Motif 473 (n=179)

Position-wise Probabilities

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uniprot genes site source protein function
A0JNW5 BLTP3B S423 ochoa Bridge-like lipid transfer protein family member 3B (Syntaxin-6 Habc-interacting protein of 164 kDa) (UHRF1-binding protein 1-like) Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:20163565, PubMed:35499567). {ECO:0000269|PubMed:20163565, ECO:0000269|PubMed:35499567}.
A8MQ03 CYSRT1 S94 ochoa Cysteine-rich tail protein 1 Component of the stratum corneum that may contribute to epidermal antimicrobial host defenses. {ECO:0000269|PubMed:36804407}.
C9JLW8 MCRIP1 S26 ochoa Mapk-regulated corepressor-interacting protein 1 (Granulin-2) (Protein FAM195B) The phosphorylation status of MCRIP1 functions as a molecular switch to regulate epithelial-mesenchymal transition. Unphosphorylated MCRIP1 binds to and inhibits the transcriptional corepressor CTBP(s). When phosphorylated by MAPK/ERK, MCRIP1 releases CTBP(s) resulting in transcriptional silencing of the E-cadherin gene and induction of epithelial-mesenchymal transition (PubMed:25728771). {ECO:0000269|PubMed:25728771}.
O00560 SDCBP S33 ochoa Syntenin-1 (Melanoma differentiation-associated protein 9) (MDA-9) (Pro-TGF-alpha cytoplasmic domain-interacting protein 18) (TACIP18) (Scaffold protein Pbp1) (Syndecan-binding protein 1) Multifunctional adapter protein involved in diverse array of functions including trafficking of transmembrane proteins, neuro and immunomodulation, exosome biogenesis, and tumorigenesis (PubMed:26291527). Positively regulates TGFB1-mediated SMAD2/3 activation and TGFB1-induced epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types. May increase TGFB1 signaling by enhancing cell-surface expression of TGFR1 by preventing the interaction between TGFR1 and CAV1 and subsequent CAV1-dependent internalization and degradation of TGFR1 (PubMed:25893292). In concert with SDC1/4 and PDCD6IP, regulates exosome biogenesis (PubMed:22660413). Regulates migration, growth, proliferation, and cell cycle progression in a variety of cancer types (PubMed:26539120). In adherens junctions may function to couple syndecans to cytoskeletal proteins or signaling components. Seems to couple transcription factor SOX4 to the IL-5 receptor (IL5RA) (PubMed:11498591). May also play a role in vesicular trafficking (PubMed:11179419). Seems to be required for the targeting of TGFA to the cell surface in the early secretory pathway (PubMed:10230395). {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:11179419, ECO:0000269|PubMed:11498591, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:25893292, ECO:0000269|PubMed:26539120, ECO:0000303|PubMed:26291527}.
O14745 NHERF1 S191 ochoa Na(+)/H(+) exchange regulatory cofactor NHE-RF1 (NHERF-1) (Ezrin-radixin-moesin-binding phosphoprotein 50) (EBP50) (Regulatory cofactor of Na(+)/H(+) exchanger) (Sodium-hydrogen exchanger regulatory factor 1) (Solute carrier family 9 isoform A3 regulatory factor 1) Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules. Involved in sperm capacitation. May participate in the regulation of the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250, ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}.
O15014 ZNF609 S581 ochoa Zinc finger protein 609 Transcription factor, which activates RAG1, and possibly RAG2, transcription. Through the regulation of RAG1/2 expression, may regulate thymocyte maturation. Along with NIPBL and the multiprotein complex Integrator, promotes cortical neuron migration during brain development by regulating the transcription of crucial genes in this process. Preferentially binds promoters containing paused RNA polymerase II. Up-regulates the expression of SEMA3A, NRP1, PLXND1 and GABBR2 genes, among others. {ECO:0000250|UniProtKB:Q8BZ47}.; FUNCTION: [Isoform 2]: Involved in the regulation of myoblast proliferation during myogenesis. {ECO:0000269|PubMed:28344082}.
O43149 ZZEF1 S1276 ochoa Zinc finger ZZ-type and EF-hand domain-containing protein 1 Histone H3 reader which may act as a transcriptional coactivator for KLF6 and KLF9 transcription factors. {ECO:0000269|PubMed:33227311}.
O43166 SIPA1L1 S1083 ochoa Signal-induced proliferation-associated 1-like protein 1 (SIPA1-like protein 1) (High-risk human papilloma viruses E6 oncoproteins targeted protein 1) (E6-targeted protein 1) Stimulates the GTPase activity of RAP2A. Promotes reorganization of the actin cytoskeleton and recruits DLG4 to F-actin. Contributes to the regulation of dendritic spine morphogenesis (By similarity). {ECO:0000250}.
O43524 FOXO3 S299 ochoa Forkhead box protein O3 (AF6q21 protein) (Forkhead in rhabdomyosarcoma-like 1) Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882, PubMed:30513302). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (PubMed:30513302). {ECO:0000250|UniProtKB:Q9WVH4, ECO:0000269|PubMed:10102273, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:30513302}.
O43683 BUB1 T601 ochoa Mitotic checkpoint serine/threonine-protein kinase BUB1 (hBUB1) (EC 2.7.11.1) (BUB1A) Serine/threonine-protein kinase that performs 2 crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Has a key role in the assembly of checkpoint proteins at the kinetochore, being required for the subsequent localization of CENPF, BUB1B, CENPE and MAD2L1. Required for the kinetochore localization of PLK1. Required for centromeric enrichment of AUKRB in prometaphase. Plays an important role in defining SGO1 localization and thereby affects sister chromatid cohesion. Promotes the centromeric localization of TOP2A (PubMed:35044816). Acts as a substrate for anaphase-promoting complex or cyclosome (APC/C) in complex with its activator CDH1 (APC/C-Cdh1). Necessary for ensuring proper chromosome segregation and binding to BUB3 is essential for this function. Can regulate chromosome segregation in a kinetochore-independent manner. Can phosphorylate BUB3. The BUB1-BUB3 complex plays a role in the inhibition of APC/C when spindle-assembly checkpoint is activated and inhibits the ubiquitin ligase activity of APC/C by phosphorylating its activator CDC20. This complex can also phosphorylate MAD1L1. Kinase activity is essential for inhibition of APC/CCDC20 and for chromosome alignment but does not play a major role in the spindle-assembly checkpoint activity. Mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. {ECO:0000269|PubMed:10198256, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15525512, ECO:0000269|PubMed:15723797, ECO:0000269|PubMed:16760428, ECO:0000269|PubMed:17158872, ECO:0000269|PubMed:19487456, ECO:0000269|PubMed:20739936, ECO:0000269|PubMed:35044816}.
O75694 NUP155 S1006 ochoa Nuclear pore complex protein Nup155 (155 kDa nucleoporin) (Nucleoporin Nup155) Essential component of nuclear pore complex. Could be essessential for embryogenesis. Nucleoporins may be involved both in binding and translocating proteins during nucleocytoplasmic transport. {ECO:0000250|UniProtKB:Q99P88}.
O76094 SRP72 S630 ochoa Signal recognition particle subunit SRP72 (SRP72) (Signal recognition particle 72 kDa protein) Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER) (PubMed:34020957). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER (PubMed:34020957). The SRP complex targets the ribosome-nascent chain complex to the SRP receptor (SR), which is anchored in the ER, where SR compaction and GTPase rearrangement drive cotranslational protein translocation into the ER (PubMed:34020957). Binds the signal recognition particle RNA (7SL RNA) in presence of SRP68 (PubMed:21073748, PubMed:27899666). Can bind 7SL RNA with low affinity (PubMed:21073748, PubMed:27899666). The SRP complex possibly participates in the elongation arrest function (By similarity). {ECO:0000250|UniProtKB:P38688, ECO:0000269|PubMed:21073748, ECO:0000269|PubMed:27899666, ECO:0000269|PubMed:34020957}.
O94811 TPPP S23 ochoa Tubulin polymerization-promoting protein (TPPP) (EC 3.6.5.-) (25 kDa brain-specific protein) (TPPP/p25) (p24) (p25-alpha) Regulator of microtubule dynamics that plays a key role in myelination by promoting elongation of the myelin sheath (PubMed:31522887). Acts as a microtubule nucleation factor in oligodendrocytes: specifically localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, and promotes microtubule nucleation, an important step for elongation of the myelin sheath (PubMed:31522887, PubMed:33831707). Required for both uniform polarized growth of distal microtubules as well as directing the branching of proximal processes (PubMed:31522887). Shows magnesium-dependent GTPase activity; the role of the GTPase activity is unclear (PubMed:21316364, PubMed:21995432). In addition to microtubule nucleation activity, also involved in microtubule bundling and stabilization of existing microtubules, thereby maintaining the integrity of the microtubule network (PubMed:17105200, PubMed:17693641, PubMed:18028908, PubMed:26289831). Regulates microtubule dynamics by promoting tubulin acetylation: acts by inhibiting the tubulin deacetylase activity of HDAC6 (PubMed:20308065, PubMed:23093407). Also regulates cell migration: phosphorylation by ROCK1 inhibits interaction with HDAC6, resulting in decreased acetylation of tubulin and increased cell motility (PubMed:23093407). Plays a role in cell proliferation by regulating the G1/S-phase transition (PubMed:23355470). Involved in astral microtubule organization and mitotic spindle orientation during early stage of mitosis; this process is regulated by phosphorylation by LIMK2 (PubMed:22328514). {ECO:0000269|PubMed:17105200, ECO:0000269|PubMed:17693641, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:20308065, ECO:0000269|PubMed:21316364, ECO:0000269|PubMed:21995432, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:26289831, ECO:0000269|PubMed:31522887}.
O94875 SORBS2 S235 ochoa Sorbin and SH3 domain-containing protein 2 (Arg-binding protein 2) (ArgBP2) (Arg/Abl-interacting protein 2) (Sorbin) Adapter protein that plays a role in the assembling of signaling complexes, being a link between ABL kinases and actin cytoskeleton. Can form complex with ABL1 and CBL, thus promoting ubiquitination and degradation of ABL1. May play a role in the regulation of pancreatic cell adhesion, possibly by acting on WASF1 phosphorylation, enhancing phosphorylation by ABL1, as well as dephosphorylation by PTPN12 (PubMed:18559503). Isoform 6 increases water and sodium absorption in the intestine and gall-bladder. {ECO:0000269|PubMed:12475393, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:9211900}.
O94885 SASH1 S1033 ochoa SAM and SH3 domain-containing protein 1 (Proline-glutamate repeat-containing protein) Is a positive regulator of NF-kappa-B signaling downstream of TLR4 activation. It acts as a scaffold molecule to assemble a molecular complex that includes TRAF6, MAP3K7, CHUK and IKBKB, thereby facilitating NF-kappa-B signaling activation (PubMed:23776175). Regulates TRAF6 and MAP3K7 ubiquitination (PubMed:23776175). Involved in the regulation of cell mobility (PubMed:23333244, PubMed:23776175, PubMed:25315659). Regulates lipolysaccharide (LPS)-induced endothelial cell migration (PubMed:23776175). Is involved in the regulation of skin pigmentation through the control of melanocyte migration in the epidermis (PubMed:23333244). {ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23776175, ECO:0000269|PubMed:25315659}.
P01106 MYC S82 psp Myc proto-oncogene protein (Class E basic helix-loop-helix protein 39) (bHLHe39) (Proto-oncogene c-Myc) (Transcription factor p64) Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3' (PubMed:24940000, PubMed:25956029). Activates the transcription of growth-related genes (PubMed:24940000, PubMed:25956029). Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis (PubMed:24940000, PubMed:25956029). Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells (By similarity). Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). Positively regulates transcription of HNRNPA1, HNRNPA2 and PTBP1 which in turn regulate splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform (PubMed:20010808). {ECO:0000250|UniProtKB:P01108, ECO:0000269|PubMed:20010808, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:25956029}.
P04626 ERBB2 S1078 ochoa Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}.
P06401 PGR S25 ochoa Progesterone receptor (PR) (Nuclear receptor subfamily 3 group C member 3) The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as a transcriptional activator or repressor. {ECO:0000269|PubMed:10757795, ECO:0000269|PubMed:1587864, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:9407067, ECO:0000305}.; FUNCTION: [Isoform A]: Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2. {ECO:0000269|PubMed:7969170, ECO:0000269|PubMed:8180103, ECO:0000269|PubMed:8264658, ECO:0000305, ECO:0000305|PubMed:10757795}.; FUNCTION: [Isoform B]: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. {ECO:0000269|PubMed:7969170}.; FUNCTION: [Isoform 4]: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
P07947 YES1 S45 ochoa Tyrosine-protein kinase Yes (EC 2.7.10.2) (Proto-oncogene c-Yes) (p61-Yes) Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity (PubMed:26979622). {ECO:0000269|PubMed:11901164, ECO:0000269|PubMed:18479465, ECO:0000269|PubMed:19276087, ECO:0000269|PubMed:21566460, ECO:0000269|PubMed:21713032, ECO:0000269|PubMed:26979622}.
P08588 ADRB1 S428 ochoa Beta-1 adrenergic receptor (Beta-1 adrenoreceptor) (Beta-1 adrenoceptor) Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling. Involved in the regulation of sleep/wake behaviors (PubMed:31473062). {ECO:0000269|PubMed:12391161, ECO:0000269|PubMed:31473062}.
P11474 ESRRA S27 ochoa Steroid hormone receptor ERR1 (Estrogen receptor-like 1) (Estrogen-related receptor alpha) (ERR-alpha) (Nuclear receptor subfamily 3 group B member 1) Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism. Induces the expression of PERM1 in the skeletal muscle. {ECO:0000269|PubMed:12522104, ECO:0000269|PubMed:16150865, ECO:0000269|PubMed:17676930, ECO:0000269|PubMed:18063693, ECO:0000269|PubMed:23836911, ECO:0000269|PubMed:9271417}.
P13994 YJU2B S367 ochoa Probable splicing factor YJU2B (Coiled-coil domain-containing protein 130) May be involved in mRNA splicing. {ECO:0000250|UniProtKB:Q9BW85}.
P16284 PECAM1 S647 ochoa Platelet endothelial cell adhesion molecule (PECAM-1) (EndoCAM) (GPIIA') (PECA1) (CD antigen CD31) Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions (PubMed:17580308, PubMed:19342684). Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes (PubMed:19342684). Trans-homophilic interaction may play a role in endothelial cell-cell adhesion via cell junctions (PubMed:27958302). Heterophilic interaction with CD177 plays a role in transendothelial migration of neutrophils (PubMed:17580308). Homophilic ligation of PECAM1 prevents macrophage-mediated phagocytosis of neighboring viable leukocytes by transmitting a detachment signal (PubMed:12110892). Promotes macrophage-mediated phagocytosis of apoptotic leukocytes by tethering them to the phagocytic cells; PECAM1-mediated detachment signal appears to be disabled in apoptotic leukocytes (PubMed:12110892). Modulates bradykinin receptor BDKRB2 activation (PubMed:18672896). Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in endothelial cells (PubMed:18672896). Induces susceptibility to atherosclerosis (By similarity). {ECO:0000250|UniProtKB:Q08481, ECO:0000269|PubMed:12110892, ECO:0000269|PubMed:17580308, ECO:0000269|PubMed:18672896, ECO:0000269|PubMed:19342684, ECO:0000269|PubMed:27958302}.; FUNCTION: [Isoform Delta15]: Does not protect against apoptosis. {ECO:0000269|PubMed:18388311}.
P16333 NCK1 S91 ochoa SH2/SH3 adapter protein NCK1 (Cytoplasmic protein NCK1) (NCK adapter protein 1) (Nck-1) (SH2/SH3 adapter protein NCK-alpha) Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:9430661}.
P16615 ATP2A2 S507 ochoa Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) (SR Ca(2+)-ATPase 2) (EC 7.2.2.10) (Calcium pump 2) (Calcium-transporting ATPase sarcoplasmic reticulum type, slow twitch skeletal muscle isoform) (Endoplasmic reticulum class 1/2 Ca(2+) ATPase) This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:12542527, PubMed:16402920). Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation (PubMed:28890335). Also modulates ER contacts with lipid droplets, mitochondria and endosomes (PubMed:28890335). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity). {ECO:0000250|UniProtKB:O55143, ECO:0000269|PubMed:12542527, ECO:0000269|PubMed:16402920, ECO:0000269|PubMed:28890335}.; FUNCTION: [Isoform 2]: Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation. {ECO:0000250|UniProtKB:O55143}.
P22681 CBL S714 ochoa E3 ubiquitin-protein ligase CBL (EC 2.3.2.27) (Casitas B-lineage lymphoma proto-oncogene) (Proto-oncogene c-Cbl) (RING finger protein 55) (RING-type E3 ubiquitin transferase CBL) (Signal transduction protein CBL) E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors (PubMed:10514377, PubMed:11896602, PubMed:14661060, PubMed:14739300, PubMed:15190072, PubMed:17509076, PubMed:18374639, PubMed:19689429, PubMed:21596750, PubMed:28381567). Accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome (PubMed:10514377, PubMed:14661060, PubMed:14739300, PubMed:17094949, PubMed:17509076, PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, CSF1R, EPHA8 and KDR and mediates their ubiquitination to terminate signaling (PubMed:15190072, PubMed:18374639, PubMed:21596750). Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation (PubMed:11896602). Ubiquitinates EGFR and SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates NECTIN1 following association between NECTIN1 and herpes simplex virus 1/HHV-1 envelope glycoprotein D, leading to NECTIN1 removal from cell surface (PubMed:28381567). Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis (PubMed:15190072, PubMed:18374639). Essential for osteoclastic bone resorption (PubMed:14739300). The 'Tyr-731' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity). {ECO:0000250|UniProtKB:P22682, ECO:0000269|PubMed:10514377, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:14739300, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:17094949, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17974561, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:28381567}.
P23246 SFPQ S268 ochoa Splicing factor, proline- and glutamine-rich (100 kDa DNA-pairing protein) (hPOMp100) (DNA-binding p52/p100 complex, 100 kDa subunit) (Polypyrimidine tract-binding protein-associated-splicing factor) (PSF) (PTB-associated-splicing factor) DNA- and RNA binding protein, involved in several nuclear processes. Essential pre-mRNA splicing factor required early in spliceosome formation and for splicing catalytic step II, probably as a heteromer with NONO. Binds to pre-mRNA in spliceosome C complex, and specifically binds to intronic polypyrimidine tracts. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45, a phosphorylated form is sequestered by THRAP3 from the pre-mRNA in resting T-cells; T-cell activation and subsequent reduced phosphorylation is proposed to lead to release from THRAP3 allowing binding to pre-mRNA splicing regulatotry elements which represses exon inclusion. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. May be involved in a pre-mRNA coupled splicing and polyadenylation process as component of a snRNP-free complex with SNRPA/U1A. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. SFPQ may be involved in homologous DNA pairing; in vitro, promotes the invasion of ssDNA between a duplex DNA and produces a D-loop formation. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1; in vitro, stimulates dissociation of TOP1 from DNA after cleavage and enhances its jumping between separate DNA helices. The SFPQ-NONO heteromer binds DNA (PubMed:25765647). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends; in vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. SFPQ is involved in transcriptional regulation. Functions as a transcriptional activator (PubMed:25765647). Transcriptional repression is mediated by an interaction of SFPQ with SIN3A and subsequent recruitment of histone deacetylases (HDACs). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. SFPQ isoform Long binds to the DNA binding domains (DBD) of nuclear hormone receptors, like RXRA and probably THRA, and acts as a transcriptional corepressor in absence of hormone ligands. Binds the DNA sequence 5'-CTGAGTC-3' in the insulin-like growth factor response element (IGFRE) and inhibits IGF1-stimulated transcriptional activity. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex through histone deacetylation (By similarity). Required for the assembly of nuclear speckles (PubMed:25765647). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000250|UniProtKB:Q8VIJ6, ECO:0000269|PubMed:10847580, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:10931916, ECO:0000269|PubMed:11259580, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:25765647, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:8045264, ECO:0000269|PubMed:8449401}.
P25054 APC S2794 ochoa Adenomatous polyposis coli protein (Protein APC) (Deleted in polyposis 2.5) Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization. {ECO:0000250|UniProtKB:Q61315, ECO:0000269|PubMed:10947987, ECO:0000269|PubMed:17293347, ECO:0000269|PubMed:17599059, ECO:0000269|PubMed:19151759, ECO:0000269|PubMed:19893577, ECO:0000269|PubMed:20937854}.
P29590 PML S535 ochoa Protein PML (E3 SUMO-protein ligase PML) (EC 2.3.2.-) (Promyelocytic leukemia protein) (RING finger protein 71) (RING-type E3 SUMO transferase PML) (Tripartite motif-containing protein 19) (TRIM19) Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration. {ECO:0000269|PubMed:11500381, ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:18391071}.; FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HHV-5) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. Functions as an E3 SUMO-protein ligase that sumoylates (HHV-5) immediate early protein IE1, thereby participating in the antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 and PML-6 display the highest levels of sumoylation activity (PubMed:20972456, PubMed:28250117). {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}.
P29692 EEF1D S71 ochoa Elongation factor 1-delta (EF-1-delta) (Antigen NY-CO-4) [Isoform 1]: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome.; FUNCTION: [Isoform 2]: Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE).
P30305 CDC25B S209 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}.
P35568 IRS1 S1070 psp Insulin receptor substrate 1 (IRS-1) Signaling adapter protein that participates in the signal transduction from two prominent receptor tyrosine kinases, insulin receptor/INSR and insulin-like growth factor I receptor/IGF1R (PubMed:7541045, PubMed:33991522, PubMed:38625937). Plays therefore an important role in development, growth, glucose homeostasis as well as lipid metabolism (PubMed:19639489). Upon phosphorylation by the insulin receptor, functions as a signaling scaffold that propagates insulin action through binding to SH2 domain-containing proteins including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 or SHP2 (PubMed:11171109, PubMed:8265614). Recruitment of GRB2 leads to the activation of the guanine nucleotide exchange factor SOS1 which in turn triggers the Ras/Raf/MEK/MAPK signaling cascade (By similarity). Activation of the PI3K/AKT pathway is responsible for most of insulin metabolic effects in the cell, and the Ras/Raf/MEK/MAPK is involved in the regulation of gene expression and in cooperation with the PI3K pathway regulates cell growth and differentiation. Acts a positive regulator of the Wnt/beta-catenin signaling pathway through suppression of DVL2 autophagy-mediated degradation leading to cell proliferation (PubMed:24616100). {ECO:0000250|UniProtKB:P35570, ECO:0000269|PubMed:11171109, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:19639489, ECO:0000269|PubMed:38625937, ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:8265614}.
P35716 SOX11 S283 ochoa Transcription factor SOX-11 Transcription factor that acts as a transcriptional activator (PubMed:24886874, PubMed:26543203). Binds cooperatively with POU3F2/BRN2 or POU3F1/OCT6 to gene promoters, which enhances transcriptional activation (By similarity). Acts as a transcriptional activator of TEAD2 by binding to its gene promoter and first intron (By similarity). Plays a redundant role with SOX4 and SOX12 in cell survival of developing tissues such as the neural tube, branchial arches and somites, thereby contributing to organogenesis (By similarity). {ECO:0000250|UniProtKB:Q7M6Y2, ECO:0000269|PubMed:24886874, ECO:0000269|PubMed:26543203}.
