34874266). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:29954836, PubMed:30257210). Following interaction with NMNAT1, catalyzes glutamate and aspartate ADP-ribosylation of target proteins; NMNAT1 confers glutamate and aspartate specificity (By similarity). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones (H2BS6ADPr and H3S10ADPr), thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600, PubMed:34465625, PubMed:34874266). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP1 in order to limit the length of poly-ADP-ribose chains (PubMed:33683197, PubMed:34732825, PubMed:34795260). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly-ADP-ribosylation of a number of proteins, including itself, APLF, CHFR, RPA1 and NFAT5 (PubMed:17396150, PubMed:19764761, PubMed:24906880, PubMed:34049076). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). PARP1-mediated DNA repair in neurons plays a role in sleep: senses DNA damage in neurons and promotes sleep, facilitating efficient DNA repair (By similarity). In addition to DNA repair, also involved in other processes, such as transcription regulation, programmed cell death, membrane repair, adipogenesis and innate immunity (PubMed:15607977, PubMed:17177976, PubMed:19344625, PubMed:27256882, PubMed:32315358, PubMed:32844745, PubMed:35124853, PubMed:35393539, PubMed:35460603). Acts as a repressor of transcription: binds to nucleosomes and modulates chromatin structure in a manner similar to histone H1, thereby altering RNA polymerase II (PubMed:15607977, PubMed:22464733). Acts both as a positive and negative regulator of transcription elongation, depending on the context (PubMed:27256882, PubMed:35393539). Acts as a positive regulator of transcription elongation by mediating poly-ADP-ribosylation of NELFE, preventing RNA-binding activity of NELFE and relieving transcription pausing (PubMed:27256882). Acts as a negative regulator of transcription elongation in response to DNA damage by catalyzing poly-ADP-ribosylation of CCNT1, disrupting the phase separation activity of CCNT1 and subsequent activation of CDK9 (PubMed:35393539). Involved in replication fork progression following interaction with CARM1: mediates poly-ADP-ribosylation at replication forks, slowing fork progression (PubMed:33412112). Poly-ADP-ribose chains generated by PARP1 also play a role in poly-ADP-ribose-dependent cell death, a process named parthanatos (By similarity). Also acts as a negative regulator of the cGAS-STING pathway (PubMed:32315358, PubMed:32844745, PubMed:35460603). Acts by mediating poly-ADP-ribosylation of CGAS: PARP1 translocates into the cytosol following phosphorylation by PRKDC and catalyzes poly-ADP-ribosylation and inactivation of CGAS (PubMed:35460603). Acts as a negative regulator of adipogenesis: catalyzes poly-ADP-ribosylation of histone H2B on 'Glu-35' (H2BE35ADPr) following interaction with NMNAT1, inhibiting phosphorylation of H2B at 'Ser-36' (H2BS36ph), thereby blocking expression of pro-adipogenetic genes (By similarity). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). {ECO:0000250|UniProtKB:P11103, ECO:0000269|PubMed:15607977, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:17396150, ECO:0000269|PubMed:18055453, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19344625, ECO:0000269|PubMed:19661379, ECO:0000269|PubMed:19764761, ECO:0000269|PubMed:20388712, ECO:0000269|PubMed:21680843, ECO:0000269|PubMed:22464733, ECO:0000269|PubMed:22582261, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24906880, ECO:0000269|PubMed:25043379, ECO:0000269|PubMed:26344098, ECO:0000269|PubMed:26626479, ECO:0000269|PubMed:26626480, ECO:0000269|PubMed:27067600, ECO:0000269|PubMed:27256882, ECO:0000269|PubMed:27257257, ECO:0000269|PubMed:27471034, ECO:0000269|PubMed:28190768, ECO:0000269|PubMed:29954836, ECO:0000269|PubMed:30104678, ECO:0000269|PubMed:30257210, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31796734, ECO:0000269|PubMed:32028527, ECO:0000269|PubMed:32241924, ECO:0000269|PubMed:32315358, ECO:0000269|PubMed:32358582, ECO:0000269|PubMed:32844745, ECO:0000269|PubMed:33186521, ECO:0000269|PubMed:33412112, ECO:0000269|PubMed:33589610, ECO:0000269|PubMed:33683197, ECO:0000269|PubMed:34049076, ECO:0000269|PubMed:34465625, ECO:0000269|PubMed:34625544, ECO:0000269|PubMed:34732825, ECO:0000269|PubMed:34737271, ECO:0000269|PubMed:34795260, ECO:0000269|PubMed:34874266, ECO:0000269|PubMed:35124853, ECO:0000269|PubMed:35393539, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:7852410, ECO:0000269|PubMed:9315851}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed C-terminus]: Promotes AIFM1-mediated apoptosis (PubMed:33168626). This form, which translocates into the cytoplasm following cleavage by caspase-3 (CASP3) and caspase-7 (CASP7) in response to apoptosis, is auto-poly-ADP-ribosylated and serves as a poly-ADP-ribose carrier to induce AIFM1-mediated apoptosis (PubMed:33168626). {ECO:0000269|PubMed:33168626}.; FUNCTION: [Poly [ADP-ribose] polymerase 1, processed N-terminus]: This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis. {ECO:0000269|PubMed:35104452}.
P0C7P1 RBMY1D S176 ochoa RNA-binding motif protein, Y chromosome, family 1 member D RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis.
P0C7T5 ATXN1L S215 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}.
P0DJD3 RBMY1A1 S176 ochoa RNA-binding motif protein, Y chromosome, family 1 member A1 (RNA-binding motif protein 1) (RNA-binding motif protein 2) (Y chromosome RNA recognition motif 1) (hRBMY) RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:8269511}.
P0DJD4 RBMY1C S176 ochoa RNA-binding motif protein, Y chromosome, family 1 member C RNA-binding protein involved in pre-mRNA splicing. Required for sperm development. Acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN. Binds non-specifically to mRNAs.
P11137 MAP2 S1799 ochoa Microtubule-associated protein 2 (MAP-2) The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules.
P13498 CYBA S168 ochoa Cytochrome b-245 light chain (Cytochrome b(558) alpha chain) (Cytochrome b558 subunit alpha) (Neutrophil cytochrome b 22 kDa polypeptide) (Superoxide-generating NADPH oxidase light chain subunit) (p22 phagocyte B-cytochrome) (p22-phox) (p22phox) Subunit of NADPH oxidase complexes that is required for the NADPH oxidase activity that generates, in various cell types, superoxide from molecular oxygen utilizing NADPH as an electron donor (PubMed:15824103, PubMed:17140397, PubMed:38355798). Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:38355798). 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 (PubMed:38355798). 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 (PubMed:38355798). This activation process is initiated by phosphorylation dependent binding of the cytosolic NCF1/p47-phox subunit to the C-terminus of CYBA/p22-phox (PubMed:19948736). Aassociates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide (PubMed:15824103, PubMed:17140397). {ECO:0000269|PubMed:15824103, ECO:0000269|PubMed:17140397, ECO:0000269|PubMed:19948736, ECO:0000269|PubMed:38355798}.
P16871 IL7R S366 ochoa Interleukin-7 receptor subunit alpha (IL-7 receptor subunit alpha) (IL-7R subunit alpha) (IL-7R-alpha) (IL-7RA) (CDw127) (CD antigen CD127) Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).
P18146 EGR1 S104 psp Early growth response protein 1 (EGR-1) (AT225) (Nerve growth factor-induced protein A) (NGFI-A) (Transcription factor ETR103) (Transcription factor Zif268) (Zinc finger protein 225) (Zinc finger protein Krox-24) Transcriptional regulator (PubMed:20121949). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (PubMed:25258363, PubMed:25999311). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. Required for normal progress through mitosis and normal proliferation of hepatocytes after partial hepatectomy. Mediates responses to ischemia and hypoxia; regulates the expression of proteins such as IL1B and CXCL2 that are involved in inflammatory processes and development of tissue damage after ischemia. Regulates biosynthesis of luteinizing hormone (LHB) in the pituitary (By similarity). Regulates the amplitude of the expression rhythms of clock genes: BMAL1, PER2 and NR1D1 in the liver via the activation of PER1 (clock repressor) transcription. Regulates the rhythmic expression of core-clock gene BMAL1 in the suprachiasmatic nucleus (SCN) (By similarity). {ECO:0000250|UniProtKB:P08046, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:25258363, ECO:0000269|PubMed:25999311}.
P20823 HNF1A S313 ochoa Hepatocyte nuclear factor 1-alpha (HNF-1-alpha) (HNF-1A) (Liver-specific transcription factor LF-B1) (LFB1) (Transcription factor 1) (TCF-1) Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver (By similarity). Binds to the inverted palindrome 5'-GTTAATNATTAAC-3' (PubMed:10966642, PubMed:12453420). Activates the transcription of CYP1A2, CYP2E1 and CYP3A11 (By similarity). {ECO:0000250|UniProtKB:P22361, ECO:0000269|PubMed:10966642, ECO:0000269|PubMed:12453420}.; FUNCTION: (Microbial infection) Plays a crucial role for hepatitis B virus gene transcription and DNA replication. Mechanistically, synergistically cooperates with NR5A2 to up-regulate the activity of one of the critical cis-elements in the hepatitis B virus genome enhancer II (ENII). {ECO:0000269|PubMed:14728801, ECO:0000269|PubMed:38018242}.
P21554 CNR1 S429 psp Cannabinoid receptor 1 (CB-R) (CB1) (CANN6) G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission (By similarity). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (PubMed:17895407). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (By similarity). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712). {ECO:0000250|UniProtKB:O02777, ECO:0000250|UniProtKB:P47746, ECO:0000269|PubMed:15620723, ECO:0000269|PubMed:1718258, ECO:0000269|PubMed:17895407, ECO:0000269|PubMed:21895628, ECO:0000269|PubMed:23955712, ECO:0000269|PubMed:27768894, ECO:0000269|PubMed:27851727}.; FUNCTION: [Isoform 1]: Binds both 2-arachidonoylglycerol (2-AG) and anandamide. {ECO:0000269|PubMed:15620723}.; FUNCTION: [Isoform 2]: Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 2 in assays measuring GTP binding to membranes. {ECO:0000269|PubMed:15620723}.; FUNCTION: [Isoform 3]: Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 3 in assays measuring GTP binding to membranes. {ECO:0000269|PubMed:15620723}.
P30305 CDC25B S169 psp M-phase inducer phosphatase 2 (EC 3.1.3.48) (Dual specificity phosphatase Cdc25B) Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression (PubMed:1836978, PubMed:20360007). Directly dephosphorylates CDK1 and stimulates its kinase activity (PubMed:20360007). Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner (PubMed:17332740). The three isoforms seem to have a different level of activity (PubMed:1836978). {ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:1836978, ECO:0000269|PubMed:20360007}.
P31260 HOXA10 S322 ochoa Homeobox protein Hox-A10 (Homeobox protein Hox-1.8) (Homeobox protein Hox-1H) (PL) Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to the DNA sequence 5'-AA[AT]TTTTATTAC-3'.
P31930 UQCRC1 S212 ochoa Cytochrome b-c1 complex subunit 1, mitochondrial (Complex III subunit 1) (Core protein I) (Ubiquinol-cytochrome-c reductase complex core protein 1) Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c (By similarity). The 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2 are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively, and they seem to have preserved their MPP processing properties (By similarity). May be involved in the in situ processing of UQCRFS1 into the mature Rieske protein and its mitochondrial targeting sequence (MTS)/subunit 9 when incorporated into complex III (Probable). Seems to play an important role in the maintenance of proper mitochondrial function in nigral dopaminergic neurons (PubMed:33141179). {ECO:0000250|UniProtKB:P07256, ECO:0000250|UniProtKB:P31800, ECO:0000269|PubMed:33141179, ECO:0000305|PubMed:29243944}.
P35568 IRS1 S463 ochoa Insulin receptor substrate 1 (IRS-1) Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:11171109, PubMed:8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}.
P40337 VHL S111 psp von Hippel-Lindau disease tumor suppressor (Protein G7) (pVHL) Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions (PubMed:10944113, PubMed:17981124). Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases (PubMed:10944113, PubMed:17981124). Ubiquitinates, in an oxygen-responsive manner, ADRB2 (PubMed:19584355). Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR (PubMed:34290272). {ECO:0000269|PubMed:10944113, ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:19584355, ECO:0000269|PubMed:34290272}.
P43268 ETV4 S149 ochoa ETS translocation variant 4 (Adenovirus E1A enhancer-binding protein) (E1A-F) (Polyomavirus enhancer activator 3 homolog) (Protein PEA3) Transcriptional activator (PubMed:19307308, PubMed:31552090). May play a role in keratinocyte differentiation (PubMed:31552090). {ECO:0000269|PubMed:19307308, ECO:0000269|PubMed:31552090}.; FUNCTION: (Microbial infection) Binds to the enhancer of the adenovirus E1A gene and acts as a transcriptional activator; the core-binding sequence is 5'-[AC]GGA[AT]GT-3'. {ECO:0000269|PubMed:8441666}.
P46821 MAP1B S2218 ochoa Microtubule-associated protein 1B (MAP-1B) [Cleaved into: MAP1B heavy chain; MAP1 light chain LC1] Facilitates tyrosination of alpha-tubulin in neuronal microtubules (By similarity). Phosphorylated MAP1B is required for proper microtubule dynamics and plays a role in the cytoskeletal changes that accompany neuronal differentiation and neurite extension (PubMed:33268592). Possibly MAP1B binds to at least two tubulin subunits in the polymer, and this bridging of subunits might be involved in nucleating microtubule polymerization and in stabilizing microtubules. Acts as a positive cofactor in DAPK1-mediated autophagic vesicle formation and membrane blebbing. {ECO:0000250, ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:33268592}.
P46937 YAP1 S298 ochoa Transcriptional coactivator YAP1 (Yes-associated protein 1) (Protein yorkie homolog) (Yes-associated protein YAP65 homolog) Transcriptional regulator with dual roles as a coactivator and corepressor. Critical downstream regulatory target in the Hippo signaling pathway, crucial for organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The Hippo signaling pathway core involves a kinase cascade featuring STK3/MST2 and STK4/MST1, along with its regulatory partner SAV1, which phosphorylates and activates LATS1/2 in complex with their regulatory protein, MOB1. This activation leads to the phosphorylation and inactivation of the YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Phosphorylation of YAP1 by LATS1/2 prevents its nuclear translocation, thereby regulating the expression of its target genes (PubMed:18158288, PubMed:26598551, PubMed:34404733). The transcriptional regulation of gene expression requires TEAD transcription factors and modulates cell growth, anchorage-independent growth, and induction of epithelial-mesenchymal transition (EMT) (PubMed:18579750). Plays a key role in tissue tension and 3D tissue shape by regulating the cortical actomyosin network, acting via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). It also suppresses ciliogenesis by acting as a transcriptional corepressor of TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, regulates TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). Synergizes with WBP2 to enhance PGR activity (PubMed:16772533). {ECO:0000250|UniProtKB:P46938, ECO:0000269|PubMed:16772533, ECO:0000269|PubMed:17974916, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:25778702, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:30447097, ECO:0000269|PubMed:34404733}.; FUNCTION: [Isoform 2]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.; FUNCTION: [Isoform 3]: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3). {ECO:0000269|PubMed:12807903}.
P50570 DNM2 S848 psp 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}.
P51532 SMARCA4 S613 ochoa|psp SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4 (SMARCA4) (EC 3.6.4.-) (BRG1-associated factor 190A) (BAF190A) (Mitotic growth and transcription activator) (Protein BRG-1) (Protein brahma homolog 1) (SNF2-beta) (Transcription activator BRG1) ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:15075294, PubMed:29374058, PubMed:30339381, PubMed:32459350). Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves the release of HDAC1 and recruitment of CREBBP (By similarity). 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. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1 (PubMed:20418909). Binds via DLX1 to enhancers located in the intergenic region between DLX5 and DLX6 and this binding is stabilized by the long non-coding RNA (lncRNA) Evf2 (By similarity). Binds to RNA in a promiscuous manner (By similarity). In brown adipose tissue, involved in the regulation of thermogenic genes expression (By similarity). {ECO:0000250|UniProtKB:Q3TKT4, ECO:0000250|UniProtKB:Q8K1P7, ECO:0000269|PubMed:15075294, ECO:0000269|PubMed:19571879, ECO:0000269|PubMed:20418909, ECO:0000269|PubMed:29374058, ECO:0000269|PubMed:30339381, ECO:0000269|PubMed:32459350, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
P53350 PLK1 S331 ochoa Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13) Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250|UniProtKB:P70032, ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080, ECO:0000269|PubMed:8991084}.
P54296 MYOM2 S549 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.
P55198 MLLT6 S438 ochoa Protein AF-17 (ALL1-fused gene from chromosome 17 protein) None
P55287 CDH11 S714 ochoa Cadherin-11 (OSF-4) (Osteoblast cadherin) (OB-cadherin) Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Required for proper focal adhesion assembly (PubMed:33811546). Involved in the regulation of cell migration (PubMed:33811546). {ECO:0000269|PubMed:33811546}.
P58004 SESN2 S249 ochoa Sestrin-2 (EC 1.11.1.-) (Hypoxia-induced gene) Functions as an intracellular leucine sensor that negatively regulates the mTORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents mTORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26586190, PubMed:26612684, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100, PubMed:35831510, PubMed:36528027). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via mTORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821). {ECO:0000269|PubMed:15105503, ECO:0000269|PubMed:18692468, ECO:0000269|PubMed:19113821, ECO:0000269|PubMed:23274085, ECO:0000269|PubMed:24947615, ECO:0000269|PubMed:25263562, ECO:0000269|PubMed:25457612, ECO:0000269|PubMed:26449471, ECO:0000269|PubMed:26586190, ECO:0000269|PubMed:26612684, ECO:0000269|PubMed:35114100, ECO:0000269|PubMed:35831510, ECO:0000269|PubMed:36528027}.
P81408 ENTREP3 S493 ochoa Protein ENTREP3 (Endosomal transmembrane epsin interactor 3) (Protein COTE1) None
P81408 ENTREP3 S574 ochoa Protein ENTREP3 (Endosomal transmembrane epsin interactor 3) (Protein COTE1) None
P98095 FBLN2 S578 ochoa Fibulin-2 (FIBL-2) Its binding to fibronectin and some other ligands is calcium dependent. May act as an adapter that mediates the interaction between FBN1 and ELN (PubMed:17255108). {ECO:0000269|PubMed:17255108}.
Q02750 MAP2K1 S304 ochoa 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}.
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 S704 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 S372 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}.
Q06413 MEF2C S183 ochoa Myocyte-specific enhancer factor 2C (Myocyte enhancer factor 2C) Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Enhances transcriptional activation mediated by SOX18. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B-lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B-cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoforms that lack the repressor domain are more active than isoform 1. {ECO:0000250|UniProtKB:Q8CFN5, ECO:0000269|PubMed:11904443, ECO:0000269|PubMed:15340086, ECO:0000269|PubMed:15831463, ECO:0000269|PubMed:15834131, ECO:0000269|PubMed:9069290, ECO:0000269|PubMed:9384584}.
Q07157 TJP1 S131 ochoa Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}.
Q07157 TJP1 S411 ochoa Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}.
Q07157 TJP1 S1446 ochoa Tight junction protein 1 (Tight junction protein ZO-1) (Zona occludens protein 1) (Zonula occludens protein 1) TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). Forms a multistranded TJP1/ZO1 condensate which elongates to form a tight junction belt, the belt is anchored at the apical cell membrane via interaction with PATJ (By similarity). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). May play a role in mediating cell morphology changes during ameloblast differentiation via its role in tight junctions (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000250|UniProtKB:P39447, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}.
Q12888 TP53BP1 S782 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q12888 TP53BP1 S1435 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q12888 TP53BP1 S1665 ochoa TP53-binding protein 1 (53BP1) (p53-binding protein 1) (p53BP1) Double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics and class-switch recombination (CSR) during antibody genesis (PubMed:12364621, PubMed:17190600, PubMed:21144835, PubMed:22553214, PubMed:23333306, PubMed:27153538, PubMed:28241136, PubMed:31135337, PubMed:37696958). Plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1 (PubMed:22553214, PubMed:23333306, PubMed:23727112, PubMed:27153538, PubMed:31135337). In response to DSBs, phosphorylation by ATM promotes interaction with RIF1 and dissociation from NUDT16L1/TIRR, leading to recruitment to DSBs sites (PubMed:28241136). Recruited to DSBs sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSBs sites (PubMed:17190600, PubMed:23760478, PubMed:27153538, PubMed:28241136). Required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (PubMed:23345425). Participates in the repair and the orientation of the broken DNA ends during CSR (By similarity). In contrast, it is not required for classic NHEJ and V(D)J recombination (By similarity). Promotes NHEJ of dysfunctional telomeres via interaction with PAXIP1 (PubMed:23727112). {ECO:0000250|UniProtKB:P70399, ECO:0000269|PubMed:12364621, ECO:0000269|PubMed:17190600, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:22553214, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:23345425, ECO:0000269|PubMed:23727112, ECO:0000269|PubMed:23760478, ECO:0000269|PubMed:27153538, ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:31135337, ECO:0000269|PubMed:37696958}.
Q12906 ILF3 S744 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}.
Q13009 TIAM1 S298 ochoa 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}.
Q13094 LCP2 S417 ochoa Lymphocyte cytosolic protein 2 (SH2 domain-containing leukocyte protein of 76 kDa) (SLP-76 tyrosine phosphoprotein) (SLP76) Adapter protein primarily involved in signaling pathways within T-cells, as well as other immune cells such as platelets, mast cells, and natural killer (NK) cells (PubMed:11313406, PubMed:33159816). Plays a crucial role for transducing signal from the T-cell receptor (TCR) after antigen recognition leading to T-cell activation. Mechanistically, once phosphorylated by the kinase ZAP70, mediates interactions with the guanine-nucleotide exchange factor VAV1, the adapter protein NCK and the kinase ITK (PubMed:8673706, PubMed:8702662). In turn, stimulates the activation of PKC-theta/PRKCQ and NF-kappa-B transcriptional activity in response to CD3 and CD28 costimulation (PubMed:11313406). Also plays an essential role in AGER-induced signaling pathways including p38 MAPK and ERK1/2 activation leading to cytokine release and pro-inflammatory responses (PubMed:33436632). {ECO:0000269|PubMed:11313406, ECO:0000269|PubMed:33436632, ECO:0000269|PubMed:8673706, ECO:0000269|PubMed:8702662}.
Q13200 PSMD2 S29 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.
Q13409 DYNC1I2 S104 ochoa Cytoplasmic dynein 1 intermediate chain 2 (Cytoplasmic dynein intermediate chain 2) (Dynein intermediate chain 2, cytosolic) (DH IC-2) Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function (PubMed:31079899). Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules (PubMed:31079899). The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1 (By similarity). Involved in membrane-transport, such as Golgi apparatus, late endosomes and lysosomes (By similarity). {ECO:0000250|UniProtKB:Q62871, ECO:0000269|PubMed:31079899}.