P36873 PPP1CC S182 ochoa Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (PP-1G) (EC 3.1.3.16) (Protein phosphatase 1C catalytic subunit) Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets (PubMed:17936702, PubMed:25012651). Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1 (PubMed:17936702). Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (PubMed:20516061). In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:21712997). May dephosphorylate CSNK1D and CSNK1E (By similarity). Regulates the recruitment of the SKA complex to kinetochores (PubMed:28982702). Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Together with PPP1CA (PP1-alpha subunit), dephosphorylates IFIH1/MDA5 and RIG-I leading to their activation and a functional innate immune response (PubMed:23499489). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:35768504, PubMed:35831509). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:35768504, PubMed:35831509). Dephosphorylates MKI67 at the onset of anaphase (PubMed:25012651). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:35831509). {ECO:0000250|UniProtKB:P63087, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:25012651, ECO:0000269|PubMed:28982702, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35831509}.
P40692 MLH1 S406 ochoa|psp DNA mismatch repair protein Mlh1 (MutL protein homolog 1) Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR). DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. Heterodimerizes with MLH3 to form MutL gamma which plays a role in meiosis. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:20020535, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:39032648, ECO:0000269|PubMed:9311737}.
P41162 ETV3 S250 ochoa|psp ETS translocation variant 3 (ETS domain transcriptional repressor PE1) (PE-1) (Mitogenic Ets transcriptional suppressor) Transcriptional repressor that contribute to growth arrest during terminal macrophage differentiation by repressing target genes involved in Ras-dependent proliferation. Represses MMP1 promoter activity. {ECO:0000269|PubMed:12007404}.
P41212 ETV6 Y27 ochoa|psp Transcription factor ETV6 (ETS translocation variant 6) (ETS-related protein Tel1) (Tel) Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation. {ECO:0000269|PubMed:25581430}.
P48444 ARCN1 S223 ochoa Coatomer subunit delta (Archain) (Delta-coat protein) (Delta-COP) Component of the coatomer, a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity). {ECO:0000250}.
P48681 NES S476 ochoa Nestin Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells (By similarity). {ECO:0000250}.
P48730 CSNK1D S361 ochoa Casein kinase I isoform delta (CKI-delta) (CKId) (EC 2.7.11.1) (Tau-protein kinase CSNK1D) (EC 2.7.11.26) Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. Phosphorylates NEDD9/HEF1 (By similarity). EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate. {ECO:0000250|UniProtKB:Q9DC28, ECO:0000269|PubMed:10606744, ECO:0000269|PubMed:12270943, ECO:0000269|PubMed:14761950, ECO:0000269|PubMed:16027726, ECO:0000269|PubMed:17562708, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:19043076, ECO:0000269|PubMed:20041275, ECO:0000269|PubMed:20048001, ECO:0000269|PubMed:20407760, ECO:0000269|PubMed:20637175, ECO:0000269|PubMed:20696890, ECO:0000269|PubMed:20699359, ECO:0000269|PubMed:21084295, ECO:0000269|PubMed:21422228, ECO:0000269|PubMed:23636092}.
P49674 CSNK1E S368 psp Casein kinase I isoform epsilon (CKI-epsilon) (CKIe) (EC 2.7.11.1) Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates (Probable). Participates in Wnt signaling (PubMed:12556519, PubMed:23413191). Phosphorylates DVL1 (PubMed:12556519). Phosphorylates DVL2 (PubMed:23413191). Phosphorylates NEDD9/HEF1 (By similarity). Central component of the circadian clock (PubMed:16790549). In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:15917222, PubMed:16790549). Controls PER1 and PER2 nuclear transport and degradation (By similarity). Inhibits cytokine-induced granuloytic differentiation (PubMed:15070676). {ECO:0000250|UniProtKB:Q9JMK2, ECO:0000269|PubMed:12556519, ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:23413191, ECO:0000305|PubMed:7797465}.
P50402 EMD S29 ochoa Emerin Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. Required for proper localization of non-farnesylated prelamin-A/C. Together with NEMP1, contributes to nuclear envelope stiffness in germ cells (PubMed:32923640). EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. {ECO:0000269|PubMed:15328537, ECO:0000269|PubMed:16680152, ECO:0000269|PubMed:16858403, ECO:0000269|PubMed:17785515, ECO:0000269|PubMed:19323649, ECO:0000269|PubMed:32923640}.
P55196 AFDN S1187 ochoa Afadin (ALL1-fused gene from chromosome 6 protein) (Protein AF-6) (Afadin adherens junction formation factor) Belongs to an adhesion system, probably together with the E-cadherin-catenin system, which plays a role in the organization of homotypic, interneuronal and heterotypic cell-cell adherens junctions (AJs) (By similarity). Nectin- and actin-filament-binding protein that connects nectin to the actin cytoskeleton (PubMed:11024295). May play a key role in the organization of epithelial structures of the embryonic ectoderm (By similarity). Essential for the organization of adherens junctions (PubMed:30463011). {ECO:0000250|UniProtKB:O35889, ECO:0000250|UniProtKB:Q9QZQ1, ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:30463011}.
P62136 PPP1CA S182 ochoa Serine/threonine-protein phosphatase PP1-alpha catalytic subunit (PP-1A) (EC 3.1.3.16) Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets (PubMed:28216226, PubMed:30158517, PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39603239, PubMed:39603240). Protein phosphatase 1 (PP1) is essential for cell division, transcription elongation, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670, PubMed:39603239, PubMed:39603240). Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Catalytic component of the PNUTS-PP1 protein phosphatase complex, a protein phosphatase 1 (PP1) complex that promotes RNA polymerase II transcription pause-release, allowing transcription elongation: the PNUTS-PP1 complex mediates the release of RNA polymerase II from promoter-proximal region of genes by catalyzing dephosphorylation of proteins involved in transcription, such as AFF4, CDK9, MEPCE, INTS12, NCBP1, POLR2M/GDOWN1 and SUPT6H (PubMed:39603239, PubMed:39603240). The PNUTS-PP1 complex also regulates transcription termination by mediating dephosphorylation of SUPT5H in termination zones downstream of poly(A) sites, thereby promoting deceleration of RNA polymerase II transcription (PubMed:31677974). PNUTS-PP1 complex is also involved in the response to replication stress by mediating dephosphorylation of POLR2A at 'Ser-5' of the CTD, promoting RNA polymerase II degradation (PubMed:33264625). PNUTS-PP1 also plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase (PubMed:20516061). Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage (PubMed:17283141). Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development (By similarity). In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation (PubMed:21712997). May dephosphorylate CSNK1D and CSNK1E (PubMed:21712997). Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323). Together with PPP1CC (PP1-gamma subunit), dephosphorylates IFIH1/MDA5 and RIG-I leading to their activation and a functional innate immune response (PubMed:23499489). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:35768504, PubMed:35830882, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670). {ECO:0000250|UniProtKB:P62137, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:23499489, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26083323, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:30158517, ECO:0000269|PubMed:31677974, ECO:0000269|PubMed:33264625, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35830882, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670, ECO:0000269|PubMed:39603239, ECO:0000269|PubMed:39603240}.; FUNCTION: (Microbial infection) Necessary for alphaviruses replication. {ECO:0000269|PubMed:29769351}.
P62140 PPP1CB S181 ochoa Serine/threonine-protein phosphatase PP1-beta catalytic subunit (PP-1B) (PPP1CD) (EC 3.1.3.16) (EC 3.1.3.53) Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Core component of the SHOC2-MRAS-PP1c (SMP) holophosphatase complex that regulates the MAPK pathway activation (PubMed:35768504, PubMed:35831509, PubMed:36175670). The SMP complex specifically dephosphorylates the inhibitory phosphorylation at 'Ser-259' of RAF1 kinase, 'Ser-365' of BRAF kinase and 'Ser-214' of ARAF kinase, stimulating their kinase activities (PubMed:35768504, PubMed:35831509, PubMed:36175670). The SMP complex enhances the dephosphorylation activity and substrate specificity of PP1c (PubMed:35768504, PubMed:36175670). {ECO:0000269|PubMed:20516061, ECO:0000269|PubMed:21712997, ECO:0000269|PubMed:23396208, ECO:0000269|PubMed:35768504, ECO:0000269|PubMed:35831509, ECO:0000269|PubMed:36175670}.
P78347 GTF2I S679 ochoa General transcription factor II-I (GTFII-I) (TFII-I) (Bruton tyrosine kinase-associated protein 135) (BAP-135) (BTK-associated protein 135) (SRF-Phox1-interacting protein) (SPIN) (Williams-Beuren syndrome chromosomal region 6 protein) Interacts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes. Promotes the formation of stable high-order complexes of SRF and PHOX1 and interacts cooperatively with PHOX1 to promote serum-inducible transcription of a reporter gene deriven by the C-FOS serum response element (SRE). Acts as a coregulator for USF1 by binding independently two promoter elements, a pyrimidine-rich initiator (Inr) and an upstream E-box. Required for the formation of functional ARID3A DNA-binding complexes and for activation of immunoglobulin heavy-chain transcription upon B-lymphocyte activation. {ECO:0000269|PubMed:10373551, ECO:0000269|PubMed:11373296, ECO:0000269|PubMed:16738337}.
P78559 MAP1A T1177 ochoa Microtubule-associated protein 1A (MAP-1A) (Proliferation-related protein p80) [Cleaved into: MAP1A heavy chain; MAP1 light chain LC2] Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements.
Q00613 HSF1 S368 ochoa|psp Heat shock factor protein 1 (HSF 1) (Heat shock transcription factor 1) (HSTF 1) Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage (PubMed:11447121, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:18451878, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7760831, PubMed:8940068, PubMed:8946918, PubMed:9121459, PubMed:9341107, PubMed:9499401, PubMed:9535852, PubMed:9727490). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:11583998, PubMed:16278218, PubMed:9727490). Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes (PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:1871105, PubMed:1986252, PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7935471, PubMed:8455624, PubMed:8940068, PubMed:9499401, PubMed:9727490). Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival (PubMed:18451878). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock gene promoters (PubMed:25963659). Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 (PubMed:34723967). Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells (PubMed:9341107). Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic progression (PubMed:18794143). Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner (PubMed:26359349). Involved in stress-induced cancer cell proliferation in a IER5-dependent manner (PubMed:26754925). {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12659875, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:1871105, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:1986252, ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26727489, ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:34723967, ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831, ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624, ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9341107, ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9535852, ECO:0000269|PubMed:9727490}.; FUNCTION: (Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300. {ECO:0000269|PubMed:27189267}.
Q02750 MAP2K1 Y300 ochoa|psp Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1) Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}.
Q03164 KMT2A S523 ochoa Histone-lysine N-methyltransferase 2A (Lysine N-methyltransferase 2A) (EC 2.1.1.364) (ALL-1) (CXXC-type zinc finger protein 7) (Cysteine methyltransferase KMT2A) (EC 2.1.1.-) (Myeloid/lymphoid or mixed-lineage leukemia) (Myeloid/lymphoid or mixed-lineage leukemia protein 1) (Trithorax-like protein) (Zinc finger protein HRX) [Cleaved into: MLL cleavage product N320 (N-terminal cleavage product of 320 kDa) (p320); MLL cleavage product C180 (C-terminal cleavage product of 180 kDa) (p180)] Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:26886794). Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac) (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:24235145, PubMed:26886794). Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:12453419, PubMed:15960975, PubMed:19187761, PubMed:19556245, PubMed:20677832, PubMed:21220120, PubMed:25561738, PubMed:26886794). Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794). Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9' (PubMed:19187761). Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842). Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20010842, PubMed:20677832). Promotes PPP1R15A-induced apoptosis (PubMed:10490642). Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-BMAL1 heterodimer (By similarity). Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-BMAL1 to chromatin (By similarity). Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}.
Q03252 LMNB2 S42 ochoa Lamin-B2 Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane (PubMed:33033404). Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics (PubMed:33033404). The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively (PubMed:33033404). {ECO:0000269|PubMed:33033404}.
Q12778 FOXO1 S303 ochoa Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma) Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:15890677, PubMed:18356527, PubMed:19221179, PubMed:20543840, PubMed:21245099). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:10358076). Activity suppressed by insulin (PubMed:10358076). Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). Acts as an inhibitor of glucose sensing in pancreatic beta cells by acting as a transcription repressor and suppressing expression of PDX1 (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Also promotes gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1 (PubMed:17024043). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (PubMed:18356527, PubMed:19221179). Promotes neural cell death (PubMed:18356527). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (PubMed:20543840). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Positive regulator of apoptosis in cardiac smooth muscle cells as a result of its transcriptional activation of pro-apoptotic genes (PubMed:19483080). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). {ECO:0000250|UniProtKB:A4L7N3, ECO:0000250|UniProtKB:G3V7R4, ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:10358076, ECO:0000269|PubMed:12228231, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:17024043, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:19221179, ECO:0000269|PubMed:19483080, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:31063815}.
Q12888 TP53BP1 S557 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}.
Q13370 PDE3B S280 ochoa cGMP-inhibited 3',5'-cyclic phosphodiesterase 3B (EC 3.1.4.17) (CGIPDE1) (CGIP1) (Cyclic GMP-inhibited phosphodiesterase B) (CGI-PDE B) Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological process (PubMed:14592490, PubMed:21393242). Regulates angiogenesis by inhibiting the cAMP-dependent guanine nucleotide exchange factor RAPGEF3 and downstream phosphatidylinositol 3-kinase gamma-mediated signaling (PubMed:21393242). Controls cardiac contractility by reducing cAMP concentration in cardiocytes (By similarity). {ECO:0000250|UniProtKB:Q61409, ECO:0000269|PubMed:14592490, ECO:0000269|PubMed:21393242}.
Q13459 MYO9B T1295 ochoa Unconventional myosin-IXb (Unconventional myosin-9b) Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:26529257, PubMed:9490638). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}.
Q13501 SQSTM1 S277 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}.
Q13501 SQSTM1 S366 ochoa|psp Sequestosome-1 (EBI3-associated protein of 60 kDa) (EBIAP) (p60) (Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa) (Ubiquitin-binding protein p62) (p62) Molecular adapter required for selective macroautophagy (aggrephagy) by acting as a bridge between polyubiquitinated proteins and autophagosomes (PubMed:15340068, PubMed:15953362, PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22017874, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:33509017, PubMed:34471133, PubMed:34893540, PubMed:35831301, PubMed:37306101, PubMed:37802024). Promotes the recruitment of ubiquitinated cargo proteins to autophagosomes via multiple domains that bridge proteins and organelles in different steps (PubMed:16286508, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:29343546, PubMed:29507397, PubMed:34893540, PubMed:37802024). SQSTM1 first mediates the assembly and removal of ubiquitinated proteins by undergoing liquid-liquid phase separation upon binding to ubiquitinated proteins via its UBA domain, leading to the formation of insoluble cytoplasmic inclusions, known as p62 bodies (PubMed:15911346, PubMed:20168092, PubMed:22017874, PubMed:24128730, PubMed:29343546, PubMed:29507397, PubMed:31857589, PubMed:37802024). SQSTM1 then interacts with ATG8 family proteins on autophagosomes via its LIR motif, leading to p62 body recruitment to autophagosomes, followed by autophagic clearance of ubiquitinated proteins (PubMed:16286508, PubMed:17580304, PubMed:20168092, PubMed:22622177, PubMed:24128730, PubMed:28404643, PubMed:37802024). SQSTM1 is itself degraded along with its ubiquitinated cargos (PubMed:16286508, PubMed:17580304, PubMed:37802024). Also required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Also involved in autophagy of peroxisomes (pexophagy) in response to reactive oxygen species (ROS) by acting as a bridge between ubiquitinated PEX5 receptor and autophagosomes (PubMed:26344566). Acts as an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1: interaction inactivates the BCR(KEAP1) complex by sequestering the complex in inclusion bodies, promoting nuclear accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective genes (PubMed:20452972, PubMed:28380357, PubMed:33393215, PubMed:37306101). Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes (PubMed:29496741). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (PubMed:27368102, PubMed:33472082). Sequesters tensin TNS2 into cytoplasmic puncta, promoting TNS2 ubiquitination and proteasomal degradation (PubMed:25101860). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:10356400, PubMed:10747026, PubMed:11244088, PubMed:12471037, PubMed:16079148, PubMed:19931284). May play a role in titin/TTN downstream signaling in muscle cells (PubMed:15802564). Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). {ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:12471037, ECO:0000269|PubMed:15340068, ECO:0000269|PubMed:15802564, ECO:0000269|PubMed:15911346, ECO:0000269|PubMed:15953362, ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:16286508, ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19931284, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20452972, ECO:0000269|PubMed:22017874, ECO:0000269|PubMed:22622177, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:25101860, ECO:0000269|PubMed:26344566, ECO:0000269|PubMed:27368102, ECO:0000269|PubMed:28380357, ECO:0000269|PubMed:28404643, ECO:0000269|PubMed:29343546, ECO:0000269|PubMed:29496741, ECO:0000269|PubMed:29507397, ECO:0000269|PubMed:31857589, ECO:0000269|PubMed:33393215, ECO:0000269|PubMed:33472082, ECO:0000269|PubMed:33509017, ECO:0000269|PubMed:34471133, ECO:0000269|PubMed:34893540, ECO:0000269|PubMed:35831301, ECO:0000269|PubMed:37306101, ECO:0000269|PubMed:37802024}.
Q13535 ATR S1876 ochoa Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia telangiectasia and Rad3-related protein) (FRAP-related protein 1) Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:27723717, PubMed:27723720, PubMed:30139873, PubMed:33848395, PubMed:37788673, PubMed:37832547, PubMed:9427750, PubMed:9636169). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:23273981, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:9427750, PubMed:9636169). Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis (PubMed:11114888, PubMed:11418864, PubMed:11865061, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:9925639). Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (PubMed:11673449). Required for FANCD2 ubiquitination (PubMed:15314022). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (PubMed:12526805). Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (PubMed:30139873). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (PubMed:25083873, PubMed:37788673, PubMed:37832547). Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1 (PubMed:25083873). Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (PubMed:37832547). Involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture (PubMed:37788673). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (PubMed:37788673). Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity). {ECO:0000250|UniProtKB:Q9JKK8, ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:10608806, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12526805, ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:14742437, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15496423, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:21777809, ECO:0000269|PubMed:23273981, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:33848395, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:37832547, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9636169, ECO:0000269|PubMed:9925639}.
Q14202 ZMYM3 S54 ochoa Zinc finger MYM-type protein 3 (Zinc finger protein 261) Plays a role in the regulation of cell morphology and cytoskeletal organization. {ECO:0000269|PubMed:21834987}.
Q14686 NCOA6 S1900 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.
Q15025 TNIP1 S82 ochoa TNFAIP3-interacting protein 1 (A20-binding inhibitor of NF-kappa-B activation 1) (ABIN-1) (HIV-1 Nef-interacting protein) (Nef-associated factor 1) (Naf1) (Nip40-1) (Virion-associated nuclear shuttling protein) (VAN) (hVAN) Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG (PubMed:21885437). Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection. {ECO:0000269|PubMed:12220502, ECO:0000269|PubMed:16684768, ECO:0000269|PubMed:17016622, ECO:0000269|PubMed:17632516, ECO:0000269|PubMed:20010814, ECO:0000269|PubMed:21885437}.
Q15583 TGIF1 S291 ochoa Homeobox protein TGIF1 (5'-TG-3'-interacting factor 1) Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha transcription activation of the retinoic acid responsive element. Active transcriptional corepressor of SMAD2. Links the nodal signaling pathway to the bifurcation of the forebrain and the establishment of ventral midline structures. May participate in the transmission of nuclear signals during development and in the adult, as illustrated by the down-modulation of the RXR alpha activities.
Q15911 ZFHX3 S431 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}.
Q16204 CCDC6 S249 ochoa Coiled-coil domain-containing protein 6 (Papillary thyroid carcinoma-encoded protein) (Protein H4) None
Q16513 PKN2 S636 ochoa Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2) PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936, ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}.
Q16665 HIF1A S692 psp Hypoxia-inducible factor 1-alpha (HIF-1-alpha) (HIF1-alpha) (ARNT-interacting protein) (Basic-helix-loop-helix-PAS protein MOP1) (Class E basic helix-loop-helix protein 78) (bHLHe78) (Member of PAS protein 1) (PAS domain-containing protein 8) Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:30125331, PubMed:9887100). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:16543236, PubMed:9887100). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}.
Q2M2Z5 KIZ S326 ochoa Centrosomal protein kizuna (Polo-like kinase 1 substrate 1) Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole. {ECO:0000269|PubMed:16980960}.
Q4VCS5 AMOT Y719 ochoa Angiomotin Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions. Repressor of YAP1 and WWTR1/TAZ transcription of target genes, potentially via regulation of Hippo signaling-mediated phosphorylation of YAP1 which results in its recruitment to tight junctions (PubMed:21205866). {ECO:0000269|PubMed:11257124, ECO:0000269|PubMed:16678097, ECO:0000269|PubMed:21205866}.
Q53H80 AKIRIN2 S130 ochoa Akirin-2 Molecular adapter that acts as a bridge between a variety of multiprotein complexes, and which is involved in embryonic development, immunity, myogenesis and brain development (PubMed:34711951). Plays a key role in nuclear protein degradation by promoting import of proteasomes into the nucleus: directly binds to fully assembled 20S proteasomes at one end and to nuclear import receptor IPO9 at the other end, bridging them together and mediating the import of pre-assembled proteasome complexes through the nuclear pore (PubMed:34711951). Involved in innate immunity by regulating the production of interleukin-6 (IL6) downstream of Toll-like receptor (TLR): acts by bridging the NF-kappa-B inhibitor NFKBIZ and the SWI/SNF complex, leading to promote induction of IL6 (By similarity). Also involved in adaptive immunity by promoting B-cell activation (By similarity). Involved in brain development: required for the survival and proliferation of cerebral cortical progenitor cells (By similarity). Involved in myogenesis: required for skeletal muscle formation and skeletal development, possibly by regulating expression of muscle differentiation factors (By similarity). Also plays a role in facilitating interdigital tissue regression during limb development (By similarity). {ECO:0000250|UniProtKB:B1AXD8, ECO:0000269|PubMed:34711951}.
Q5FWE3 PRRT3 S813 ochoa Proline-rich transmembrane protein 3 None
Q5T1M5 FKBP15 S984 ochoa FK506-binding protein 15 (FKBP-15) (133 kDa FK506-binding protein) (133 kDa FKBP) (FKBP-133) (WASP- and FKBP-like protein) (WAFL) May be involved in the cytoskeletal organization of neuronal growth cones. Seems to be inactive as a PPIase (By similarity). Involved in the transport of early endosomes at the level of transition between microfilament-based and microtubule-based movement. {ECO:0000250, ECO:0000269|PubMed:19121306}.
Q5T1V6 DDX59 S165 ochoa Probable ATP-dependent RNA helicase DDX59 (EC 3.6.4.13) (DEAD box protein 59) (Zinc finger HIT domain-containing protein 5) None
Q5T5Y3 CAMSAP1 S1060 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}.
Q5T6F0 DCAF12 S20 ochoa DDB1- and CUL4-associated factor 12 (Centrosome-related protein TCC52) (Testis cancer centrosome-related protein) (WD repeat-containing protein 40A) Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:16949367, PubMed:16964240, PubMed:29779948). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948). The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:31267705). Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12) complex is required for starvation-induced autophagy (PubMed:31267705). Also directly recognizes the C-terminal glutamate-leucine (Glu-Leu) degron as an alternative degron in proteins such as MOV10, leading to their ubiquitination and degradation. Controls the protein level of MOV10 during spermatogenesis and in T cells, especially after their activation (PubMed:34065512). {ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:29779948, ECO:0000269|PubMed:31267705, ECO:0000269|PubMed:34065512}.
Q5UIP0 RIF1 S1777 ochoa Telomere-associated protein RIF1 (Rap1-interacting factor 1 homolog) Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}.
Q5VT06 CEP350 S1261 ochoa Centrosome-associated protein 350 (Cep350) (Centrosome-associated protein of 350 kDa) Plays an essential role in centriole growth by stabilizing a procentriolar seed composed of at least, SASS6 and CPAP (PubMed:19052644). Required for anchoring microtubules to the centrosomes and for the integrity of the microtubule network (PubMed:16314388, PubMed:17878239, PubMed:28659385). Recruits PPARA to discrete subcellular compartments and thereby modulates PPARA activity (PubMed:15615782). Required for ciliation (PubMed:28659385). {ECO:0000269|PubMed:15615782, ECO:0000269|PubMed:16314388, ECO:0000269|PubMed:17878239, ECO:0000269|PubMed:19052644, ECO:0000269|PubMed:28659385}.
Q5VTT5 MYOM3 S857 ochoa Myomesin-3 (Myomesin family member 3) May link the intermediate filament cytoskeleton to the M-disk of the myofibrils in striated muscle. {ECO:0000250}.
Q5W0Z9 ZDHHC20 S330 ochoa Palmitoyltransferase ZDHHC20 (EC 2.3.1.225) (Acyltransferase ZDHHC20) (EC 2.3.1.-) (DHHC domain-containing cysteine-rich protein 20) (DHHC20) (Zinc finger DHHC domain-containing protein 20) Palmitoyltransferase that could catalyze the addition of palmitate onto various protein substrates (PubMed:27153536, PubMed:29326245, PubMed:33219126). Catalyzes palmitoylation of Cys residues in the cytoplasmic C-terminus of EGFR, and modulates the duration of EGFR signaling by modulating palmitoylation-dependent EGFR internalization and degradation (PubMed:27153536). Has a preference for acyl-CoA with C16 fatty acid chains (PubMed:29326245). Can also utilize acyl-CoA with C14 and C18 fatty acid chains (PubMed:29326245). May palmitoylate CALHM1 subunit of gustatory voltage-gated ion channels and modulate channel gating and kinetics. {ECO:0000250|UniProtKB:Q5Y5T1, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:29326245, ECO:0000269|PubMed:33219126}.; FUNCTION: (Microbial infection) Dominant palmitoyltransferase responsible for lipidation of SARS coronavirus-2/SARS-CoV-2 spike protein. Through a sequential action with ZDHHC9, rapidly and efficiently palmitoylates spike protein following its synthesis in the endoplasmic reticulum (ER). In the infected cell, promotes spike biogenesis by protecting it from premature ER degradation, increases half-life and controls the lipid organization of its immediate membrane environment. Once the virus has formed, spike palmitoylation controls fusion with the target cell. {ECO:0000269|PubMed:34599882}.
Q641Q2 WASHC2A S1119 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}.
Q659A1 ICE2 S610 ochoa Little elongation complex subunit 2 (Interactor of little elongator complex ELL subunit 2) (NMDA receptor-regulated protein 2) Component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III. {ECO:0000269|PubMed:23932780}.
Q659C4 LARP1B S348 ochoa La-related protein 1B (La ribonucleoprotein domain family member 1B) (La ribonucleoprotein domain family member 2) (La-related protein 2) None
Q6JBY9 RCSD1 S132 ochoa CapZ-interacting protein (Protein kinase substrate CapZIP) (RCSD domain-containing protein 1) Stress-induced phosphorylation of CAPZIP may regulate the ability of F-actin-capping protein to remodel actin filament assembly. {ECO:0000269|PubMed:15850461}.
Q6P1R3 MSANTD2 S32 ochoa Myb/SANT-like DNA-binding domain-containing protein 2 None
Q6P2E9 EDC4 S38 ochoa Enhancer of mRNA-decapping protein 4 (Autoantigen Ge-1) (Autoantigen RCD-8) (Human enhancer of decapping large subunit) (Hedls) In the process of mRNA degradation, seems to play a role in mRNA decapping. Component of a complex containing DCP2 and DCP1A which functions in decapping of ARE-containing mRNAs. Promotes complex formation between DCP1A and DCP2. Enhances the catalytic activity of DCP2 (in vitro). {ECO:0000269|PubMed:16364915}.
Q6P3S6 FBXO42 S592 ochoa F-box only protein 42 (Just one F-box and Kelch domain-containing protein) Substrate-recognition component of some SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Specifically recognizes p53/TP53, promoting its ubiquitination and degradation. {ECO:0000269|PubMed:19509332}.
Q6P5W5 SLC39A4 S469 ochoa Zinc transporter ZIP4 (Solute carrier family 39 member 4) (Zrt- and Irt-like protein 4) (ZIP-4) Selective transporter that mediates the uptake of Zn(2+) (PubMed:17202136, PubMed:22242765, PubMed:27321477, PubMed:28875161, PubMed:31164399, PubMed:31914589, PubMed:31979155, PubMed:33837739, PubMed:36473915). Plays an essential role for dietary zinc uptake from small intestine (By similarity). The Zn(2+) uniporter activity is regulated by zinc availability (PubMed:17202136, PubMed:32348750). Also exhibits polyspecific binding and transport of Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations (PubMed:22242765, PubMed:31914589). {ECO:0000250|UniProtKB:Q78IQ7, ECO:0000269|PubMed:17202136, ECO:0000269|PubMed:22242765, ECO:0000269|PubMed:27321477, ECO:0000269|PubMed:28875161, ECO:0000269|PubMed:31164399, ECO:0000269|PubMed:31914589, ECO:0000269|PubMed:31979155, ECO:0000269|PubMed:32348750, ECO:0000269|PubMed:33837739, ECO:0000269|PubMed:36473915}.
Q6PGQ7 BORA S304 ochoa Protein aurora borealis (HsBora) Required for the activation of AURKA at the onset of mitosis. {ECO:0000269|PubMed:16890155}.
Q6UUV9 CRTC1 S172 ochoa CREB-regulated transcription coactivator 1 (Mucoepidermoid carcinoma translocated protein 1) (Transducer of regulated cAMP response element-binding protein 1) (TORC-1) (Transducer of CREB protein 1) Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. In the hippocampus, involved in late-phase long-term potentiation (L-LTP) maintenance at the Schaffer collateral-CA1 synapses. May be required for dendritic growth of developing cortical neurons (By similarity). In concert with SIK1, regulates the light-induced entrainment of the circadian clock. In response to light stimulus, coactivates the CREB-mediated transcription of PER1 which plays an important role in the photic entrainment of the circadian clock. {ECO:0000250|UniProtKB:Q157S1, ECO:0000250|UniProtKB:Q68ED7, ECO:0000269|PubMed:23699513}.; FUNCTION: (Microbial infection) Plays a role of coactivator for TAX activation of the human T-cell leukemia virus type 1 (HTLV-1) long terminal repeats (LTR). {ECO:0000269|PubMed:16809310}.
Q6WCQ1 MPRIP S294 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}.
Q6ZRV2 FAM83H S1003 ochoa Protein FAM83H May play a major role in the structural organization and calcification of developing enamel (PubMed:18252228). May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration (PubMed:23902688). {ECO:0000269|PubMed:18252228, ECO:0000269|PubMed:23902688}.
Q6ZS30 NBEAL1 S1349 ochoa Neurobeachin-like protein 1 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 16 protein) (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 17 protein) None
Q76FK4 NOL8 S273 ochoa Nucleolar protein 8 (Nucleolar protein Nop132) Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells. {ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:15132771, ECO:0000269|PubMed:16963496}.
Q7KZI7 MARK2 S624 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}.
Q7Z3B3 KANSL1 S999 ochoa KAT8 regulatory NSL complex subunit 1 (MLL1/MLL complex subunit KANSL1) (MSL1 homolog 1) (hMSL1v1) (NSL complex protein NSL1) (Non-specific lethal 1 homolog) Non-catalytic component of the NSL histone acetyltransferase complex, a multiprotein complex that mediates histone H4 acetylation at 'Lys-5'- and 'Lys-8' (H4K5ac and H4K8ac) at transcription start sites and promotes transcription initiation (PubMed:20018852, PubMed:22547026, PubMed:33657400). The NSL complex also acts as a regulator of gene expression in mitochondria (PubMed:27768893). In addition to its role in transcription, KANSL1 also plays an essential role in spindle assembly during mitosis (PubMed:26243146). Associates with microtubule ends and contributes to microtubule stability (PubMed:26243146). {ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:22547026, ECO:0000269|PubMed:26243146, ECO:0000269|PubMed:27768893, ECO:0000269|PubMed:33657400}.
Q7Z3U7 MON2 S1182 ochoa Protein MON2 homolog (Protein SF21) Plays a role in regulating membrane trafficking of cargo proteins. Together with ATP9A and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS away from lysosomal degradation. {ECO:0000269|PubMed:30213940}.
Q7Z434 MAVS S157 ochoa Mitochondrial antiviral-signaling protein (MAVS) (CARD adapter inducing interferon beta) (Cardif) (Interferon beta promoter stimulator protein 1) (IPS-1) (Putative NF-kappa-B-activating protein 031N) (Virus-induced-signaling adapter) (VISA) Adapter required for innate immune defense against viruses (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:21170385, PubMed:23087404, PubMed:27992402, PubMed:33139700, PubMed:37582970). Acts downstream of DHX33, RIGI and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFNB and RANTES (CCL5) (PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:16177806, PubMed:19631370, PubMed:20127681, PubMed:20451243, PubMed:20628368, PubMed:21170385, PubMed:23087404, PubMed:25636800, PubMed:27736772, PubMed:33110251). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state (PubMed:20451243). Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response (PubMed:20451243). May activate the same pathways following detection of extracellular dsRNA by TLR3 (PubMed:16153868). May protect cells from apoptosis (PubMed:16125763). Involved in NLRP3 inflammasome activation by mediating NLRP3 recruitment to mitochondria (PubMed:23582325). {ECO:0000269|PubMed:16125763, ECO:0000269|PubMed:16127453, ECO:0000269|PubMed:16153868, ECO:0000269|PubMed:16177806, ECO:0000269|PubMed:19631370, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20451243, ECO:0000269|PubMed:20628368, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:23582325, ECO:0000269|PubMed:25636800, ECO:0000269|PubMed:27736772, ECO:0000269|PubMed:27992402, ECO:0000269|PubMed:33110251, ECO:0000269|PubMed:33139700, ECO:0000269|PubMed:37582970}.
Q7Z5K2 WAPL S226 ochoa Wings apart-like protein homolog (Friend of EBNA2 protein) (WAPL cohesin release factor) Regulator of sister chromatid cohesion in mitosis which negatively regulates cohesin association with chromatin (PubMed:26299517). Involved in both sister chromatid cohesion during interphase and sister-chromatid resolution during early stages of mitosis. Couples DNA replication to sister chromatid cohesion. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. {ECO:0000269|PubMed:15150110, ECO:0000269|PubMed:17112726, ECO:0000269|PubMed:17113138, ECO:0000269|PubMed:19696148, ECO:0000269|PubMed:19907496, ECO:0000269|PubMed:21111234, ECO:0000269|PubMed:23776203, ECO:0000269|PubMed:26299517}.
Q86TI0 TBC1D1 S614 ochoa TBC1 domain family member 1 May act as a GTPase-activating protein for Rab family protein(s). May play a role in the cell cycle and differentiation of various tissues. Involved in the trafficking and translocation of GLUT4-containing vesicles and insulin-stimulated glucose uptake into cells (By similarity). {ECO:0000250}.
Q86X29 LSR S424 ochoa Lipolysis-stimulated lipoprotein receptor (Angulin-1) Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (By similarity). Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (By similarity). {ECO:0000250|UniProtKB:Q99KG5, ECO:0000250|UniProtKB:Q9WU74}.
Q86XK3 SFR1 S41 ochoa Swi5-dependent recombination DNA repair protein 1 homolog (Meiosis protein 5 homolog) Component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination (PubMed:21252223). Acts as a transcriptional modulator for ESR1 (PubMed:23874500). {ECO:0000269|PubMed:21252223, ECO:0000269|PubMed:23874500}.
Q86YW5 TREML1 S264 ochoa Trem-like transcript 1 protein (TLT-1) (Triggering receptor expressed on myeloid cells-like protein 1) Cell surface receptor that may play a role in the innate and adaptive immune response. {ECO:0000269|PubMed:15128762}.
Q8IX01 SUGP2 S1047 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}.
Q8IXJ9 ASXL1 S471 ochoa Polycomb group protein ASXL1 (Additional sex combs-like protein 1) Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG) (PubMed:16606617). Acts as a coactivator of RARA and RXRA through association with NCOA1 (PubMed:16606617). Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity (By similarity). Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:20436459, PubMed:30664650, PubMed:36180891). Acts as a sensor of N(6)-methyladenine methylation on DNA (6mA): recognizes and binds 6mA DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing (PubMed:30982744). The PR-DUB complex is an epigenetic regulator of gene expression and acts as a transcriptional coactivator, affecting genes involved in development, cell communication, signaling, cell proliferation and cell viability (PubMed:30664650, PubMed:36180891). ASXL1, ASXL2 and ASXL3 function redundantly in the PR-DUB complex (By similarity) (PubMed:30664650). The ASXL proteins are essential for chromatin recruitment and transcriptional activation of associated genes (By similarity). ASXL1 and ASXL2 are important for BAP1 protein stability (PubMed:30664650). Together with BAP1, negatively regulates epithelial-mesenchymal transition (EMT) of trophoblast stem cells during placental development by regulating genes involved in epithelial cell integrity, cell adhesion and cytoskeletal organization (PubMed:34170818). {ECO:0000250|UniProtKB:P59598, ECO:0000269|PubMed:16606617, ECO:0000269|PubMed:20436459, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:30982744, ECO:0000269|PubMed:34170818, ECO:0000269|PubMed:36180891}.
Q8N1G0 ZNF687 S145 ochoa Zinc finger protein 687 May be involved in transcriptional regulation.
Q8N1G0 ZNF687 S1196 ochoa Zinc finger protein 687 May be involved in transcriptional regulation.
Q8N2M8 CLASRP S106 ochoa CLK4-associating serine/arginine rich protein (Splicing factor, arginine/serine-rich 16) (Suppressor of white-apricot homolog 2) Probably functions as an alternative splicing regulator. May regulate the mRNA splicing of genes such as CLK1. May act by regulating members of the CLK kinase family (By similarity). {ECO:0000250}.
Q8N3F8 MICALL1 S396 ochoa MICAL-like protein 1 (Molecule interacting with Rab13) (MIRab13) Lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, acts as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation (PubMed:19864458, PubMed:20801876, PubMed:23596323, PubMed:34100897). Involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking (PubMed:21795389). Alternatively, regulates slow endocytic recycling of endocytosed proteins back to the plasma membrane (PubMed:19864458). Also involved in cargo protein delivery to the plasma membrane (PubMed:34100897). Plays a role in ciliogenesis coordination, recruits EHD1 to primary cilium where it is anchored to the centriole through interaction with tubulins (PubMed:31615969). May indirectly play a role in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q8BGT6, ECO:0000269|PubMed:19864458, ECO:0000269|PubMed:20801876, ECO:0000269|PubMed:21795389, ECO:0000269|PubMed:23596323, ECO:0000269|PubMed:31615969, ECO:0000269|PubMed:34100897}.
Q8N3F8 MICALL1 S538 ochoa MICAL-like protein 1 (Molecule interacting with Rab13) (MIRab13) Lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, acts as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation (PubMed:19864458, PubMed:20801876, PubMed:23596323, PubMed:34100897). Involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking (PubMed:21795389). Alternatively, regulates slow endocytic recycling of endocytosed proteins back to the plasma membrane (PubMed:19864458). Also involved in cargo protein delivery to the plasma membrane (PubMed:34100897). Plays a role in ciliogenesis coordination, recruits EHD1 to primary cilium where it is anchored to the centriole through interaction with tubulins (PubMed:31615969). May indirectly play a role in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q8BGT6, ECO:0000269|PubMed:19864458, ECO:0000269|PubMed:20801876, ECO:0000269|PubMed:21795389, ECO:0000269|PubMed:23596323, ECO:0000269|PubMed:31615969, ECO:0000269|PubMed:34100897}.
Q8N5H7 SH2D3C S348 ochoa SH2 domain-containing protein 3C (Cas/HEF1-associated signal transducer) (Chat-H) (Novel SH2-containing protein 3) (SH2 domain-containing Eph receptor-binding protein 1) (SHEP1) Acts as an adapter protein that mediates cell signaling pathways involved in cellular functions such as cell adhesion and migration, tissue organization, and the regulation of the immune response (PubMed:12432078, PubMed:20881139). Plays a role in integrin-mediated cell adhesion through BCAR1-CRK-RAPGEF1 signaling and activation of the small GTPase RAP1 (PubMed:12432078). Promotes cell migration and invasion through the extracellular matrix (PubMed:20881139). Required for marginal zone B-cell development and thymus-independent type 2 immune responses (By similarity). Mediates migration and adhesion of B cells in the splenic marginal zone via promoting hyperphosphorylation of NEDD9/CASL (By similarity). Plays a role in CXCL13-induced chemotaxis of B-cells (By similarity). Plays a role in the migration of olfactory sensory neurons (OSNs) into the forebrain and the innervation of the olfactory bulb by the OSN axons during development (By similarity). Required for the efficient tyrosine phosphorylation of BCAR1 in OSN axons (By similarity). {ECO:0000250|UniProtKB:Q9QZS8, ECO:0000269|PubMed:12432078, ECO:0000269|PubMed:20881139}.; FUNCTION: [Isoform 1]: Important regulator of chemokine-induced, integrin-mediated T lymphocyte adhesion and migration, acting upstream of RAP1 (By similarity). Required for tissue-specific adhesion of T lymphocytes to peripheral tissues (By similarity). Required for basal and CXCL2 stimulated serine-threonine phosphorylation of NEDD9 (By similarity). May be involved in the regulation of T-cell receptor-mediated IL2 production through the activation of the JNK pathway in T-cells (By similarity). {ECO:0000250|UniProtKB:Q9QZS8}.; FUNCTION: [Isoform 2]: May be involved in the BCAR1/CAS-mediated JNK activation pathway. {ECO:0000250|UniProtKB:Q9QZS8}.
Q8N612 FHIP1B S487 ochoa FHF complex subunit HOOK-interacting protein 1B (FHIP1B) (FTS- and Hook-interacting protein) (FHIP) Component of the FTS/Hook/FHIP complex (FHF complex). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). {ECO:0000269|PubMed:18799622, ECO:0000269|PubMed:32073997}.
Q8NC06 ACBD4 S171 ochoa|psp Acyl-CoA-binding domain-containing protein 4 Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.
Q8ND24 RNF214 S21 ochoa RING finger protein 214 None
Q8ND24 RNF214 S506 ochoa RING finger protein 214 None
Q8NF91 SYNE1 S8255 ochoa Nesprin-1 (Enaptin) (KASH domain-containing protein 1) (KASH1) (Myocyte nuclear envelope protein 1) (Myne-1) (Nuclear envelope spectrin repeat protein 1) (Synaptic nuclear envelope protein 1) (Syne-1) Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. May be involved in nucleus-centrosome attachment and nuclear migration in neural progenitors implicating LINC complex association with SUN1/2 and probably association with cytoplasmic dynein-dynactin motor complexes; SYNE1 and SYNE2 may act redundantly. Required for centrosome migration to the apical cell surface during early ciliogenesis. May be involved in nuclear remodeling during sperm head formation in spermatogenesis; a probable SUN3:SYNE1/KASH1 LINC complex may tether spermatid nuclei to posterior cytoskeletal structures such as the manchette. {ECO:0000250|UniProtKB:Q6ZWR6, ECO:0000269|PubMed:11792814, ECO:0000269|PubMed:18396275}.
Q8NFQ8 TOR1AIP2 S168 ochoa Torsin-1A-interacting protein 2 (Lumenal domain-like LAP1) Required for endoplasmic reticulum integrity. Regulates the distribution of TOR1A between the endoplasmic reticulum and the nuclear envelope as well as induces TOR1A, TOR1B and TOR3A ATPase activity. {ECO:0000269|PubMed:19339278, ECO:0000269|PubMed:23569223, ECO:0000269|PubMed:24275647}.
Q8NFU7 TET1 S1976 psp Methylcytosine dioxygenase TET1 (EC 1.14.11.80) (CXXC-type zinc finger protein 6) (Leukemia-associated protein with a CXXC domain) (Ten-eleven translocation 1 gene protein) Dioxygenase that plays a key role in active DNA demethylation, by catalyzing the sequential oxidation of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) (PubMed:19372391, PubMed:21496894, PubMed:21778364, PubMed:35798741). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression (PubMed:33833093). Plays therefore a role in many biological processes, including stem cell maintenance, T- and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair (PubMed:31278917). Involved in the balance between pluripotency and lineage commitment of cells and plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Together with QSER1, plays an essential role in the protection and maintenance of transcriptional and developmental programs to inhibit the binding of DNMT3A/3B and therefore de novo methylation (PubMed:33833093). May play a role in pancreatic beta-cell specification during development. In this context, may function as an upstream epigenetic regulator of PAX4 presumably through direct recruitment by FOXA2 to a PAX4 enhancer to preserve its unmethylated status, thereby potentiating PAX4 expression to adopt beta-cell fate during endocrine lineage commitment (PubMed:35798741). Under DNA hypomethylation conditions, such as in female meiotic germ cells, may induce epigenetic reprogramming of pericentromeric heterochromatin (PCH), the constitutive heterochromatin of pericentromeric regions. PCH forms chromocenters in the interphase nucleus and chromocenters cluster at the prophase of meiosis. In this context, may also be essential for chromocenter clustering in a catalytic activity-independent manner, possibly through the recruitment polycomb repressive complex 1 (PRC1) to the chromocenters (By similarity). During embryonic development, may be required for normal meiotic progression in oocytes and meiotic gene activation (By similarity). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:12124344, ECO:0000269|PubMed:19372391, ECO:0000269|PubMed:19372393, ECO:0000269|PubMed:21496894, ECO:0000269|PubMed:21778364, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:29276034, ECO:0000269|PubMed:31278917, ECO:0000269|PubMed:33833093, ECO:0000269|PubMed:35798741}.; FUNCTION: [Isoform 1]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:28531272). Binds to promoters, particularly to those with high CG content (By similarity). In hippocampal neurons, isoform 1 regulates the expression of a unique subset of genes compared to isoform 2, although some overlap exists between both isoforms, hence differentially regulates excitatory synaptic transmission (By similarity). In hippocampal neuron cell cultures, isoform 1 controls both miniature excitatory postsynaptic current amplitude and frequency (By similarity). Isoform 1 may regulate genes involved in hippocampal-dependent memory, leading to positive regulation of memory, contrary to isoform 2 that may decrease memory (By similarity). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:28531272}.; FUNCTION: [Isoform 2]: Dioxygenase that plays a key role in active DNA demethylation (PubMed:28531272). As isoform 1, binds to promoters, particularly to those with high CG content, however displays reduced global chromatin affinity compared with isoform 1, leading to decreased global DNA demethylation compared with isoform 1 (By similarity). Contrary to isoform 1, isoform 2 localizes during S phase to sites of ongoing DNA replication in heterochromatin, causing a significant de novo 5hmC formation, globally, and more so in heterochromatin, including LINE 1 interspersed DNA repeats leading to their activation (By similarity). In hippocampal neurons, isoform 2 regulates the expression of a unique subset of genes compared to isoform 1, although some overlap between both isoforms, hence differentially regulates excitatory synaptic transmission (By similarity). In hippocampal neuron cell cultures, isoform 2 controls miniature excitatory postsynaptic current frequency, but not amplitude (By similarity). Isoform 2 may regulate genes involved in hippocampal-dependent memory, leading to negative regulation of memory, contrary to isoform 1 that may improve memory (By similarity). In immature and partially differentiated gonadotrope cells, directly represses luteinizing hormone gene LHB expression and does not catalyze 5hmC at the gene promoter (By similarity). {ECO:0000250|UniProtKB:Q3URK3, ECO:0000269|PubMed:28531272}.