Q13428 TCOF1 S674 ochoa Treacle protein (Treacher Collins syndrome protein) Nucleolar protein that acts as a regulator of RNA polymerase I by connecting RNA polymerase I with enzymes responsible for ribosomal processing and modification (PubMed:12777385, PubMed:26399832). Required for neural crest specification: following monoubiquitination by the BCR(KBTBD8) complex, associates with NOLC1 and acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). {ECO:0000269|PubMed:12777385, ECO:0000269|PubMed:26399832}.
Q13443 ADAM9 S799 ochoa Disintegrin and metalloproteinase domain-containing protein 9 (ADAM 9) (EC 3.4.24.-) (Cellular disintegrin-related protein) (Meltrin-gamma) (Metalloprotease/disintegrin/cysteine-rich protein 9) (Myeloma cell metalloproteinase) Metalloprotease that cleaves and releases a number of molecules with important roles in tumorigenesis and angiogenesis, such as TEK, KDR, EPHB4, CD40, VCAM1 and CDH5. May mediate cell-cell, cell-matrix interactions and regulate the motility of cells via interactions with integrins. {ECO:0000250|UniProtKB:Q61072}.; FUNCTION: [Isoform 2]: May act as alpha-secretase for amyloid precursor protein (APP). {ECO:0000269|PubMed:12054541}.
Q13501 SQSTM1 S226 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}.
Q13554 CAMK2B S395 ochoa Calcium/calmodulin-dependent protein kinase type II subunit beta (CaM kinase II subunit beta) (CaMK-II subunit beta) (EC 2.7.11.17) Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle (PubMed:16690701). In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Also regulates the migration of developing neurons (PubMed:29100089). Participates in the modulation of skeletal muscle function in response to exercise (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity). Phosphorylates reticulophagy regulator RETREG1 at 'Ser-151' under endoplasmic reticulum stress conditions which enhances RETREG1 oligomerization and its membrane scission and reticulophagy activity (PubMed:31930741). {ECO:0000250|UniProtKB:P08413, ECO:0000269|PubMed:16690701, ECO:0000269|PubMed:29100089, ECO:0000269|PubMed:31930741}.
Q13671 RIN1 S291 ochoa|psp Ras and Rab interactor 1 (Ras inhibitor JC99) (Ras interaction/interference protein 1) Ras effector protein, which may serve as an inhibitory modulator of neuronal plasticity in aversive memory formation. Can affect Ras signaling at different levels. First, by competing with RAF1 protein for binding to activated Ras. Second, by enhancing signaling from ABL1 and ABL2, which regulate cytoskeletal remodeling. Third, by activating RAB5A, possibly by functioning as a guanine nucleotide exchange factor (GEF) for RAB5A, by exchanging bound GDP for free GTP, and facilitating Ras-activated receptor endocytosis. {ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9208849}.
Q13905 RAPGEF1 S313 ochoa Rap guanine nucleotide exchange factor 1 (CRK SH3-binding GNRP) (Guanine nucleotide-releasing factor 2) (Protein C3G) Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Involved in cell branching and adhesion mediated by BCAR1-CRK-RAPGEF1 signaling and activation of RAP1 (PubMed:12432078). Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. {ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:17724123, ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:7806500}.
Q14160 SCRIB S1353 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}.
Q14566 MCM6 S268 ochoa DNA replication licensing factor MCM6 (EC 3.6.4.12) (p105MCM) Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:16899510, PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232, PubMed:9305914). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). {ECO:0000269|PubMed:16899510, ECO:0000269|PubMed:32453425, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:34700328, ECO:0000269|PubMed:35585232, ECO:0000269|PubMed:9305914}.
Q14653 IRF3 S82 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}.
Q14686 NCOA6 S1238 ochoa Nuclear receptor coactivator 6 (Activating signal cointegrator 2) (ASC-2) (Amplified in breast cancer protein 3) (Cancer-amplified transcriptional coactivator ASC-2) (Nuclear receptor coactivator RAP250) (NRC RAP250) (Nuclear receptor-activating protein, 250 kDa) (Peroxisome proliferator-activated receptor-interacting protein) (PPAR-interacting protein) (PRIP) (Thyroid hormone receptor-binding protein) Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Coactivates expression in an agonist- and AF2-dependent manner. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ERs), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Probably functions as a general coactivator, rather than just a nuclear receptor coactivator. May also be involved in the coactivation of the NF-kappa-B pathway. May coactivate expression via a remodeling of chromatin and its interaction with histone acetyltransferase proteins.
Q14738 PPP2R5D S60 ochoa|psp Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform (PP2A B subunit isoform B'-delta) (PP2A B subunit isoform B56-delta) (PP2A B subunit isoform PR61-delta) (PP2A B subunit isoform R5-delta) The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.
Q14738 PPP2R5D S533 ochoa Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform (PP2A B subunit isoform B'-delta) (PP2A B subunit isoform B56-delta) (PP2A B subunit isoform PR61-delta) (PP2A B subunit isoform R5-delta) The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment.
Q14814 MEF2D S472 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}.
Q14980 NUMA1 S1750 ochoa Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}.
Q14980 NUMA1 S1947 ochoa Nuclear mitotic apparatus protein 1 (Nuclear matrix protein-22) (NMP-22) (Nuclear mitotic apparatus protein) (NuMA protein) (SP-H antigen) Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074, PubMed:7769006). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:11956313, PubMed:12445386). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:22327364, PubMed:23027904, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein-dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24371089, PubMed:24996901). Also binds to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24371089, PubMed:24996901). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}.
Q15415 RBMY1F S176 ochoa RNA-binding motif protein, Y chromosome, family 1 member F/J (Y chromosome RNA recognition motif 2) RNA-binding protein which may be involved in spermatogenesis. Required for sperm development, possibly by participating in pre-mRNA splicing in the testis. {ECO:0000269|PubMed:8269511}.
Q15637 SF1 S89 ochoa Splicing factor 1 (Mammalian branch point-binding protein) (BBP) (mBBP) (Transcription factor ZFM1) (Zinc finger gene in MEN1 locus) (Zinc finger protein 162) Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor. {ECO:0000269|PubMed:10449420, ECO:0000269|PubMed:8752089, ECO:0000269|PubMed:9660765}.
Q15642 TRIP10 S506 ochoa Cdc42-interacting protein 4 (Protein Felic) (Salt tolerant protein) (hSTP) (Thyroid receptor-interacting protein 10) (TR-interacting protein 10) (TRIP-10) Required for translocation of GLUT4 to the plasma membrane in response to insulin signaling (By similarity). Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Binds to lipids such as phosphatidylinositol 4,5-bisphosphate and phosphatidylserine and promotes membrane invagination and the formation of tubules. Also promotes CDC42-induced actin polymerization by recruiting WASL/N-WASP which in turn activates the Arp2/3 complex. Actin polymerization may promote the fission of membrane tubules to form endocytic vesicles. Required for the formation of podosomes, actin-rich adhesion structures specific to monocyte-derived cells. May be required for the lysosomal retention of FASLG/FASL. {ECO:0000250, ECO:0000269|PubMed:11069762, ECO:0000269|PubMed:16318909, ECO:0000269|PubMed:16326391}.
Q15652 JMJD1C S943 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}.
Q15654 TRIP6 S156 ochoa Thyroid receptor-interacting protein 6 (TR-interacting protein 6) (TRIP-6) (Opa-interacting protein 1) (OIP-1) (Zyxin-related protein 1) (ZRP-1) Relays signals from the cell surface to the nucleus to weaken adherens junction and promote actin cytoskeleton reorganization and cell invasiveness. Involved in lysophosphatidic acid-induced cell adhesion and migration. Acts as a transcriptional coactivator for NF-kappa-B and JUN, and mediates the transrepression of these transcription factors induced by glucocorticoid receptor. {ECO:0000269|PubMed:14688263, ECO:0000269|PubMed:15489293, ECO:0000269|PubMed:16624523, ECO:0000269|PubMed:19017743}.
Q15811 ITSN1 S313 ochoa Intersectin-1 (SH3 domain-containing protein 1A) (SH3P17) Adapter protein that provides a link between the endocytic membrane traffic and the actin assembly machinery (PubMed:11584276, PubMed:29887380). Acts as a guanine nucleotide exchange factor (GEF) for CDC42, and thereby stimulates actin nucleation mediated by WASL and the ARP2/3 complex (PubMed:11584276). Plays a role in the assembly and maturation of clathrin-coated vesicles (By similarity). Recruits FCHSD2 to clathrin-coated pits (PubMed:29887380). Involved in endocytosis of activated EGFR, and probably also other growth factor receptors (By similarity). Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2 (PubMed:22648170). Promotes ubiquitination and subsequent degradation of EGFR, and thereby contributes to the down-regulation of EGFR-dependent signaling pathways. In chromaffin cells, required for normal exocytosis of catecholamines. Required for rapid replenishment of release-ready synaptic vesicles at presynaptic active zones (By similarity). Inhibits ARHGAP31 activity toward RAC1 (PubMed:11744688). {ECO:0000250|UniProtKB:Q9WVE9, ECO:0000250|UniProtKB:Q9Z0R4, ECO:0000269|PubMed:11584276, ECO:0000269|PubMed:11744688, ECO:0000269|PubMed:22648170, ECO:0000269|PubMed:29887380}.; FUNCTION: [Isoform 1]: Plays a role in synaptic vesicle endocytosis in brain neurons. {ECO:0000250|UniProtKB:Q9Z0R4}.
Q15911 ZFHX3 S3418 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}.
Q15942 ZYX S143 ochoa Zyxin (Zyxin-2) Adhesion plaque protein. Binds alpha-actinin and the CRP protein. Important for targeting TES and ENA/VASP family members to focal adhesions and for the formation of actin-rich structures. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression (By similarity). {ECO:0000250}.
Q16849 PTPRN S302 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}.
Q24JP5 TMEM132A S988 ochoa Transmembrane protein 132A (HSPA5-binding protein 1) May play a role in embryonic and postnatal development of the brain. Increased resistance to cell death induced by serum starvation in cultured cells. Regulates cAMP-induced GFAP gene expression via STAT3 phosphorylation (By similarity). {ECO:0000250}.
Q3T8J9 GON4L S1436 ochoa GON-4-like protein (GON-4 homolog) Has transcriptional repressor activity, probably as part of a complex with YY1, SIN3A and HDAC1. Required for B cell lymphopoiesis. {ECO:0000250|UniProtKB:Q9DB00}.
Q53GL0 PLEKHO1 S271 ochoa Pleckstrin homology domain-containing family O member 1 (PH domain-containing family O member 1) (C-Jun-binding protein) (JBP) (Casein kinase 2-interacting protein 1) (CK2-interacting protein 1) (CKIP-1) (Osteoclast maturation-associated gene 120 protein) Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP). May function to target CK2 to the plasma membrane thereby serving as an adapter to facilitate the phosphorylation of CP by protein kinase 2 (CK2). Appears to target ATM to the plasma membrane. Appears to also inhibit tumor cell growth by inhibiting AKT-mediated cell-survival. Also implicated in PI3K-regulated muscle differentiation, the regulation of AP-1 activity (plasma membrane bound AP-1 regulator that translocates to the nucleus) and the promotion of apoptosis induced by tumor necrosis factor TNF. When bound to PKB, it inhibits it probably by decreasing PKB level of phosphorylation. {ECO:0000269|PubMed:14729969, ECO:0000269|PubMed:15706351, ECO:0000269|PubMed:15831458, ECO:0000269|PubMed:16325375, ECO:0000269|PubMed:16987810, ECO:0000269|PubMed:17197158, ECO:0000269|PubMed:17942896}.
Q5T5Y3 CAMSAP1 S470 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}.
Q5T6C5 ATXN7L2 S477 ochoa Ataxin-7-like protein 2 None
Q5T6F2 UBAP2 S468 ochoa Ubiquitin-associated protein 2 (UBAP-2) (RNA polymerase II degradation factor UBAP2) Recruits the ubiquitination machinery to RNA polymerase II for polyubiquitination, removal and degradation, when the transcription-coupled nucleotide excision repair (TC-NER) machinery fails to resolve DNA damage (PubMed:35633597). May promote the degradation of ANXA2 (PubMed:27121050). {ECO:0000269|PubMed:27121050, ECO:0000269|PubMed:35633597}.
Q5THJ4 VPS13D S1727 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}.
Q5THJ4 VPS13D S2861 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}.
Q641Q2 WASHC2A S441 ochoa WASH complex subunit 2A Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}.
Q641Q2 WASHC2A S1123 ochoa WASH complex subunit 2A Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission. Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1. Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35. Required for the endosomal recruitment of CCC complex subunits COMMD1 and CCDC93 as well as the retriever complex subunit VPS35L. {ECO:0000269|PubMed:25355947, ECO:0000269|PubMed:28892079}.
Q66K74 MAP1S S929 ochoa Microtubule-associated protein 1S (MAP-1S) (BPY2-interacting protein 1) (Microtubule-associated protein 8) (Variable charge Y chromosome 2-interacting protein 1) (VCY2-interacting protein 1) (VCY2IP-1) [Cleaved into: MAP1S heavy chain; MAP1S light chain] Microtubule-associated protein that mediates aggregation of mitochondria resulting in cell death and genomic destruction (MAGD). Plays a role in anchoring the microtubule organizing center to the centrosomes. Binds to DNA. Plays a role in apoptosis. Involved in the formation of microtubule bundles (By similarity). {ECO:0000250, ECO:0000269|PubMed:15899810, ECO:0000269|PubMed:17234756}.
Q6AI39 BICRAL S596 ochoa BRD4-interacting chromatin-remodeling complex-associated protein-like (Glioma tumor suppressor candidate region gene 1 protein-like) Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. {ECO:0000269|PubMed:29374058}.
Q6IQ32 ADNP2 S1024 ochoa Activity-dependent neuroprotector homeobox protein 2 (ADNP homeobox protein 2) (Zinc finger protein 508) May be involved in transcriptional regulation. May play a role in neuronal function; perhaps involved in protection of brain tissues from oxidative stress. May be involved in erythroid differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CHC8}.
Q6NUJ5 PWWP2B S456 ochoa PWWP domain-containing protein 2B Chromatin-binding protein that acts as an adapter between distinct nucleosome components (H3K36me3 or H2A.Z) and chromatin-modifying complexes, contributing to the regulation of the levels of histone acetylation at actively transcribed genes (PubMed:30228260). Competes with CHD4 and MBD3 for interaction with MTA1 to form a NuRD subcomplex, preventing the formation of full NuRD complex (containing CHD4 and MBD3), leading to recruitment of HDACs to gene promoters resulting in turn in the deacetylation of nearby H3K27 and H2A.Z (PubMed:30228260). Plays a role in facilitating transcriptional elongation through regulation of histone acetylation (By similarity). Negatively regulates brown adipocyte thermogenesis by interacting with and stabilizing HDAC1 at the UCP1 gene promoter, thereby promoting histone deacetylation at the promoter leading to the repression of UCP1 expression (By similarity). {ECO:0000250|UniProtKB:Q69Z61, ECO:0000269|PubMed:30228260}.
Q6NXT4 SLC30A6 S388 ochoa Zinc transporter 6 (ZnT-6) (Solute carrier family 30 member 6) Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway (PubMed:15994300, PubMed:19366695, PubMed:19759014). As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis (PubMed:15994300, PubMed:19759014, PubMed:35525268). {ECO:0000269|PubMed:15994300, ECO:0000269|PubMed:19366695, ECO:0000269|PubMed:19759014, ECO:0000269|PubMed:35525268}.
Q6PIY7 TENT2 S116 psp Poly(A) RNA polymerase GLD2 (hGLD-2) (EC 2.7.7.19) (PAP-associated domain-containing protein 4) (Terminal nucleotidyltransferase 2) (Terminal uridylyltransferase 2) (TUTase 2) Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail (PubMed:15070731, PubMed:31792053). In contrast to the canonical nuclear poly(A) RNA polymerase, it only adds poly(A) to selected cytoplasmic mRNAs (PubMed:15070731). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Adds a single nucleotide to the 3' end of specific miRNAs, monoadenylation stabilizes and prolongs the activity of some but not all miRNAs (PubMed:23200856, PubMed:31792053). {ECO:0000269|PubMed:15070731, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:23200856, ECO:0000269|PubMed:31792053}.
Q6PJT7 ZC3H14 S132 ochoa Zinc finger CCCH domain-containing protein 14 (Mammalian suppressor of tau pathology-2) (MSUT-2) (Renal carcinoma antigen NY-REN-37) RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs (PubMed:39461343). Acts by binding to both exon-intron boundary and 3'-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome (PubMed:39461343). Required for spermatogenesis via involvement in circRNA biogenesis (PubMed:39461343). Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation (PubMed:27563065). Also binds the poly(A) tail of mRNAs; controlling poly(A) length in neuronal cells (PubMed:17630287, PubMed:24671764). {ECO:0000269|PubMed:17630287, ECO:0000269|PubMed:24671764, ECO:0000269|PubMed:27563065, ECO:0000269|PubMed:39461343}.
Q6QNY0 BLOC1S3 S89 ochoa Biogenesis of lysosome-related organelles complex 1 subunit 3 (BLOC-1 subunit 3) Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking. {ECO:0000269|PubMed:16385460, ECO:0000269|PubMed:17182842}.
Q6RI45 BRWD3 S702 ochoa Bromodomain and WD repeat-containing protein 3 Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape. {ECO:0000269|PubMed:21834987}.
Q6UWD8 C16orf54 S92 ochoa Transmembrane protein C16orf54 None
Q6V0I7 FAT4 S4876 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}.
Q6VUC0 TFAP2E S230 ochoa Transcription factor AP-2-epsilon (AP2-epsilon) (Activating enhancer-binding protein 2-epsilon) Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-epsilon may play a role in the development of the CNS and in cartilage differentiation (By similarity). {ECO:0000250}.
Q6WCQ1 MPRIP S301 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}.
Q6WCQ1 MPRIP S663 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}.
Q6ZUT6 CCDC9B S210 ochoa Coiled-coil domain-containing protein 9B None
Q76N32 CEP68 S332 psp Centrosomal protein of 68 kDa (Cep68) Involved in maintenance of centrosome cohesion, probably as part of a linker structure which prevents centrosome splitting (PubMed:18042621). Required for localization of CDK5RAP2 to the centrosome during interphase (PubMed:24554434, PubMed:25503564). Contributes to CROCC/rootletin filament formation (PubMed:30404835). {ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:30404835}.
Q76N32 CEP68 S374 ochoa Centrosomal protein of 68 kDa (Cep68) Involved in maintenance of centrosome cohesion, probably as part of a linker structure which prevents centrosome splitting (PubMed:18042621). Required for localization of CDK5RAP2 to the centrosome during interphase (PubMed:24554434, PubMed:25503564). Contributes to CROCC/rootletin filament formation (PubMed:30404835). {ECO:0000269|PubMed:18042621, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:30404835}.
Q7KZI7 MARK2 S578 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}.
Q7L3V2 RTL10 S290 ochoa Protein Bop (BH3-only protein) (Retrotransposon Gag-like protein 10) Could induce apoptosis in a BH3 domain-dependent manner. The direct interaction network of Bcl-2 family members may play a key role in modulation RTL10/BOP intrinsic apoptotic signaling activity. {ECO:0000269|PubMed:23055042}.
Q7L8J4 SH3BP5L S44 ochoa SH3 domain-binding protein 5-like (SH3BP-5-like) Functions as a guanine nucleotide exchange factor (GEF) for RAB11A. {ECO:0000269|PubMed:30217979}.
Q7LFL8 CXXC5 S62 ochoa CXXC-type zinc finger protein 5 (CF5) (Putative MAPK-activating protein PM08) (Putative NF-kappa-B-activating protein 102) (Retinoid-inducible nuclear factor) (RINF) May indirectly participate in activation of the NF-kappa-B and MAPK pathways. Acts as a mediator of BMP4-mediated modulation of canonical Wnt signaling activity in neural stem cells (By similarity). Required for DNA damage-induced ATM phosphorylation, p53 activation and cell cycle arrest. Involved in myelopoiesis. Transcription factor. Binds to the oxygen responsive element of COX4I2 and represses its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen) (PubMed:23303788). May repress COX4I2 transactivation induced by CHCHD2 and RBPJ (PubMed:23303788). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q5XIQ3, ECO:0000269|PubMed:19182210, ECO:0000269|PubMed:19557330, ECO:0000269|PubMed:23303788, ECO:0000269|PubMed:29276034}.
Q7RTP6 MICAL3 S1300 ochoa [F-actin]-monooxygenase MICAL3 (EC 1.14.13.225) (Molecule interacting with CasL protein 3) (MICAL-3) Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission. {ECO:0000269|PubMed:21596566, ECO:0000269|PubMed:24440334}.
Q7Z2K8 GPRIN1 S73 ochoa G protein-regulated inducer of neurite outgrowth 1 (GRIN1) May be involved in neurite outgrowth. {ECO:0000250}.
Q7Z2T5 TRMT1L S71 ochoa tRNA (guanine(27)-N(2))-dimethyltransferase (EC 2.1.1.-) (tRNA methyltransferase 1-like protein) (TRMT1-like protein) Specifically dimethylates a single guanine residue at position 27 of tRNA(Tyr) using S-adenosyl-L-methionine as donor of the methyl groups (PubMed:39786990, PubMed:39786998). Dimethylation at position 27 of tRNA(Tyr) is required for efficient translation of tyrosine codons (PubMed:39786990, PubMed:39786998). Also required to maintain 3-(3-amino-3-carboxypropyl)uridine (acp3U) in the D-loop of several cytoplasmic tRNAs (PubMed:39786990, PubMed:39786998). {ECO:0000269|PubMed:39786990, ECO:0000269|PubMed:39786998}.
Q7Z406 MYH14 S42 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}.
Q7Z5H3 ARHGAP22 S569 ochoa Rho GTPase-activating protein 22 (Rho-type GTPase-activating protein 22) Rho GTPase-activating protein involved in the signal transduction pathway that regulates endothelial cell capillary tube formation during angiogenesis. Acts as a GTPase activator for the RAC1 by converting it to an inactive GDP-bound state. Inhibits RAC1-dependent lamellipodia formation. May also play a role in transcription regulation via its interaction with VEZF1, by regulating activity of the endothelin-1 (EDN1) promoter (By similarity). {ECO:0000250}.