Q8NHM5 KDM2B S1054 ochoa Lysine-specific demethylase 2B (EC 1.14.11.27) (CXXC-type zinc finger protein 2) (F-box and leucine-rich repeat protein 10) (F-box protein FBL10) (F-box/LRR-repeat protein 10) (JmjC domain-containing histone demethylation protein 1B) (Jumonji domain-containing EMSY-interactor methyltransferase motif protein) (Protein JEMMA) (Protein-containing CXXC domain 2) ([Histone-H3]-lysine-36 demethylase 1B) Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36' (PubMed:16362057, PubMed:17994099, PubMed:26237645). Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation (PubMed:16362057, PubMed:17994099). May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (Probable). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:17994099, ECO:0000269|PubMed:26237645, ECO:0000305}.
Q8NI27 THOC2 S1422 ochoa THO complex subunit 2 (Tho2) (hTREX120) Component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA (PubMed:15833825, PubMed:15998806, PubMed:17190602). Required for efficient export of polyadenylated RNA and spliced mRNA (PubMed:23222130). The THOC1-THOC2-THOC3 core complex alone is sufficient to bind export factor NXF1-NXT1 and promote ATPase activity of DDX39B; in the complex THOC2 is the only component that directly interacts with DDX39B (PubMed:33191911). TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway (PubMed:15833825, PubMed:15998806, PubMed:17190602). Required for NXF1 localization to the nuclear rim (PubMed:22893130). THOC2 (and probably the THO complex) is involved in releasing mRNA from nuclear speckle domains. {ECO:0000269|PubMed:11979277, ECO:0000269|PubMed:15833825, ECO:0000269|PubMed:15998806, ECO:0000269|PubMed:17190602, ECO:0000269|PubMed:22893130, ECO:0000269|PubMed:23222130, ECO:0000269|PubMed:33191911}.; FUNCTION: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. {ECO:0000269|PubMed:18974867}.
Q8TBE0 BAHD1 S106 ochoa Bromo adjacent homology domain-containing 1 protein (BAH domain-containing protein 1) Heterochromatin protein that acts as a transcription repressor and has the ability to promote the formation of large heterochromatic domains. May act by recruiting heterochromatin proteins such as CBX5 (HP1 alpha), HDAC5 and MBD1. Represses IGF2 expression by binding to its CpG-rich P3 promoter and recruiting heterochromatin proteins. At specific stages of Listeria infection, in complex with TRIM28, corepresses interferon-stimulated genes, including IFNL1, IFNL2 and IFNL3. {ECO:0000269|PubMed:19666599, ECO:0000269|PubMed:21252314}.
Q8TD16 BICD2 S334 ochoa Protein bicaudal D homolog 2 (Bic-D 2) Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates and stabilizes the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track) (PubMed:25814576). Facilitates the binding of RAB6A to the Golgi by stabilizing its GTP-bound form. Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport via its interaction with RAB6A and recruitment of the dynein-dynactin motor complex (PubMed:25962623). Contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1. During G2 phase of the cell cycle, associates with RANBP2 at the nuclear pores and recruits dynein and dynactin to the nuclear envelope to ensure proper positioning of the nucleus relative to centrosomes prior to the onset of mitosis (By similarity). {ECO:0000250|UniProtKB:Q921C5, ECO:0000269|PubMed:25814576, ECO:0000269|PubMed:25962623}.
Q8TD19 NEK9 S832 ochoa Serine/threonine-protein kinase Nek9 (EC 2.7.11.1) (Nercc1 kinase) (Never in mitosis A-related kinase 9) (NimA-related protein kinase 9) (NimA-related kinase 8) (Nek8) Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation (PubMed:12101123, PubMed:12840024, PubMed:14660563, PubMed:19941817). Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2 (PubMed:11864968). Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues (PubMed:11864968). Important for G1/S transition and S phase progression (PubMed:12840024, PubMed:14660563, PubMed:19941817). Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively (PubMed:12840024, PubMed:14660563, PubMed:19941817, PubMed:26522158). {ECO:0000269|PubMed:11864968, ECO:0000269|PubMed:12101123, ECO:0000269|PubMed:12840024, ECO:0000269|PubMed:14660563, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158}.
Q8TF76 HASPIN S288 ochoa|psp Serine/threonine-protein kinase haspin (EC 2.7.11.1) (Germ cell-specific gene 2 protein) (H-haspin) (Haploid germ cell-specific nuclear protein kinase) Serine/threonine-protein kinase that phosphorylates histone H3 at 'Thr-3' (H3T3ph) during mitosis. May act through H3T3ph to both position and modulate activation of AURKB and other components of the chromosomal passenger complex (CPC) at centromeres to ensure proper chromatid cohesion, metaphase alignment and normal progression through the cell cycle. {ECO:0000269|PubMed:11228240, ECO:0000269|PubMed:15681610, ECO:0000269|PubMed:17084365, ECO:0000269|PubMed:20705812, ECO:0000269|PubMed:20929775}.
Q8WXD9 CASKIN1 S724 ochoa Caskin-1 (CASK-interacting protein 1) May link the scaffolding protein CASK to downstream intracellular effectors. {ECO:0000250}.
Q8WXD9 CASKIN1 S954 ochoa Caskin-1 (CASK-interacting protein 1) May link the scaffolding protein CASK to downstream intracellular effectors. {ECO:0000250}.
Q8WXG6 MADD S935 ochoa MAP kinase-activating death domain protein (Differentially expressed in normal and neoplastic cells) (Insulinoma glucagonoma clone 20) (Rab3 GDP/GTP exchange factor) (RabGEF) (Rab3 GDP/GTP exchange protein) (Rab3GEP) Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064). {ECO:0000250|UniProtKB:O08873, ECO:0000250|UniProtKB:Q80U28, ECO:0000269|PubMed:11577081, ECO:0000269|PubMed:18559336, ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:32761064, ECO:0000269|PubMed:9115275}.
Q92508 PIEZO1 S1396 ochoa Piezo-type mechanosensitive ion channel component 1 (Membrane protein induced by beta-amyloid treatment) (Mib) (Protein FAM38A) Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain (PubMed:23479567, PubMed:23695678, PubMed:25955826, PubMed:37590348). Piezo channels are homotrimeric three-blade propeller-shaped structures that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (PubMed:37590348). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium (By similarity). Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+) (PubMed:25955826). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents (PubMed:25955826). Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling (PubMed:20016066). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing (By similarity). Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells (By similarity). In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007). {ECO:0000250|UniProtKB:E2JF22, ECO:0000250|UniProtKB:Q91X60, ECO:0000269|PubMed:25955826, ECO:0000269|PubMed:29799007}.
Q92538 GBF1 T319 ochoa Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (BFA-resistant GEF 1) Guanine-nucleotide exchange factor (GEF) for members of the Arf family of small GTPases involved in trafficking in the early secretory pathway; its GEF activity initiates the coating of nascent vesicles via the localized generation of activated ARFs through replacement of GDP with GTP. Recruitment to cis-Golgi membranes requires membrane association of Arf-GDP and can be regulated by ARF1, ARF3, ARF4 and ARF5. Involved in the recruitment of the COPI coat complex to the endoplasmic reticulum exit sites (ERES), and the endoplasmic reticulum-Golgi intermediate (ERGIC) and cis-Golgi compartments which implicates ARF1 activation. Involved in COPI vesicle-dependent retrograde transport from the ERGIC and cis-Golgi compartments to the endoplasmic reticulum (ER) (PubMed:12047556, PubMed:12808027, PubMed:16926190, PubMed:17956946, PubMed:18003980, PubMed:19039328, PubMed:24213530). Involved in the trans-Golgi network recruitment of GGA1, GGA2, GGA3, BIG1, BIG2, and the AP-1 adaptor protein complex related to chlathrin-dependent transport; the function requires its GEF activity (probably at least in part on ARF4 and ARF5) (PubMed:23386609). Has GEF activity towards ARF1 (PubMed:15616190). Has in vitro GEF activity towards ARF5 (By similarity). Involved in the processing of PSAP (PubMed:17666033). Required for the assembly of the Golgi apparatus (PubMed:12808027, PubMed:18003980). The AMPK-phosphorylated form is involved in Golgi disassembly during mitotis and under stress conditions (PubMed:18063581, PubMed:23418352). May be involved in the COPI vesicle-dependent recruitment of PNPLA2 to lipid droplets; however, this function is under debate (PubMed:19461073, PubMed:22185782). In neutrophils, involved in G protein-coupled receptor (GPCR)-mediated chemotaxis und superoxide production. Proposed to be recruited by phosphatidylinositol-phosphates generated upon GPCR stimulation to the leading edge where it recruits and activates ARF1, and is involved in recruitment of GIT2 and the NADPH oxidase complex (PubMed:22573891). Plays a role in maintaining mitochondrial morphology (PubMed:25190516). {ECO:0000250|UniProtKB:Q9R1D7, ECO:0000269|PubMed:12047556, ECO:0000269|PubMed:12808027, ECO:0000269|PubMed:15616190, ECO:0000269|PubMed:16926190, ECO:0000269|PubMed:17666033, ECO:0000269|PubMed:17956946, ECO:0000269|PubMed:18003980, ECO:0000269|PubMed:18063581, ECO:0000269|PubMed:19461073, ECO:0000269|PubMed:22185782, ECO:0000269|PubMed:22573891, ECO:0000269|PubMed:23386609, ECO:0000269|PubMed:23418352, ECO:0000269|PubMed:24213530, ECO:0000269|PubMed:25190516, ECO:0000305|PubMed:19039328, ECO:0000305|PubMed:22573891}.
Q92575 UBXN4 S458 ochoa UBX domain-containing protein 4 (Erasin) (UBX domain-containing protein 2) Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD (PubMed:19822669). {ECO:0000269|PubMed:16968747, ECO:0000269|PubMed:19822669}.
Q92585 MAML1 S164 ochoa Mastermind-like protein 1 (Mam-1) Acts as a transcriptional coactivator for NOTCH proteins. Has been shown to amplify NOTCH-induced transcription of HES1. Enhances phosphorylation and proteolytic turnover of the NOTCH intracellular domain in the nucleus through interaction with CDK8. Binds to CREBBP/CBP which promotes nucleosome acetylation at NOTCH enhancers and activates transcription. Induces phosphorylation and localization of CREBBP to nuclear foci. Plays a role in hematopoietic development by regulating NOTCH-mediated lymphoid cell fate decisions. {ECO:0000269|PubMed:11101851, ECO:0000269|PubMed:11390662, ECO:0000269|PubMed:12050117, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:17317671}.
Q92598 HSPH1 S562 ochoa Heat shock protein 105 kDa (Antigen NY-CO-25) (Heat shock 110 kDa protein) (Heat shock protein family H member 1) Acts as a nucleotide-exchange factor (NEF) for chaperone proteins HSPA1A and HSPA1B, promoting the release of ADP from HSPA1A/B thereby triggering client/substrate protein release (PubMed:24318877). Prevents the aggregation of denatured proteins in cells under severe stress, on which the ATP levels decrease markedly. Inhibits HSPA8/HSC70 ATPase and chaperone activities (By similarity). {ECO:0000250|UniProtKB:Q60446, ECO:0000250|UniProtKB:Q61699, ECO:0000269|PubMed:24318877}.
Q92613 JADE3 S571 ochoa Protein Jade-3 (Jade family PHD finger protein 3) (PHD finger protein 16) Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity. {ECO:0000269|PubMed:16387653}.
Q92794 KAT6A S1001 ochoa Histone acetyltransferase KAT6A (EC 2.3.1.48) (MOZ, YBF2/SAS3, SAS2 and TIP60 protein 3) (MYST-3) (Monocytic leukemia zinc finger protein) (Runt-related transcription factor-binding protein 2) (Zinc finger protein 220) Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML. {ECO:0000269|PubMed:11742995, ECO:0000269|PubMed:11965546, ECO:0000269|PubMed:12771199, ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:17925393, ECO:0000269|PubMed:23431171}.
Q92835 INPP5D S294 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}.
Q96I25 RBM17 S227 ochoa Splicing factor 45 (45 kDa-splicing factor) (RNA-binding motif protein 17) Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites. Promotes the utilization of a cryptic splice site created by the beta-110 mutation in the HBB gene. The resulting frameshift leads to sickle cell anemia. {ECO:0000269|PubMed:12015979, ECO:0000269|PubMed:17589525}.
Q96JY6 PDLIM2 S202 ochoa PDZ and LIM domain protein 2 (PDZ-LIM protein mystique) Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity. {ECO:0000269|PubMed:15659642}.
Q96T17 MAP7D2 S703 ochoa MAP7 domain-containing protein 2 Microtubule-stabilizing protein that plays a role in the control of cell motility and neurite outgrowth via direct binding to the microtubule (By similarity). Acts as a critical cofactor for kinesin transport. In the proximal axon, regulates kinesin-1 family members, KIF5A, KIF5B and KIF5C recruitment to microtubules and contributes to kinesin-1-mediated transport in the axons (By similarity). {ECO:0000250|UniProtKB:A2AG50, ECO:0000250|UniProtKB:D4A4L4}.
Q96T58 SPEN S1641 ochoa Msx2-interacting protein (SMART/HDAC1-associated repressor protein) (SPEN homolog) May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA. {ECO:0000250|UniProtKB:Q62504, ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:12374742}.
Q96TA1 NIBAN2 T651 ochoa Protein Niban 2 (Meg-3) (Melanoma invasion by ERK) (MINERVA) (Niban-like protein 1) (Protein FAM129B) May play a role in apoptosis suppression. May promote melanoma cell invasion in vitro. {ECO:0000269|PubMed:19362540, ECO:0000269|PubMed:21148485}.
Q99638 RAD9A S341 ochoa|psp Cell cycle checkpoint control protein RAD9A (hRAD9) (EC 3.1.11.2) (DNA repair exonuclease rad9 homolog A) Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair (PubMed:10713044, PubMed:17575048, PubMed:20545769, PubMed:21659603, PubMed:31135337). The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex (PubMed:21659603). Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER) (PubMed:21659603). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates (PubMed:21659603). The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase (PubMed:21659603). RAD9A possesses 3'->5' double stranded DNA exonuclease activity (PubMed:10713044). {ECO:0000269|PubMed:10713044, ECO:0000269|PubMed:17575048, ECO:0000269|PubMed:20545769, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:31135337}.
Q9BXL7 CARD11 S655 psp Caspase recruitment domain-containing protein 11 (CARD-containing MAGUK protein 1) (Carma 1) Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement (PubMed:11278692, PubMed:11356195, PubMed:12356734). Transduces signals downstream TCR or BCR activation via the formation of a multiprotein complex together with BCL10 and MALT1 that induces NF-kappa-B and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11356195). Upon activation in response to TCR or BCR triggering, CARD11 homooligomerizes to form a nucleating helical template that recruits BCL10 via CARD-CARD interaction, thereby promoting polymerization of BCL10 and subsequent recruitment of MALT1: this leads to I-kappa-B kinase (IKK) phosphorylation and degradation, and release of NF-kappa-B proteins for nuclear translocation (PubMed:24074955). Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (PubMed:17287217). Promotes linear ubiquitination of BCL10 by promoting the targeting of BCL10 to RNF31/HOIP (PubMed:27777308). Stimulates the phosphorylation of BCL10 (PubMed:11356195). Also activates the TORC1 signaling pathway (PubMed:28628108). {ECO:0000269|PubMed:11278692, ECO:0000269|PubMed:11356195, ECO:0000269|PubMed:12356734, ECO:0000269|PubMed:17287217, ECO:0000269|PubMed:24074955, ECO:0000269|PubMed:27777308, ECO:0000269|PubMed:28628108}.
Q9C0C2 TNKS1BP1 S280 ochoa 182 kDa tankyrase-1-binding protein None
Q9C0K0 BCL11B S102 ochoa B-cell lymphoma/leukemia 11B (BCL-11B) (B-cell CLL/lymphoma 11B) (COUP-TF-interacting protein 2) (Radiation-induced tumor suppressor gene 1 protein) (hRit1) Key regulator of both differentiation and survival of T-lymphocytes during thymocyte development in mammals. Essential in controlling the responsiveness of hematopoietic stem cells to chemotactic signals by modulating the expression of the receptors CCR7 and CCR9, which direct the movement of progenitor cells from the bone marrow to the thymus (PubMed:27959755). Is a regulator of IL2 promoter and enhances IL2 expression in activated CD4(+) T-lymphocytes (PubMed:16809611). Tumor-suppressor that represses transcription through direct, TFCOUP2-independent binding to a GC-rich response element (By similarity). May also function in the P53-signaling pathway (By similarity). {ECO:0000250|UniProtKB:Q99PV8, ECO:0000269|PubMed:16809611, ECO:0000269|PubMed:27959755}.
Q9H0F6 SHARPIN T170 ochoa Sharpin (Shank-associated RH domain-interacting protein) (Shank-interacting protein-like 1) (hSIPL1) Component of the LUBAC complex which conjugates linear polyubiquitin chains in a head-to-tail manner to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways (PubMed:21455173, PubMed:21455180, PubMed:21455181). Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation (PubMed:21455173, PubMed:21455180, PubMed:21455181). LUBAC is recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex (PubMed:21455173, PubMed:21455180, PubMed:21455181). The LUBAC complex is also involved in innate immunity by conjugating linear polyubiquitin chains at the surface of bacteria invading the cytosol to form the ubiquitin coat surrounding bacteria (PubMed:28481331). LUBAC is not able to initiate formation of the bacterial ubiquitin coat, and can only promote formation of linear polyubiquitins on pre-existing ubiquitin (PubMed:28481331). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:28481331). Together with OTULIN, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis (PubMed:23708998). {ECO:0000269|PubMed:21455173, ECO:0000269|PubMed:21455180, ECO:0000269|PubMed:21455181, ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:28481331}.
Q9H1A4 ANAPC1 S51 ochoa Anaphase-promoting complex subunit 1 (APC1) (Cyclosome subunit 1) (Mitotic checkpoint regulator) (Testis-specific gene 24 protein) Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle (PubMed:18485873). The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:18485873). The APC/C complex catalyzes assembly of branched 'Lys-11'-/'Lys-48'-linked branched ubiquitin chains on target proteins (PubMed:29033132). {ECO:0000269|PubMed:18485873, ECO:0000269|PubMed:29033132}.
Q9H1B7 IRF2BPL S220 ochoa Probable E3 ubiquitin-protein ligase IRF2BPL (EC 2.3.2.27) (Enhanced at puberty protein 1) (Interferon regulatory factor 2-binding protein-like) Probable E3 ubiquitin protein ligase involved in the proteasome-mediated ubiquitin-dependent degradation of target proteins (PubMed:29374064). Through the degradation of CTNNB1, functions downstream of FOXF2 to negatively regulate the Wnt signaling pathway (PubMed:29374064). Probably plays a role in the development of the central nervous system and in neuronal maintenance (Probable). Also acts as a transcriptional regulator of genes controlling female reproductive function. May play a role in gene transcription by transactivating GNRH1 promoter and repressing PENK promoter (By similarity). {ECO:0000250|UniProtKB:Q5EIC4, ECO:0000269|PubMed:29374064, ECO:0000305|PubMed:17334524, ECO:0000305|PubMed:29374064, ECO:0000305|PubMed:30057031}.
Q9H4L7 SMARCAD1 S34 ochoa SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 (SMARCAD1) (EC 3.6.4.12) (ATP-dependent helicase 1) (hHEL1) DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}.
Q9H4L7 SMARCAD1 S39 ochoa SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A containing DEAD/H box 1 (SMARCAD1) (EC 3.6.4.12) (ATP-dependent helicase 1) (hHEL1) DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication. Acts at replication sites to facilitate the maintenance of heterochromatin by directing H3 and H4 histones deacetylation, H3 'Lys-9' trimethylation (H3K9me3) and restoration of silencing. {ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:22960744}.
Q9H5H4 ZNF768 S144 ochoa Zinc finger protein 768 Binds to mammalian-wide interspersed repeat (MIRs) sequences in euchromatin and promoter regions of genes at the consensus sequence 5'-GCTGTGTG-[N20]-CCTCTCTG-3', consisting of two anchor regions connected by a linker region; the linker region probably does not contribute to the binding specificity (PubMed:30476274). Required for cell homeostasis (PubMed:34404770). May be involved in transcriptional regulation (Probable). {ECO:0000269|PubMed:30476274, ECO:0000269|PubMed:34404770, ECO:0000305}.
Q9H9J4 USP42 S759 ochoa Ubiquitin carboxyl-terminal hydrolase 42 (EC 3.4.19.12) (Deubiquitinating enzyme 42) (Ubiquitin thioesterase 42) (Ubiquitin-specific-processing protease 42) Deubiquitinating enzyme which may play an important role during spermatogenesis. {ECO:0000250}.
Q9HAU0 PLEKHA5 S549 ochoa Pleckstrin homology domain-containing family A member 5 (PH domain-containing family A member 5) (Phosphoinositol 3-phosphate-binding protein 2) (PEPP-2) None
Q9HAW4 CLSPN S839 ochoa Claspin (hClaspin) Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15096610, PubMed:15707391, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:34694004, PubMed:35585232). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717). {ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15096610, ECO:0000269|PubMed:15190204, ECO:0000269|PubMed:15226314, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:27401717, ECO:0000269|PubMed:34694004, ECO:0000269|PubMed:35585232}.
Q9HCM4 EPB41L5 S423 ochoa Band 4.1-like protein 5 (Erythrocyte membrane protein band 4.1-like 5) Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells. {ECO:0000269|PubMed:17920587}.
Q9NPA3 MID1IP1 S75 ochoa Mid1-interacting protein 1 (Gastrulation-specific G12-like protein) (Mid1-interacting G12-like protein) (Protein STRAIT11499) (Spot 14-related protein) (S14R) (Spot 14-R) Plays a role in the regulation of lipogenesis in liver. Up-regulates ACACA enzyme activity. Required for efficient lipid biosynthesis, including triacylglycerol, diacylglycerol and phospholipid. Involved in stabilization of microtubules (By similarity). {ECO:0000250}.
Q9NQ66 PLCB1 S987 ochoa 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 (EC 3.1.4.11) (PLC-154) (Phosphoinositide phospholipase C-beta-1) (Phospholipase C-I) (PLC-I) (Phospholipase C-beta-1) (PLC-beta-1) Catalyzes the hydrolysis of 1-phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) and mediates intracellular signaling downstream of G protein-coupled receptors (PubMed:9188725). Regulates the function of the endothelial barrier. {ECO:0000250|UniProtKB:Q9Z1B3, ECO:0000269|PubMed:9188725}.
Q9NQ75 CASS4 Y113 ochoa Cas scaffolding protein family member 4 (HEF-like protein) (HEF1-EFS-p130Cas-like protein) (HEPL) Docking protein that plays a role in tyrosine kinase-based signaling related to cell adhesion and cell spreading. Regulates PTK2/FAK1 activity, focal adhesion integrity, and cell spreading. {ECO:0000269|PubMed:18256281}.
Q9NQ84 GPRC5C Y361 ochoa G-protein coupled receptor family C group 5 member C (Retinoic acid-induced gene 3 protein) (RAIG-3) This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways. {ECO:0000250}.
Q9NQG5 RPRD1B S171 ochoa Regulation of nuclear pre-mRNA domain-containing protein 1B (Cell cycle-related and expression-elevated protein in tumor) Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. Transcriptional regulator which enhances expression of CCND1. Promotes binding of RNA polymerase II to the CCDN1 promoter and to the termination region before the poly-A site but decreases its binding after the poly-A site. Prevents RNA polymerase II from reading through the 3' end termination site and may allow it to be recruited back to the promoter through promotion of the formation of a chromatin loop. Also enhances the transcription of a number of other cell cycle-related genes including CDK2, CDK4, CDK6 and cyclin-E but not CDKN1A, CDKN1B or cyclin-A. Promotes cell proliferation. {ECO:0000269|PubMed:22231121, ECO:0000269|PubMed:22264791, ECO:0000269|PubMed:24399136, ECO:0000269|PubMed:24997600}.
Q9NQG6 MIEF1 S64 ochoa Mitochondrial dynamics protein MIEF1 (Mitochondrial dynamics protein of 51 kDa) (Mitochondrial elongation factor 1) (Smith-Magenis syndrome chromosomal region candidate gene 7 protein-like) (SMCR7-like protein) Mitochondrial outer membrane protein which regulates mitochondrial fission/fusion dynamics (PubMed:21701560, PubMed:23921378, PubMed:33632269). Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface independently of the mitochondrial fission FIS1 and MFF proteins. Regulates DNM1L GTPase activity and DNM1L oligomerization. Binds ADP and can also bind GDP, although with lower affinity. Does not bind CDP, UDP, ATP, AMP or GTP. Inhibits DNM1L GTPase activity in the absence of bound ADP. Requires ADP to stimulate DNM1L GTPase activity and the assembly of DNM1L into long, oligomeric tubules with a spiral pattern, as opposed to the ring-like DNM1L oligomers observed in the absence of bound ADP. Does not require ADP for its function in recruiting DNM1L. {ECO:0000269|PubMed:21508961, ECO:0000269|PubMed:21701560, ECO:0000269|PubMed:23283981, ECO:0000269|PubMed:23530241, ECO:0000269|PubMed:23921378, ECO:0000269|PubMed:24515348, ECO:0000269|PubMed:29083303, ECO:0000269|PubMed:33632269}.
Q9NQS7 INCENP T153 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}.
Q9NQZ2 UTP3 S42 ochoa Something about silencing protein 10 (Charged amino acid-rich leucine zipper 1) (CRL1) (Disrupter of silencing SAS10) (UTP3 homolog) Essential for gene silencing: has a role in the structure of silenced chromatin. Plays a role in the developing brain (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). {ECO:0000250|UniProtKB:Q12136, ECO:0000250|UniProtKB:Q9JI13, ECO:0000269|PubMed:34516797}.
Q9NZJ0 DTL Y628 ochoa Denticleless protein homolog (DDB1- and CUL4-associated factor 2) (Lethal(2) denticleless protein homolog) (Retinoic acid-regulated nuclear matrix-associated protein) Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). The DDB1-CUL4A-DTL E3 ligase complex regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 (PubMed:26431207). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:26431207, ECO:0000269|PubMed:27906959}.
Q9NZT2 OGFR S403 ochoa Opioid growth factor receptor (OGFr) (Protein 7-60) (Zeta-type opioid receptor) Receptor for opioid growth factor (OGF), also known as Met-enkephalin. Seems to be involved in growth regulation.
Q9ULD4 BRPF3 S792 ochoa Bromodomain and PHD finger-containing protein 3 Scaffold subunit of various histone acetyltransferase (HAT) complexes, such as the MOZ/MORF and HBO1 complexes, which have a histone H3 acetyltransferase activity (PubMed:16387653, PubMed:26620551, PubMed:26677226). Plays a role in DNA replication initiation by directing KAT7/HBO1 specificity towards histone H3 'Lys-14' acetylation (H3K14ac), thereby facilitating the activation of replication origins (PubMed:26620551). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (PubMed:16387653). {ECO:0000269|PubMed:16387653, ECO:0000269|PubMed:26620551, ECO:0000269|PubMed:26677226}.
Q9ULJ3 ZBTB21 S1008 ochoa Zinc finger and BTB domain-containing protein 21 (Zinc finger protein 295) Acts as a transcription repressor. {ECO:0000269|PubMed:15629158}.
Q9Y2I7 PIKFYVE S25 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}.
Q9Y2K6 USP20 S373 ochoa Ubiquitin carboxyl-terminal hydrolase 20 (EC 3.4.19.12) (Deubiquitinating enzyme 20) (Ubiquitin thioesterase 20) (Ubiquitin-specific-processing protease 20) (VHL-interacting deubiquitinating enzyme 2) (hVDU2) Deubiquitinating enzyme that plays a role in many cellular processes including autophagy, cellular antiviral response or membrane protein biogenesis (PubMed:27801882, PubMed:29487085). Attenuates TLR4-mediated NF-kappa-B signaling by cooperating with beta-arrestin-2/ARRB2 and inhibiting TRAF6 autoubiquitination (PubMed:26839314). Promotes cellular antiviral responses by deconjugating 'Lys-33' and 'Lys-48'-linked ubiquitination of STING1 leading to its stabilization (PubMed:27801882). Plays an essential role in autophagy induction by regulating the ULK1 stability through deubiquitination of ULK1 (PubMed:29487085). Acts as a positive regulator for NF-kappa-B activation by TNF-alpha through deubiquitinating 'Lys-48'-linked polyubiquitination of SQSTM1, leading to its increased stability (PubMed:32354117). Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (ADRB2) (PubMed:19424180). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, possibly leading to beta-arrestins deubiquitination and disengagement from ADRB2 (PubMed:19424180). This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Deubiquitinates HIF1A, leading to stabilize HIF1A and enhance HIF1A-mediated activity (PubMed:15776016). Deubiquitinates MCL1, a pivotal member of the anti-apoptotic Bcl-2 protein family to regulate its stability (PubMed:35063767). Within the endoplasmic reticulum, participates with USP33 in the rescue of post-translationally targeted membrane proteins that are inappropriately ubiquitinated by the cytosolic protein quality control in the cytosol (PubMed:33792613). {ECO:0000269|PubMed:12056827, ECO:0000269|PubMed:12865408, ECO:0000269|PubMed:15776016, ECO:0000269|PubMed:19424180, ECO:0000269|PubMed:26839314, ECO:0000269|PubMed:27801882, ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:32354117, ECO:0000269|PubMed:33792613, ECO:0000269|PubMed:35063767}.
Q9Y4B4 RAD54L2 S1177 ochoa Helicase ARIP4 (EC 3.6.4.12) (Androgen receptor-interacting protein 4) (RAD54-like protein 2) DNA helicase that modulates androgen receptor (AR)-dependent transactivation in a promoter-dependent manner. Not able to remodel mononucleosomes in vitro (By similarity). {ECO:0000250}.
Q9Y4C1 KDM3A S819 ochoa Lysine-specific demethylase 3A (EC 1.14.11.65) (JmjC domain-containing histone demethylation protein 2A) (Jumonji domain-containing protein 1A) ([histone H3]-dimethyl-L-lysine(9) demethylase 3A) Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate. Involved in hormone-dependent transcriptional activation, by participating in recruitment to androgen-receptor target genes, resulting in H3 'Lys-9' demethylation and transcriptional activation. Involved in spermatogenesis by regulating expression of target genes such as PRM1 and TNP1 which are required for packaging and condensation of sperm chromatin. Involved in obesity resistance through regulation of metabolic genes such as PPARA and UCP1. {ECO:0000269|PubMed:16603237, ECO:0000269|PubMed:28262558}.
Q9Y4E6 WDR7 S1068 ochoa WD repeat-containing protein 7 (Rabconnectin-3 beta) (TGF-beta resistance-associated protein TRAG) None
Q9Y4G2 PLEKHM1 S440 ochoa Pleckstrin homology domain-containing family M member 1 (PH domain-containing family M member 1) (162 kDa adapter protein) (AP162) Acts as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Acts as a dual effector of RAB7A and ARL8B that simultaneously binds these GTPases, bringing about clustering and fusion of late endosomes and lysosomes (PubMed:25498145, PubMed:28325809). Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Interaction with Arl8b is a crucial factor in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725). Involved in bone resorption (By similarity). {ECO:0000250|UniProtKB:Q5PQS0, ECO:0000250|UniProtKB:Q7TSI1, ECO:0000269|PubMed:12820725, ECO:0000269|PubMed:20943950, ECO:0000269|PubMed:25498145, ECO:0000269|PubMed:28325809}.; FUNCTION: (Microbial infection) In case of infection contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella-containing vacuole (SCV) probably in concert with the HOPS complex and Rab7. {ECO:0000269|PubMed:25500191}.
Q9Y6B7 AP4B1 S593 ochoa AP-4 complex subunit beta-1 (AP-4 adaptor complex subunit beta) (Adaptor-related protein complex 4 subunit beta-1) (Beta subunit of AP-4) (Beta4-adaptin) Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). {ECO:0000269|PubMed:10066790, ECO:0000269|PubMed:10436028, ECO:0000305|PubMed:10066790, ECO:0000305|PubMed:10436028}.
Q96RT7 TUBGCP6 S1465 SIGNOR Gamma-tubulin complex component 6 (GCP-6) Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation (PubMed:11694571, PubMed:38305685, PubMed:38609661, PubMed:39321809). The gTuRC regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments, a critical step in centrosome duplication and spindle formation (PubMed:38305685, PubMed:38609661, PubMed:39321809). {ECO:0000269|PubMed:11694571, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}.
Q7Z4V5 HDGFL2 S301 Sugiyama Hepatoma-derived growth factor-related protein 2 (HDGF-related protein 2) (HRP-2) (Hepatoma-derived growth factor 2) (HDGF-2) Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719). {ECO:0000269|PubMed:25689719, ECO:0000269|PubMed:26721387, ECO:0000269|PubMed:32459350}.
Q14687 GSE1 Y724 Sugiyama Genetic suppressor element 1 None
Q9HC52 CBX8 S196 PSP Chromobox protein homolog 8 (Polycomb 3 homolog) (Pc3) (hPc3) (Rectachrome 1) Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. {ECO:0000269|PubMed:21282530}.
P05556 ITGB1 S689 Sugiyama Integrin beta-1 (Fibronectin receptor subunit beta) (Glycoprotein IIa) (GPIIA) (VLA-4 subunit beta) (CD antigen CD29) Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen. Integrins alpha-1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence G-F-P-G-E-R in collagen. Integrins alpha-2/beta-1, alpha-3/beta-1, alpha-4/beta-1, alpha-5/beta-1, alpha-8/beta-1, alpha-10/beta-1, alpha-11/beta-1 and alpha-V/beta-1 are receptors for fibronectin. Alpha-4/beta-1 recognizes one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. Integrin alpha-5/beta-1 is a receptor for fibrinogen. Integrin alpha-1/beta-1, alpha-2/beta-1, alpha-6/beta-1 and alpha-7/beta-1 are receptors for lamimin. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-4/beta-1 is a receptor for VCAM1. It recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-9/beta-1 is a receptor for VCAM1, cytotactin and osteopontin. It recognizes the sequence A-E-I-D-G-I-E-L in cytotactin. Integrin alpha-3/beta-1 is a receptor for epiligrin, thrombospondin and CSPG4. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration. Integrin alpha-V/beta-1 is a receptor for vitronectin. Beta-1 integrins recognize the sequence R-G-D in a wide array of ligands. When associated with alpha-7 integrin, regulates cell adhesion and laminin matrix deposition. Involved in promoting endothelial cell motility and angiogenesis. Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process and the formation of mineralized bone nodules. May be involved in up-regulation of the activity of kinases such as PKC via binding to KRT1. Together with KRT1 and RACK1, serves as a platform for SRC activation or inactivation. Plays a mechanistic adhesive role during telophase, required for the successful completion of cytokinesis. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (PubMed:23125415, PubMed:24789099). ITGA4:ITGB1 and ITGA5:ITGB1 bind to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (PubMed:18635536, PubMed:25398877). ITGA5:ITGB1 acts as a receptor for fibrillin-1 (FBN1) and mediates R-G-D-dependent cell adhesion to FBN1 (PubMed:12807887, PubMed:17158881). ITGA5:ITGB1 acts as a receptor for fibronectin FN1 and mediates R-G-D-dependent cell adhesion to FN1 (PubMed:33962943). ITGA5:ITGB1 is a receptor for IL1B and binding is essential for IL1B signaling (PubMed:29030430). ITGA5:ITGB3 is a receptor for soluble CD40LG and is required for CD40/CD40LG signaling (PubMed:31331973). Plays an important role in myoblast differentiation and fusion during skeletal myogenesis (By similarity). ITGA9:ITGB1 may play a crucial role in SVEP1/polydom-mediated myoblast cell adhesion (By similarity). Integrins ITGA9:ITGB1 and ITGA4:ITGB1 repress PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via their interaction with SVEP1, thereby inhibit vasocontraction (PubMed:35802072). {ECO:0000250|UniProtKB:P07228, ECO:0000250|UniProtKB:P09055, ECO:0000269|PubMed:10455171, ECO:0000269|PubMed:12473654, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:16256741, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:18635536, ECO:0000269|PubMed:18804435, ECO:0000269|PubMed:19064666, ECO:0000269|PubMed:21768292, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:25398877, ECO:0000269|PubMed:29030430, ECO:0000269|PubMed:31331973, ECO:0000269|PubMed:33962943, ECO:0000269|PubMed:35802072, ECO:0000269|PubMed:7523423}.; FUNCTION: [Isoform 2]: Interferes with isoform 1 resulting in a dominant negative effect on cell adhesion and migration (in vitro). {ECO:0000305|PubMed:2249781}.; FUNCTION: [Isoform 5]: Isoform 5 displaces isoform 1 in striated muscles. {ECO:0000250|UniProtKB:P09055}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human echoviruses 1 and 8. {ECO:0000269|PubMed:8411387}.; FUNCTION: (Microbial infection) Acts as a receptor for Cytomegalovirus/HHV-5. {ECO:0000269|PubMed:20660204}.; FUNCTION: (Microbial infection) Acts as a receptor for Epstein-Barr virus/HHV-4. {ECO:0000269|PubMed:17945327}.; FUNCTION: (Microbial infection) Integrin ITGA5:ITGB1 acts as a receptor for Human parvovirus B19. {ECO:0000269|PubMed:12907437}.; FUNCTION: (Microbial infection) Integrin ITGA2:ITGB1 acts as a receptor for Human rotavirus. {ECO:0000269|PubMed:12941907}.; FUNCTION: (Microbial infection) Acts as a receptor for Mammalian reovirus. {ECO:0000269|PubMed:16501085}.; FUNCTION: (Microbial infection) In case of HIV-1 infection, integrin ITGA5:ITGB1 binding to extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions. {ECO:0000269|PubMed:10397733}.; FUNCTION: (Microbial infection) Interacts with CotH proteins expressed by fungi of the order mucorales, the causative agent of mucormycosis, which plays an important role in epithelial cell invasion by the fungi (PubMed:32487760). Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression (PubMed:32487760). {ECO:0000269|PubMed:32487760}.; FUNCTION: (Microbial infection) May serve as a receptor for adhesin A (nadA) of N.meningitidis. {ECO:0000305|PubMed:21471204}.; FUNCTION: (Microbial infection) Facilitates rabies infection in a fibronectin-dependent manner and participates in rabies virus traffic after internalization. {ECO:0000269|PubMed:31666383}.
P49137 MAPKAPK2 S339 Sugiyama MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.
Q9H093 NUAK2 S590 Sugiyama NUAK family SNF1-like kinase 2 (EC 2.7.11.1) (Omphalocele kinase 2) (SNF1/AMP kinase-related kinase) (SNARK) Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958). {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:32845958}.
Q9UM73 ALK S1449 Sugiyama ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}.
Download
reactome_id name p -log10_p
R-HSA-9931530 Phosphorylation and nuclear translocation of the CRY:PER:kinase complex 0.000002 5.627
R-HSA-201556 Signaling by ALK 0.000032 4.495
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 0.000051 4.296
R-HSA-170834 Signaling by TGF-beta Receptor Complex 0.000086 4.067
R-HSA-1640170 Cell Cycle 0.000176 3.754
R-HSA-9938206 Developmental Lineage of Mammary Stem Cells 0.000495 3.306
R-HSA-9924644 Developmental Lineages of the Mammary Gland 0.000621 3.207
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 0.000567 3.246
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 0.000542 3.266
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 0.000428 3.369
R-HSA-9909396 Circadian clock 0.000694 3.159
R-HSA-210990 PECAM1 interactions 0.000815 3.089
R-HSA-9927432 Developmental Lineage of Mammary Gland Myoepithelial Cells 0.001127 2.948
R-HSA-68877 Mitotic Prometaphase 0.001748 2.757
R-HSA-9006936 Signaling by TGFB family members 0.002204 2.657
R-HSA-9931521 The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CL... 0.002579 2.589
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 0.003498 2.456
R-HSA-5210891 Uptake and function of anthrax toxins 0.002937 2.532
R-HSA-69620 Cell Cycle Checkpoints 0.003257 2.487
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 0.003328 2.478
R-HSA-5688426 Deubiquitination 0.003019 2.520
R-HSA-69278 Cell Cycle, Mitotic 0.003731 2.428
R-HSA-449147 Signaling by Interleukins 0.004008 2.397
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 0.004666 2.331
R-HSA-5357905 Regulation of TNFR1 signaling 0.005299 2.276
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 0.005176 2.286
R-HSA-2173788 Downregulation of TGF-beta receptor signaling 0.005728 2.242
R-HSA-68886 M Phase 0.005924 2.227
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription 0.006389 2.195
R-HSA-9726840 SHOC2 M1731 mutant abolishes MRAS complex function 0.007417 2.130
R-HSA-4411364 Binding of TCF/LEF:CTNNB1 to target gene promoters 0.007417 2.130
R-HSA-8951430 RUNX3 regulates WNT signaling 0.007417 2.130
R-HSA-6794361 Neurexins and neuroligins 0.007617 2.118
R-HSA-9700649 Drug resistance of ALK mutants 0.012650 1.898
R-HSA-5467333 APC truncation mutants are not K63 polyubiquitinated 0.012650 1.898
R-HSA-9717316 alectinib-resistant ALK mutants 0.012650 1.898
R-HSA-9717264 ASP-3026-resistant ALK mutants 0.012650 1.898
R-HSA-9717326 crizotinib-resistant ALK mutants 0.012650 1.898
R-HSA-9717329 lorlatinib-resistant ALK mutants 0.012650 1.898
R-HSA-9717323 ceritinib-resistant ALK mutants 0.012650 1.898
R-HSA-9717301 NVP-TAE684-resistant ALK mutants 0.012650 1.898
R-HSA-9717319 brigatinib-resistant ALK mutants 0.012650 1.898
R-HSA-9660537 Signaling by MRAS-complex mutants 0.008900 2.051
R-HSA-9726842 Gain-of-function MRAS complexes activate RAF signaling 0.008900 2.051
R-HSA-3371556 Cellular response to heat stress 0.008102 2.091
R-HSA-75893 TNF signaling 0.009484 2.023
R-HSA-68882 Mitotic Anaphase 0.011367 1.944
R-HSA-2555396 Mitotic Metaphase and Anaphase 0.011635 1.934
R-HSA-9616222 Transcriptional regulation of granulopoiesis 0.012804 1.893
R-HSA-198693 AKT phosphorylates targets in the nucleus 0.010504 1.979
R-HSA-8878159 Transcriptional regulation by RUNX3 0.012954 1.888
R-HSA-9828806 Maturation of hRSV A proteins 0.008954 2.048