Q7Z5R6 APBB1IP S525 ochoa Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1-interacting protein 1) (Proline-rich EVH1 ligand 1) (PREL-1) (Proline-rich protein 73) (Rap1-GTP-interacting adapter molecule) (RIAM) (Retinoic acid-responsive proline-rich protein 1) (RARP-1) Appears to function in the signal transduction from Ras activation to actin cytoskeletal remodeling. Suppresses insulin-induced promoter activities through AP1 and SRE. Mediates Rap1-induced adhesion. {ECO:0000269|PubMed:14530287, ECO:0000269|PubMed:15469846}.
Q7Z6R9 TFAP2D S223 ochoa Transcription factor AP-2-delta (AP2-delta) (Activating enhancer-binding protein 2-delta) (Transcription factor AP-2-beta-like 1) Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC (By similarity). {ECO:0000250}.
Q86UR5 RIMS1 S713 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}.
Q86V48 LUZP1 S996 ochoa Leucine zipper protein 1 (Filamin mechanobinding actin cross-linking protein) (Fimbacin) F-actin cross-linking protein (PubMed:30990684). Stabilizes actin and acts as a negative regulator of primary cilium formation (PubMed:32496561). Positively regulates the phosphorylation of both myosin II and protein phosphatase 1 regulatory subunit PPP1R12A/MYPT1 and promotes the assembly of myosin II stacks within actin stress fibers (PubMed:38832964). Inhibits the phosphorylation of myosin light chain MYL9 by DAPK3 and suppresses the constriction velocity of the contractile ring during cytokinesis (PubMed:38009294). Binds to microtubules and promotes epithelial cell apical constriction by up-regulating levels of diphosphorylated myosin light chain (MLC) through microtubule-dependent inhibition of MLC dephosphorylation by myosin phosphatase (By similarity). Involved in regulation of cell migration, nuclear size and centriole number, probably through regulation of the actin cytoskeleton (By similarity). Component of the CERF-1 and CERF-5 chromatin remodeling complexes in embryonic stem cells where it acts to stabilize the complexes (By similarity). Plays a role in embryonic brain and cardiovascular development (By similarity). {ECO:0000250|UniProtKB:Q8R4U7, ECO:0000269|PubMed:30990684, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:38009294, ECO:0000269|PubMed:38832964}.
Q86WR7 PROSER2 S179 ochoa Proline and serine-rich protein 2 None
Q86X27 RALGPS2 S343 ochoa Ras-specific guanine nucleotide-releasing factor RalGPS2 (Ral GEF with PH domain and SH3-binding motif 2) (RalA exchange factor RalGPS2) Guanine nucleotide exchange factor for the small GTPase RALA. May be involved in cytoskeletal organization. May also be involved in the stimulation of transcription in a Ras-independent fashion (By similarity). {ECO:0000250}.
Q86YP4 GATAD2A S512 ochoa Transcriptional repressor p66-alpha (Hp66alpha) (GATA zinc finger domain-containing protein 2A) Transcriptional repressor (PubMed:12183469, PubMed:16415179). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, PubMed:16415179). Efficient repression requires the presence of GATAD2B (PubMed:16415179). {ECO:0000269|PubMed:12183469, ECO:0000269|PubMed:16415179, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:28977666}.
Q8IV50 LYSMD2 S31 ochoa LysM and putative peptidoglycan-binding domain-containing protein 2 None
Q8IV56 PRR15 S55 ochoa Proline-rich protein 15 May have a role in proliferation and/or differentiation. {ECO:0000250}.
Q8IX01 SUGP2 S754 ochoa SURP and G-patch domain-containing protein 2 (Arginine/serine-rich-splicing factor 14) (Splicing factor, arginine/serine-rich 14) May play a role in mRNA splicing. {ECO:0000305}.
Q8IX07 ZFPM1 S637 ochoa Zinc finger protein ZFPM1 (Friend of GATA protein 1) (FOG-1) (Friend of GATA 1) (Zinc finger protein 89A) (Zinc finger protein multitype 1) Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA1, GATA2 and GATA3. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. The heterodimer formed with GATA proteins is essential to activate expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, while it represses expression of KLF1. May be involved in regulation of some genes in gonads. May also be involved in cardiac development, in a non-redundant way with ZFPM2/FOG2 (By similarity). {ECO:0000250}.
Q8IZ21 PHACTR4 S182 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}.
Q8IZW8 TNS4 S416 ochoa Tensin-4 (C-terminal tensin-like protein) Promotes EGF-induced cell migration by displacing tensin TNS3 from the cytoplasmic tail of integrin ITGB1 which results in dissociation of TNS3 from focal adhesions, disassembly of actin stress fibers and initiation of cell migration (PubMed:17643115). Suppresses ligand-induced degradation of EGFR by reducing EGFR ubiquitination in the presence of EGF (PubMed:23774213). Increases MET protein stability by inhibiting MET endocytosis and subsequent lysosomal degradation which leads to increased cell survival, proliferation and migration (PubMed:24814316). {ECO:0000269|PubMed:17643115, ECO:0000269|PubMed:23774213, ECO:0000269|PubMed:24814316}.
Q8N3V7 SYNPO S244 ochoa Synaptopodin Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity). {ECO:0000250}.
Q8N3V7 SYNPO S863 ochoa Synaptopodin Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity). {ECO:0000250}.
Q8N3V7 SYNPO S899 ochoa Synaptopodin Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity). {ECO:0000250}.
Q8N4S9 MARVELD2 S63 ochoa MARVEL domain-containing protein 2 (Tricellulin) Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:17186462). {ECO:0000250|UniProtKB:Q3UZP0, ECO:0000269|PubMed:17186462}.
Q8N4S9 MARVELD2 Y137 ochoa MARVEL domain-containing protein 2 (Tricellulin) Plays a role in the formation of tricellular tight junctions and of epithelial barriers (By similarity). Required for normal hearing via its role in the separation of the endolymphatic and perilymphatic spaces of the organ of Corti in the inner ear, and for normal survival of hair cells in the organ of Corti (PubMed:17186462). {ECO:0000250|UniProtKB:Q3UZP0, ECO:0000269|PubMed:17186462}.
Q8N884 CGAS S116 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}.
Q8ND82 ZNF280C S114 ochoa Zinc finger protein 280C (Suppressor of hairy wing homolog 3) (Zinc finger protein 633) May function as a transcription factor.
Q8NFC6 BOD1L1 S980 ochoa Biorientation of chromosomes in cell division protein 1-like 1 Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705). {ECO:0000269|PubMed:26166705, ECO:0000269|PubMed:29937342}.
Q8NFH8 REPS2 S240 ochoa RalBP1-associated Eps domain-containing protein 2 (Partner of RalBP1) (RalBP1-interacting protein 2) Involved in ligand-dependent receptor mediated endocytosis of the EGF and insulin receptors as part of the Ral signaling pathway (PubMed:10393179, PubMed:12771942, PubMed:9422736). By controlling growth factor receptors endocytosis may regulate cell survival (PubMed:12771942). Through ASAP1 may regulate cell adhesion and migration (PubMed:12149250). {ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:12149250, ECO:0000269|PubMed:12771942, ECO:0000269|PubMed:9422736}.
Q8NFU5 IPMK S22 ochoa Inositol polyphosphate multikinase (EC 2.7.1.140) (EC 2.7.1.151) (EC 2.7.1.153) (Inositol 1,3,4,6-tetrakisphosphate 5-kinase) Inositol phosphate kinase with a broad substrate specificity (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30420721, PubMed:30624931). Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30624931). Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (PubMed:12223481). Phosphorylates inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4) (By similarity). Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate (PubMed:28882892, PubMed:30420721). Plays an important role in MLKL-mediated necroptosis via its role in the biosynthesis of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Binding of these highly phosphorylated inositol phosphates to MLKL mediates the release of an N-terminal auto-inhibitory region, leading to activation of the kinase. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:29883610). Required for normal embryonic development, probably via its role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6) (By similarity). {ECO:0000250|UniProtKB:Q7TT16, ECO:0000269|PubMed:12027805, ECO:0000269|PubMed:12223481, ECO:0000269|PubMed:28882892, ECO:0000269|PubMed:29883610, ECO:0000269|PubMed:30420721, ECO:0000269|PubMed:30624931}.
Q8NG31 KNL1 S629 ochoa Outer kinetochore KNL1 complex subunit KNL1 (ALL1-fused gene from chromosome 15q14 protein) (AF15q14) (Bub-linking kinetochore protein) (Blinkin) (Cancer susceptibility candidate gene 5 protein) (Cancer/testis antigen 29) (CT29) (Kinetochore scaffold 1) (Kinetochore-null protein 1) (Protein CASC5) (Protein D40/AF15q14) Acts as a component of the outer kinetochore KNL1 complex that serves as a docking point for spindle assembly checkpoint components and mediates microtubule-kinetochore interactions (PubMed:15502821, PubMed:17981135, PubMed:18045986, PubMed:19893618, PubMed:21199919, PubMed:22000412, PubMed:22331848, PubMed:27881301, PubMed:30100357). Kinetochores, consisting of a centromere-associated inner segment and a microtubule-contacting outer segment, play a crucial role in chromosome segregation by mediating the physical connection between centromeric DNA and spindle microtubules (PubMed:18045986, PubMed:19893618, PubMed:27881301). The outer kinetochore is made up of the ten-subunit KMN network, comprising the MIS12, NDC80 and KNL1 complexes, and auxiliary microtubule-associated components; together they connect the outer kinetochore with the inner kinetochore, bind microtubules, and mediate interactions with mitotic checkpoint proteins that delay anaphase until chromosomes are bioriented on the spindle (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:38459127, PubMed:38459128). Required for kinetochore binding by a distinct subset of kMAPs (kinetochore-bound microtubule-associated proteins) and motors (PubMed:19893618). Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore (PubMed:18045986, PubMed:27881301). Can bind either to microtubules or to the protein phosphatase 1 (PP1) catalytic subunits PPP1CA and PPP1CC (via overlapping binding sites), it has higher affinity for PP1 (PubMed:30100357). Recruits MAD2L1 to the kinetochore and also directly links BUB1 and BUB1B to the kinetochore (PubMed:17981135, PubMed:19893618, PubMed:22000412, PubMed:22331848, PubMed:25308863). In addition to orienting mitotic chromosomes, it is also essential for alignment of homologous chromosomes during meiotic metaphase I (By similarity). In meiosis I, required to activate the spindle assembly checkpoint at unattached kinetochores to correct erroneous kinetochore-microtubule attachments (By similarity). {ECO:0000250|UniProtKB:Q66JQ7, ECO:0000269|PubMed:15502821, ECO:0000269|PubMed:17981135, ECO:0000269|PubMed:18045986, ECO:0000269|PubMed:19893618, ECO:0000269|PubMed:21199919, ECO:0000269|PubMed:22000412, ECO:0000269|PubMed:22331848, ECO:0000269|PubMed:25308863, ECO:0000269|PubMed:27881301, ECO:0000269|PubMed:30100357, ECO:0000269|PubMed:38459127, ECO:0000269|PubMed:38459128}.
Q8NI35 PATJ S1212 ochoa InaD-like protein (Inadl protein) (hINADL) (Channel-interacting PDZ domain-containing protein) (Pals1-associated tight junction protein) (Protein associated to tight junctions) Scaffolding protein that facilitates the localization of proteins to the cell membrane (PubMed:11927608, PubMed:16678097, PubMed:22006950). Required for the correct formation of tight junctions and epithelial apico-basal polarity (PubMed:11927608, PubMed:16678097). Acts (via its L27 domain) as an apical connector and elongation factor for multistranded TJP1/ZO1 condensates that form a tight junction belt, thereby required for the formation of the tight junction-mediated cell barrier (By similarity). Positively regulates epithelial cell microtubule elongation and cell migration, possibly via facilitating localization of PRKCI/aPKC and PAR3D/PAR3 at the leading edge of migrating cells (By similarity). Plays a role in the correct reorientation of the microtubule-organizing center during epithelial migration (By similarity). May regulate the surface expression and/or function of ASIC3 in sensory neurons (By similarity). May recruit ARHGEF18 to apical cell-cell boundaries (PubMed:22006950). {ECO:0000250|UniProtKB:E2QYC9, ECO:0000250|UniProtKB:Q63ZW7, ECO:0000269|PubMed:11927608, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:22006950}.
Q8TEW0 PARD3 S1335 ochoa Partitioning defective 3 homolog (PAR-3) (PARD-3) (Atypical PKC isotype-specific-interacting protein) (ASIP) (CTCL tumor antigen se2-5) (PAR3-alpha) Adapter protein involved in asymmetrical cell division and cell polarization processes (PubMed:10954424, PubMed:27925688). Seems to play a central role in the formation of epithelial tight junctions (PubMed:27925688). Targets the phosphatase PTEN to cell junctions (By similarity). Involved in Schwann cell peripheral myelination (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (By similarity). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10934474). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (PubMed:19812038, PubMed:27925688). {ECO:0000250|UniProtKB:Q99NH2, ECO:0000250|UniProtKB:Q9Z340, ECO:0000269|PubMed:10934474, ECO:0000269|PubMed:10954424, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:27925688}.
Q8TF72 SHROOM3 S927 ochoa Protein Shroom3 (Shroom-related protein) (hShrmL) Controls cell shape changes in the neuroepithelium during neural tube closure. Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers (By similarity). Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays (By similarity). {ECO:0000250|UniProtKB:Q27IV2, ECO:0000250|UniProtKB:Q9QXN0}.
Q8WU20 FRS2 S155 ochoa Fibroblast growth factor receptor substrate 2 (FGFR substrate 2) (FGFR-signaling adaptor SNT) (Suc1-associated neurotrophic factor target 1) (SNT-1) Adapter protein that links activated FGR and NGF receptors to downstream signaling pathways. Plays an important role in the activation of MAP kinases and in the phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, in response to ligand-mediated activation of FGFR1. Modulates signaling via SHC1 by competing for a common binding site on NTRK1. {ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:21765395}.
Q8WUB8 PHF10 S36 ochoa PHD finger protein 10 (BRG1-associated factor 45a) (BAF45a) (XAP135) Involved in transcription activity regulation by chromatin remodeling. 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 post-mitotic 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 post-mitotic 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}.
Q8WUF5 PPP1R13L S72 ochoa RelA-associated inhibitor (Inhibitor of ASPP protein) (Protein iASPP) (NFkB-interacting protein 1) (PPP1R13B-like protein) Regulator that plays a central role in regulation of apoptosis and transcription via its interaction with NF-kappa-B and p53/TP53 proteins. Blocks transcription of HIV-1 virus by inhibiting the action of both NF-kappa-B and SP1. Also inhibits p53/TP53 function, possibly by preventing the association between p53/TP53 and ASPP1 or ASPP2, and therefore suppressing the subsequent activation of apoptosis (PubMed:12524540). Is involved in NF-kappa-B dependent negative regulation of inflammatory response (PubMed:28069640). {ECO:0000269|PubMed:10336463, ECO:0000269|PubMed:12134007, ECO:0000269|PubMed:12524540, ECO:0000269|PubMed:15489900, ECO:0000269|PubMed:28069640}.
Q8WUI4 HDAC7 S507 ochoa Histone deacetylase 7 (HD7) (EC 3.5.1.98) (Histone deacetylase 7A) (HD7a) (Protein deacetylase HDAC7) (EC 3.5.1.-) Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (By similarity). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C (By similarity). During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene (PubMed:12239305). Positively regulates the transcriptional repressor activity of FOXP3 (PubMed:17360565). Serves as a corepressor of RARA, causing its deacetylation and inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). Also acetylates non-histone proteins, such as ALKBH5 (PubMed:37369679). {ECO:0000250|UniProtKB:Q8C2B3, ECO:0000269|PubMed:12239305, ECO:0000269|PubMed:17360565, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:37369679}.
Q8WXE0 CASKIN2 S800 ochoa Caskin-2 (CASK-interacting protein 2) None
Q8WXE1 ATRIP S38 ochoa ATR-interacting protein (ATM and Rad3-related-interacting protein) Required for checkpoint signaling after DNA damage. Required for ATR expression, possibly by stabilizing the protein. {ECO:0000269|PubMed:12791985}.
Q8WYL5 SSH1 S744 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}.
Q92574 TSC1 S403 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}.
Q92619 ARHGAP45 S569 ochoa Rho GTPase-activating protein 45 [Cleaved into: Minor histocompatibility antigen HA-1 (mHag HA-1)] Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity. {ECO:0000269|PubMed:24086303}.; FUNCTION: Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL. {ECO:0000269|PubMed:12601144, ECO:0000269|PubMed:8260714, ECO:0000269|PubMed:8532022, ECO:0000269|PubMed:9798702}.
Q92667 AKAP1 S73 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}.
Q92667 AKAP1 S108 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}.
Q92754 TFAP2C S236 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}.
Q92769 HDAC2 S394 ochoa|psp Histone deacetylase 2 (HD2) (EC 3.5.1.98) (Protein deacylase HDAC2) (EC 3.5.1.-) Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR (PubMed:12724404). 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 (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity (PubMed:19343227). May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A (PubMed:21965678). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:35044827). {ECO:0000250|UniProtKB:P70288, ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:16428440, ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:28977666, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:37137925}.
Q92835 INPP5D S1059 ochoa Phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 (EC 3.1.3.86) (Inositol polyphosphate-5-phosphatase D) (EC 3.1.3.56) (Inositol polyphosphate-5-phosphatase of 145 kDa) (SIP-145) (Phosphatidylinositol 4,5-bisphosphate 5-phosphatase) (EC 3.1.3.36) (SH2 domain-containing inositol 5'-phosphatase 1) (SH2 domain-containing inositol phosphatase 1) (SHIP-1) (p150Ship) (hp51CN) Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (PubMed:10764818, PubMed:8723348, PubMed:8769125). Able also to hydrolyzes the 5-phosphate of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P3) and inositol 1,3,4,5-tetrakisphosphate (PubMed:10764818, PubMed:8769125, PubMed:9108392). Acts as a negative regulator of B-cell antigen receptor signaling. Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Acts as a negative regulator of myeloid cell proliferation/survival and chemotaxis, mast cell degranulation, immune cells homeostasis, integrin alpha-IIb/beta-3 signaling in platelets and JNK signaling in B-cells. Regulates proliferation of osteoclast precursors, macrophage programming, phagocytosis and activation and is required for endotoxin tolerance. Involved in the control of cell-cell junctions, CD32a signaling in neutrophils and modulation of EGF-induced phospholipase C activity (PubMed:16682172). Key regulator of neutrophil migration, by governing the formation of the leading edge and polarization required for chemotaxis. Modulates FCGR3/CD16-mediated cytotoxicity in NK cells. Mediates the activin/TGF-beta-induced apoptosis through its Smad-dependent expression. {ECO:0000269|PubMed:10764818, ECO:0000269|PubMed:12421919, ECO:0000269|PubMed:16682172, ECO:0000269|PubMed:8723348, ECO:0000269|PubMed:8769125, ECO:0000269|PubMed:9108392}.
Q93052 LPP S375 ochoa Lipoma-preferred partner (LIM domain-containing preferred translocation partner in lipoma) May play a structural role at sites of cell adhesion in maintaining cell shape and motility. In addition to these structural functions, it may also be implicated in signaling events and activation of gene transcription. May be involved in signal transduction from cell adhesion sites to the nucleus allowing successful integration of signals arising from soluble factors and cell-cell adhesion sites. Also suggested to serve as a scaffold protein upon which distinct protein complexes are assembled in the cytoplasm and in the nucleus. {ECO:0000269|PubMed:10637295}.
Q96BY7 ATG2B S493 ochoa 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}.
Q96EC8 YIPF6 S24 ochoa Protein YIPF6 (YIP1 family member 6) May be required for stable YIPF1 and YIPF2 protein expression. {ECO:0000269|PubMed:28286305}.
Q96F45 ZNF503 S237 ochoa Zinc finger protein 503 May function as a transcriptional repressor. {ECO:0000250}.
Q96FF9 CDCA5 S33 ochoa|psp Sororin (Cell division cycle-associated protein 5) (p35) Regulator of sister chromatid cohesion in mitosis stabilizing cohesin complex association with chromatin. May antagonize the action of WAPL which stimulates cohesin dissociation from chromatin. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Required for efficient DNA double-stranded break repair. {ECO:0000269|PubMed:15837422, ECO:0000269|PubMed:17349791, ECO:0000269|PubMed:21111234}.
Q96FS4 SIPA1 S912 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}.
Q96HZ4 HES6 S183 psp Transcription cofactor HES-6 (C-HAIRY1) (Class B basic helix-loop-helix protein 41) (bHLHb41) (Hairy and enhancer of split 6) Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences. Also suppresses HES1-mediated inhibition of the heterodimer formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-regulate transcription in its presence. Promotes cell differentiation (By similarity). {ECO:0000250}.
Q96IJ6 GMPPA S373 ochoa Mannose-1-phosphate guanylyltransferase regulatory subunit alpha (GDP-mannose pyrophosphorylase A) (GMPP-alpha) (GTP-mannose-1-phosphate guanylyltransferase alpha) Regulatory subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex; reduces the catalytic activity of GMPPB when part of the complex (PubMed:24035193, PubMed:33986552). Mediates allosteric feedback inhibition of GMPPB catalytic activity upon binding GDP-alpha-D-mannose (PubMed:24035193, PubMed:33986552). Together with GMPPB regulates GDP-alpha-D-mannose levels (PubMed:33986552). {ECO:0000269|PubMed:24035193, ECO:0000269|PubMed:33986552}.
Q96JM3 CHAMP1 S223 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}.
Q96JM3 CHAMP1 S507 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}.
Q96KG9 SCYL1 S754 ochoa|psp N-terminal kinase-like protein (Coated vesicle-associated kinase of 90 kDa) (SCY1-like protein 1) (Telomerase regulation-associated protein) (Telomerase transcriptional element-interacting factor) (Teratoma-associated tyrosine kinase) Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum (PubMed:18556652). Involved in the maintenance of the Golgi apparatus morphology (PubMed:26581903). {ECO:0000269|PubMed:18556652, ECO:0000269|PubMed:26581903}.; FUNCTION: [Isoform 6]: Acts as a transcriptional activator. It binds to three different types of GC-rich DNA binding sites (box-A, -B and -C) in the beta-polymerase promoter region. It also binds to the TERT promoter region. {ECO:0000269|PubMed:15963946}.
Q96KQ7 EHMT2 S211 ochoa|psp Histone-lysine N-methyltransferase EHMT2 (EC 2.1.1.-) (EC 2.1.1.367) (Euchromatic histone-lysine N-methyltransferase 2) (HLA-B-associated transcript 8) (Histone H3-K9 methyltransferase 3) (H3-K9-HMTase 3) (Lysine N-methyltransferase 1C) (Protein G9a) Histone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys-373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself. {ECO:0000250|UniProtKB:Q9Z148, ECO:0000269|PubMed:11316813, ECO:0000269|PubMed:18438403, ECO:0000269|PubMed:20084102, ECO:0000269|PubMed:20118233, ECO:0000269|PubMed:22387026, ECO:0000269|PubMed:8457211}.