R-HSA-111465 Apoptotic cleavage of cellular proteins 0.013057 1.884
R-HSA-176187 Activation of ATR in response to replication stress 0.013986 1.854
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 0.013986 1.854
R-HSA-8848021 Signaling by PTK6 0.013420 1.872
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 0.013420 1.872
R-HSA-9614399 Regulation of localization of FOXO transcription factors 0.014062 1.852
R-HSA-69618 Mitotic Spindle Checkpoint 0.014416 1.841
R-HSA-9680350 Signaling by CSF1 (M-CSF) in myeloid cells 0.015955 1.797
R-HSA-5673000 RAF activation 0.015955 1.797
R-HSA-428540 Activation of RAC1 0.016010 1.796
R-HSA-4641265 Repression of WNT target genes 0.018066 1.743
R-HSA-9617629 Regulation of FOXO transcriptional activity by acetylation 0.018066 1.743
R-HSA-9772755 Formation of WDR5-containing histone-modifying complexes 0.016994 1.770
R-HSA-5689896 Ovarian tumor domain proteases 0.019185 1.717
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 0.019185 1.717
R-HSA-163560 Triglyceride catabolism 0.018071 1.743
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 0.020077 1.697
R-HSA-1433559 Regulation of KIT signaling 0.022490 1.648
R-HSA-1980143 Signaling by NOTCH1 0.023187 1.635
R-HSA-4839726 Chromatin organization 0.022872 1.641
R-HSA-1280215 Cytokine Signaling in Immune system 0.023305 1.633
R-HSA-9820965 Respiratory syncytial virus (RSV) genome replication, transcription and translat... 0.021524 1.667
R-HSA-5632987 Defective Mismatch Repair Associated With PMS2 0.025141 1.600
R-HSA-5545483 Defective Mismatch Repair Associated With MLH1 0.025141 1.600
R-HSA-5619088 Defective SLC39A4 causes acrodermatitis enteropathica, zinc-deficiency type (AEZ... 0.025141 1.600
R-HSA-141430 Inactivation of APC/C via direct inhibition of the APC/C complex 0.029864 1.525
R-HSA-141424 Amplification of signal from the kinetochores 0.033026 1.481
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 0.033026 1.481
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 0.030189 1.520
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 0.030891 1.510
R-HSA-2467813 Separation of Sister Chromatids 0.030063 1.522
R-HSA-6802957 Oncogenic MAPK signaling 0.031948 1.496
R-HSA-141405 Inhibition of the proteolytic activity of APC/C required for the onset of anapha... 0.029864 1.525
R-HSA-5693607 Processing of DNA double-strand break ends 0.027846 1.555
R-HSA-5687128 MAPK6/MAPK4 signaling 0.031948 1.496
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 0.026650 1.574
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis 0.027846 1.555
R-HSA-9701898 STAT3 nuclear events downstream of ALK signaling 0.024852 1.605
R-HSA-6794362 Protein-protein interactions at synapses 0.031948 1.496
R-HSA-162582 Signal Transduction 0.031262 1.505
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 0.029436 1.531
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 0.029864 1.525
R-HSA-9675135 Diseases of DNA repair 0.032370 1.490
R-HSA-75153 Apoptotic execution phase 0.032370 1.490
R-HSA-9614657 FOXO-mediated transcription of cell death genes 0.035240 1.453
R-HSA-3928664 Ephrin signaling 0.035240 1.453
R-HSA-9665230 Drug resistance in ERBB2 KD mutants 0.049653 1.304
R-HSA-9652282 Drug-mediated inhibition of ERBB2 signaling 0.049653 1.304
R-HSA-9665249 Resistance of ERBB2 KD mutants to afatinib 0.049653 1.304
R-HSA-9665247 Resistance of ERBB2 KD mutants to osimertinib 0.049653 1.304
R-HSA-9665251 Resistance of ERBB2 KD mutants to lapatinib 0.049653 1.304
R-HSA-9665246 Resistance of ERBB2 KD mutants to neratinib 0.049653 1.304
R-HSA-9665233 Resistance of ERBB2 KD mutants to trastuzumab 0.049653 1.304
R-HSA-9665245 Resistance of ERBB2 KD mutants to tesevatinib 0.049653 1.304
R-HSA-9665250 Resistance of ERBB2 KD mutants to AEE788 0.049653 1.304
R-HSA-9665244 Resistance of ERBB2 KD mutants to sapitinib 0.049653 1.304
R-HSA-9665737 Drug resistance in ERBB2 TMD/JMD mutants 0.049653 1.304
R-HSA-1251932 PLCG1 events in ERBB2 signaling 0.073552 1.133
R-HSA-211163 AKT-mediated inactivation of FOXO1A 0.073552 1.133
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription 0.073552 1.133
R-HSA-1306955 GRB7 events in ERBB2 signaling 0.073552 1.133
R-HSA-9652169 Signaling by MAP2K mutants 0.073552 1.133
R-HSA-74713 IRS activation 0.085276 1.069
R-HSA-9673768 Signaling by membrane-tethered fusions of PDGFRA or PDGFRB 0.085276 1.069
R-HSA-9706377 FLT3 signaling by CBL mutants 0.085276 1.069
R-HSA-165160 PDE3B signalling 0.096853 1.014
R-HSA-109703 PKB-mediated events 0.096853 1.014
R-HSA-8985586 SLIT2:ROBO1 increases RHOA activity 0.096853 1.014
R-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7 0.108283 0.965
R-HSA-112412 SOS-mediated signalling 0.119570 0.922
R-HSA-2470946 Cohesin Loading onto Chromatin 0.119570 0.922
R-HSA-912631 Regulation of signaling by CBL 0.038057 1.420
R-HSA-9700645 ALK mutants bind TKIs 0.141719 0.849
R-HSA-179409 APC-Cdc20 mediated degradation of Nek2A 0.043939 1.357
R-HSA-110056 MAPK3 (ERK1) activation 0.152584 0.816
R-HSA-2468052 Establishment of Sister Chromatid Cohesion 0.152584 0.816
R-HSA-933543 NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 0.163313 0.787
R-HSA-4839744 Signaling by APC mutants 0.163313 0.787
R-HSA-5467337 APC truncation mutants have impaired AXIN binding 0.163313 0.787
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex 0.163313 0.787
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex 0.163313 0.787
R-HSA-1234158 Regulation of gene expression by Hypoxia-inducible Factor 0.173906 0.760
R-HSA-9931512 Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters 0.173906 0.760
R-HSA-5339716 Signaling by GSK3beta mutants 0.173906 0.760
R-HSA-2197563 NOTCH2 intracellular domain regulates transcription 0.184366 0.734
R-HSA-9634285 Constitutive Signaling by Overexpressed ERBB2 0.184366 0.734
R-HSA-4839743 Signaling by CTNNB1 phospho-site mutants 0.184366 0.734
R-HSA-3000484 Scavenging by Class F Receptors 0.184366 0.734
R-HSA-5358752 CTNNB1 T41 mutants aren't phosphorylated 0.184366 0.734
R-HSA-5358749 CTNNB1 S37 mutants aren't phosphorylated 0.184366 0.734
R-HSA-5358751 CTNNB1 S45 mutants aren't phosphorylated 0.184366 0.734
R-HSA-5358747 CTNNB1 S33 mutants aren't phosphorylated 0.184366 0.734
R-HSA-9709570 Impaired BRCA2 binding to RAD51 0.073999 1.131
R-HSA-8847993 ERBB2 Activates PTK6 Signaling 0.204893 0.688
R-HSA-196299 Beta-catenin phosphorylation cascade 0.214962 0.668
R-HSA-6785631 ERBB2 Regulates Cell Motility 0.214962 0.668
R-HSA-176412 Phosphorylation of the APC/C 0.224905 0.648
R-HSA-9687136 Aberrant regulation of mitotic exit in cancer due to RB1 defects 0.224905 0.648
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 0.100708 0.997
R-HSA-1963640 GRB2 events in ERBB2 signaling 0.234722 0.629
R-HSA-3371511 HSF1 activation 0.104716 0.980
R-HSA-1963642 PI3K events in ERBB2 signaling 0.244415 0.612
R-HSA-9665348 Signaling by ERBB2 ECD mutants 0.253987 0.595
R-HSA-418217 G beta:gamma signalling through PLC beta 0.253987 0.595
R-HSA-3371568 Attenuation phase 0.121160 0.917
R-HSA-174048 APC/C:Cdc20 mediated degradation of Cyclin B 0.263437 0.579
R-HSA-9934037 Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) 0.272769 0.564
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 0.085660 1.067
R-HSA-380287 Centrosome maturation 0.090534 1.043
R-HSA-383280 Nuclear Receptor transcription pathway 0.098057 1.009
R-HSA-3371571 HSF1-dependent transactivation 0.173587 0.760
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 0.178113 0.749
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 0.182657 0.738
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 0.191796 0.717
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 0.196387 0.707
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 0.127645 0.894
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 0.228855 0.640
R-HSA-380259 Loss of Nlp from mitotic centrosomes 0.228855 0.640
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 0.238206 0.623
R-HSA-8854518 AURKA Activation by TPX2 0.242889 0.615
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 0.275736 0.560
R-HSA-9617828 FOXO-mediated transcription of cell cycle genes 0.046998 1.328
R-HSA-9931510 Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... 0.063381 1.198
R-HSA-9013695 NOTCH4 Intracellular Domain Regulates Transcription 0.281983 0.550
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes 0.129606 0.887
R-HSA-1227986 Signaling by ERBB2 0.214881 0.668
R-HSA-198203 PI3K/AKT activation 0.152584 0.816
R-HSA-195253 Degradation of beta-catenin by the destruction complex 0.078568 1.105
R-HSA-8866911 TFAP2 (AP-2) family regulates transcription of cell cycle factors 0.073552 1.133
R-HSA-453276 Regulation of mitotic cell cycle 0.266347 0.575
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 0.266347 0.575
R-HSA-9851151 MDK and PTN in ALK signaling 0.073552 1.133
R-HSA-8941856 RUNX3 regulates NOTCH signaling 0.184366 0.734
R-HSA-9609523 Insertion of tail-anchored proteins into the endoplasmic reticulum membrane 0.272769 0.564
R-HSA-8849473 PTK6 Expression 0.119570 0.922
R-HSA-5685938 HDR through Single Strand Annealing (SSA) 0.088957 1.051
R-HSA-176407 Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase 0.244415 0.612
R-HSA-112399 IRS-mediated signalling 0.200993 0.697
R-HSA-2428928 IRS-related events triggered by IGF1R 0.219531 0.659
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 0.214962 0.668
R-HSA-2980766 Nuclear Envelope Breakdown 0.051100 1.292
R-HSA-5221030 TET1,2,3 and TDG demethylate DNA 0.152584 0.816
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 0.177760 0.750
R-HSA-918233 TRAF3-dependent IRF activation pathway 0.234722 0.629
R-HSA-5358508 Mismatch Repair 0.253987 0.595
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 0.066859 1.175
R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer 0.056946 1.245
R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer 0.056946 1.245
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants 0.056946 1.245
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants 0.056946 1.245
R-HSA-446343 Localization of the PINCH-ILK-PARVIN complex to focal adhesions 0.049653 1.304
R-HSA-8985801 Regulation of cortical dendrite branching 0.049653 1.304
R-HSA-8875513 MET interacts with TNS proteins 0.061678 1.210
R-HSA-390696 Adrenoceptors 0.130715 0.884
R-HSA-209560 NF-kB is activated and signals survival 0.173906 0.760
R-HSA-68884 Mitotic Telophase/Cytokinesis 0.173906 0.760
R-HSA-4839748 Signaling by AMER1 mutants 0.173906 0.760
R-HSA-4839735 Signaling by AXIN mutants 0.173906 0.760
R-HSA-9764562 Regulation of CDH1 mRNA translation by microRNAs 0.204893 0.688
R-HSA-418885 DCC mediated attractive signaling 0.214962 0.668
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 0.096744 1.014
R-HSA-1566977 Fibronectin matrix formation 0.234722 0.629
R-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) 0.244415 0.612
R-HSA-500657 Presynaptic function of Kainate receptors 0.253987 0.595
R-HSA-109704 PI3K Cascade 0.169080 0.772
R-HSA-1221632 Meiotic synapsis 0.182657 0.738
R-HSA-1433557 Signaling by SCF-KIT 0.138183 0.860
R-HSA-74751 Insulin receptor signalling cascade 0.233528 0.632
R-HSA-9860927 Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... 0.100708 0.997
R-HSA-2428924 IGF1R signaling cascade 0.233528 0.632
R-HSA-193639 p75NTR signals via NF-kB 0.214962 0.668
R-HSA-9856532 Mechanical load activates signaling by PIEZO1 and integrins in osteocytes 0.038057 1.420
R-HSA-209543 p75NTR recruits signalling complexes 0.184366 0.734
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) 0.244415 0.612
R-HSA-432142 Platelet sensitization by LDL 0.253987 0.595
R-HSA-74749 Signal attenuation 0.152584 0.816
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane 0.244415 0.612
R-HSA-416572 Sema4D induced cell migration and growth-cone collapse 0.272769 0.564
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 0.238206 0.623
R-HSA-6807004 Negative regulation of MET activity 0.272769 0.564
R-HSA-9603381 Activated NTRK3 signals through PI3K 0.119570 0.922
R-HSA-389513 Co-inhibition by CTLA4 0.272769 0.564
R-HSA-2682334 EPH-Ephrin signaling 0.142031 0.848
R-HSA-199992 trans-Golgi Network Vesicle Budding 0.271042 0.567
R-HSA-9734767 Developmental Cell Lineages 0.154543 0.811
R-HSA-9855142 Cellular responses to mechanical stimuli 0.078613 1.105
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 0.224189 0.649
R-HSA-9860931 Response of endothelial cells to shear stress 0.060541 1.218
R-HSA-5423599 Diseases of Mismatch Repair (MMR) 0.061678 1.210
R-HSA-8941855 RUNX3 regulates CDKN1A transcription 0.096853 1.014
R-HSA-5674499 Negative feedback regulation of MAPK pathway 0.096853 1.014
R-HSA-8857538 PTK6 promotes HIF1A stabilization 0.108283 0.965
R-HSA-8964046 VLDL clearance 0.119570 0.922
R-HSA-428359 Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... 0.152584 0.816
R-HSA-418359 Reduction of cytosolic Ca++ levels 0.173906 0.760
R-HSA-434316 Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion 0.224905 0.648
R-HSA-430039 mRNA decay by 5' to 3' exoribonuclease 0.234722 0.629
R-HSA-5357786 TNFR1-induced proapoptotic signaling 0.281983 0.550
R-HSA-69473 G2/M DNA damage checkpoint 0.088083 1.055
R-HSA-69481 G2/M Checkpoints 0.109100 0.962
R-HSA-9700206 Signaling by ALK in cancer 0.194455 0.711
R-HSA-157118 Signaling by NOTCH 0.238189 0.623
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 0.056620 1.247
R-HSA-8863678 Neurodegenerative Diseases 0.056620 1.247
R-HSA-9664873 Pexophagy 0.152584 0.816
R-HSA-170968 Frs2-mediated activation 0.194695 0.711
R-HSA-5693571 Nonhomologous End-Joining (NHEJ) 0.160130 0.796
R-HSA-202403 TCR signaling 0.204166 0.690
R-HSA-200425 Carnitine shuttle 0.053341 1.273
R-HSA-9842663 Signaling by LTK 0.184366 0.734
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 0.066859 1.175
R-HSA-9818749 Regulation of NFE2L2 gene expression 0.108283 0.965
R-HSA-205043 NRIF signals cell death from the nucleus 0.204893 0.688
R-HSA-399997 Acetylcholine regulates insulin secretion 0.234722 0.629
R-HSA-2644603 Signaling by NOTCH1 in Cancer 0.056946 1.245
R-HSA-9909649 Regulation of PD-L1(CD274) transcription 0.069536 1.158
R-HSA-1295596 Spry regulation of FGF signaling 0.214962 0.668
R-HSA-3214847 HATs acetylate histones 0.053147 1.275
R-HSA-69275 G2/M Transition 0.048623 1.313
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 0.103208 0.986
R-HSA-453274 Mitotic G2-G2/M phases 0.050509 1.297
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 0.078613 1.105
R-HSA-199920 CREB phosphorylation 0.108283 0.965
R-HSA-8948747 Regulation of PTEN localization 0.119570 0.922
R-HSA-8849469 PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 0.130715 0.884
R-HSA-201688 WNT mediated activation of DVL 0.141719 0.849
R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling 0.184366 0.734
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA 0.214962 0.668
R-HSA-9706369 Negative regulation of FLT3 0.224905 0.648
R-HSA-210744 Regulation of gene expression in late stage (branching morphogenesis) pancreatic... 0.224905 0.648
R-HSA-9701190 Defective homologous recombination repair (HRR) due to BRCA2 loss of function 0.096744 1.014
R-HSA-1500620 Meiosis 0.116541 0.934
R-HSA-5683057 MAPK family signaling cascades 0.046762 1.330
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 0.194455 0.711
R-HSA-3214842 HDMs demethylate histones 0.059967 1.222
R-HSA-73887 Death Receptor Signaling 0.070339 1.153
R-HSA-68875 Mitotic Prophase 0.244006 0.613
R-HSA-9682385 FLT3 signaling in disease 0.104716 0.980
R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex 0.205611 0.687
R-HSA-5693538 Homology Directed Repair 0.089482 1.048
R-HSA-5693532 DNA Double-Strand Break Repair 0.068990 1.161
R-HSA-169893 Prolonged ERK activation events 0.224905 0.648
R-HSA-447041 CHL1 interactions 0.119570 0.922
R-HSA-9933946 Formation of the embryonic stem cell BAF (esBAF) complex 0.214962 0.668
R-HSA-171007 p38MAPK events 0.214962 0.668
R-HSA-9931509 Expression of BMAL (ARNTL), CLOCK, and NPAS2 0.116991 0.932
R-HSA-429914 Deadenylation-dependent mRNA decay 0.210241 0.677
R-HSA-195721 Signaling by WNT 0.220952 0.656
R-HSA-445144 Signal transduction by L1 0.040958 1.388
R-HSA-9018519 Estrogen-dependent gene expression 0.132692 0.877
R-HSA-8953897 Cellular responses to stimuli 0.107897 0.967
R-HSA-1852241 Organelle biogenesis and maintenance 0.145450 0.837
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 0.088957 1.051
R-HSA-442380 Zinc influx into cells by the SLC39 gene family 0.141719 0.849
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA 0.214962 0.668
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol 0.088957 1.051
R-HSA-4419969 Depolymerization of the Nuclear Lamina 0.253987 0.595
R-HSA-1592230 Mitochondrial biogenesis 0.087623 1.057
R-HSA-2262752 Cellular responses to stress 0.251303 0.600
R-HSA-9607240 FLT3 Signaling 0.125366 0.902
R-HSA-74160 Gene expression (Transcription) 0.045729 1.340
R-HSA-187687 Signalling to ERKs 0.100708 0.997
R-HSA-450294 MAP kinase activation 0.219531 0.659
R-HSA-1483249 Inositol phosphate metabolism 0.210702 0.676
R-HSA-373753 Nephrin family interactions 0.040958 1.388
R-HSA-186712 Regulation of beta-cell development 0.210241 0.677
R-HSA-5689880 Ub-specific processing proteases 0.037436 1.427
R-HSA-212436 Generic Transcription Pathway 0.101849 0.992
R-HSA-4086398 Ca2+ pathway 0.085660 1.067
R-HSA-73857 RNA Polymerase II Transcription 0.069753 1.156
R-HSA-8849468 PTK6 Regulates Proteins Involved in RNA Processing 0.085276 1.069
R-HSA-447043 Neurofascin interactions 0.108283 0.965
R-HSA-9635465 Suppression of apoptosis 0.163313 0.787
R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange 0.100708 0.997
R-HSA-448424 Interleukin-17 signaling 0.261653 0.582
R-HSA-4420097 VEGFA-VEGFR2 Pathway 0.227235 0.644
R-HSA-2028269 Signaling by Hippo 0.244415 0.612
R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer 0.281983 0.550
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants 0.281983 0.550
R-HSA-3247509 Chromatin modifying enzymes 0.045316 1.344
R-HSA-194138 Signaling by VEGF 0.264381 0.578
R-HSA-69242 S Phase 0.162995 0.788
R-HSA-75892 Platelet Adhesion to exposed collagen 0.194695 0.711
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation 0.204893 0.688
R-HSA-1912420 Pre-NOTCH Processing in Golgi 0.263437 0.579
R-HSA-8939211 ESR-mediated signaling 0.231207 0.636
R-HSA-201681 TCF dependent signaling in response to WNT 0.257236 0.590
R-HSA-416700 Other semaphorin interactions 0.214962 0.668
R-HSA-9675136 Diseases of DNA Double-Strand Break Repair 0.096744 1.014
R-HSA-73894 DNA Repair 0.212501 0.673
R-HSA-5339562 Uptake and actions of bacterial toxins 0.042050 1.376
R-HSA-2586552 Signaling by Leptin 0.152584 0.816
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 0.271042 0.567
R-HSA-1483255 PI Metabolism 0.175406 0.756
R-HSA-264870 Caspase-mediated cleavage of cytoskeletal proteins 0.141719 0.849
R-HSA-9762292 Regulation of CDH11 function 0.152584 0.816
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 0.046998 1.328
R-HSA-446353 Cell-extracellular matrix interactions 0.214962 0.668
R-HSA-5693579 Homologous DNA Pairing and Strand Exchange 0.112859 0.947
R-HSA-5620916 VxPx cargo-targeting to cilium 0.272769 0.564
R-HSA-167044 Signalling to RAS 0.281983 0.550
R-HSA-210991 Basigin interactions 0.281983 0.550
R-HSA-187037 Signaling by NTRK1 (TRKA) 0.274649 0.561
R-HSA-373755 Semaphorin interactions 0.228855 0.640
R-HSA-2219528 PI3K/AKT Signaling in Cancer 0.089482 1.048
R-HSA-1474165 Reproduction 0.284957 0.545
R-HSA-1181150 Signaling by NODAL 0.272769 0.564
R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex 0.272769 0.564
R-HSA-9707616 Heme signaling 0.224189 0.649
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 0.049220 1.308
R-HSA-435354 Zinc transporters 0.204893 0.688
R-HSA-373760 L1CAM interactions 0.230572 0.637
R-HSA-1500931 Cell-Cell communication 0.139382 0.856
R-HSA-186763 Downstream signal transduction 0.081370 1.090
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 0.224189 0.649
R-HSA-1251985 Nuclear signaling by ERBB4 0.121160 0.917
R-HSA-1257604 PIP3 activates AKT signaling 0.214909 0.668
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 0.053341 1.273
R-HSA-5637810 Constitutive Signaling by EGFRvIII 0.244415 0.612
R-HSA-5637812 Signaling by EGFRvIII in Cancer 0.244415 0.612
R-HSA-5633007 Regulation of TP53 Activity 0.078730 1.104
R-HSA-1059683 Interleukin-6 signaling 0.194695 0.711
R-HSA-9759194 Nuclear events mediated by NFE2L2 0.247385 0.607
R-HSA-3700989 Transcriptional Regulation by TP53 0.094152 1.026
R-HSA-8979227 Triglyceride metabolism 0.054963 1.260
R-HSA-5685942 HDR through Homologous Recombination (HRR) 0.247576 0.606
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 0.134934 0.870
R-HSA-1236394 Signaling by ERBB4 0.280428 0.552
R-HSA-186797 Signaling by PDGF 0.224189 0.649
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 0.291080 0.536
R-HSA-8876384 Listeria monocytogenes entry into host cells 0.291080 0.536
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 0.291080 0.536
R-HSA-9034015 Signaling by NTRK3 (TRKC) 0.291080 0.536
R-HSA-9671555 Signaling by PDGFR in disease 0.291080 0.536
R-HSA-8856688 Golgi-to-ER retrograde transport 0.291848 0.535
R-HSA-9609690 HCMV Early Events 0.293700 0.532
R-HSA-216083 Integrin cell surface interactions 0.299168 0.524
R-HSA-9670439 Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... 0.300063 0.523
R-HSA-350054 Notch-HLH transcription pathway 0.300063 0.523
R-HSA-112409 RAF-independent MAPK1/3 activation 0.300063 0.523
R-HSA-9669938 Signaling by KIT in disease 0.300063 0.523
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in ... 0.300063 0.523
R-HSA-8964038 LDL clearance 0.300063 0.523
R-HSA-6806834 Signaling by MET 0.308512 0.511
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 0.308512 0.511
R-HSA-9833482 PKR-mediated signaling 0.308512 0.511
R-HSA-400451 Free fatty acids regulate insulin secretion 0.308933 0.510
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 0.308933 0.510
R-HSA-912526 Interleukin receptor SHC signaling 0.308933 0.510
R-HSA-9830674 Formation of the ureteric bud 0.308933 0.510
R-HSA-3000170 Syndecan interactions 0.308933 0.510
R-HSA-982772 Growth hormone receptor signaling 0.308933 0.510
R-HSA-3858494 Beta-catenin independent WNT signaling 0.309121 0.510
R-HSA-9006925 Intracellular signaling by second messengers 0.314919 0.502
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 0.317691 0.498
R-HSA-933542 TRAF6 mediated NF-kB activation 0.317691 0.498
R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex 0.317691 0.498
R-HSA-429947 Deadenylation of mRNA 0.317691 0.498
R-HSA-6783589 Interleukin-6 family signaling 0.317691 0.498
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 0.317831 0.498
R-HSA-5357801 Programmed Cell Death 0.322196 0.492
R-HSA-9664422 FCGR3A-mediated phagocytosis 0.322967 0.491
R-HSA-9664407 Parasite infection 0.322967 0.491
R-HSA-9664417 Leishmania phagocytosis 0.322967 0.491
R-HSA-3000157 Laminin interactions 0.326338 0.486
R-HSA-1482801 Acyl chain remodelling of PS 0.326338 0.486
R-HSA-400685 Sema4D in semaphorin signaling 0.326338 0.486
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane 0.326338 0.486
R-HSA-9932451 SWI/SNF chromatin remodelers 0.326338 0.486
R-HSA-9932444 ATP-dependent chromatin remodelers 0.326338 0.486
R-HSA-1266695 Interleukin-7 signaling 0.326338 0.486
R-HSA-446728 Cell junction organization 0.330551 0.481
R-HSA-9703465 Signaling by FLT3 fusion proteins 0.334877 0.475
R-HSA-9615933 Postmitotic nuclear pore complex (NPC) reformation 0.334877 0.475
R-HSA-8874081 MET activates PTK2 signaling 0.334877 0.475
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane 0.334877 0.475
R-HSA-1643713 Signaling by EGFR in Cancer 0.334877 0.475
R-HSA-8934593 Regulation of RUNX1 Expression and Activity 0.334877 0.475
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 0.340991 0.467
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 0.340991 0.467
R-HSA-3928663 EPHA-mediated growth cone collapse 0.343307 0.464
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 0.343307 0.464
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane 0.343307 0.464
R-HSA-9645723 Diseases of programmed cell death 0.350189 0.456
R-HSA-9663891 Selective autophagy 0.350189 0.456
R-HSA-199977 ER to Golgi Anterograde Transport 0.350652 0.455
R-HSA-5654732 Negative regulation of FGFR3 signaling 0.351632 0.454
R-HSA-5205685 PINK1-PRKN Mediated Mitophagy 0.351632 0.454
R-HSA-451326 Activation of kainate receptors upon glutamate binding 0.351632 0.454
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 0.351632 0.454
R-HSA-166520 Signaling by NTRKs 0.354107 0.451
R-HSA-5673001 RAF/MAP kinase cascade 0.358088 0.446
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 0.359344 0.444
R-HSA-202424 Downstream TCR signaling 0.359344 0.444
R-HSA-418990 Adherens junctions interactions 0.359506 0.444
R-HSA-9664565 Signaling by ERBB2 KD Mutants 0.359851 0.444
R-HSA-5654733 Negative regulation of FGFR4 signaling 0.359851 0.444
R-HSA-210745 Regulation of gene expression in beta cells 0.359851 0.444
R-HSA-418360 Platelet calcium homeostasis 0.359851 0.444
R-HSA-180024 DARPP-32 events 0.359851 0.444
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 0.359851 0.444
R-HSA-9759475 Regulation of CDH11 Expression and Function 0.359851 0.444
R-HSA-9006931 Signaling by Nuclear Receptors 0.361985 0.441
R-HSA-9755511 KEAP1-NFE2L2 pathway 0.364458 0.438
R-HSA-1227990 Signaling by ERBB2 in Cancer 0.367966 0.434
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 0.367966 0.434
R-HSA-9013508 NOTCH3 Intracellular Domain Regulates Transcription 0.367966 0.434
R-HSA-1250196 SHC1 events in ERBB2 signaling 0.367966 0.434
R-HSA-8863795 Downregulation of ERBB2 signaling 0.367966 0.434
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 0.367966 0.434
R-HSA-9933387 RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression 0.367966 0.434
R-HSA-74752 Signaling by Insulin receptor 0.372987 0.428
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 0.374782 0.426
R-HSA-5684996 MAPK1/MAPK3 signaling 0.375666 0.425
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 0.375980 0.425
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 0.375980 0.425
R-HSA-182971 EGFR downregulation 0.375980 0.425
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling 0.375980 0.425
R-HSA-2129379 Molecules associated with elastic fibres 0.375980 0.425
R-HSA-9833109 Evasion by RSV of host interferon responses 0.375980 0.425
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 0.382017 0.418
R-HSA-4791275 Signaling by WNT in cancer 0.383892 0.416
R-HSA-9675126 Diseases of mitotic cell cycle 0.383892 0.416
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 0.383892 0.416
R-HSA-1538133 G0 and Early G1 0.383892 0.416
R-HSA-1855170 IPs transport between nucleus and cytosol 0.391704 0.407
R-HSA-159227 Transport of the SLBP independent Mature mRNA 0.391704 0.407
R-HSA-5654726 Negative regulation of FGFR1 signaling 0.391704 0.407
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 0.391704 0.407
R-HSA-397795 G-protein beta:gamma signalling 0.391704 0.407
R-HSA-5675482 Regulation of necroptotic cell death 0.391704 0.407
R-HSA-9764260 Regulation of Expression and Function of Type II Classical Cadherins 0.391704 0.407
R-HSA-6807878 COPI-mediated anterograde transport 0.395458 0.403
R-HSA-6811434 COPI-dependent Golgi-to-ER retrograde traffic 0.395458 0.403
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 0.399418 0.399
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 0.399418 0.399
R-HSA-1482788 Acyl chain remodelling of PC 0.399418 0.399
R-HSA-109581 Apoptosis 0.402139 0.396
R-HSA-975871 MyD88 cascade initiated on plasma membrane 0.404345 0.393
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 0.404345 0.393
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 0.404345 0.393
R-HSA-1980145 Signaling by NOTCH2 0.407034 0.390
R-HSA-5654727 Negative regulation of FGFR2 signaling 0.407034 0.390
R-HSA-180746 Nuclear import of Rev protein 0.407034 0.390
R-HSA-5205647 Mitophagy 0.407034 0.390
R-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian expression 0.407034 0.390
R-HSA-9614085 FOXO-mediated transcription 0.408765 0.389
R-HSA-202733 Cell surface interactions at the vascular wall 0.413895 0.383
R-HSA-1482839 Acyl chain remodelling of PE 0.414554 0.382
R-HSA-9020702 Interleukin-1 signaling 0.417557 0.379
R-HSA-2559580 Oxidative Stress Induced Senescence 0.421929 0.375
R-HSA-432720 Lysosome Vesicle Biogenesis 0.421979 0.375
R-HSA-8941326 RUNX2 regulates bone development 0.421979 0.375
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 0.429311 0.367
R-HSA-933541 TRAF6 mediated IRF7 activation 0.429311 0.367
R-HSA-180910 Vpr-mediated nuclear import of PICs 0.429311 0.367
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 0.429311 0.367
R-HSA-111885 Opioid Signalling 0.430621 0.366
R-HSA-422475 Axon guidance 0.432410 0.364
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 0.432502 0.364
R-HSA-418555 G alpha (s) signalling events 0.435843 0.361
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 0.436550 0.360
R-HSA-1566948 Elastic fibre formation 0.436550 0.360
R-HSA-8875878 MET promotes cell motility 0.436550 0.360
R-HSA-5213460 RIPK1-mediated regulated necrosis 0.436550 0.360
R-HSA-9909648 Regulation of PD-L1(CD274) expression 0.439176 0.357
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 0.439245 0.357
R-HSA-212165 Epigenetic regulation of gene expression 0.443154 0.353
R-HSA-418346 Platelet homeostasis 0.443530 0.353
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 0.443698 0.353
R-HSA-9725554 Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin 0.443698 0.353
R-HSA-168276 NS1 Mediated Effects on Host Pathways 0.443698 0.353
R-HSA-8964043 Plasma lipoprotein clearance 0.443698 0.353
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 0.445821 0.351
R-HSA-9609646 HCMV Infection 0.450571 0.346
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 0.450755 0.346
R-HSA-177243 Interactions of Rev with host cellular proteins 0.450755 0.346
R-HSA-176033 Interactions of Vpr with host cellular proteins 0.450755 0.346
R-HSA-202433 Generation of second messenger molecules 0.450755 0.346
R-HSA-9646399 Aggrephagy 0.450755 0.346
R-HSA-451927 Interleukin-2 family signaling 0.450755 0.346
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 0.452045 0.345
R-HSA-421270 Cell-cell junction organization 0.453364 0.344
R-HSA-975155 MyD88 dependent cascade initiated on endosome 0.456275 0.341
R-HSA-9820841 M-decay: degradation of maternal mRNAs by maternally stored factors 0.457723 0.339
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 0.457723 0.339
R-HSA-3214841 PKMTs methylate histone lysines 0.457723 0.339
R-HSA-9694548 Maturation of spike protein 0.457723 0.339
R-HSA-8853884 Transcriptional Regulation by VENTX 0.457723 0.339
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 0.460487 0.337
R-HSA-166166 MyD88-independent TLR4 cascade 0.460487 0.337
R-HSA-5674135 MAP2K and MAPK activation 0.464604 0.333
R-HSA-9656223 Signaling by RAF1 mutants 0.464604 0.333
R-HSA-5675221 Negative regulation of MAPK pathway 0.464604 0.333
R-HSA-2559583 Cellular Senescence 0.465564 0.332
R-HSA-388841 Regulation of T cell activation by CD28 family 0.467261 0.330
R-HSA-1912422 Pre-NOTCH Expression and Processing 0.473007 0.325
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 0.473007 0.325
R-HSA-5654743 Signaling by FGFR4 0.478105 0.320
R-HSA-9637690 Response of Mtb to phagocytosis 0.478105 0.320
R-HSA-3928662 EPHB-mediated forward signaling 0.484728 0.315
R-HSA-373752 Netrin-1 signaling 0.484728 0.315
R-HSA-375280 Amine ligand-binding receptors 0.484728 0.315
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX) 0.484728 0.315
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 0.485351 0.314
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 0.491267 0.309
R-HSA-6783310 Fanconi Anemia Pathway 0.491267 0.309
R-HSA-5654741 Signaling by FGFR3 0.491267 0.309
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 0.491267 0.309
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 0.491267 0.309
R-HSA-8868773 rRNA processing in the nucleus and cytosol 0.491400 0.309
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C 0.497724 0.303
R-HSA-9649948 Signaling downstream of RAS mutants 0.497724 0.303
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 0.497724 0.303
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 0.497724 0.303
R-HSA-6802949 Signaling by RAS mutants 0.497724 0.303
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 0.497724 0.303
R-HSA-5617833 Cilium Assembly 0.497764 0.303
R-HSA-9711123 Cellular response to chemical stress 0.500074 0.301
R-HSA-9675108 Nervous system development 0.502917 0.299
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin 0.504099 0.297
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 0.504099 0.297
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 0.505523 0.296
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 0.505523 0.296
R-HSA-8878166 Transcriptional regulation by RUNX2 0.505523 0.296
R-HSA-9634597 GPER1 signaling 0.510393 0.292
R-HSA-389356 Co-stimulation by CD28 0.510393 0.292
R-HSA-425410 Metal ion SLC transporters 0.510393 0.292
R-HSA-73893 DNA Damage Bypass 0.516609 0.287
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 0.516614 0.287
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 0.517380 0.286
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 0.517380 0.286
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 0.521290 0.283
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 0.528804 0.277
R-HSA-1169091 Activation of NF-kappaB in B cells 0.528804 0.277
R-HSA-912446 Meiotic recombination 0.528804 0.277
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 0.528969 0.277
R-HSA-389948 Co-inhibition by PD-1 0.528969 0.277
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 0.532893 0.273
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 0.532893 0.273
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 0.532893 0.273
R-HSA-72187 mRNA 3'-end processing 0.534787 0.272
R-HSA-9692916 SARS-CoV-1 activates/modulates innate immune responses 0.534787 0.272
R-HSA-948021 Transport to the Golgi and subsequent modification 0.535082 0.272
R-HSA-376176 Signaling by ROBO receptors 0.538121 0.269
R-HSA-114608 Platelet degranulation 0.540522 0.267
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 0.540694 0.267
R-HSA-432722 Golgi Associated Vesicle Biogenesis 0.540694 0.267
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 0.546526 0.262
R-HSA-199418 Negative regulation of the PI3K/AKT network 0.551804 0.258
R-HSA-9012852 Signaling by NOTCH3 0.552285 0.258
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 0.552285 0.258
R-HSA-177929 Signaling by EGFR 0.557970 0.253
R-HSA-5654736 Signaling by FGFR1 0.557970 0.253
R-HSA-5578775 Ion homeostasis 0.557970 0.253
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 0.563584 0.249
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 0.566542 0.247
R-HSA-597592 Post-translational protein modification 0.568831 0.245
R-HSA-9029569 NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflu... 0.569127 0.245
R-HSA-1483257 Phospholipid metabolism 0.570451 0.244
R-HSA-194441 Metabolism of non-coding RNA 0.574600 0.241
R-HSA-191859 snRNP Assembly 0.574600 0.241
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 0.574600 0.241
R-HSA-8943724 Regulation of PTEN gene transcription 0.580004 0.237
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 0.580004 0.237
R-HSA-168325 Viral Messenger RNA Synthesis 0.585339 0.233
R-HSA-73856 RNA Polymerase II Transcription Termination 0.585339 0.233
R-HSA-8939902 Regulation of RUNX2 expression and activity 0.585339 0.233
R-HSA-112043 PLC beta mediated events 0.585339 0.233
R-HSA-9793380 Formation of paraxial mesoderm 0.585339 0.233
R-HSA-913531 Interferon Signaling 0.586730 0.232
R-HSA-6784531 tRNA processing in the nucleus 0.590607 0.229
R-HSA-6807070 PTEN Regulation 0.591490 0.228
R-HSA-8951664 Neddylation 0.593648 0.226
R-HSA-6790901 rRNA modification in the nucleus and cytosol 0.595809 0.225
R-HSA-2426168 Activation of gene expression by SREBF (SREBP) 0.595809 0.225
R-HSA-69615 G1/S DNA Damage Checkpoints 0.595809 0.225
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 0.598420 0.223
R-HSA-1632852 Macroautophagy 0.598420 0.223
R-HSA-936837 Ion transport by P-type ATPases 0.600944 0.221
R-HSA-9824439 Bacterial Infection Pathways 0.601933 0.220
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 0.605262 0.218
R-HSA-1234174 Cellular response to hypoxia 0.606015 0.218
R-HSA-8878171 Transcriptional regulation by RUNX1 0.607528 0.216
R-HSA-5693606 DNA Double Strand Break Response 0.615965 0.210
R-HSA-112040 G-protein mediated events 0.615965 0.210
R-HSA-9830369 Kidney development 0.615965 0.210
R-HSA-199991 Membrane Trafficking 0.620732 0.207
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 0.620846 0.207
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 0.620846 0.207
R-HSA-5218859 Regulated Necrosis 0.620846 0.207
R-HSA-72312 rRNA processing 0.623767 0.205
R-HSA-1643685 Disease 0.624562 0.204
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 0.625259 0.204
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 0.630423 0.200
R-HSA-69202 Cyclin E associated events during G1/S transition 0.630423 0.200
R-HSA-204005 COPII-mediated vesicle transport 0.630423 0.200
R-HSA-9764560 Regulation of CDH1 Gene Transcription 0.630423 0.200
R-HSA-9679191 Potential therapeutics for SARS 0.631749 0.199
R-HSA-9856651 MITF-M-dependent gene expression 0.631749 0.199
R-HSA-3000178 ECM proteoglycans 0.635121 0.197
R-HSA-5620920 Cargo trafficking to the periciliary membrane 0.635121 0.197
R-HSA-446652 Interleukin-1 family signaling 0.638151 0.195
R-HSA-5578749 Transcriptional regulation by small RNAs 0.639759 0.194
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 0.639759 0.194
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 0.639759 0.194
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 0.644339 0.191
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 0.644339 0.191
R-HSA-69052 Switching of origins to a post-replicative state 0.644339 0.191
R-HSA-1989781 PPARA activates gene expression 0.647591 0.189
R-HSA-9013694 Signaling by NOTCH4 0.648861 0.188
R-HSA-9612973 Autophagy 0.650695 0.187
R-HSA-1169408 ISG15 antiviral mechanism 0.653325 0.185
R-HSA-3000171 Non-integrin membrane-ECM interactions 0.653325 0.185