Q96KR1 ZFR S546 ochoa Zinc finger RNA-binding protein (hZFR) (M-phase phosphoprotein homolog) Involved in postimplantation and gastrulation stages of development. Involved in the nucleocytoplasmic shuttling of STAU2. Binds to DNA and RNA (By similarity). {ECO:0000250}.
Q96L73 NSD1 S2341 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}.
Q96MH2 HEXIM2 S169 ochoa Protein HEXIM2 (Hexamethylene bis-acetamide-inducible protein 2) Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:15713661, PubMed:15713662). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:15713661, PubMed:15713662). {ECO:0000269|PubMed:15713661, ECO:0000269|PubMed:15713662}.
Q96RG2 PASK S106 ochoa PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}.
Q96ST3 SIN3A S254 ochoa Paired amphipathic helix protein Sin3a (Histone deacetylase complex subunit Sin3a) (Transcriptional corepressor Sin3a) Acts as a transcriptional repressor. Corepressor for REST. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Also interacts with MXD1-MAX heterodimers to repress transcription by tethering SIN3A to DNA. Acts cooperatively with OGT to repress transcription in parallel with histone deacetylation. Involved in the control of the circadian rhythms. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation. Cooperates with FOXK1 to regulate cell cycle progression probably by repressing cell cycle inhibitor genes expression (By similarity). Required for cortical neuron differentiation and callosal axon elongation (By similarity). {ECO:0000250|UniProtKB:Q60520, ECO:0000269|PubMed:12150998}.
Q96SY0 INTS14 S387 ochoa Integrator complex subunit 14 (von Willebrand factor A domain-containing protein 9) Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes (PubMed:38570683, 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:32647223). Within the integrator complex, INTS14 is part of the integrator tail module that acts as a platform for the recruitment of transcription factors at promoters (PubMed:38823386, PubMed:38906142). {ECO:0000269|PubMed:32647223, ECO:0000269|PubMed:38570683, ECO:0000269|PubMed:38823386, ECO:0000269|PubMed:38906142}.
Q99501 GAS2L1 Y351 ochoa GAS2-like protein 1 (GAS2-related protein on chromosome 22) (Growth arrest-specific protein 2-like 1) Involved in the cross-linking of microtubules and microfilaments (PubMed:12584248, PubMed:24706950). Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers (PubMed:24706950). {ECO:0000269|PubMed:12584248, ECO:0000269|PubMed:24706950}.
Q99700 ATXN2 S597 ochoa Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}.
Q99700 ATXN2 S600 ochoa Ataxin-2 (Spinocerebellar ataxia type 2 protein) (Trinucleotide repeat-containing gene 13 protein) Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane. {ECO:0000269|PubMed:18602463}.
Q99941 ATF6B S564 ochoa Cyclic AMP-dependent transcription factor ATF-6 beta (cAMP-dependent transcription factor ATF-6 beta) (Activating transcription factor 6 beta) (ATF6-beta) (Protein G13) (cAMP response element-binding protein-related protein) (Creb-rp) (cAMP-responsive element-binding protein-like 1) [Cleaved into: Processed cyclic AMP-dependent transcription factor ATF-6 beta] [Cyclic AMP-dependent transcription factor ATF-6 beta]: Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 beta), which is embedded in the endoplasmic reticulum membrane (PubMed:11256944). Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR) (PubMed:11256944). {ECO:0000269|PubMed:11256944}.; FUNCTION: [Processed cyclic AMP-dependent transcription factor ATF-6 beta]: Transcription factor that acts in the unfolded protein response (UPR) pathway by activating UPR target genes induced during ER stress (PubMed:11256944). Binds DNA on the 5'-CCAC[GA]-3' half of the ER stress response element (ERSE) (5'-CCAATN(9)CCAC[GA]-3') when NF-Y is bound to ERSE (PubMed:11256944). {ECO:0000269|PubMed:11256944}.
Q9BQE5 APOL2 S250 ochoa Apolipoprotein L2 (Apolipoprotein L-II) (ApoL-II) May affect the movement of lipids in the cytoplasm or allow the binding of lipids to organelles.
Q9BRK4 LZTS2 S276 ochoa Leucine zipper putative tumor suppressor 2 (hLZTS2) (Protein LAPSER1) Negative regulator of katanin-mediated microtubule severing and release from the centrosome. Required for central spindle formation and the completion of cytokinesis. May negatively regulate axonal outgrowth by preventing the formation of microtubule bundles that are necessary for transport within the elongating axon. Negative regulator of the Wnt signaling pathway. Represses beta-catenin-mediated transcriptional activation by promoting the nuclear exclusion of beta-catenin. {ECO:0000255|HAMAP-Rule:MF_03026, ECO:0000269|PubMed:17000760, ECO:0000269|PubMed:17351128, ECO:0000269|PubMed:17950943, ECO:0000269|PubMed:18490357}.
Q9BUK6 MSTO1 S495 ochoa Protein misato homolog 1 Involved in the regulation of mitochondrial distribution and morphology (PubMed:17349998, PubMed:28544275, PubMed:28554942). Required for mitochondrial fusion and mitochondrial network formation (PubMed:28544275, PubMed:28554942). {ECO:0000269|PubMed:17349998, ECO:0000269|PubMed:28544275, ECO:0000269|PubMed:28554942}.
Q9BX66 SORBS1 S452 ochoa Sorbin and SH3 domain-containing protein 1 (Ponsin) (SH3 domain protein 5) (SH3P12) (c-Cbl-associated protein) (CAP) Plays a role in tyrosine phosphorylation of CBL by linking CBL to the insulin receptor. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). {ECO:0000250|UniProtKB:Q62417}.
Q9BXF3 CECR2 S1306 ochoa Chromatin remodeling regulator CECR2 (Cat eye syndrome critical region protein 2) Regulatory subunit of the ATP-dependent CERF-1 and CERF-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:15640247, PubMed:22464331, PubMed:26365797, PubMed:28801535). The complexes do not have the ability to slide mononucleosomes to the center of a DNA template (PubMed:28801535). The CERF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the CERF-5 ISWI chromatin remodeling complex (PubMed:28801535). Plays a role in various processes during development: required during embryogenesis for neural tube closure and inner ear development. In adults, required for spermatogenesis, via the formation of ISWI-type chromatin complexes (By similarity). In histone-modifying complexes, CECR2 recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated (PubMed:22464331, PubMed:26365797). May also be involved through its interaction with LRPPRC in the integration of cytoskeletal network with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling and cytokinesis (PubMed:11827465). {ECO:0000250|UniProtKB:E9Q2Z1, ECO:0000269|PubMed:11827465, ECO:0000269|PubMed:15640247, ECO:0000269|PubMed:22464331, ECO:0000269|PubMed:26365797, ECO:0000269|PubMed:28801535}.
Q9C0C2 TNKS1BP1 S315 ochoa 182 kDa tankyrase-1-binding protein None
Q9C0C9 UBE2O S50 ochoa (E3-independent) E2 ubiquitin-conjugating enzyme (EC 2.3.2.24) (E2/E3 hybrid ubiquitin-protein ligase UBE2O) (Ubiquitin carrier protein O) (Ubiquitin-conjugating enzyme E2 O) (Ubiquitin-conjugating enzyme E2 of 230 kDa) (Ubiquitin-conjugating enzyme E2-230K) (Ubiquitin-protein ligase O) E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853). {ECO:0000269|PubMed:23381138, ECO:0000269|PubMed:23452853, ECO:0000269|PubMed:23455153, ECO:0000269|PubMed:24703950}.
Q9C0H5 ARHGAP39 S253 ochoa Rho GTPase-activating protein 39 None
Q9GZN7 ROGDI S227 ochoa Protein rogdi homolog None
Q9H211 CDT1 S73 ochoa DNA replication factor Cdt1 (Double parked homolog) (DUP) Required for both DNA replication and mitosis (PubMed:11125146, PubMed:14993212, PubMed:21856198, PubMed:22581055, PubMed:26842564). DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC) (PubMed:14672932). Required also for mitosis by promoting stable kinetochore-microtubule attachments (PubMed:22581055). Potential oncogene (By similarity). {ECO:0000250|UniProtKB:Q8R4E9, ECO:0000269|PubMed:11125146, ECO:0000269|PubMed:14672932, ECO:0000269|PubMed:14993212, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22581055, ECO:0000269|PubMed:26842564}.
Q9H2Y7 ZNF106 S509 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}.
Q9H3T3 SEMA6B S748 ochoa Semaphorin-6B (Semaphorin-Z) (Sema Z) Functions as a cell surface repellent for mossy fibers of developing neurons in the hippocampus where it plays a role in axon guidance. May function through the PLXNA4 receptor expressed by mossy cell axons. {ECO:0000250|UniProtKB:O54951}.; FUNCTION: (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium. {ECO:0000269|PubMed:32302524, ECO:0000269|PubMed:32589945}.
Q9H6I2 SOX17 S349 ochoa Transcription factor SOX-17 Acts as a transcription regulator that binds target promoter DNA and bends the DNA. Binds to the sequences 5'-AACAAT-'3 or 5'-AACAAAG-3'. Modulates transcriptional regulation via WNT3A. Inhibits Wnt signaling. Promotes degradation of activated CTNNB1. Plays a key role in the regulation of embryonic development. Required for normal development of the definitive gut endoderm. Required for normal looping of the embryonic heart tube. Plays an important role in embryonic and postnatal vascular development, including development of arteries. Plays an important role in postnatal angiogenesis, where it is functionally redundant with SOX18. Required for the generation and maintenance of fetal hematopoietic stem cells, and for fetal hematopoiesis. Probable transcriptional activator in the premeiotic germ cells. {ECO:0000250|UniProtKB:Q61473}.
Q9H792 PEAK1 S792 ochoa Inactive tyrosine-protein kinase PEAK1 (Pseudopodium-enriched atypical kinase 1) (Sugen kinase 269) (Tyrosine-protein kinase SgK269) Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics (PubMed:20534451, PubMed:23105102, PubMed:35687021). Acts as a scaffold for mediating EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654, ECO:0000269|PubMed:35687021}.
Q9H7N4 SCAF1 S734 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}.
Q9H7N4 SCAF1 S819 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}.
Q9H987 SYNPO2L S615 ochoa Synaptopodin 2-like protein Actin-associated protein that may play a role in modulating actin-based shape. {ECO:0000250}.
Q9HCM7 FBRSL1 S1017 ochoa Fibrosin-1-like protein (AUTS2-like protein) (HBV X-transactivated gene 9 protein) (HBV XAg-transactivated protein 9) None
Q9NP61 ARFGAP3 S211 ochoa ADP-ribosylation factor GTPase-activating protein 3 (ARF GAP 3) GTPase-activating protein (GAP) for ADP ribosylation factor 1 (ARF1). Hydrolysis of ARF1-bound GTP may lead to dissociation of coatomer from Golgi-derived membranes to allow fusion with target membranes. {ECO:0000269|PubMed:11172815}.
Q9NQS1 AVEN S268 ochoa Cell death regulator Aven Protects against apoptosis mediated by Apaf-1.
Q9NQS7 INCENP S323 ochoa Inner centromere protein Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB or AURKC, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB/C toward substrates near microtubules (PubMed:12925766, PubMed:15316025, PubMed:27332895). The flexibility of the SAH domain is proposed to allow AURKB/C to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin (By similarity). Activates AURKB and AURKC (PubMed:27332895). Required for localization of CBX5 to mitotic centromeres (PubMed:21346195). Controls the kinetochore localization of BUB1 (PubMed:16760428). {ECO:0000250|UniProtKB:P53352, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:21346195, ECO:0000269|PubMed:27332895}.
Q9NTJ3 SMC4 S50 ochoa Structural maintenance of chromosomes protein 4 (SMC protein 4) (SMC-4) (Chromosome-associated polypeptide C) (hCAP-C) (XCAP-C homolog) Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases. {ECO:0000269|PubMed:11136719}.
Q9NUE0 ZDHHC18 S53 ochoa Palmitoyltransferase ZDHHC18 (EC 2.3.1.225) (DHHC domain-containing cysteine-rich protein 18) (DHHC-18) (Zinc finger DHHC domain-containing protein 18) Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates, such as CGAS, HRAS and LCK (PubMed:23034182, PubMed:27481942, PubMed:35438208). Acts as a negative regulator of the cGAS-STING pathway be mediating palmitoylation and inactivation of CGAS (PubMed:35438208). May also have a palmitoyltransferase activity toward the beta-2 adrenergic receptor/ADRB2 and therefore regulate G protein-coupled receptor signaling (PubMed:27481942). {ECO:0000269|PubMed:23034182, ECO:0000269|PubMed:27481942, ECO:0000269|PubMed:35438208}.
Q9P206 NHSL3 S912 ochoa NHS-like protein 3 Able to directly activate the TNF-NFkappaB signaling pathway. {ECO:0000269|PubMed:32854746}.
Q9UEG4 ZNF629 S625 ochoa Zinc finger protein 629 (Zinc finger protein 65) May be involved in transcriptional regulation.
Q9UF83 None S519 ochoa Uncharacterized protein DKFZp434B061 None
Q9UHB6 LIMA1 S371 ochoa LIM domain and actin-binding protein 1 (Epithelial protein lost in neoplasm) Actin-binding protein involved in actin cytoskeleton regulation and dynamics. Increases the number and size of actin stress fibers and inhibits membrane ruffling. Inhibits actin filament depolymerization. Bundles actin filaments, delays filament nucleation and reduces formation of branched filaments (PubMed:12566430, PubMed:33999101). Acts as a negative regulator of primary cilium formation (PubMed:32496561). Plays a role in cholesterol homeostasis. Influences plasma cholesterol levels through regulation of intestinal cholesterol absorption. May act as a scaffold protein by regulating NPC1L1 transportation, an essential protein for cholesterol absorption, to the plasma membrane by recruiting MYO5B to NPC1L1, and thus facilitates cholesterol uptake (By similarity). {ECO:0000250|UniProtKB:Q9ERG0, ECO:0000269|PubMed:12566430, ECO:0000269|PubMed:32496561, ECO:0000269|PubMed:33999101}.
Q9UHG2 PCSK1N S44 ochoa ProSAAS (Proprotein convertase subtilisin/kexin type 1 inhibitor) (Proprotein convertase 1 inhibitor) (pro-SAAS) [Cleaved into: KEP; Big SAAS (b-SAAS); Little SAAS (l-SAAS) (N-proSAAS); Big PEN-LEN (b-PEN-LEN) (SAAS CT(1-49)); PEN; Little LEN (l-LEN); Big LEN (b-LEN) (SAAS CT(25-40))] May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the further processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 84 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity (By similarity). {ECO:0000250|UniProtKB:Q9QXV0}.; FUNCTION: [Big LEN]: Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. {ECO:0000250|UniProtKB:Q9QXV0}.; FUNCTION: [PEN]: Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding. {ECO:0000250|UniProtKB:Q9QXV0}.
Q9UHW9 SLC12A6 S93 ochoa Solute carrier family 12 member 6 (Electroneutral potassium-chloride cotransporter 3) (K-Cl cotransporter 3) [Isoform 1]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:10600773, PubMed:11551954, PubMed:16048901, PubMed:18566107, PubMed:19665974, PubMed:21628467, PubMed:27485015). May contribute to cell volume homeostasis in single cells (PubMed:16048901, PubMed:27485015). {ECO:0000269|PubMed:10600773, ECO:0000269|PubMed:11551954, ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:18566107, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21628467, ECO:0000269|PubMed:27485015, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 2]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901, PubMed:33199848, PubMed:34031912). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000269|PubMed:33199848, ECO:0000269|PubMed:34031912, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 3]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 4]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 5]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.; FUNCTION: [Isoform 6]: Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:16048901). May contribute to cell volume homeostasis in single cells (Probable). {ECO:0000269|PubMed:16048901, ECO:0000305|PubMed:16048901}.
Q9UJY1 HSPB8 S57 ochoa|psp Heat shock protein beta-8 (HspB8) (Alpha-crystallin C chain) (E2-induced gene 1 protein) (Heat shock protein family B member 8) (Protein kinase H11) (Small stress protein-like protein HSP22) Involved in the chaperone-assisted selective autophagy (CASA), a crucial process for protein quality control, particularly in mechanical strained cells and tissues such as muscle. Displays temperature-dependent chaperone activity. {ECO:0000250|UniProtKB:Q9JK92}.
Q9UK61 TASOR S971 ochoa Protein TASOR (CTCL tumor antigen se89-1) (Retinoblastoma-associated protein RAP140) (Transgene activation suppressor protein) Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression (PubMed:26022416, PubMed:28581500). The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2 (PubMed:26022416, PubMed:28581500). Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602). Plays a crucial role in early embryonic development (By similarity). Involved in the organization of spindle poles and spindle apparatus assembly during zygotic division (By similarity). Plays an important role in maintaining epiblast fitness or potency (By similarity). {ECO:0000250|UniProtKB:Q69ZR9, ECO:0000269|PubMed:26022416, ECO:0000269|PubMed:28581500, ECO:0000269|PubMed:29211708, ECO:0000269|PubMed:30487602}.
Q9UKF7 PITPNC1 S270 ochoa Cytoplasmic phosphatidylinositol transfer protein 1 (Mammalian rdgB homolog beta) (M-rdgB beta) (MrdgBbeta) (Retinal degeneration B homolog beta) (RdgBbeta) [Isoform 1]: Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes (PubMed:10531358, PubMed:22822086). Binds PA derived from the phospholipase D signaling pathway and among the cellular PA species, preferably binds to the C16:0/16:1 and C16:1/18:1 PA species (PubMed:22822086). {ECO:0000269|PubMed:10531358, ECO:0000269|PubMed:22822086}.; FUNCTION: [Isoform 2]: Catalyzes the transfer of phosphatidylinositol between membranes. {ECO:0000269|PubMed:22822086}.
Q9UKK3 PARP4 S1223 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}.
Q9ULL8 SHROOM4 S282 ochoa Protein Shroom4 (Second homolog of apical protein) Probable regulator of cytoskeletal architecture that plays an important role in development. May regulate cellular and cytoskeletal architecture by modulating the spatial distribution of myosin II (By similarity). {ECO:0000250, ECO:0000269|PubMed:16684770}.
Q9ULT8 HECTD1 S1543 ochoa E3 ubiquitin-protein ligase HECTD1 (EC 2.3.2.26) (E3 ligase for inhibin receptor) (EULIR) (HECT domain-containing protein 1) E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:33711283). Mediates 'Lys-63'-linked polyubiquitination of HSP90AA1 which leads to its intracellular localization and reduced secretion (By similarity). Negatively regulating HSP90AA1 secretion in cranial mesenchyme cells may impair their emigration and may be essential for the correct development of the cranial neural folds and neural tube closure (By similarity). Catalyzes ubiquitination and degradation of ZNF622, an assembly factor for the ribosomal 60S subunit, in hematopoietic cells, thereby promoting hematopoietic stem cell renewal (PubMed:33711283). {ECO:0000250|UniProtKB:Q69ZR2, ECO:0000269|PubMed:33711283}.
Q9UMS6 SYNPO2 S805 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}.
Q9UPS6 SETD1B S1431 ochoa Histone-lysine N-methyltransferase SETD1B (EC 2.1.1.364) (Lysine N-methyltransferase 2G) (SET domain-containing protein 1B) (hSET1B) Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism (PubMed:17355966, PubMed:25561738). Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:17355966, PubMed:25561738). Plays an essential role in regulating the transcriptional programming of multipotent hematopoietic progenitor cells and lymphoid lineage specification during hematopoiesis (By similarity). {ECO:0000250|UniProtKB:Q8CFT2, ECO:0000269|PubMed:17355966, ECO:0000269|PubMed:25561738}.
Q9Y242 TCF19 S167 ochoa Transcription factor 19 (TCF-19) (Transcription factor SC1) Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition (PubMed:1868030, PubMed:31141247). May bind to regulatory elements of genes, including the promoter of the transcription factor FOXO1 (PubMed:31141247). {ECO:0000269|PubMed:1868030, ECO:0000269|PubMed:31141247}.
Q9Y250 LZTS1 S140 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}.
Q9Y2G1 MYRF S148 ochoa Myelin regulatory factor (EC 3.4.-.-) (Myelin gene regulatory factor) [Cleaved into: Myelin regulatory factor, N-terminal; Myelin regulatory factor, C-terminal] [Myelin regulatory factor]: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes (PubMed:23966832). {ECO:0000269|PubMed:23966832}.; FUNCTION: [Myelin regulatory factor, C-terminal]: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage. {ECO:0000269|PubMed:23966832}.; FUNCTION: [Myelin regulatory factor, N-terminal]: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:23966832). {ECO:0000269|PubMed:23966832}.
Q9Y2I7 PIKFYVE S85 ochoa 1-phosphatidylinositol 3-phosphate 5-kinase (Phosphatidylinositol 3-phosphate 5-kinase) (EC 2.7.1.150) (FYVE finger-containing phosphoinositide kinase) (PIKfyve) (Phosphatidylinositol 3-phosphate 5-kinase type III) (PIPkin-III) (Type III PIP kinase) (Serine-protein kinase PIKFYVE) (EC 2.7.11.1) Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:23086417). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:17556371). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:22621786). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:33098764). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (PubMed:30612035). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (By similarity). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (PubMed:30612035). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (By similarity). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, through association with SPAG9 and RABEPK (By similarity). Mediates EGFR trafficking to the nucleus (PubMed:17909029). {ECO:0000250|UniProtKB:Q9Z1T6, ECO:0000269|PubMed:17556371, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:22621786, ECO:0000269|PubMed:27623384, ECO:0000269|PubMed:28779020, ECO:0000269|PubMed:29584722, ECO:0000269|PubMed:30612035, ECO:0000269|PubMed:33098764, ECO:0000303|PubMed:23086417}.; FUNCTION: (Microbial infection) Required for cell entry of coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus EMC (HCoV-EMC) by endocytosis. {ECO:0000269|PubMed:32221306}.
Q9Y2T7 YBX2 S74 ochoa Y-box-binding protein 2 (Contrin) (DNA-binding protein C) (Dbpc) (Germ cell-specific Y-box-binding protein) (MSY2 homolog) Major constituent of messenger ribonucleoprotein particles (mRNPs). Involved in the regulation of the stability and/or translation of germ cell mRNAs. Binds to Y-box consensus promoter element. Binds to full-length mRNA with high affinity in a sequence-independent manner. Binds to short RNA sequences containing the consensus site 5'-UCCAUCA-3' with low affinity and limited sequence specificity. Its binding with maternal mRNAs is necessary for its cytoplasmic retention. May mark specific mRNAs (those transcribed from Y-box promoters) in the nucleus for cytoplasmic storage, thereby linking transcription and mRNA storage/translational delay (By similarity). {ECO:0000250|UniProtKB:Q9Z2C8}.
Q9Y4B5 MTCL1 S192 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}.
Q9Y4H2 IRS2 S1109 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}.
Q9Y5S2 CDC42BPB S1640 ochoa 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}.
Q9Y617 PSAT1 S20 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}.
Q9Y6I3 EPN1 S473 ochoa Epsin-1 (EH domain-binding mitotic phosphoprotein) (EPS-15-interacting protein 1) Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Modifies membrane curvature and facilitates the formation of clathrin-coated invaginations (By similarity). Regulates receptor-mediated endocytosis (PubMed:10393179, PubMed:10557078). {ECO:0000250|UniProtKB:O88339, ECO:0000269|PubMed:10393179, ECO:0000269|PubMed:10557078}.
Q01082 SPTBN1 S2197 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}.
P47756 CAPZB S90 Sugiyama F-actin-capping protein subunit beta (CapZ beta) F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:A9XFX6, ECO:0000269|PubMed:21834987}.
Q15759 MAPK11 S37 Sugiyama Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}.
P29144 TPP2 S25 Sugiyama Tripeptidyl-peptidase 2 (TPP-2) (EC 3.4.14.10) (Tripeptidyl aminopeptidase) (Tripeptidyl-peptidase II) (TPP-II) Cytosolic tripeptidyl-peptidase that releases N-terminal tripeptides from polypeptides and is a component of the proteolytic cascade acting downstream of the 26S proteasome in the ubiquitin-proteasome pathway (PubMed:25525876, PubMed:30533531). It plays an important role in intracellular amino acid homeostasis (PubMed:25525876). Stimulates adipogenesis (By similarity). {ECO:0000250|UniProtKB:Q64514, ECO:0000269|PubMed:25525876, ECO:0000269|PubMed:30533531}.
Q8TD08 MAPK15 S505 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}.
Q9UQ07 MOK S321 Sugiyama MAPK/MAK/MRK overlapping kinase (EC 2.7.11.22) (MOK protein kinase) (Renal tumor antigen 1) (RAGE-1) Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner. {ECO:0000250|UniProtKB:Q9WVS4}.
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reactome_id name p -log10_p
R-HSA-187037 Signaling by NTRK1 (TRKA) 3.148155e-07 6.502
R-HSA-166520 Signaling by NTRKs 3.248676e-07 6.488
R-HSA-8866904 Negative regulation of activity of TFAP2 (AP-2) family transcription factors 1.760320e-06 5.754
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 1.412286e-05 4.850
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 4.218843e-05 4.375
R-HSA-9759475 Regulation of CDH11 Expression and Function 4.022368e-05 4.396
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 5.619179e-05 4.250
R-HSA-9762293 Regulation of CDH11 gene transcription 6.560548e-05 4.183
R-HSA-8866907 Activation of the TFAP2 (AP-2) family of transcription factors 6.560548e-05 4.183
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 7.267335e-05 4.139
R-HSA-1500931 Cell-Cell communication 1.034669e-04 3.985
R-HSA-9759811 Regulation of CDH11 mRNA translation by microRNAs 1.182768e-04 3.927
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 1.250968e-04 3.903
R-HSA-1266695 Interleukin-7 signaling 2.359285e-04 3.627
R-HSA-446728 Cell junction organization 2.770974e-04 3.557
R-HSA-421270 Cell-cell junction organization 3.410254e-04 3.467
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 4.585471e-04 3.339
R-HSA-9031628 NGF-stimulated transcription 4.986883e-04 3.302
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 5.444666e-04 3.264
R-HSA-9827857 Specification of primordial germ cells 6.469920e-04 3.189
R-HSA-193704 p75 NTR receptor-mediated signalling 7.807551e-04 3.107
R-HSA-162582 Signal Transduction 8.206914e-04 3.086
R-HSA-418990 Adherens junctions interactions 1.095754e-03 2.960
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 1.440702e-03 2.841
R-HSA-141424 Amplification of signal from the kinetochores 1.440702e-03 2.841
R-HSA-1257604 PIP3 activates AKT signaling 1.432329e-03 2.844
R-HSA-9938206 Developmental Lineage of Mammary Stem Cells 1.565293e-03 2.805
R-HSA-3214841 PKMTs methylate histone lysines 1.654566e-03 2.781
R-HSA-212436 Generic Transcription Pathway 2.057592e-03 2.687
R-HSA-8986944 Transcriptional Regulation by MECP2 2.036261e-03 2.691
R-HSA-9006925 Intracellular signaling by second messengers 1.927262e-03 2.715
R-HSA-8856828 Clathrin-mediated endocytosis 2.283935e-03 2.641
R-HSA-8866906 TFAP2 (AP-2) family regulates transcription of other transcription factors 3.555937e-03 2.449
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 2.781957e-03 2.556
R-HSA-170968 Frs2-mediated activation 3.425311e-03 2.465
R-HSA-9924644 Developmental Lineages of the Mammary Gland 3.007084e-03 2.522
R-HSA-69618 Mitotic Spindle Checkpoint 3.604672e-03 2.443
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 3.477540e-03 2.459
R-HSA-4839726 Chromatin organization 2.981275e-03 2.526
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 2.530085e-03 2.597
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 3.193956e-03 2.496
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 2.966169e-03 2.528
R-HSA-73857 RNA Polymerase II Transcription 3.504974e-03 2.455
R-HSA-69620 Cell Cycle Checkpoints 3.863537e-03 2.413
R-HSA-68877 Mitotic Prometaphase 4.428206e-03 2.354
R-HSA-199418 Negative regulation of the PI3K/AKT network 4.255858e-03 2.371
R-HSA-8878171 Transcriptional regulation by RUNX1 4.307986e-03 2.366
R-HSA-8866911 TFAP2 (AP-2) family regulates transcription of cell cycle factors 5.062402e-03 2.296
R-HSA-9705677 SARS-CoV-2 targets PDZ proteins in cell-cell junction 5.062402e-03 2.296
R-HSA-2467813 Separation of Sister Chromatids 5.046265e-03 2.297
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 4.777846e-03 2.321
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 5.462438e-03 2.263
R-HSA-169893 Prolonged ERK activation events 5.369009e-03 2.270
R-HSA-5683057 MAPK family signaling cascades 5.517577e-03 2.258
R-HSA-193648 NRAGE signals death through JNK 5.580240e-03 2.253
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 5.706211e-03 2.244
R-HSA-74713 IRS activation 6.812358e-03 2.167
R-HSA-187687 Signalling to ERKs 6.564543e-03 2.183
R-HSA-450294 MAP kinase activation 7.584263e-03 2.120
R-HSA-8943724 Regulation of PTEN gene transcription 7.148649e-03 2.146
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 5.958038e-03 2.225
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 6.564543e-03 2.183
R-HSA-166166 MyD88-independent TLR4 cascade 5.958038e-03 2.225
R-HSA-74160 Gene expression (Transcription) 7.744719e-03 2.111
R-HSA-8935964 RUNX1 regulates expression of components of tight junctions 8.797021e-03 2.056
R-HSA-9834899 Specification of the neural plate border 8.819422e-03 2.055
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 1.116178e-02 1.952
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 1.032561e-02 1.986
R-HSA-198753 ERK/MAPK targets 1.093344e-02 1.961
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 1.081083e-02 1.966
R-HSA-201556 Signaling by ALK 8.953789e-03 2.048
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 9.241569e-03 2.034
R-HSA-73887 Death Receptor Signaling 1.125086e-02 1.949
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor 1.209068e-02 1.918
R-HSA-448424 Interleukin-17 signaling 1.236412e-02 1.908
R-HSA-112412 SOS-mediated signalling 1.343648e-02 1.872
R-HSA-350054 Notch-HLH transcription pathway 1.331561e-02 1.876
R-HSA-199992 trans-Golgi Network Vesicle Budding 1.365137e-02 1.865
R-HSA-9022707 MECP2 regulates transcription factors 1.343648e-02 1.872
R-HSA-199991 Membrane Trafficking 1.401246e-02 1.853
R-HSA-3247509 Chromatin modifying enzymes 1.447383e-02 1.839
R-HSA-975871 MyD88 cascade initiated on plasma membrane 1.275338e-02 1.894
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 1.275338e-02 1.894
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 1.275338e-02 1.894
R-HSA-1266738 Developmental Biology 1.531044e-02 1.815
R-HSA-450341 Activation of the AP-1 family of transcription factors 1.891501e-02 1.723
R-HSA-9932444 ATP-dependent chromatin remodelers 1.740142e-02 1.759
R-HSA-9932451 SWI/SNF chromatin remodelers 1.740142e-02 1.759
R-HSA-525793 Myogenesis 1.890154e-02 1.724
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 1.945044e-02 1.711
R-HSA-449147 Signaling by Interleukins 1.906343e-02 1.720
R-HSA-416482 G alpha (12/13) signalling events 1.804663e-02 1.744
R-HSA-975155 MyD88 dependent cascade initiated on endosome 2.015844e-02 1.696
R-HSA-5673001 RAF/MAP kinase cascade 2.067536e-02 1.685
R-HSA-9762292 Regulation of CDH11 function 2.194930e-02 1.659
R-HSA-198203 PI3K/AKT activation 2.194930e-02 1.659
R-HSA-74749 Signal attenuation 2.194930e-02 1.659
R-HSA-2586552 Signaling by Leptin 2.194930e-02 1.659
R-HSA-432722 Golgi Associated Vesicle Biogenesis 2.268282e-02 1.644
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 2.316543e-02 1.635
R-HSA-68882 Mitotic Anaphase 2.366953e-02 1.626
R-HSA-5684996 MAPK1/MAPK3 signaling 2.384402e-02 1.623
R-HSA-2555396 Mitotic Metaphase and Anaphase 2.423139e-02 1.616
R-HSA-209560 NF-kB is activated and signals survival 2.857051e-02 1.544
R-HSA-9734767 Developmental Cell Lineages 2.782709e-02 1.556
R-HSA-9706019 RHOBTB3 ATPase cycle 2.517023e-02 1.599
R-HSA-182971 EGFR downregulation 2.744516e-02 1.562
R-HSA-9758941 Gastrulation 2.815642e-02 1.550
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 2.560897e-02 1.592
R-HSA-9856651 MITF-M-dependent gene expression 2.894342e-02 1.538
R-HSA-3700989 Transcriptional Regulation by TP53 2.431841e-02 1.614
R-HSA-2219528 PI3K/AKT Signaling in Cancer 2.912592e-02 1.536
R-HSA-69278 Cell Cycle, Mitotic 2.922776e-02 1.534
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 3.005232e-02 1.522
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 3.005232e-02 1.522
R-HSA-1640170 Cell Cycle 3.117488e-02 1.506
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 3.134839e-02 1.504
R-HSA-9022692 Regulation of MECP2 expression and activity 3.134839e-02 1.504
R-HSA-168898 Toll-like Receptor Cascades 3.205543e-02 1.494
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 3.294678e-02 1.482
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 3.294678e-02 1.482
R-HSA-9619665 EGR2 and SOX10-mediated initiation of Schwann cell myelination 3.340331e-02 1.476
R-HSA-2428928 IRS-related events triggered by IGF1R 3.341451e-02 1.476
R-HSA-2682334 EPH-Ephrin signaling 3.403299e-02 1.468
R-HSA-5673000 RAF activation 3.552666e-02 1.449
R-HSA-9933947 Formation of the non-canonical BAF (ncBAF) complex 3.588093e-02 1.445
R-HSA-9675108 Nervous system development 3.622230e-02 1.441
R-HSA-5633007 Regulation of TP53 Activity 3.764143e-02 1.424
R-HSA-9027284 Erythropoietin activates RAS 4.382607e-02 1.358
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 3.971949e-02 1.401
R-HSA-193639 p75NTR signals via NF-kB 4.382607e-02 1.358
R-HSA-432720 Lysosome Vesicle Biogenesis 3.997701e-02 1.398
R-HSA-6807878 COPI-mediated anterograde transport 4.039143e-02 1.394
R-HSA-9701898 STAT3 nuclear events downstream of ALK signaling 4.382607e-02 1.358
R-HSA-212165 Epigenetic regulation of gene expression 3.941610e-02 1.404
R-HSA-2428924 IGF1R signaling cascade 3.808404e-02 1.419
R-HSA-9933946 Formation of the embryonic stem cell BAF (esBAF) complex 4.382607e-02 1.358
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 3.971949e-02 1.401
R-HSA-9933939 Formation of the polybromo-BAF (pBAF) complex 3.977746e-02 1.400
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 4.715421e-02 1.326
R-HSA-1280215 Cytokine Signaling in Immune system 4.357997e-02 1.361
R-HSA-9673324 WNT5:FZD7-mediated leishmania damping 4.802042e-02 1.319
R-HSA-9664420 Killing mechanisms 4.802042e-02 1.319
R-HSA-9842860 Regulation of endogenous retroelements 4.891381e-02 1.311
R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression 4.967810e-02 1.304
R-HSA-5619039 Defective SLC12A6 causes agenesis of the corpus callosum, with peripheral neurop... 5.083161e-02 1.294
R-HSA-9635644 Inhibition of membrane repair 5.083161e-02 1.294
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 5.197289e-02 1.284
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 5.226667e-02 1.282
R-HSA-9675151 Disorders of Developmental Biology 5.235432e-02 1.281
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 5.484438e-02 1.261
R-HSA-9656223 Signaling by RAF1 mutants 5.491921e-02 1.260
R-HSA-2028269 Signaling by Hippo 5.682174e-02 1.245
R-HSA-6807070 PTEN Regulation 5.684058e-02 1.245
R-HSA-73762 RNA Polymerase I Transcription Initiation 5.763500e-02 1.239
R-HSA-1606322 ZBP1(DAI) mediated induction of type I IFNs 6.141684e-02 1.212
R-HSA-156711 Polo-like kinase mediated events 6.141684e-02 1.212
R-HSA-3928662 EPHB-mediated forward signaling 6.325323e-02 1.199
R-HSA-1834941 STING mediated induction of host immune responses 6.613392e-02 1.180
R-HSA-8874177 ATF6B (ATF6-beta) activates chaperones 6.719667e-02 1.173
R-HSA-8854521 Interaction between PHLDA1 and AURKA 6.719667e-02 1.173
R-HSA-68881 Mitotic Metaphase/Anaphase Transition 6.719667e-02 1.173
R-HSA-9944997 Loss of Function of KMT2D in MLL4 Complex Formation in Kabuki Syndrome 8.328057e-02 1.079
R-HSA-9944971 Loss of Function of KMT2D in Kabuki Syndrome 8.328057e-02 1.079
R-HSA-9934037 Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) 7.096744e-02 1.149
R-HSA-438066 Unblocking of NMDA receptors, glutamate binding and activation 8.096242e-02 1.092
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 6.911489e-02 1.160
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 6.911489e-02 1.160
R-HSA-9649948 Signaling downstream of RAS mutants 6.911489e-02 1.160
R-HSA-6802957 Oncogenic MAPK signaling 8.062551e-02 1.094
R-HSA-6802949 Signaling by RAS mutants 6.911489e-02 1.160
R-HSA-8985801 Regulation of cortical dendrite branching 6.719667e-02 1.173
R-HSA-9022538 Loss of MECP2 binding ability to 5mC-DNA 8.328057e-02 1.079
R-HSA-8875513 MET interacts with TNS proteins 8.328057e-02 1.079
R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission 8.096242e-02 1.092
R-HSA-68949 Orc1 removal from chromatin 8.808988e-02 1.055
R-HSA-373753 Nephrin family interactions 7.096744e-02 1.149
R-HSA-9823730 Formation of definitive endoderm 7.096744e-02 1.149
R-HSA-5653656 Vesicle-mediated transport 8.903447e-02 1.050
R-HSA-5687128 MAPK6/MAPK4 signaling 8.062551e-02 1.094
R-HSA-109704 PI3K Cascade 8.154062e-02 1.089
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 8.808988e-02 1.055
R-HSA-9711123 Cellular response to chemical stress 6.683279e-02 1.175
R-HSA-446652 Interleukin-1 family signaling 7.848191e-02 1.105
R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specif... 8.611357e-02 1.065
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription 7.834866e-02 1.106
R-HSA-9663891 Selective autophagy 9.061309e-02 1.043
R-HSA-982772 Growth hormone receptor signaling 9.136051e-02 1.039
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 9.144523e-02 1.039
R-HSA-9816359 Maternal to zygotic transition (MZT) 9.278732e-02 1.033
R-HSA-9652169 Signaling by MAP2K mutants 9.908812e-02 1.004
R-HSA-9833576 CDH11 homotypic and heterotypic interactions 1.298930e-01 0.886
R-HSA-5603029 IkBA variant leads to EDA-ID 1.298930e-01 0.886
R-HSA-8869496 TFAP2A acts as a transcriptional repressor during retinoic acid induced cell dif... 1.448995e-01 0.839
R-HSA-9027283 Erythropoietin activates STAT5 1.448995e-01 0.839
R-HSA-8951671 RUNX3 regulates YAP1-mediated transcription 1.448995e-01 0.839
R-HSA-8931987 RUNX1 regulates estrogen receptor mediated transcription 1.596482e-01 0.797
R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors 1.596482e-01 0.797
R-HSA-110056 MAPK3 (ERK1) activation 2.023905e-01 0.694
R-HSA-9027277 Erythropoietin activates Phospholipase C gamma (PLCG) 2.023905e-01 0.694
R-HSA-5467337 APC truncation mutants have impaired AXIN binding 2.161509e-01 0.665
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex 2.161509e-01 0.665
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex 2.161509e-01 0.665
R-HSA-429947 Deadenylation of mRNA 9.669843e-02 1.015
R-HSA-428540 Activation of RAC1 2.296748e-01 0.639
R-HSA-2514853 Condensation of Prometaphase Chromosomes 2.296748e-01 0.639
R-HSA-5339716 Signaling by GSK3beta mutants 2.296748e-01 0.639
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 2.429662e-01 0.614
R-HSA-4839743 Signaling by CTNNB1 phospho-site mutants 2.429662e-01 0.614
R-HSA-9820865 Z-decay: degradation of maternal mRNAs by zygotically expressed factors 2.429662e-01 0.614
R-HSA-5358752 CTNNB1 T41 mutants aren't phosphorylated 2.429662e-01 0.614
R-HSA-5358747 CTNNB1 S33 mutants aren't phosphorylated 2.429662e-01 0.614
R-HSA-5358751 CTNNB1 S45 mutants aren't phosphorylated 2.429662e-01 0.614
R-HSA-5358749 CTNNB1 S37 mutants aren't phosphorylated 2.429662e-01 0.614
R-HSA-9006335 Signaling by Erythropoietin 1.245941e-01 0.905
R-HSA-68962 Activation of the pre-replicative complex 1.303845e-01 0.885
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) 2.814847e-01 0.551
R-HSA-3270619 IRF3-mediated induction of type I IFN 2.814847e-01 0.551
R-HSA-196299 Beta-catenin phosphorylation cascade 2.814847e-01 0.551
R-HSA-9843970 Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex 1.601768e-01 0.795
R-HSA-9845323 Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) 1.163448e-01 0.934
R-HSA-5674135 MAP2K and MAPK activation 2.099323e-01 0.678
R-HSA-8854518 AURKA Activation by TPX2 1.394630e-01 0.856
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 2.162687e-01 0.665
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 2.390042e-01 0.622
R-HSA-9018519 Estrogen-dependent gene expression 2.768332e-01 0.558
R-HSA-9937080 Developmental Lineage of Multipotent Pancreatic Progenitor Cells 1.421444e-01 0.847
R-HSA-191650 Regulation of gap junction activity 9.908812e-02 1.004
R-HSA-203641 NOSTRIN mediated eNOS trafficking 1.596482e-01 0.797
R-HSA-190873 Gap junction degradation 1.883894e-01 0.725
R-HSA-9796292 Formation of axial mesoderm 2.560290e-01 0.592
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA 1.724196e-01 0.763
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 2.737837e-01 0.563
R-HSA-9620244 Long-term potentiation 1.021227e-01 0.991