R-HSA-400206 Regulation of lipid metabolism by PPARalpha 0.653776 0.185
R-HSA-9610379 HCMV Late Events 0.653776 0.185
R-HSA-8953854 Metabolism of RNA 0.653998 0.184
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 0.656836 0.183
R-HSA-5689603 UCH proteinases 0.657733 0.182
R-HSA-877300 Interferon gamma signaling 0.659875 0.181
R-HSA-9024446 NR1H2 and NR1H3-mediated signaling 0.662086 0.179
R-HSA-9694635 Translation of Structural Proteins 0.662086 0.179
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF) 0.670626 0.174
R-HSA-5654738 Signaling by FGFR2 0.674815 0.171
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 0.683035 0.166
R-HSA-5619102 SLC transporter disorders 0.683415 0.165
R-HSA-9707564 Cytoprotection by HMOX1 0.687067 0.163
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 0.691048 0.160
R-HSA-390918 Peroxisomal lipid metabolism 0.691048 0.160
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 0.698859 0.156
R-HSA-1266738 Developmental Biology 0.700292 0.155
R-HSA-9764265 Regulation of CDH1 Expression and Function 0.702909 0.153
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 0.702909 0.153
R-HSA-1912408 Pre-NOTCH Transcription and Translation 0.721134 0.142
R-HSA-156842 Eukaryotic Translation Elongation 0.728188 0.138
R-HSA-174824 Plasma lipoprotein assembly, remodeling, and clearance 0.728188 0.138
R-HSA-9772573 Late SARS-CoV-2 Infection Events 0.728188 0.138
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 0.731649 0.136
R-HSA-2029481 FCGR activation 0.731649 0.136
R-HSA-68867 Assembly of the pre-replicative complex 0.731649 0.136
R-HSA-5653656 Vesicle-mediated transport 0.732694 0.135
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 0.734864 0.134
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta 0.738438 0.132
R-HSA-9824443 Parasitic Infection Pathways 0.738963 0.131
R-HSA-9658195 Leishmania infection 0.738963 0.131
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 0.745057 0.128
R-HSA-5607764 CLEC7A (Dectin-1) signaling 0.745057 0.128
R-HSA-112316 Neuronal System 0.748207 0.126
R-HSA-168898 Toll-like Receptor Cascades 0.748499 0.126
R-HSA-190236 Signaling by FGFR 0.751509 0.124
R-HSA-422356 Regulation of insulin secretion 0.751509 0.124
R-HSA-193704 p75 NTR receptor-mediated signalling 0.754673 0.122
R-HSA-70171 Glycolysis 0.757798 0.120
R-HSA-9009391 Extra-nuclear estrogen signaling 0.760883 0.119
R-HSA-9937383 Mitochondrial ribosome-associated quality control 0.766936 0.115
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 0.769906 0.114
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogen... 0.772837 0.112
R-HSA-5619507 Activation of HOX genes during differentiation 0.772837 0.112
R-HSA-9833110 RSV-host interactions 0.772837 0.112
R-HSA-9692914 SARS-CoV-1-host interactions 0.778589 0.109
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 0.781411 0.107
R-HSA-69239 Synthesis of DNA 0.781411 0.107
R-HSA-211000 Gene Silencing by RNA 0.781411 0.107
R-HSA-69002 DNA Replication Pre-Initiation 0.786947 0.104
R-HSA-8978868 Fatty acid metabolism 0.796231 0.099
R-HSA-9730414 MITF-M-regulated melanocyte development 0.797932 0.098
R-HSA-1280218 Adaptive Immune System 0.804148 0.095
R-HSA-9007101 Rab regulation of trafficking 0.812602 0.090
R-HSA-70326 Glucose metabolism 0.812602 0.090
R-HSA-9635486 Infection with Mycobacterium tuberculosis 0.821982 0.085
R-HSA-168256 Immune System 0.823931 0.084
R-HSA-9705683 SARS-CoV-2-host interactions 0.825372 0.083
R-HSA-9816359 Maternal to zygotic transition (MZT) 0.826495 0.083
R-HSA-198933 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell 0.827077 0.082
R-HSA-162909 Host Interactions of HIV factors 0.828708 0.082
R-HSA-69206 G1/S Transition 0.833051 0.079
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 0.835182 0.078
R-HSA-9843745 Adipogenesis 0.847408 0.072
R-HSA-5576891 Cardiac conduction 0.847408 0.072
R-HSA-9694516 SARS-CoV-2 Infection 0.850585 0.070
R-HSA-5619115 Disorders of transmembrane transporters 0.855318 0.068
R-HSA-163685 Integration of energy metabolism 0.858731 0.066
R-HSA-9679506 SARS-CoV Infections 0.860008 0.065
R-HSA-5368287 Mitochondrial translation 0.862316 0.064
R-HSA-162599 Late Phase of HIV Life Cycle 0.870888 0.060
R-HSA-8856828 Clathrin-mediated endocytosis 0.872538 0.059
R-HSA-2871837 FCERI mediated NF-kB activation 0.874166 0.058
R-HSA-453279 Mitotic G1 phase and G1/S transition 0.877361 0.057
R-HSA-9758941 Gastrulation 0.882004 0.055
R-HSA-2173782 Binding and Uptake of Ligands by Scavenger Receptors 0.883512 0.054
R-HSA-2142753 Arachidonate metabolism 0.886471 0.052
R-HSA-9609507 Protein localization 0.887922 0.052
R-HSA-69306 DNA Replication 0.887922 0.052
R-HSA-5663205 Infectious disease 0.888012 0.052
R-HSA-76002 Platelet activation, signaling and aggregation 0.889879 0.051
R-HSA-168273 Influenza Viral RNA Transcription and Replication 0.890770 0.050
R-HSA-162587 HIV Life Cycle 0.893546 0.049
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation 0.898552 0.046
R-HSA-72306 tRNA processing 0.911105 0.040
R-HSA-5621481 C-type lectin receptors (CLRs) 0.912243 0.040
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 0.914476 0.039
R-HSA-9664433 Leishmania parasite growth and survival 0.914476 0.039
R-HSA-9678108 SARS-CoV-1 Infection 0.916651 0.038
R-HSA-168255 Influenza Infection 0.920839 0.036
R-HSA-446203 Asparagine N-linked glycosylation 0.922717 0.035
R-HSA-9824446 Viral Infection Pathways 0.924287 0.034
R-HSA-72766 Translation 0.927560 0.033
R-HSA-983712 Ion channel transport 0.930415 0.031
R-HSA-392499 Metabolism of proteins 0.930587 0.031
R-HSA-72163 mRNA Splicing - Major Pathway 0.934761 0.029
R-HSA-1474244 Extracellular matrix organization 0.939239 0.027
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 0.941915 0.026
R-HSA-1483206 Glycerophospholipid biosynthesis 0.941915 0.026
R-HSA-72172 mRNA Splicing 0.943395 0.025
R-HSA-6798695 Neutrophil degranulation 0.944281 0.025
R-HSA-109582 Hemostasis 0.946117 0.024
R-HSA-397014 Muscle contraction 0.948951 0.023
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 0.948951 0.023
R-HSA-556833 Metabolism of lipids 0.952775 0.021
R-HSA-162906 HIV Infection 0.957946 0.019
R-HSA-983169 Class I MHC mediated antigen processing & presentation 0.965683 0.015
R-HSA-418594 G alpha (i) signalling events 0.973635 0.012
R-HSA-416476 G alpha (q) signalling events 0.973950 0.011
R-HSA-388396 GPCR downstream signalling 0.975576 0.011
R-HSA-168249 Innate Immune System 0.980432 0.009
R-HSA-112315 Transmission across Chemical Synapses 0.987890 0.005
R-HSA-8957322 Metabolism of steroids 0.988047 0.005
R-HSA-372790 Signaling by GPCR 0.988338 0.005
R-HSA-373076 Class A/1 (Rhodopsin-like receptors) 0.995263 0.002
R-HSA-425407 SLC-mediated transmembrane transport 0.995446 0.002
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 0.997869 0.001
R-HSA-500792 GPCR ligand binding 0.999635 0.000
R-HSA-382551 Transport of small molecules 0.999797 0.000
R-HSA-1430728 Metabolism 1.000000 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
CLK3CLK3 0.768 0.173 1 0.854
GRK1GRK1 0.762 0.248 -2 0.763
COTCOT 0.762 0.115 2 0.861
MOSMOS 0.761 0.216 1 0.891
KISKIS 0.758 0.137 1 0.698
CDC7CDC7 0.752 0.073 1 0.868
HIPK4HIPK4 0.750 0.148 1 0.794
PIM3PIM3 0.750 0.064 -3 0.791
GRK7GRK7 0.749 0.190 1 0.730
NDR2NDR2 0.748 0.084 -3 0.783
PRPKPRPK 0.745 0.032 -1 0.742
CDKL1CDKL1 0.744 0.054 -3 0.760
CDKL5CDKL5 0.743 0.082 -3 0.745
SRPK1SRPK1 0.743 0.063 -3 0.722
ATRATR 0.743 0.038 1 0.813
ERK5ERK5 0.742 0.072 1 0.837
SKMLCKSKMLCK 0.741 0.089 -2 0.807
GRK5GRK5 0.738 0.030 -3 0.839
NLKNLK 0.738 0.016 1 0.804
MTORMTOR 0.738 -0.023 1 0.741
IKKBIKKB 0.737 0.026 -2 0.669
CHAK2CHAK2 0.737 0.065 -1 0.710
ICKICK 0.737 0.083 -3 0.785
BMPR2BMPR2 0.736 -0.022 -2 0.803
HIPK2HIPK2 0.736 0.122 1 0.624
BMPR1BBMPR1B 0.734 0.073 1 0.794
SRPK2SRPK2 0.733 0.061 -3 0.639
DYRK2DYRK2 0.733 0.075 1 0.703
CDK1CDK1 0.733 0.096 1 0.634
CAMK2GCAMK2G 0.733 -0.028 2 0.825
PDHK4PDHK4 0.732 -0.123 1 0.807
IKKAIKKA 0.732 0.055 -2 0.669
FAM20CFAM20C 0.732 0.060 2 0.635
PIM1PIM1 0.732 0.011 -3 0.740
RAF1RAF1 0.731 -0.100 1 0.790
TBK1TBK1 0.731 -0.022 1 0.663
GRK6GRK6 0.731 0.028 1 0.793
LATS1LATS1 0.730 0.064 -3 0.790
CAMK1BCAMK1B 0.730 -0.066 -3 0.806
LATS2LATS2 0.729 -0.005 -5 0.427
NDR1NDR1 0.729 -0.032 -3 0.774
MLK1MLK1 0.729 0.009 2 0.784
DSTYKDSTYK 0.728 -0.077 2 0.867
CDK8CDK8 0.728 0.043 1 0.654
RIPK3RIPK3 0.728 -0.023 3 0.705
RSK2RSK2 0.728 -0.008 -3 0.719
CDK5CDK5 0.728 0.085 1 0.701
MARK4MARK4 0.728 -0.002 4 0.835
AURCAURC 0.728 0.049 -2 0.597
CAMLCKCAMLCK 0.727 -0.025 -2 0.781
P38BP38B 0.727 0.097 1 0.653
AMPKA1AMPKA1 0.727 0.003 -3 0.790
WNK1WNK1 0.727 -0.059 -2 0.822
NEK6NEK6 0.727 -0.009 -2 0.780
DAPK2DAPK2 0.726 -0.017 -3 0.809
PRP4PRP4 0.726 0.123 -3 0.877
CLK2CLK2 0.726 0.072 -3 0.713
NIKNIK 0.726 -0.070 -3 0.823
CK1ECK1E 0.726 0.060 -3 0.629
HIPK1HIPK1 0.726 0.073 1 0.717
SRPK3SRPK3 0.726 0.024 -3 0.698
GCN2GCN2 0.725 -0.130 2 0.800
CDK19CDK19 0.725 0.050 1 0.619
TGFBR2TGFBR2 0.725 -0.043 -2 0.723
IKKEIKKE 0.725 -0.053 1 0.658
P38AP38A 0.724 0.074 1 0.718
NUAK2NUAK2 0.724 -0.047 -3 0.788
ERK1ERK1 0.724 0.080 1 0.637
GRK4GRK4 0.724 -0.013 -2 0.778
CDK7CDK7 0.724 0.045 1 0.679
PDHK1PDHK1 0.724 -0.118 1 0.782
MLK3MLK3 0.724 0.061 2 0.711
CDK18CDK18 0.724 0.072 1 0.615
JNK3JNK3 0.724 0.061 1 0.654
MST4MST4 0.723 -0.029 2 0.837
P90RSKP90RSK 0.723 -0.020 -3 0.728
PKN3PKN3 0.723 -0.050 -3 0.775
CDK13CDK13 0.723 0.044 1 0.654
ULK2ULK2 0.722 -0.095 2 0.780
AMPKA2AMPKA2 0.722 0.004 -3 0.755
JNK2JNK2 0.722 0.061 1 0.613
CK1DCK1D 0.722 0.057 -3 0.583
RSK4RSK4 0.721 0.031 -3 0.695
MLK2MLK2 0.721 0.041 2 0.800
DLKDLK 0.721 -0.014 1 0.758
ACVR2BACVR2B 0.721 0.036 -2 0.721
MPSK1MPSK1 0.721 0.121 1 0.783
ALK4ALK4 0.721 -0.003 -2 0.759
TGFBR1TGFBR1 0.721 0.013 -2 0.729
PKRPKR 0.720 0.004 1 0.820
P38GP38G 0.720 0.065 1 0.548
BCKDKBCKDK 0.720 -0.068 -1 0.673
MAKMAK 0.720 0.145 -2 0.832
PKACGPKACG 0.719 -0.019 -2 0.666
PRKD1PRKD1 0.719 -0.073 -3 0.749
MASTLMASTL 0.719 -0.104 -2 0.748
P70S6KBP70S6KB 0.719 -0.036 -3 0.736
ATMATM 0.719 -0.021 1 0.761
CDK3CDK3 0.719 0.082 1 0.581
ALK2ALK2 0.719 0.026 -2 0.742
PKCDPKCD 0.718 -0.021 2 0.763
IRE1IRE1 0.717 -0.022 1 0.782
CAMK2DCAMK2D 0.717 -0.056 -3 0.764
NEK7NEK7 0.717 -0.120 -3 0.789
RIPK1RIPK1 0.717 -0.080 1 0.766
VRK2VRK2 0.717 0.020 1 0.832
PAK1PAK1 0.716 -0.011 -2 0.744
ACVR2AACVR2A 0.716 0.010 -2 0.706
PRKXPRKX 0.716 0.037 -3 0.641
CLK4CLK4 0.716 0.004 -3 0.726
PKN2PKN2 0.716 -0.068 -3 0.785
RSK3RSK3 0.716 -0.041 -3 0.714
P38DP38D 0.716 0.077 1 0.585
PKACBPKACB 0.716 0.017 -2 0.605
MAPKAPK2MAPKAPK2 0.716 -0.033 -3 0.663
GSK3AGSK3A 0.716 0.076 4 0.523
DYRK1ADYRK1A 0.716 0.049 1 0.734
HUNKHUNK 0.716 -0.120 2 0.798
CAMK2ACAMK2A 0.715 0.011 2 0.804
QSKQSK 0.715 0.002 4 0.814
CDK12CDK12 0.715 0.039 1 0.623
TTBK2TTBK2 0.715 -0.076 2 0.713
CAMK2BCAMK2B 0.715 -0.006 2 0.804
WNK3WNK3 0.714 -0.148 1 0.767
SMG1SMG1 0.714 -0.021 1 0.771
PASKPASK 0.714 0.056 -3 0.811
DYRK4DYRK4 0.714 0.058 1 0.632
ANKRD3ANKRD3 0.714 -0.091 1 0.794
BMPR1ABMPR1A 0.714 0.044 1 0.776
CDK17CDK17 0.713 0.052 1 0.556
NEK9NEK9 0.713 -0.090 2 0.832
CK1A2CK1A2 0.713 0.039 -3 0.583
PRKD2PRKD2 0.713 -0.069 -3 0.703
TSSK1TSSK1 0.713 -0.074 -3 0.807
MAPKAPK3MAPKAPK3 0.712 -0.091 -3 0.697
GRK2GRK2 0.712 -0.014 -2 0.671
PKCZPKCZ 0.712 0.014 2 0.762
MNK2MNK2 0.712 0.002 -2 0.712
MLK4MLK4 0.712 0.005 2 0.690
NIM1NIM1 0.711 -0.072 3 0.763
TSSK2TSSK2 0.711 -0.125 -5 0.464
PKCAPKCA 0.711 0.006 2 0.700
ULK1ULK1 0.711 -0.103 -3 0.764
HIPK3HIPK3 0.711 0.038 1 0.708
TLK2TLK2 0.711 -0.006 1 0.760
PKCBPKCB 0.710 -0.012 2 0.706
DYRK1BDYRK1B 0.710 0.029 1 0.665
ERK2ERK2 0.710 0.023 1 0.680
AURBAURB 0.709 -0.011 -2 0.595
PIM2PIM2 0.709 -0.023 -3 0.690
PAK3PAK3 0.709 -0.049 -2 0.727
PLK1PLK1 0.709 -0.054 -2 0.720
MNK1MNK1 0.709 -0.012 -2 0.717
CLK1CLK1 0.709 -0.012 -3 0.694
YSK4YSK4 0.708 -0.049 1 0.705
PKCGPKCG 0.708 -0.032 2 0.705
CK2A2CK2A2 0.708 0.057 1 0.729
IRE2IRE2 0.708 -0.050 2 0.735
MEKK3MEKK3 0.708 0.021 1 0.731
MSK1MSK1 0.707 -0.007 -3 0.694
GRK3GRK3 0.707 0.010 -2 0.641
CDK10CDK10 0.707 0.040 1 0.638
MSK2MSK2 0.707 -0.037 -3 0.693
MEK1MEK1 0.707 -0.136 2 0.817
CDK14CDK14 0.707 0.036 1 0.648
CHAK1CHAK1 0.707 -0.059 2 0.768
DYRK3DYRK3 0.706 0.029 1 0.716
CDK9CDK9 0.706 0.008 1 0.657
SIKSIK 0.706 -0.029 -3 0.694
DNAPKDNAPK 0.706 -0.016 1 0.674
CK1G1CK1G1 0.706 0.010 -3 0.632
QIKQIK 0.706 -0.089 -3 0.762
CDK16CDK16 0.706 0.046 1 0.579
MARK3MARK3 0.706 -0.011 4 0.785
MEKK2MEKK2 0.705 0.015 2 0.788
AKT2AKT2 0.705 -0.007 -3 0.646
PKG2PKG2 0.705 -0.013 -2 0.602
GSK3BGSK3B 0.705 0.028 4 0.513
MELKMELK 0.705 -0.067 -3 0.730
BRSK1BRSK1 0.705 -0.018 -3 0.727
PAK2PAK2 0.705 -0.045 -2 0.726
JNK1JNK1 0.704 0.045 1 0.604
NUAK1NUAK1 0.704 -0.068 -3 0.720
MYLK4MYLK4 0.704 -0.048 -2 0.702
GAKGAK 0.704 0.019 1 0.831
AURAAURA 0.703 -0.005 -2 0.576
MST3MST3 0.703 0.012 2 0.807
TAO3TAO3 0.703 0.032 1 0.733
MOKMOK 0.703 0.071 1 0.763
SGK3SGK3 0.702 -0.027 -3 0.710
BRSK2BRSK2 0.702 -0.021 -3 0.739
CAMK4CAMK4 0.702 -0.126 -3 0.751
BRAFBRAF 0.702 -0.077 -4 0.234
PERKPERK 0.702 -0.088 -2 0.753
CDK2CDK2 0.701 -0.015 1 0.695
MARK2MARK2 0.701 -0.035 4 0.747
PAK6PAK6 0.701 -0.013 -2 0.647
NEK5NEK5 0.701 -0.018 1 0.796
MEK5MEK5 0.700 -0.087 2 0.804
CK2A1CK2A1 0.700 0.062 1 0.700
MEKK1MEKK1 0.700 -0.072 1 0.744
DCAMKL1DCAMKL1 0.700 -0.041 -3 0.727
PLK3PLK3 0.700 -0.076 2 0.770
LKB1LKB1 0.700 0.013 -3 0.791
WNK4WNK4 0.700 -0.095 -2 0.828
PINK1PINK1 0.699 -0.081 1 0.826
PKCHPKCH 0.699 -0.057 2 0.695
PRKD3PRKD3 0.699 -0.092 -3 0.683
IRAK4IRAK4 0.699 -0.041 1 0.778
PHKG1PHKG1 0.698 -0.062 -3 0.761
NEK2NEK2 0.698 -0.113 2 0.800
GCKGCK 0.698 0.057 1 0.736
EEF2KEEF2K 0.696 0.021 3 0.843
DAPK3DAPK3 0.695 -0.010 -3 0.748
ZAKZAK 0.695 -0.072 1 0.690
HRIHRI 0.695 -0.152 -2 0.765
PKACAPKACA 0.694 -0.012 -2 0.550
CHK1CHK1 0.694 -0.153 -3 0.732
ERK7ERK7 0.694 0.014 2 0.512
CK1ACK1A 0.694 0.045 -3 0.509
PDK1PDK1 0.694 -0.014 1 0.739
MARK1MARK1 0.694 -0.061 4 0.793
SMMLCKSMMLCK 0.694 -0.075 -3 0.759
CAMK1GCAMK1G 0.693 -0.083 -3 0.700
SSTKSSTK 0.693 -0.068 4 0.782
DRAK1DRAK1 0.692 -0.081 1 0.689
PLK4PLK4 0.692 -0.070 2 0.626
TLK1TLK1 0.691 -0.146 -2 0.756
TNIKTNIK 0.691 0.013 3 0.869
AKT1AKT1 0.691 -0.020 -3 0.657
CDK6CDK6 0.691 0.029 1 0.630
NEK8NEK8 0.690 -0.071 2 0.797
TAO2TAO2 0.690 -0.054 2 0.833
BUB1BUB1 0.689 0.024 -5 0.438
NEK11NEK11 0.689 -0.071 1 0.717
P70S6KP70S6K 0.688 -0.063 -3 0.645
ROCK2ROCK2 0.688 0.004 -3 0.731
MINKMINK 0.688 -0.023 1 0.730
LRRK2LRRK2 0.688 -0.044 2 0.835
MAPKAPK5MAPKAPK5 0.688 -0.119 -3 0.651
MAP3K15MAP3K15 0.687 0.001 1 0.682
CDK4CDK4 0.687 0.024 1 0.612
SNRKSNRK 0.687 -0.140 2 0.665
DAPK1DAPK1 0.687 -0.019 -3 0.740
HGKHGK 0.687 -0.030 3 0.863
HPK1HPK1 0.687 -0.011 1 0.720
PKCEPKCE 0.687 -0.023 2 0.691
CAMKK1CAMKK1 0.687 -0.117 -2 0.674
KHS1KHS1 0.686 0.022 1 0.722
VRK1VRK1 0.686 -0.038 2 0.827
PLK2PLK2 0.686 -0.026 -3 0.762
KHS2KHS2 0.686 0.031 1 0.731
PKCTPKCT 0.686 -0.061 2 0.707
MST2MST2 0.685 -0.070 1 0.748
MEKK6MEKK6 0.684 -0.077 1 0.748
SGK1SGK1 0.684 -0.008 -3 0.572
PBKPBK 0.684 0.000 1 0.776
CAMKK2CAMKK2 0.683 -0.108 -2 0.666
TAK1TAK1 0.683 -0.078 1 0.768
TTBK1TTBK1 0.683 -0.105 2 0.629
PDHK3_TYRPDHK3_TYR 0.683 0.115 4 0.881
DCAMKL2DCAMKL2 0.683 -0.085 -3 0.739
CAMK1DCAMK1D 0.683 -0.075 -3 0.617
PAK5PAK5 0.682 -0.037 -2 0.598
AKT3AKT3 0.682 -0.012 -3 0.589
PKCIPKCI 0.682 -0.072 2 0.719
MRCKAMRCKA 0.682 -0.033 -3 0.691
PDHK4_TYRPDHK4_TYR 0.681 0.145 2 0.862
MRCKBMRCKB 0.681 -0.034 -3 0.681
NEK1NEK1 0.680 -0.055 1 0.759
HASPINHASPIN 0.679 0.005 -1 0.587
NEK4NEK4 0.679 -0.113 1 0.744
PAK4PAK4 0.679 -0.032 -2 0.602
DMPK1DMPK1 0.679 -0.019 -3 0.711
PHKG2PHKG2 0.678 -0.104 -3 0.734
SLKSLK 0.678 -0.009 -2 0.626
ALPHAK3ALPHAK3 0.677 0.030 -1 0.660
TTKTTK 0.677 0.004 -2 0.749
IRAK1IRAK1 0.676 -0.199 -1 0.614
MAP2K6_TYRMAP2K6_TYR 0.676 0.098 -1 0.765
BMPR2_TYRBMPR2_TYR 0.676 0.076 -1 0.805
MAP2K4_TYRMAP2K4_TYR 0.675 0.068 -1 0.753
PDHK1_TYRPDHK1_TYR 0.675 0.082 -1 0.783
OSR1OSR1 0.675 -0.005 2 0.777
LOKLOK 0.675 -0.067 -2 0.667
TESK1_TYRTESK1_TYR 0.674 0.023 3 0.873
STK33STK33 0.672 -0.081 2 0.607
CK1G3CK1G3 0.671 0.047 -3 0.471
YSK1YSK1 0.671 -0.079 2 0.796
PKMYT1_TYRPKMYT1_TYR 0.671 -0.006 3 0.827
CHK2CHK2 0.670 -0.074 -3 0.588
CRIKCRIK 0.670 -0.026 -3 0.651
MAP2K7_TYRMAP2K7_TYR 0.670 0.018 2 0.848
MST1MST1 0.670 -0.137 1 0.728
CAMK1ACAMK1A 0.670 -0.078 -3 0.604
SBKSBK 0.669 -0.064 -3 0.524
ROCK1ROCK1 0.669 -0.032 -3 0.695
BLKBLK 0.668 0.131 -1 0.785
LCKLCK 0.668 0.119 -1 0.785
EPHA6EPHA6 0.667 0.054 -1 0.783
EPHB4EPHB4 0.667 0.076 -1 0.732
LIMK2_TYRLIMK2_TYR 0.667 0.006 -3 0.820
YANK3YANK3 0.667 -0.016 2 0.402
TXKTXK 0.666 0.089 1 0.803
MYO3BMYO3B 0.666 -0.030 2 0.806
MEK2MEK2 0.666 -0.167 2 0.800
PKN1PKN1 0.665 -0.094 -3 0.660
ABL2ABL2 0.664 0.059 -1 0.698
BIKEBIKE 0.663 -0.022 1 0.725
FYNFYN 0.663 0.120 -1 0.795
PINK1_TYRPINK1_TYR 0.663 -0.094 1 0.803
FGRFGR 0.663 0.032 1 0.823
ASK1ASK1 0.662 -0.057 1 0.669
HCKHCK 0.662 0.067 -1 0.767
YES1YES1 0.662 0.037 -1 0.756
CK1G2CK1G2 0.661 0.061 -3 0.557
RIPK2RIPK2 0.659 -0.194 1 0.651
MYO3AMYO3A 0.659 -0.063 1 0.739
FERFER 0.658 0.001 1 0.855
ABL1ABL1 0.657 0.021 -1 0.687
PKG1PKG1 0.657 -0.065 -2 0.517
EPHA4EPHA4 0.657 0.026 2 0.761
RETRET 0.656 -0.046 1 0.744
LIMK1_TYRLIMK1_TYR 0.656 -0.100 2 0.845
CSF1RCSF1R 0.655 0.006 3 0.770
TNK2TNK2 0.655 0.016 3 0.721
SRMSSRMS 0.655 0.029 1 0.822
TYRO3TYRO3 0.655 -0.024 3 0.785
TYK2TYK2 0.655 -0.071 1 0.745
MST1RMST1R 0.654 -0.052 3 0.788
NEK3NEK3 0.654 -0.173 1 0.701
ROS1ROS1 0.654 -0.029 3 0.751
TAO1TAO1 0.653 -0.071 1 0.656
EPHB1EPHB1 0.653 0.020 1 0.808
ITKITK 0.653 0.012 -1 0.712
EPHB2EPHB2 0.652 0.017 -1 0.719
JAK2JAK2 0.652 -0.054 1 0.733
BMXBMX 0.652 0.025 -1 0.662
EPHB3EPHB3 0.652 0.002 -1 0.722
SYKSYK 0.652 0.099 -1 0.752
METMET 0.651 0.023 3 0.761
INSRRINSRR 0.650 -0.030 3 0.721
AAK1AAK1 0.649 -0.004 1 0.637
JAK3JAK3 0.649 -0.038 1 0.721
PTK2PTK2 0.648 0.071 -1 0.786
KITKIT 0.648 -0.026 3 0.774
SRCSRC 0.648 0.045 -1 0.760
KDRKDR 0.648 -0.002 3 0.731
DDR1DDR1 0.647 -0.111 4 0.776
LYNLYN 0.646 0.013 3 0.687
EPHA7EPHA7 0.645 0.022 2 0.764
WEE1_TYRWEE1_TYR 0.644 -0.039 -1 0.631
STLK3STLK3 0.644 -0.103 1 0.664
MERTKMERTK 0.644 -0.015 3 0.748
FRKFRK 0.644 -0.004 -1 0.762
FLT1FLT1 0.643 -0.004 -1 0.741
TECTEC 0.643 -0.029 -1 0.637
TNNI3K_TYRTNNI3K_TYR 0.643 -0.050 1 0.765
TNK1TNK1 0.643 -0.023 3 0.761
BTKBTK 0.642 -0.064 -1 0.668
FGFR2FGFR2 0.642 -0.070 3 0.765
FLT3FLT3 0.642 -0.094 3 0.783
JAK1JAK1 0.641 -0.027 1 0.664
EPHA3EPHA3 0.641 -0.036 2 0.739
EPHA5EPHA5 0.639 0.006 2 0.745
PTK6PTK6 0.639 -0.072 -1 0.614
PDGFRBPDGFRB 0.639 -0.102 3 0.787
NEK10_TYRNEK10_TYR 0.639 -0.072 1 0.633
YANK2YANK2 0.637 -0.024 2 0.415
LTKLTK 0.637 -0.054 3 0.708
EPHA8EPHA8 0.637 -0.004 -1 0.747
ALKALK 0.637 -0.049 3 0.690
EPHA1EPHA1 0.637 -0.045 3 0.747
TEKTEK 0.636 -0.098 3 0.715
AXLAXL 0.636 -0.091 3 0.751
ZAP70ZAP70 0.636 0.090 -1 0.677
MATKMATK 0.635 -0.063 -1 0.625
PTK2BPTK2B 0.635 -0.025 -1 0.664
ERBB2ERBB2 0.635 -0.070 1 0.685
FGFR1FGFR1 0.634 -0.100 3 0.740
FGFR3FGFR3 0.634 -0.051 3 0.737
NTRK1NTRK1 0.633 -0.091 -1 0.697
DDR2DDR2 0.633 -0.004 3 0.699
PDGFRAPDGFRA 0.632 -0.133 3 0.782
EGFREGFR 0.632 -0.029 1 0.585
INSRINSR 0.631 -0.080 3 0.696
NTRK3NTRK3 0.630 -0.068 -1 0.662
EPHA2EPHA2 0.628 0.008 -1 0.712
CSKCSK 0.628 -0.068 2 0.769
NTRK2NTRK2 0.627 -0.117 3 0.722
ERBB4ERBB4 0.627 0.007 1 0.622
FGFR4FGFR4 0.625 -0.051 -1 0.656
FLT4FLT4 0.623 -0.125 3 0.713
IGF1RIGF1R 0.619 -0.066 3 0.636
MUSKMUSK 0.613 -0.088 1 0.597
FESFES 0.610 -0.068 -1 0.625