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3 2.429662e-01 0.614
R-HSA-2299718 Condensation of Prophase Chromosomes 2.417604e-01 0.617
R-HSA-1606341 IRF3 mediated activation of type 1 IFN 1.146240e-01 0.941
R-HSA-420029 Tight junction interactions 1.021227e-01 0.991
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis 1.662783e-01 0.779
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 1.785975e-01 0.748
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 2.162668e-01 0.665
R-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression 2.688672e-01 0.570
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 2.073050e-01 0.683
R-HSA-165181 Inhibition of TSC complex formation by PKB 9.908812e-02 1.004
R-HSA-176417 Phosphorylation of Emi1 1.298930e-01 0.886
R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling 1.448995e-01 0.839
R-HSA-9032845 Activated NTRK2 signals through CDK5 1.596482e-01 0.797
R-HSA-196025 Formation of annular gap junctions 1.741433e-01 0.759
R-HSA-176974 Unwinding of DNA 1.883894e-01 0.725
R-HSA-428543 Inactivation of CDC42 and RAC1 1.883894e-01 0.725
R-HSA-2468052 Establishment of Sister Chromatid Cohesion 2.023905e-01 0.694
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 2.023905e-01 0.694
R-HSA-192814 vRNA Synthesis 2.161509e-01 0.665
R-HSA-4839744 Signaling by APC mutants 2.161509e-01 0.665
R-HSA-110362 POLB-Dependent Long Patch Base Excision Repair 2.296748e-01 0.639
R-HSA-68884 Mitotic Telophase/Cytokinesis 2.296748e-01 0.639
R-HSA-202670 ERKs are inactivated 2.296748e-01 0.639
R-HSA-4839748 Signaling by AMER1 mutants 2.296748e-01 0.639
R-HSA-4839735 Signaling by AXIN mutants 2.296748e-01 0.639
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 2.560290e-01 0.592
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 2.814847e-01 0.551
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 1.601768e-01 0.795
R-HSA-69052 Switching of origins to a post-replicative state 1.681810e-01 0.774
R-HSA-1169091 Activation of NF-kappaB in B cells 2.737837e-01 0.563
R-HSA-5655291 Signaling by FGFR4 in disease 2.688672e-01 0.570
R-HSA-209543 p75NTR recruits signalling complexes 2.429662e-01 0.614
R-HSA-176187 Activation of ATR in response to replication stress 1.481064e-01 0.829
R-HSA-112399 IRS-mediated signalling 1.053813e-01 0.977
R-HSA-69275 G2/M Transition 1.497818e-01 0.825
R-HSA-1474165 Reproduction 2.502632e-01 0.602
R-HSA-427413 NoRC negatively regulates rRNA expression 1.598037e-01 0.796
R-HSA-4608870 Asymmetric localization of PCP proteins 2.353703e-01 0.628
R-HSA-453274 Mitotic G2-G2/M phases 1.545369e-01 0.811
R-HSA-418885 DCC mediated attractive signaling 2.814847e-01 0.551
R-HSA-9603381 Activated NTRK3 signals through PI3K 1.596482e-01 0.797
R-HSA-8875555 MET activates RAP1 and RAC1 2.023905e-01 0.694
R-HSA-1855191 Synthesis of IPs in the nucleus 2.688672e-01 0.570
R-HSA-171007 p38MAPK events 2.814847e-01 0.551
R-HSA-74751 Insulin receptor signalling cascade 1.315904e-01 0.881
R-HSA-68886 M Phase 9.634284e-02 1.016
R-HSA-68867 Assembly of the pre-replicative complex 2.667815e-01 0.574
R-HSA-5685939 HDR through MMEJ (alt-NHEJ) 2.560290e-01 0.592
R-HSA-9843743 Transcriptional regulation of brown and beige adipocyte differentiation 1.973208e-01 0.705
R-HSA-9844594 Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 1.973208e-01 0.705
R-HSA-2559580 Oxidative Stress Induced Senescence 1.359427e-01 0.867
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1 9.908812e-02 1.004
R-HSA-8941855 RUNX3 regulates CDKN1A transcription 1.298930e-01 0.886
R-HSA-5674499 Negative feedback regulation of MAPK pathway 1.298930e-01 0.886
R-HSA-1236973 Cross-presentation of particulate exogenous antigens (phagosomes) 2.023905e-01 0.694
R-HSA-177504 Retrograde neurotrophin signalling 2.688672e-01 0.570
R-HSA-9646399 Aggrephagy 1.973208e-01 0.705
R-HSA-69481 G2/M Checkpoints 2.353384e-01 0.628
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 2.761286e-01 0.559
R-HSA-9664873 Pexophagy 2.023905e-01 0.694
R-HSA-202403 TCR signaling 1.647702e-01 0.783
R-HSA-9842663 Signaling by LTK 2.429662e-01 0.614
R-HSA-446353 Cell-extracellular matrix interactions 2.814847e-01 0.551
R-HSA-9733709 Cardiogenesis 1.481064e-01 0.829
R-HSA-74752 Signaling by Insulin receptor 2.621223e-01 0.581
R-HSA-2559583 Cellular Senescence 1.359268e-01 0.867
R-HSA-9818749 Regulation of NFE2L2 gene expression 1.448995e-01 0.839
R-HSA-205043 NRIF signals cell death from the nucleus 2.688672e-01 0.570
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 9.831236e-02 1.007
R-HSA-5250913 Positive epigenetic regulation of rRNA expression 1.598037e-01 0.796
R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA 1.556645e-01 0.808
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7 2.296748e-01 0.639
R-HSA-1251985 Nuclear signaling by ERBB4 1.973208e-01 0.705
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 2.353703e-01 0.628
R-HSA-5660668 CLEC7A/inflammasome pathway 1.298930e-01 0.886
R-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7 1.448995e-01 0.839
R-HSA-426117 Cation-coupled Chloride cotransporters 1.596482e-01 0.797
R-HSA-9022702 MECP2 regulates transcription of neuronal ligands 2.023905e-01 0.694
R-HSA-446205 Synthesis of GDP-mannose 2.429662e-01 0.614
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 1.188686e-01 0.925
R-HSA-8875878 MET promotes cell motility 1.848089e-01 0.733
R-HSA-453276 Regulation of mitotic cell cycle 1.598037e-01 0.796
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 1.598037e-01 0.796
R-HSA-157858 Gap junction trafficking and regulation 2.609681e-01 0.583
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 1.984310e-01 0.702
R-HSA-3371571 HSF1-dependent transactivation 2.737837e-01 0.563
R-HSA-9843745 Adipogenesis 2.540262e-01 0.595
R-HSA-5628897 TP53 Regulates Metabolic Genes 1.851034e-01 0.733
R-HSA-111932 CaMK IV-mediated phosphorylation of CREB 2.023905e-01 0.694
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 1.394630e-01 0.856
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling 2.353703e-01 0.628
R-HSA-8856688 Golgi-to-ER retrograde transport 2.578009e-01 0.589
R-HSA-69242 S Phase 1.650920e-01 0.782
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 1.785975e-01 0.748
R-HSA-9006115 Signaling by NTRK2 (TRKB) 1.132121e-01 0.946
R-HSA-202424 Downstream TCR signaling 2.482123e-01 0.605
R-HSA-438064 Post NMDA receptor activation events 2.344226e-01 0.630
R-HSA-3134973 LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production 1.146240e-01 0.941
R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production 1.146240e-01 0.941
R-HSA-448706 Interleukin-1 processing 1.883894e-01 0.725
R-HSA-193692 Regulated proteolysis of p75NTR 1.883894e-01 0.725
R-HSA-111458 Formation of apoptosome 2.023905e-01 0.694
R-HSA-9005895 Pervasive developmental disorders 2.429662e-01 0.614
R-HSA-9005891 Loss of function of MECP2 in Rett syndrome 2.429662e-01 0.614
R-HSA-9697154 Disorders of Nervous System Development 2.429662e-01 0.614
R-HSA-9933937 Formation of the canonical BAF (cBAF) complex 2.688672e-01 0.570
R-HSA-9766229 Degradation of CDH1 2.609681e-01 0.583
R-HSA-69206 G1/S Transition 2.279593e-01 0.642
R-HSA-2132295 MHC class II antigen presentation 2.170058e-01 0.664
R-HSA-1169408 ISG15 antiviral mechanism 1.766834e-01 0.753
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 2.353703e-01 0.628
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 2.353703e-01 0.628
R-HSA-5205647 Mitophagy 1.601768e-01 0.795
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 1.662783e-01 0.779
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 1.481064e-01 0.829
R-HSA-201681 TCF dependent signaling in response to WNT 2.763095e-01 0.559
R-HSA-9627069 Regulation of the apoptosome activity 2.023905e-01 0.694
R-HSA-111461 Cytochrome c-mediated apoptotic response 2.296748e-01 0.639
R-HSA-422475 Axon guidance 1.203317e-01 0.920
R-HSA-8853884 Transcriptional Regulation by VENTX 2.036154e-01 0.691
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 1.639762e-01 0.785
R-HSA-199977 ER to Golgi Anterograde Transport 1.622941e-01 0.790
R-HSA-9755511 KEAP1-NFE2L2 pathway 1.735997e-01 0.760
R-HSA-9020702 Interleukin-1 signaling 1.328764e-01 0.877
R-HSA-1632852 Macroautophagy 1.432698e-01 0.844
R-HSA-9764790 Positive Regulation of CDH1 Gene Transcription 2.023905e-01 0.694
R-HSA-210990 PECAM1 interactions 2.161509e-01 0.665
R-HSA-2262752 Cellular responses to stress 9.671177e-02 1.015
R-HSA-177929 Signaling by EGFR 1.018221e-01 0.992
R-HSA-165159 MTOR signalling 2.162687e-01 0.665
R-HSA-9707564 Cytoprotection by HMOX1 2.117754e-01 0.674
R-HSA-8953897 Cellular responses to stimuli 1.641730e-01 0.785
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 1.549249e-01 0.810
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 2.429662e-01 0.614
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation 2.688672e-01 0.570
R-HSA-186763 Downstream signal transduction 1.362358e-01 0.866
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 2.814847e-01 0.551
R-HSA-9612973 Autophagy 1.881425e-01 0.726
R-HSA-5675221 Negative regulation of MAPK pathway 2.099323e-01 0.678
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 2.298571e-01 0.639
R-HSA-9700206 Signaling by ALK in cancer 1.549249e-01 0.810
R-HSA-9683610 Maturation of nucleoprotein 2.560290e-01 0.592
R-HSA-442729 CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde 1.741433e-01 0.759
R-HSA-351906 Apoptotic cleavage of cell adhesion proteins 1.741433e-01 0.759
R-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors 2.560290e-01 0.592
R-HSA-73854 RNA Polymerase I Promoter Clearance 1.809788e-01 0.742
R-HSA-186797 Signaling by PDGF 1.238815e-01 0.907
R-HSA-9730414 MITF-M-regulated melanocyte development 1.145788e-01 0.941
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 9.669843e-02 1.015
R-HSA-8863678 Neurodegenerative Diseases 9.669843e-02 1.015
R-HSA-9909396 Circadian clock 2.578009e-01 0.589
R-HSA-9764560 Regulation of CDH1 Gene Transcription 1.556645e-01 0.808
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 1.205753e-01 0.919
R-HSA-9764265 Regulation of CDH1 Expression and Function 1.205753e-01 0.919
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 1.132121e-01 0.946
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol 1.481064e-01 0.829
R-HSA-8853659 RET signaling 1.724196e-01 0.763
R-HSA-1592230 Mitochondrial biogenesis 1.955642e-01 0.709
R-HSA-9707616 Heme signaling 1.238815e-01 0.907
R-HSA-909733 Interferon alpha/beta signaling 1.885697e-01 0.725
R-HSA-6806834 Signaling by MET 1.984310e-01 0.702
R-HSA-9008059 Interleukin-37 signaling 1.303845e-01 0.885
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 1.481064e-01 0.829
R-HSA-69205 G1/S-Specific Transcription 1.724196e-01 0.763
R-HSA-73864 RNA Polymerase I Transcription 1.896529e-01 0.722
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 2.028565e-01 0.693
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 2.099323e-01 0.678
R-HSA-9759194 Nuclear events mediated by NFE2L2 2.097863e-01 0.678
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 2.162687e-01 0.665
R-HSA-9682706 Replication of the SARS-CoV-1 genome 2.560290e-01 0.592
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 1.163448e-01 0.934
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 1.163448e-01 0.934
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 1.163448e-01 0.934
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 1.163448e-01 0.934
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 1.474906e-01 0.831
R-HSA-9678108 SARS-CoV-1 Infection 2.501588e-01 0.602
R-HSA-9609736 Assembly and cell surface presentation of NMDA receptors 2.099323e-01 0.678
R-HSA-9679514 SARS-CoV-1 Genome Replication and Transcription 2.688672e-01 0.570
R-HSA-2644603 Signaling by NOTCH1 in Cancer 1.163448e-01 0.934
R-HSA-1980143 Signaling by NOTCH1 1.809788e-01 0.742
R-HSA-8878159 Transcriptional regulation by RUNX3 2.902079e-01 0.537
R-HSA-8939211 ESR-mediated signaling 2.910033e-01 0.536
R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins 2.938852e-01 0.532
R-HSA-176412 Phosphorylation of the APC/C 2.938852e-01 0.532
R-HSA-9634600 Regulation of glycolysis by fructose 2,6-bisphosphate metabolism 2.938852e-01 0.532
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 2.938852e-01 0.532
R-HSA-3214815 HDACs deacetylate histones 2.993718e-01 0.524
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 3.057497e-01 0.515
R-HSA-918233 TRAF3-dependent IRF activation pathway 3.060724e-01 0.514
R-HSA-9690406 Transcriptional regulation of testis differentiation 3.060724e-01 0.514
R-HSA-936964 Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) 3.060724e-01 0.514
R-HSA-3134975 Regulation of innate immune responses to cytosolic DNA 3.060724e-01 0.514
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 3.060724e-01 0.514
R-HSA-9009391 Extra-nuclear estrogen signaling 3.090559e-01 0.510
R-HSA-9764561 Regulation of CDH1 Function 3.121168e-01 0.506
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 3.121168e-01 0.506
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 3.137762e-01 0.503
R-HSA-1483255 PI Metabolism 3.137762e-01 0.503
R-HSA-372708 p130Cas linkage to MAPK signaling for integrins 3.180500e-01 0.498
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane 3.180500e-01 0.498
R-HSA-5210891 Uptake and function of anthrax toxins 3.180500e-01 0.498
R-HSA-9694686 Replication of the SARS-CoV-2 genome 3.180500e-01 0.498
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 3.184714e-01 0.497
R-HSA-453279 Mitotic G1 phase and G1/S transition 3.193995e-01 0.496
R-HSA-429914 Deadenylation-dependent mRNA decay 3.248122e-01 0.488
R-HSA-5619507 Activation of HOX genes during differentiation 3.279446e-01 0.484
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 3.279446e-01 0.484
R-HSA-3928664 Ephrin signaling 3.298216e-01 0.482
R-HSA-181429 Serotonin Neurotransmitter Release Cycle 3.298216e-01 0.482
R-HSA-73980 RNA Polymerase III Transcription Termination 3.298216e-01 0.482
R-HSA-432142 Platelet sensitization by LDL 3.298216e-01 0.482
R-HSA-6804760 Regulation of TP53 Activity through Methylation 3.298216e-01 0.482
R-HSA-111471 Apoptotic factor-mediated response 3.298216e-01 0.482
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 3.311377e-01 0.480
R-HSA-9692914 SARS-CoV-1-host interactions 3.373894e-01 0.472
R-HSA-8939902 Regulation of RUNX2 expression and activity 3.374467e-01 0.472
R-HSA-948021 Transport to the Golgi and subsequent modification 3.402607e-01 0.468
R-HSA-5654710 PI-3K cascade:FGFR3 3.413907e-01 0.467
R-HSA-392517 Rap1 signalling 3.413907e-01 0.467
R-HSA-912631 Regulation of signaling by CBL 3.413907e-01 0.467
R-HSA-9694631 Maturation of nucleoprotein 3.413907e-01 0.467
R-HSA-844456 The NLRP3 inflammasome 3.413907e-01 0.467
R-HSA-9694682 SARS-CoV-2 Genome Replication and Transcription 3.413907e-01 0.467
R-HSA-69239 Synthesis of DNA 3.421094e-01 0.466
R-HSA-9820448 Developmental Cell Lineages of the Exocrine Pancreas 3.428502e-01 0.465
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 3.437376e-01 0.464
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 3.437376e-01 0.464
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 3.437376e-01 0.464
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 3.500095e-01 0.456
R-HSA-380259 Loss of Nlp from mitotic centrosomes 3.500095e-01 0.456
R-HSA-69615 G1/S DNA Damage Checkpoints 3.500095e-01 0.456
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 3.506818e-01 0.455
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 3.506818e-01 0.455
R-HSA-69002 DNA Replication Pre-Initiation 3.515415e-01 0.454
R-HSA-5654720 PI-3K cascade:FGFR4 3.527608e-01 0.453
R-HSA-389513 Co-inhibition by CTLA4 3.527608e-01 0.453
R-HSA-5620916 VxPx cargo-targeting to cilium 3.527608e-01 0.453
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse 3.527608e-01 0.453
R-HSA-445144 Signal transduction by L1 3.527608e-01 0.453
R-HSA-6807004 Negative regulation of MET activity 3.527608e-01 0.453
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 3.562609e-01 0.448
R-HSA-1234174 Cellular response to hypoxia 3.624908e-01 0.441
R-HSA-264642 Acetylcholine Neurotransmitter Release Cycle 3.639353e-01 0.439
R-HSA-167044 Signalling to RAS 3.639353e-01 0.439
R-HSA-9824594 Regulation of MITF-M-dependent genes involved in apoptosis 3.639353e-01 0.439
R-HSA-9819196 Zygotic genome activation (ZGA) 3.639353e-01 0.439
R-HSA-9636383 Prevention of phagosomal-lysosomal fusion 3.639353e-01 0.439
R-HSA-1483249 Inositol phosphate metabolism 3.656596e-01 0.437
R-HSA-5654706 FRS-mediated FGFR3 signaling 3.749176e-01 0.426
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 3.749176e-01 0.426
R-HSA-977347 Serine metabolism 3.749176e-01 0.426
R-HSA-9034015 Signaling by NTRK3 (TRKC) 3.749176e-01 0.426
R-HSA-8949215 Mitochondrial calcium ion transport 3.749176e-01 0.426
R-HSA-8876384 Listeria monocytogenes entry into host cells 3.749176e-01 0.426
R-HSA-1852241 Organelle biogenesis and maintenance 3.793983e-01 0.421
R-HSA-9662360 Sensory processing of sound by inner hair cells of the cochlea 3.810402e-01 0.419
R-HSA-5654689 PI-3K cascade:FGFR1 3.857109e-01 0.414
R-HSA-5654712 FRS-mediated FGFR4 signaling 3.857109e-01 0.414
R-HSA-212676 Dopamine Neurotransmitter Release Cycle 3.857109e-01 0.414
R-HSA-112409 RAF-independent MAPK1/3 activation 3.857109e-01 0.414
R-HSA-166208 mTORC1-mediated signalling 3.857109e-01 0.414
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 3.857109e-01 0.414
R-HSA-9925563 Developmental Lineage of Pancreatic Ductal Cells 3.871733e-01 0.412
R-HSA-4420097 VEGFA-VEGFR2 Pathway 3.890688e-01 0.410
R-HSA-195253 Degradation of beta-catenin by the destruction complex 3.932796e-01 0.405
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 3.932796e-01 0.405
R-HSA-9843940 Regulation of endogenous retroelements by KRAB-ZFP proteins 3.932796e-01 0.405
R-HSA-373760 L1CAM interactions 3.937272e-01 0.405
R-HSA-912526 Interleukin receptor SHC signaling 3.963185e-01 0.402
R-HSA-9007101 Rab regulation of trafficking 3.983764e-01 0.400
R-HSA-5693538 Homology Directed Repair 4.030161e-01 0.395
R-HSA-913531 Interferon Signaling 4.050173e-01 0.393
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 4.054087e-01 0.392
R-HSA-9865881 Complex III assembly 4.067435e-01 0.391
R-HSA-933542 TRAF6 mediated NF-kB activation 4.067435e-01 0.391
R-HSA-5621575 CD209 (DC-SIGN) signaling 4.067435e-01 0.391
R-HSA-181430 Norepinephrine Neurotransmitter Release Cycle 4.067435e-01 0.391
R-HSA-8878166 Transcriptional regulation by RUNX2 4.076456e-01 0.390
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 4.114297e-01 0.386
R-HSA-68875 Mitotic Prophase 4.122644e-01 0.385
R-HSA-5654695 PI-3K cascade:FGFR2 4.169892e-01 0.380
R-HSA-5654693 FRS-mediated FGFR1 signaling 4.169892e-01 0.380
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane 4.169892e-01 0.380
R-HSA-3214842 HDMs demethylate histones 4.169892e-01 0.380
R-HSA-400685 Sema4D in semaphorin signaling 4.169892e-01 0.380
R-HSA-69473 G2/M DNA damage checkpoint 4.174207e-01 0.379
R-HSA-1236394 Signaling by ERBB4 4.174207e-01 0.379
R-HSA-380287 Centrosome maturation 4.233809e-01 0.373
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes 4.233809e-01 0.373
R-HSA-9909648 Regulation of PD-L1(CD274) expression 4.247442e-01 0.372
R-HSA-9703465 Signaling by FLT3 fusion proteins 4.270585e-01 0.370
R-HSA-110373 Resolution of AP sites via the multiple-nucleotide patch replacement pathway 4.270585e-01 0.370
R-HSA-210500 Glutamate Neurotransmitter Release Cycle 4.270585e-01 0.370
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane 4.270585e-01 0.370
R-HSA-1855183 Synthesis of IP2, IP, and Ins in the cytosol 4.270585e-01 0.370
R-HSA-9637687 Suppression of phagosomal maturation 4.270585e-01 0.370
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 4.284373e-01 0.368
R-HSA-445095 Interaction between L1 and Ankyrins 4.369545e-01 0.360
R-HSA-5655332 Signaling by FGFR3 in disease 4.369545e-01 0.360
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane 4.369545e-01 0.360
R-HSA-3928663 EPHA-mediated growth cone collapse 4.369545e-01 0.360
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 4.369545e-01 0.360
R-HSA-194138 Signaling by VEGF 4.397262e-01 0.357
R-HSA-383280 Nuclear Receptor transcription pathway 4.410695e-01 0.355
R-HSA-4086400 PCP/CE pathway 4.410695e-01 0.355
R-HSA-5654700 FRS-mediated FGFR2 signaling 4.466802e-01 0.350
R-HSA-5576892 Phase 0 - rapid depolarisation 4.466802e-01 0.350
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 4.466802e-01 0.350
R-HSA-5654732 Negative regulation of FGFR3 signaling 4.466802e-01 0.350
R-HSA-622312 Inflammasomes 4.466802e-01 0.350
R-HSA-9659379 Sensory processing of sound 4.468995e-01 0.350
R-HSA-9709570 Impaired BRCA2 binding to RAD51 4.562385e-01 0.341
R-HSA-5654708 Downstream signaling of activated FGFR3 4.562385e-01 0.341
R-HSA-210745 Regulation of gene expression in beta cells 4.562385e-01 0.341
R-HSA-917729 Endosomal Sorting Complex Required For Transport (ESCRT) 4.562385e-01 0.341
R-HSA-5654733 Negative regulation of FGFR4 signaling 4.562385e-01 0.341
R-HSA-180024 DARPP-32 events 4.562385e-01 0.341
R-HSA-5693607 Processing of DNA double-strand break ends 4.584568e-01 0.339
R-HSA-5654716 Downstream signaling of activated FGFR4 4.656323e-01 0.332
R-HSA-2424491 DAP12 signaling 4.656323e-01 0.332
R-HSA-1250196 SHC1 events in ERBB2 signaling 4.656323e-01 0.332
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK 4.656323e-01 0.332
R-HSA-888590 GABA synthesis, release, reuptake and degradation 4.656323e-01 0.332
R-HSA-9933387 RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression 4.656323e-01 0.332
R-HSA-8863795 Downregulation of ERBB2 signaling 4.656323e-01 0.332
R-HSA-1227990 Signaling by ERBB2 in Cancer 4.656323e-01 0.332
R-HSA-157118 Signaling by NOTCH 4.726602e-01 0.325
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 4.748643e-01 0.323
R-HSA-2129379 Molecules associated with elastic fibres 4.748643e-01 0.323
R-HSA-399719 Trafficking of AMPA receptors 4.748643e-01 0.323
R-HSA-9833109 Evasion by RSV of host interferon responses 4.748643e-01 0.323
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 4.748643e-01 0.323
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 4.755278e-01 0.323
R-HSA-195721 Signaling by WNT 4.770159e-01 0.321
R-HSA-4791275 Signaling by WNT in cancer 4.839374e-01 0.315
R-HSA-350562 Regulation of ornithine decarboxylase (ODC) 4.839374e-01 0.315
R-HSA-69190 DNA strand elongation 4.839374e-01 0.315
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 4.839374e-01 0.315
R-HSA-111465 Apoptotic cleavage of cellular proteins 4.839374e-01 0.315
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 4.867262e-01 0.313
R-HSA-354192 Integrin signaling 4.928543e-01 0.307
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 4.928543e-01 0.307
R-HSA-5654726 Negative regulation of FGFR1 signaling 4.928543e-01 0.307
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 4.928543e-01 0.307
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 4.928543e-01 0.307
R-HSA-5696394 DNA Damage Recognition in GG-NER 5.016177e-01 0.300
R-HSA-180534 Vpu mediated degradation of CD4 5.016177e-01 0.300
R-HSA-9768727 Regulation of CDH1 posttranslational processing and trafficking to plasma membra... 5.016177e-01 0.300
R-HSA-9645723 Diseases of programmed cell death 5.032424e-01 0.298
R-HSA-5696400 Dual Incision in GG-NER 5.102302e-01 0.292
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 5.102302e-01 0.292
R-HSA-5654727 Negative regulation of FGFR2 signaling 5.102302e-01 0.292
R-HSA-9680350 Signaling by CSF1 (M-CSF) in myeloid cells 5.102302e-01 0.292
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1 5.102302e-01 0.292
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 5.102302e-01 0.292
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 5.102302e-01 0.292
R-HSA-168638 NOD1/2 Signaling Pathway 5.102302e-01 0.292
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian expression 5.102302e-01 0.292
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 5.140615e-01 0.289
R-HSA-5654696 Downstream signaling of activated FGFR2 5.186943e-01 0.285
R-HSA-5654687 Downstream signaling of activated FGFR1 5.186943e-01 0.285
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 5.186943e-01 0.285
R-HSA-169911 Regulation of Apoptosis 5.186943e-01 0.285
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 5.186943e-01 0.285
R-HSA-388841 Regulation of T cell activation by CD28 family 5.248367e-01 0.280
R-HSA-180585 Vif-mediated degradation of APOBEC3G 5.270127e-01 0.278
R-HSA-9682385 FLT3 signaling in disease 5.270127e-01 0.278
R-HSA-8941326 RUNX2 regulates bone development 5.270127e-01 0.278
R-HSA-111933 Calmodulin induced events 5.270127e-01 0.278
R-HSA-111997 CaM pathway 5.270127e-01 0.278
R-HSA-114604 GPVI-mediated activation cascade 5.270127e-01 0.278
R-HSA-749476 RNA Polymerase III Abortive And Retractive Initiation 5.270127e-01 0.278
R-HSA-74158 RNA Polymerase III Transcription 5.270127e-01 0.278
R-HSA-389948 Co-inhibition by PD-1 5.292779e-01 0.276
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 5.292779e-01 0.276
R-HSA-4641258 Degradation of DVL 5.351879e-01 0.271
R-HSA-4641257 Degradation of AXIN 5.351879e-01 0.271
R-HSA-9762114 GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 5.351879e-01 0.271
R-HSA-933541 TRAF6 mediated IRF7 activation 5.351879e-01 0.271
R-HSA-5689896 Ovarian tumor domain proteases 5.351879e-01 0.271
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 5.399483e-01 0.268
R-HSA-376176 Signaling by ROBO receptors 5.399483e-01 0.268
R-HSA-1566948 Elastic fibre formation 5.432222e-01 0.265
R-HSA-202131 Metabolism of nitric oxide: NOS3 activation and regulation 5.432222e-01 0.265
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 5.432222e-01 0.265
R-HSA-9958790 SLC-mediated transport of inorganic anions 5.432222e-01 0.265
R-HSA-452723 Transcriptional regulation of pluripotent stem cells 5.432222e-01 0.265
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 5.511182e-01 0.259
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes) 5.511182e-01 0.259
R-HSA-9929356 GSK3B-mediated proteasomal degradation of PD-L1(CD274) 5.511182e-01 0.259
R-HSA-8953750 Transcriptional Regulation by E2F6 5.511182e-01 0.259
R-HSA-69541 Stabilization of p53 5.511182e-01 0.259
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 5.557581e-01 0.255
R-HSA-5607764 CLEC7A (Dectin-1) signaling 5.557581e-01 0.255
R-HSA-983169 Class I MHC mediated antigen processing & presentation 5.559104e-01 0.255
R-HSA-5696395 Formation of Incision Complex in GG-NER 5.588781e-01 0.253
R-HSA-202433 Generation of second messenger molecules 5.588781e-01 0.253
R-HSA-9604323 Negative regulation of NOTCH4 signaling 5.588781e-01 0.253
R-HSA-5602358 Diseases associated with the TLR signaling cascade 5.588781e-01 0.253
R-HSA-5260271 Diseases of Immune System 5.588781e-01 0.253
R-HSA-8941858 Regulation of RUNX3 expression and activity 5.588781e-01 0.253
R-HSA-451927 Interleukin-2 family signaling 5.588781e-01 0.253
R-HSA-170834 Signaling by TGF-beta Receptor Complex 5.607892e-01 0.251
R-HSA-8957275 Post-translational protein phosphorylation 5.657796e-01 0.247
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 5.665043e-01 0.247
R-HSA-5362768 Hh mutants are degraded by ERAD 5.665043e-01 0.247
R-HSA-73933 Resolution of Abasic Sites (AP sites) 5.665043e-01 0.247
R-HSA-5676590 NIK-->noncanonical NF-kB signaling 5.665043e-01 0.247
R-HSA-9821002 Chromatin modifications during the maternal to zygotic transition (MZT) 5.665043e-01 0.247
R-HSA-9614085 FOXO-mediated transcription 5.707292e-01 0.244
R-HSA-69306 DNA Replication 5.719895e-01 0.243
R-HSA-5693532 DNA Double-Strand Break Repair 5.719895e-01 0.243
R-HSA-9932298 Degradation of CRY and PER proteins 5.739992e-01 0.241
R-HSA-5610780 Degradation of GLI1 by the proteasome 5.739992e-01 0.241
R-HSA-5655302 Signaling by FGFR1 in disease 5.739992e-01 0.241
R-HSA-5610783 Degradation of GLI2 by the proteasome 5.739992e-01 0.241
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome 5.739992e-01 0.241
R-HSA-9683701 Translation of Structural Proteins 5.739992e-01 0.241
R-HSA-111996 Ca-dependent events 5.813650e-01 0.236
R-HSA-1280218 Adaptive Immune System 5.870293e-01 0.231
R-HSA-5654743 Signaling by FGFR4 5.886038e-01 0.230
R-HSA-5387390 Hh mutants abrogate ligand secretion 5.886038e-01 0.230
R-HSA-8854214 TBC/RABGAPs 5.886038e-01 0.230
R-HSA-9637690 Response of Mtb to phagocytosis 5.886038e-01 0.230
R-HSA-9860931 Response of endothelial cells to shear stress 5.948631e-01 0.226
R-HSA-111885 Opioid Signalling 5.948631e-01 0.226
R-HSA-877300 Interferon gamma signaling 5.952877e-01 0.225
R-HSA-2172127 DAP12 interactions 5.957179e-01 0.225
R-HSA-190828 Gap junction trafficking 5.957179e-01 0.225
R-HSA-373752 Netrin-1 signaling 5.957179e-01 0.225
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 5.957179e-01 0.225
R-HSA-3214858 RMTs methylate histone arginines 5.957179e-01 0.225
R-HSA-9907900 Proteasome assembly 5.957179e-01 0.225
R-HSA-9833110 RSV-host interactions 5.995667e-01 0.222
R-HSA-606279 Deposition of new CENPA-containing nucleosomes at the centromere 6.027094e-01 0.220
R-HSA-774815 Nucleosome assembly 6.027094e-01 0.220
R-HSA-76009 Platelet Aggregation (Plug Formation) 6.027094e-01 0.220
R-HSA-5654741 Signaling by FGFR3 6.027094e-01 0.220
R-HSA-6783310 Fanconi Anemia Pathway 6.027094e-01 0.220
R-HSA-5678895 Defective CFTR causes cystic fibrosis 6.027094e-01 0.220
R-HSA-1489509 DAG and IP3 signaling 6.027094e-01 0.220
R-HSA-9824272 Somitogenesis 6.027094e-01 0.220
R-HSA-8951664 Neddylation 6.045071e-01 0.219
R-HSA-109581 Apoptosis 6.066246e-01 0.217
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 6.095805e-01 0.215
R-HSA-9660826 Purinergic signaling in leishmaniasis infection 6.095805e-01 0.215
R-HSA-9664424 Cell recruitment (pro-inflammatory response) 6.095805e-01 0.215
R-HSA-9675135 Diseases of DNA repair 6.095805e-01 0.215
R-HSA-75153 Apoptotic execution phase 6.095805e-01 0.215
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 6.163331e-01 0.210
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 6.163331e-01 0.210
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 6.163331e-01 0.210
R-HSA-437239 Recycling pathway of L1 6.163331e-01 0.210
R-HSA-1236975 Antigen processing-Cross presentation 6.179710e-01 0.209
R-HSA-9694516 SARS-CoV-2 Infection 6.210952e-01 0.207
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 6.229693e-01 0.206
R-HSA-389356 Co-stimulation by CD28 6.229693e-01 0.206
R-HSA-9705683 SARS-CoV-2-host interactions 6.268680e-01 0.203
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 6.294912e-01 0.201
R-HSA-69563 p53-Dependent G1 DNA Damage Response 6.294912e-01 0.201
R-HSA-2871796 FCERI mediated MAPK activation 6.357204e-01 0.197
R-HSA-5655253 Signaling by FGFR2 in disease 6.359006e-01 0.197
R-HSA-5658442 Regulation of RAS by GAPs 6.359006e-01 0.197
R-HSA-9864848 Complex IV assembly 6.421995e-01 0.192
R-HSA-5358346 Hedgehog ligand biogenesis 6.421995e-01 0.192
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 6.443508e-01 0.191
R-HSA-9855142 Cellular responses to mechanical stimuli 6.443508e-01 0.191
R-HSA-72187 mRNA 3'-end processing 6.483899e-01 0.188
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 6.483899e-01 0.188
R-HSA-9931269 AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) 6.483899e-01 0.188
R-HSA-5339562 Uptake and actions of bacterial toxins 6.483899e-01 0.188
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-l... 6.486053e-01 0.188
R-HSA-5689880 Ub-specific processing proteases 6.498363e-01 0.187
R-HSA-445355 Smooth Muscle Contraction 6.544735e-01 0.184
R-HSA-9639288 Amino acids regulate mTORC1 6.544735e-01 0.184
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 6.544735e-01 0.184
R-HSA-8948751 Regulation of PTEN stability and activity 6.544735e-01 0.184
R-HSA-9006931 Signaling by Nuclear Receptors 6.565289e-01 0.183
R-HSA-72649 Translation initiation complex formation 6.604523e-01 0.180
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 6.604523e-01 0.180
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 6.663279e-01 0.176
R-HSA-72702 Ribosomal scanning and start codon recognition 6.721022e-01 0.173
R-HSA-5654736 Signaling by FGFR1 6.721022e-01 0.173
R-HSA-9662361 Sensory processing of sound by outer hair cells of the cochlea 6.721022e-01 0.173
R-HSA-3299685 Detoxification of Reactive Oxygen Species 6.721022e-01 0.173
R-HSA-5578775 Ion homeostasis 6.721022e-01 0.173
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 6.721022e-01 0.173
R-HSA-109606 Intrinsic Pathway for Apoptosis 6.721022e-01 0.173
R-HSA-9679506 SARS-CoV Infections 6.730560e-01 0.172
R-HSA-2980766 Nuclear Envelope Breakdown 6.777770e-01 0.169
R-HSA-3371556 Cellular response to heat stress 6.812002e-01 0.167
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 6.833539e-01 0.165
R-HSA-9772572 Early SARS-CoV-2 Infection Events 6.833539e-01 0.165
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 6.888346e-01 0.162
R-HSA-186712 Regulation of beta-cell development 6.888346e-01 0.162
R-HSA-1227986 Signaling by ERBB2 6.942208e-01 0.159
R-HSA-351202 Metabolism of polyamines 6.942208e-01 0.159
R-HSA-73856 RNA Polymerase II Transcription Termination 6.995140e-01 0.155
R-HSA-112043 PLC beta mediated events 6.995140e-01 0.155
R-HSA-9793380 Formation of paraxial mesoderm 6.995140e-01 0.155
R-HSA-1442490 Collagen degradation 6.995140e-01 0.155
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 7.002942e-01 0.155
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 7.002942e-01 0.155
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 7.002942e-01 0.155
R-HSA-375165 NCAM signaling for neurite out-growth 7.047160e-01 0.152
R-HSA-1268020 Mitochondrial protein import 7.047160e-01 0.152
R-HSA-5617833 Cilium Assembly 7.051067e-01 0.152
R-HSA-5688426 Deubiquitination 7.053307e-01 0.152
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 7.098282e-01 0.149
R-HSA-373755 Semaphorin interactions 7.098282e-01 0.149
R-HSA-936837 Ion transport by P-type ATPases 7.148523e-01 0.146
R-HSA-9609690 HCMV Early Events 7.229551e-01 0.141
R-HSA-5693606 DNA Double Strand Break Response 7.294102e-01 0.137
R-HSA-112040 G-protein mediated events 7.294102e-01 0.137
R-HSA-5685942 HDR through Homologous Recombination (HRR) 7.294102e-01 0.137
R-HSA-196807 Nicotinate metabolism 7.294102e-01 0.137
R-HSA-168256 Immune System 7.360801e-01 0.133
R-HSA-69202 Cyclin E associated events during G1/S transition 7.432274e-01 0.129
R-HSA-3858494 Beta-catenin independent WNT signaling 7.455320e-01 0.128
R-HSA-5620920 Cargo trafficking to the periciliary membrane 7.476751e-01 0.126
R-HSA-5632684 Hedgehog 'on' state 7.476751e-01 0.126
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 7.487579e-01 0.126
R-HSA-5357801 Programmed Cell Death 7.508216e-01 0.124
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 7.563415e-01 0.121
R-HSA-1226099 Signaling by FGFR in disease 7.605628e-01 0.119
R-HSA-9013694 Signaling by NOTCH4 7.605628e-01 0.119
R-HSA-1222556 ROS and RNS production in phagocytes 7.605628e-01 0.119
R-HSA-597592 Post-translational protein modification 7.622038e-01 0.118
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 7.673853e-01 0.115
R-HSA-5689603 UCH proteinases 7.687880e-01 0.114
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 7.689639e-01 0.114
R-HSA-9694635 Translation of Structural Proteins 7.727944e-01 0.112
R-HSA-2871837 FCERI mediated NF-kB activation 7.733231e-01 0.112
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 7.767317e-01 0.110
R-HSA-5619084 ABC transporter disorders 7.767317e-01 0.110
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 7.806009e-01 0.108
R-HSA-446203 Asparagine N-linked glycosylation 7.838511e-01 0.106
R-HSA-5654738 Signaling by FGFR2 7.844033e-01 0.105
R-HSA-9833482 PKR-mediated signaling 7.844033e-01 0.105
R-HSA-9679191 Potential therapeutics for SARS 7.903509e-01 0.102
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 7.918123e-01 0.101
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway 7.954211e-01 0.099
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 7.957719e-01 0.099
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 7.989676e-01 0.097
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 8.058778e-01 0.094
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 8.087868e-01 0.092
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 8.092436e-01 0.092
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 8.112997e-01 0.091
R-HSA-9006936 Signaling by TGFB family members 8.162375e-01 0.088
R-HSA-1236974 ER-Phagosome pathway 8.189961e-01 0.087
R-HSA-112310 Neurotransmitter release cycle 8.221352e-01 0.085
R-HSA-73884 Base Excision Repair 8.221352e-01 0.085
R-HSA-1912408 Pre-NOTCH Transcription and Translation 8.252201e-01 0.083
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 8.282517e-01 0.082
R-HSA-109582 Hemostasis 8.309126e-01 0.080
R-HSA-9772573 Late SARS-CoV-2 Infection Events 8.312309e-01 0.080
R-HSA-9954709 Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide 8.426414e-01 0.074
R-HSA-5621481 C-type lectin receptors (CLRs) 8.435112e-01 0.074
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 8.453718e-01 0.073
R-HSA-112315 Transmission across Chemical Synapses 8.484513e-01 0.071
R-HSA-9609646 HCMV Infection 8.494616e-01 0.071
R-HSA-190236 Signaling by FGFR 8.506918e-01 0.070
R-HSA-5610787 Hedgehog 'off' state 8.558294e-01 0.068
R-HSA-70171 Glycolysis 8.558294e-01 0.068
R-HSA-382556 ABC-family proteins mediated transport 8.558294e-01 0.068
R-HSA-611105 Respiratory electron transport 8.576778e-01 0.067
R-HSA-5696398 Nucleotide Excision Repair 8.702091e-01 0.060
R-HSA-418346 Platelet homeostasis 8.724627e-01 0.059
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 8.768536e-01 0.057
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 8.768536e-01 0.057
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 8.825605e-01 0.054
R-HSA-927802 Nonsense-Mediated Decay (NMD) 8.851886e-01 0.053
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 8.851886e-01 0.053
R-HSA-1912422 Pre-NOTCH Expression and Processing 8.871830e-01 0.052
R-HSA-2871809 FCERI mediated Ca+2 mobilization 8.948212e-01 0.048
R-HSA-9658195 Leishmania infection 8.959238e-01 0.048
R-HSA-9824443 Parasitic Infection Pathways 8.959238e-01 0.048
R-HSA-72737 Cap-dependent Translation Initiation 8.966488e-01 0.047
R-HSA-72613 Eukaryotic Translation Initiation 8.966488e-01 0.047
R-HSA-70326 Glucose metabolism 8.984447e-01 0.047
R-HSA-9824446 Viral Infection Pathways 9.021176e-01 0.045
R-HSA-73886 Chromosome Maintenance 9.053230e-01 0.043
R-HSA-9635486 Infection with Mycobacterium tuberculosis 9.053230e-01 0.043
R-HSA-162909 Host Interactions of HIV factors 9.101752e-01 0.041
R-HSA-1483257 Phospholipid metabolism 9.123447e-01 0.040
R-HSA-397014 Muscle contraction 9.124465e-01 0.040
R-HSA-6798695 Neutrophil degranulation 9.200040e-01 0.036
R-HSA-5576891 Cardiac conduction 9.232946e-01 0.035
R-HSA-446219 Synthesis of substrates in N-glycan biosythesis 9.232946e-01 0.035
R-HSA-1474228 Degradation of the extracellular matrix 9.246290e-01 0.034
R-HSA-163685 Integration of energy metabolism 9.309616e-01 0.031
R-HSA-9948299 Ribosome-associated quality control 9.333436e-01 0.030
R-HSA-5358351 Signaling by Hedgehog 9.333436e-01 0.030
R-HSA-381119 Unfolded Protein Response (UPR) 9.345038e-01 0.029
R-HSA-5619115 Disorders of transmembrane transporters 9.469971e-01 0.024
R-HSA-9609507 Protein localization 9.496753e-01 0.022
R-HSA-1989781 PPARA activates gene expression 9.514135e-01 0.022
R-HSA-168273 Influenza Viral RNA Transcription and Replication 9.514135e-01 0.022
R-HSA-9610379 HCMV Late Events 9.530920e-01 0.021
R-HSA-446193 Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, L... 9.530920e-01 0.021
R-HSA-9711097 Cellular response to starvation 9.539094e-01 0.020
R-HSA-416476 G alpha (q) signalling events 9.586651e-01 0.018
R-HSA-5619102 SLC transporter disorders 9.606560e-01 0.017
R-HSA-73894 DNA Repair 9.618506e-01 0.017
R-HSA-1643685 Disease 9.624804e-01 0.017
R-HSA-168249 Innate Immune System 9.633768e-01 0.016
R-HSA-76002 Platelet activation, signaling and aggregation 9.643366e-01 0.016
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 9.668850e-01 0.015
R-HSA-388396 GPCR downstream signalling 9.683451e-01 0.014
R-HSA-168255 Influenza Infection 9.687013e-01 0.014
R-HSA-112316 Neuronal System 9.716742e-01 0.012
R-HSA-983712 Ion channel transport 9.737550e-01 0.012
R-HSA-72163 mRNA Splicing - Major Pathway 9.759680e-01 0.011
R-HSA-418594 G alpha (i) signalling events 9.799869e-01 0.009
R-HSA-72172 mRNA Splicing 9.802039e-01 0.009
R-HSA-1474244 Extracellular matrix organization 9.848718e-01 0.007
R-HSA-372790 Signaling by GPCR 9.865518e-01 0.006
R-HSA-162906 HIV Infection 9.868078e-01 0.006
R-HSA-1428517 Aerobic respiration and respiratory electron transport 9.870181e-01 0.006
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 9.874886e-01 0.005
R-HSA-202733 Cell surface interactions at the vascular wall 9.889439e-01 0.005
R-HSA-5663205 Infectious disease 9.893760e-01 0.005
R-HSA-9824439 Bacterial Infection Pathways 9.940178e-01 0.003
R-HSA-72766 Translation 9.967637e-01 0.001
R-HSA-392499 Metabolism of proteins 9.972095e-01 0.001
R-HSA-8953854 Metabolism of RNA 9.974960e-01 0.001
R-HSA-8957322 Metabolism of steroids 9.976334e-01 0.001
R-HSA-196854 Metabolism of vitamins and cofactors 9.988384e-01 0.001
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 9.993316e-01 0.000
R-HSA-425407 SLC-mediated transmembrane transport 9.993665e-01 0.000
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 9.997755e-01 0.000
R-HSA-71291 Metabolism of amino acids and derivatives 9.998502e-01 0.000
R-HSA-500792 GPCR ligand binding 9.999799e-01 0.000
R-HSA-382551 Transport of small molecules 9.999808e-01 0.000
R-HSA-556833 Metabolism of lipids 1.000000e+00 0.000
R-HSA-9709957 Sensory Perception 1.000000e+00 0.000
R-HSA-1430728 Metabolism 1.000000e+00 -0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
CLK3CLK3 0.875 0.361 1 0.853
COTCOT 0.873 0.205 2 0.849
PIM3PIM3 0.870 0.330 -3 0.894
NDR2NDR2 0.869 0.267 -3 0.878
HIPK4HIPK4 0.867 0.347 1 0.822
RSK2RSK2 0.866 0.337 -3 0.861
CDC7CDC7 0.865 0.156 1 0.863
SRPK1SRPK1 0.864 0.314 -3 0.851
PRKD1PRKD1 0.863 0.288 -3 0.867
SKMLCKSKMLCK 0.862 0.329 -2 0.909
MOSMOS 0.861 0.219 1 0.884
P90RSKP90RSK 0.860 0.306 -3 0.864
PIM1PIM1 0.859 0.320 -3 0.869
CDKL1CDKL1 0.857 0.278 -3 0.875
PRKD2PRKD2 0.857 0.279 -3 0.844
RSK3RSK3 0.857 0.287 -3 0.851
MAPKAPK2MAPKAPK2 0.857 0.288 -3 0.830
AURCAURC 0.856 0.280 -2 0.726
IKKBIKKB 0.856 0.038 -2 0.761
NDR1NDR1 0.856 0.200 -3 0.878
CLK2CLK2 0.856 0.376 -3 0.849
LATS2LATS2 0.856 0.186 -5 0.723
CAMK1BCAMK1B 0.856 0.227 -3 0.889
CDKL5CDKL5 0.856 0.268 -3 0.873
MTORMTOR 0.855 0.043 1 0.848
GRK1GRK1 0.855 0.220 -2 0.805
SRPK2SRPK2 0.855 0.296 -3 0.798
RSK4RSK4 0.855 0.336 -3 0.846
NLKNLK 0.854 0.158 1 0.885
ICKICK 0.854 0.301 -3 0.893
DYRK2DYRK2 0.852 0.277 1 0.772
CLK4CLK4 0.852 0.327 -3 0.855
KISKIS 0.851 0.154 1 0.765
PKACBPKACB 0.851 0.313 -2 0.736
RAF1RAF1 0.851 0.024 1 0.866
PRPKPRPK 0.851 -0.060 -1 0.834
PKACGPKACG 0.850 0.223 -2 0.787
P70S6KBP70S6KB 0.850 0.248 -3 0.862
HIPK2HIPK2 0.850 0.312 1 0.694
PKN3PKN3 0.850 0.170 -3 0.869
CAMLCKCAMLCK 0.850 0.242 -2 0.895
DAPK2DAPK2 0.850 0.275 -3 0.886
ERK5ERK5 0.849 0.107 1 0.854
MSK1MSK1 0.849 0.305 -3 0.842
NUAK2NUAK2 0.849 0.166 -3 0.891
MAPKAPK3MAPKAPK3 0.849 0.216 -3 0.845
TBK1TBK1 0.849 -0.037 1 0.777
CAMK2DCAMK2D 0.848 0.168 -3 0.861
PRKXPRKX 0.848 0.320 -3 0.794
CAMK2ACAMK2A 0.848 0.243 2 0.809
ATRATR 0.847 0.050 1 0.839
CAMK2GCAMK2G 0.847 0.003 2 0.816
MSK2MSK2 0.847 0.255 -3 0.841
CAMK2BCAMK2B 0.847 0.203 2 0.789
IKKAIKKA 0.846 0.062 -2 0.754
CLK1CLK1 0.846 0.306 -3 0.831
GCN2GCN2 0.846 -0.120 2 0.786
LATS1LATS1 0.846 0.257 -3 0.886
MST4MST4 0.846 0.092 2 0.847
HIPK1HIPK1 0.845 0.312 1 0.786
AMPKA1AMPKA1 0.845 0.164 -3 0.881
IKKEIKKE 0.845 -0.058 1 0.768
SRPK3SRPK3 0.845 0.230 -3 0.825
PAK1PAK1 0.845 0.205 -2 0.841
DSTYKDSTYK 0.845 -0.046 2 0.864
TGFBR2TGFBR2 0.844 0.044 -2 0.834
BMPR2BMPR2 0.844 -0.085 -2 0.898
NIKNIK 0.844 0.127 -3 0.875
PDHK4PDHK4 0.844 -0.226 1 0.880
PKN2PKN2 0.844 0.133 -3 0.866
PKCDPKCD 0.843 0.158 2 0.764
WNK1WNK1 0.843 0.068 -2 0.903
GRK5GRK5 0.843 -0.021 -3 0.815
GRK7GRK7 0.842 0.186 1 0.801
NEK6NEK6 0.842 -0.001 -2 0.882
AKT2AKT2 0.842 0.303 -3 0.804
BMPR1BBMPR1B 0.842 0.182 1 0.823
GRK6GRK6 0.841 0.070 1 0.852
AMPKA2AMPKA2 0.841 0.180 -3 0.869
MARK4MARK4 0.841 0.058 4 0.842
ULK2ULK2 0.841 -0.134 2 0.764
RIPK3RIPK3 0.841 -0.023 3 0.706
CHAK2CHAK2 0.840 0.018 -1 0.852
PDHK1PDHK1 0.840 -0.166 1 0.857
DYRK4DYRK4 0.840 0.261 1 0.709
AURBAURB 0.839 0.214 -2 0.725
SGK3SGK3 0.839 0.269 -3 0.840
PRKD3PRKD3 0.839 0.217 -3 0.826
DYRK1ADYRK1A 0.839 0.282 1 0.802
MNK2MNK2 0.838 0.169 -2 0.843
TSSK1TSSK1 0.838 0.140 -3 0.890
BCKDKBCKDK 0.838 -0.064 -1 0.833
JNK2JNK2 0.838 0.199 1 0.711
PAK3PAK3 0.838 0.148 -2 0.832
HUNKHUNK 0.838 -0.047 2 0.783
CDK7CDK7 0.838 0.139 1 0.756
TGFBR1TGFBR1 0.838 0.134 -2 0.837
PKG2PKG2 0.837 0.221 -2 0.727
PIM2PIM2 0.837 0.273 -3 0.837
CDK8CDK8 0.836 0.102 1 0.746
MYLK4MYLK4 0.836 0.218 -2 0.827
NEK7NEK7 0.835 -0.134 -3 0.808
AURAAURA 0.835 0.196 -2 0.710
FAM20CFAM20C 0.835 0.065 2 0.609
MASTLMASTL 0.835 -0.115 -2 0.823
ALK4ALK4 0.835 0.087 -2 0.862
JNK3JNK3 0.834 0.169 1 0.738
TSSK2TSSK2 0.834 0.072 -5 0.788
PKACAPKACA 0.834 0.273 -2 0.685
PAK6PAK6 0.834 0.169 -2 0.762
CAMK4CAMK4 0.834 0.081 -3 0.855
CDK1CDK1 0.834 0.148 1 0.716
MLK1MLK1 0.833 -0.117 2 0.787
MAKMAK 0.833 0.362 -2 0.799
CDK19CDK19 0.833 0.113 1 0.713
MNK1MNK1 0.833 0.155 -2 0.847
HIPK3HIPK3 0.833 0.256 1 0.791
DYRK3DYRK3 0.833 0.295 1 0.785
DLKDLK 0.833 -0.039 1 0.850
QSKQSK 0.833 0.123 4 0.818
DYRK1BDYRK1B 0.832 0.240 1 0.739
GRK4GRK4 0.832 -0.079 -2 0.848
CDK18CDK18 0.832 0.150 1 0.691
PKCBPKCB 0.831 0.108 2 0.710
MELKMELK 0.831 0.129 -3 0.852
ATMATM 0.831 0.005 1 0.781
PAK2PAK2 0.831 0.130 -2 0.826
BRSK1BRSK1 0.831 0.130 -3 0.850
NIM1NIM1 0.831 -0.011 3 0.736
NUAK1NUAK1 0.831 0.104 -3 0.853
P38AP38A 0.830 0.151 1 0.783
WNK3WNK3 0.830 -0.160 1 0.825
RIPK1RIPK1 0.830 -0.068 1 0.820
DCAMKL1DCAMKL1 0.830 0.197 -3 0.850
PKCAPKCA 0.830 0.113 2 0.702
ANKRD3ANKRD3 0.830 -0.081 1 0.867
MLK2MLK2 0.830 -0.046 2 0.796
PLK1PLK1 0.830 0.001 -2 0.825
P38BP38B 0.830 0.165 1 0.718
ULK1ULK1 0.829 -0.189 -3 0.767
PKCGPKCG 0.829 0.080 2 0.713
PHKG1PHKG1 0.829 0.072 -3 0.865
CDK5CDK5 0.829 0.130 1 0.769
NEK9NEK9 0.828 -0.130 2 0.812
MLK3MLK3 0.828 -0.018 2 0.718
AKT1AKT1 0.828 0.270 -3 0.814
P38GP38G 0.828 0.151 1 0.639
ALK2ALK2 0.827 0.090 -2 0.844
CDK13CDK13 0.827 0.091 1 0.732
SIKSIK 0.827 0.121 -3 0.828
DNAPKDNAPK 0.827 0.055 1 0.740
TTBK2TTBK2 0.826 -0.141 2 0.687
PASKPASK 0.826 0.220 -3 0.896
ACVR2BACVR2B 0.826 0.068 -2 0.829
ERK1ERK1 0.826 0.131 1 0.714
PKRPKR 0.826 0.029 1 0.832
PKCZPKCZ 0.825 0.064 2 0.755
ACVR2AACVR2A 0.825 0.047 -2 0.817
CDK3CDK3 0.825 0.155 1 0.661
TLK2TLK2 0.824 0.006 1 0.798
SGK1SGK1 0.824 0.309 -3 0.751
AKT3AKT3 0.824 0.302 -3 0.764
P70S6KP70S6K 0.824 0.212 -3 0.805
IRE1IRE1 0.824 -0.089 1 0.783
BRSK2BRSK2 0.824 0.049 -3 0.848
MARK3MARK3 0.824 0.071 4 0.779
CHK1CHK1 0.823 0.059 -3 0.855
VRK2VRK2 0.823 -0.043 1 0.885
CDK12CDK12 0.823 0.108 1 0.708
MAPKAPK5MAPKAPK5 0.823 0.090 -3 0.810
YSK4YSK4 0.823 -0.074 1 0.810
CDK17CDK17 0.823 0.119 1 0.643
PLK3PLK3 0.822 -0.028 2 0.766
MEK1MEK1 0.822 -0.115 2 0.833
DAPK3DAPK3 0.822 0.263 -3 0.866
PKCHPKCH 0.822 0.055 2 0.694
QIKQIK 0.822 -0.025 -3 0.852
CAMK1GCAMK1G 0.822 0.139 -3 0.836
CDK14CDK14 0.822 0.157 1 0.735
BMPR1ABMPR1A 0.821 0.114 1 0.799
SMG1SMG1 0.821 -0.034 1 0.790
DRAK1DRAK1 0.821 0.033 1 0.808
CDK10CDK10 0.820 0.178 1 0.721
CAMK1DCAMK1D 0.820 0.218 -3 0.787
SMMLCKSMMLCK 0.820 0.180 -3 0.865
CDK9CDK9 0.819 0.080 1 0.740
MARK2MARK2 0.819 0.031 4 0.751
NEK2NEK2 0.819 -0.075 2 0.795
ERK2ERK2 0.819 0.078 1 0.750
P38DP38D 0.819 0.152 1 0.656
MPSK1MPSK1 0.818 0.151 1 0.808
GRK2GRK2 0.818 -0.012 -2 0.749
DAPK1DAPK1 0.817 0.251 -3 0.857
CK1ECK1E 0.817 0.020 -3 0.566
MLK4MLK4 0.817 -0.091 2 0.692
MOKMOK 0.817 0.298 1 0.789
IRE2IRE2 0.816 -0.100 2 0.728
DCAMKL2DCAMKL2 0.816 0.087 -3 0.860
PAK5PAK5 0.815 0.144 -2 0.708
GSK3AGSK3A 0.815 0.091 4 0.472
PAK4PAK4 0.815 0.156 -2 0.720
PRP4PRP4 0.815 0.041 -3 0.712
CDK2CDK2 0.815 0.030 1 0.787
MST3MST3 0.814 0.038 2 0.822
BRAFBRAF 0.814 -0.042 -4 0.789
PLK4PLK4 0.814 -0.088 2 0.619
MARK1MARK1 0.814 0.014 4 0.795
PKCTPKCT 0.814 0.090 2 0.703
CHAK1CHAK1 0.813 -0.139 2 0.760
SNRKSNRK 0.813 -0.083 2 0.669
SSTKSSTK 0.813 0.056 4 0.794
JNK1JNK1 0.812 0.125 1 0.695
CDK16CDK16 0.812 0.113 1 0.659
ROCK2ROCK2 0.812 0.265 -3 0.855
WNK4WNK4 0.811 -0.041 -2 0.893
GSK3BGSK3B 0.811 0.036 4 0.464
NEK5NEK5 0.811 -0.045 1 0.838
TAO3TAO3 0.811 -0.002 1 0.829
SBKSBK 0.811 0.268 -3 0.715
MEKK1MEKK1 0.811 -0.125 1 0.825
PERKPERK 0.811 -0.114 -2 0.852
MEKK3MEKK3 0.811 -0.142 1 0.837
CK2A2CK2A2 0.811 0.134 1 0.734
MRCKBMRCKB 0.810 0.240 -3 0.818
MEK5MEK5 0.810 -0.195 2 0.807
GAKGAK 0.809 0.107 1 0.875
MRCKAMRCKA 0.809 0.221 -3 0.830
TLK1TLK1 0.809 -0.096 -2 0.857
CHK2CHK2 0.809 0.212 -3 0.758
CK1DCK1D 0.808 0.018 -3 0.515
MEKK2MEKK2 0.808 -0.113 2 0.782
ZAKZAK 0.808 -0.144 1 0.796
PKCEPKCE 0.808 0.126 2 0.698
GRK3GRK3 0.807 -0.006 -2 0.712
PHKG2PHKG2 0.807 0.015 -3 0.835
IRAK4IRAK4 0.807 -0.082 1 0.789
CAMK1ACAMK1A 0.807 0.214 -3 0.765
PKCIPKCI 0.807 0.050 2 0.725
LKB1LKB1 0.807 0.044 -3 0.791
PDK1PDK1 0.806 0.056 1 0.816
PKN1PKN1 0.806 0.144 -3 0.814
GCKGCK 0.806 0.064 1 0.837
HRIHRI 0.806 -0.205 -2 0.868
CK1A2CK1A2 0.805 0.008 -3 0.521
DMPK1DMPK1 0.805 0.272 -3 0.836
CK1G1CK1G1 0.804 -0.038 -3 0.552
CRIKCRIK 0.804 0.278 -3 0.818
ERK7ERK7 0.803 0.029 2 0.523
NEK11NEK11 0.801 -0.139 1 0.823
PINK1PINK1 0.800 -0.194 1 0.837
NEK8NEK8 0.800 -0.122 2 0.794
CK2A1CK2A1 0.800 0.112 1 0.714
CAMKK2CAMKK2 0.800 -0.079 -2 0.759
BUB1BUB1 0.799 0.134 -5 0.748
TNIKTNIK 0.799 0.031 3 0.812
HPK1HPK1 0.799 0.035 1 0.824
TAO2TAO2 0.799 -0.098 2 0.824
CDK4CDK4 0.799 0.106 1 0.692
PLK2PLK2 0.799 -0.009 -3 0.750
CDK6CDK6 0.798 0.082 1 0.717
PBKPBK 0.798 0.121 1 0.809
CAMKK1CAMKK1 0.798 -0.155 -2 0.758
TAK1TAK1 0.797 -0.025 1 0.833
MAP3K15MAP3K15 0.797 -0.056 1 0.793
MINKMINK 0.796 -0.039 1 0.815
KHS1KHS1 0.796 0.064 1 0.809
PDHK3_TYRPDHK3_TYR 0.796 0.330 4 0.891
MST2MST2 0.796 -0.097 1 0.842
PKG1PKG1 0.796 0.163 -2 0.645
MEKK6MEKK6 0.795 -0.082 1 0.816
TTBK1TTBK1 0.795 -0.203 2 0.608
ROCK1ROCK1 0.795 0.222 -3 0.828
HGKHGK 0.795 -0.055 3 0.803
NEK4NEK4 0.795 -0.110 1 0.807
KHS2KHS2 0.794 0.063 1 0.821
LRRK2LRRK2 0.794 -0.082 2 0.829
LOKLOK 0.794 -0.015 -2 0.781
EEF2KEEF2K 0.793 -0.078 3 0.783
NEK1NEK1 0.792 -0.054 1 0.809
IRAK1IRAK1 0.792 -0.267 -1 0.766
VRK1VRK1 0.791 -0.087 2 0.820
SLKSLK 0.790 -0.052 -2 0.726
MST1MST1 0.786 -0.121 1 0.817
PDHK4_TYRPDHK4_TYR 0.786 0.148 2 0.874
MAP2K4_TYRMAP2K4_TYR 0.784 0.112 -1 0.852
YSK1YSK1 0.784 -0.085 2 0.788
TESK1_TYRTESK1_TYR 0.784 0.075 3 0.847
STK33STK33 0.783 -0.149 2 0.603
MAP2K6_TYRMAP2K6_TYR 0.783 0.093 -1 0.862
MEK2MEK2 0.782 -0.231 2 0.800
HASPINHASPIN 0.781 0.043 -1 0.733
TTKTTK 0.781 -0.024 -2 0.850
OSR1OSR1 0.780 -0.055 2 0.786
LIMK2_TYRLIMK2_TYR 0.780 0.112 -3 0.858
YANK3YANK3 0.780 -0.034 2 0.401
PKMYT1_TYRPKMYT1_TYR 0.779 -0.002 3 0.819
RIPK2RIPK2 0.779 -0.258 1 0.772
PDHK1_TYRPDHK1_TYR 0.778 0.016 -1 0.868
MAP2K7_TYRMAP2K7_TYR 0.778 -0.091 2 0.846
BMPR2_TYRBMPR2_TYR 0.778 0.034 -1 0.855
BIKEBIKE 0.777 0.069 1 0.772
EPHA6EPHA6 0.776 0.075 -1 0.853
NEK3NEK3 0.776 -0.149 1 0.782
ASK1ASK1 0.774 -0.105 1 0.781
CK1ACK1A 0.773 -0.014 -3 0.429
PINK1_TYRPINK1_TYR 0.772 -0.138 1 0.858
EPHB4EPHB4 0.772 0.041 -1 0.828
RETRET 0.772 -0.047 1 0.819
MYO3BMYO3B 0.770 -0.066 2 0.809
TAO1TAO1 0.768 -0.107 1 0.762
TXKTXK 0.767 0.083 1 0.857
TNK2TNK2 0.766 0.028 3 0.718
MST1RMST1R 0.766 -0.110 3 0.765
DDR1DDR1 0.766 -0.088 4 0.800
ABL2ABL2 0.766 -0.012 -1 0.783
LIMK1_TYRLIMK1_TYR 0.765 -0.156 2 0.834
FGRFGR 0.765 -0.033 1 0.869
TYRO3TYRO3 0.765 -0.114 3 0.743
AAK1AAK1 0.765 0.117 1 0.676
ROS1ROS1 0.765 -0.091 3 0.712
ALPHAK3ALPHAK3 0.764 -0.119 -1 0.741
CSF1RCSF1R 0.763 -0.093 3 0.735
MYO3AMYO3A 0.763 -0.135 1 0.792
YES1YES1 0.763 -0.050 -1 0.818
TYK2TYK2 0.762 -0.202 1 0.815
EPHA4EPHA4 0.761 -0.027 2 0.768
INSRRINSRR 0.761 -0.078 3 0.696
SRMSSRMS 0.761 -0.034 1 0.862
ABL1ABL1 0.761 -0.046 -1 0.775
JAK3JAK3 0.761 -0.101 1 0.811
LCKLCK 0.761 0.020 -1 0.812
JAK2JAK2 0.760 -0.174 1 0.811
BLKBLK 0.759 0.037 -1 0.809
FERFER 0.759 -0.137 1 0.874
HCKHCK 0.759 -0.065 -1 0.807
TNK1TNK1 0.759 -0.014 3 0.728
EPHB1EPHB1 0.758 -0.068 1 0.862
FGFR2FGFR2 0.758 -0.119 3 0.756
NEK10_TYRNEK10_TYR 0.758 -0.049 1 0.715
EPHB3EPHB3 0.757 -0.051 -1 0.818
EPHB2EPHB2 0.757 -0.039 -1 0.806
ITKITK 0.757 -0.061 -1 0.785
MERTKMERTK 0.757 -0.058 3 0.730
STLK3STLK3 0.756 -0.199 1 0.774
KDRKDR 0.756 -0.095 3 0.705
DDR2DDR2 0.754 0.053 3 0.691
FYNFYN 0.754 0.029 -1 0.789
JAK1JAK1 0.754 -0.061 1 0.779
AXLAXL 0.754 -0.105 3 0.728
PDGFRBPDGFRB 0.753 -0.178 3 0.747
KITKIT 0.752 -0.157 3 0.738
TNNI3K_TYRTNNI3K_TYR 0.752 -0.061 1 0.807
EPHA7EPHA7 0.751 -0.049 2 0.761
METMET 0.751 -0.111 3 0.737
BMXBMX 0.750 -0.061 -1 0.693
FGFR1FGFR1 0.750 -0.176 3 0.722
FGFR3FGFR3 0.748 -0.133 3 0.728
TEKTEK 0.748 -0.188 3 0.679
FLT1FLT1 0.747 -0.117 -1 0.826
FLT3FLT3 0.747 -0.222 3 0.732
EPHA1EPHA1 0.747 -0.096 3 0.711
EPHA3EPHA3 0.747 -0.119 2 0.737
LTKLTK 0.746 -0.140 3 0.698
ALKALK 0.746 -0.151 3 0.666
TECTEC 0.746 -0.129 -1 0.710
NTRK1NTRK1 0.746 -0.198 -1 0.813
PTK2BPTK2B 0.745 -0.058 -1 0.748
WEE1_TYRWEE1_TYR 0.745 -0.140 -1 0.742
BTKBTK 0.745 -0.219 -1 0.759
PTK6PTK6 0.744 -0.199 -1 0.718
EPHA5EPHA5 0.744 -0.064 2 0.748
CK1G3CK1G3 0.744 -0.061 -3 0.384
PDGFRAPDGFRA 0.743 -0.260 3 0.746
INSRINSR 0.742 -0.169 3 0.677
PTK2PTK2 0.742 0.031 -1 0.790
NTRK3NTRK3 0.740 -0.152 -1 0.766
LYNLYN 0.740 -0.127 3 0.670
ERBB2ERBB2 0.740 -0.207 1 0.780
FRKFRK 0.740 -0.148 -1 0.814
EPHA8EPHA8 0.739 -0.087 -1 0.799
SRCSRC 0.739 -0.085 -1 0.778
FLT4FLT4 0.738 -0.223 3 0.709
NTRK2NTRK2 0.738 -0.250 3 0.703
YANK2YANK2 0.738 -0.097 2 0.413
EGFREGFR 0.737 -0.107 1 0.691
SYKSYK 0.737 -0.003 -1 0.766
MATKMATK 0.736 -0.161 -1 0.710
FGFR4FGFR4 0.734 -0.134 -1 0.743
CSKCSK 0.734 -0.177 2 0.763
EPHA2EPHA2 0.731 -0.082 -1 0.768
IGF1RIGF1R 0.727 -0.167 3 0.620
CK1G2CK1G2 0.727 -0.062 -3 0.472
ERBB4ERBB4 0.725 -0.084 1 0.709
MUSKMUSK 0.721 -0.201 1 0.692
ZAP70ZAP70 0.716 -0.049 -1 0.680
FESFES 0.712 -0.187 -1 0.673