Motif 984 (n=65)
Position-wise Probabilities
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uniprot | genes | site | source | protein | function |
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O00141 | SGK1 | T256 | ochoa|psp | Serine/threonine-protein kinase Sgk1 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 1) | Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}. |
O00444 | PLK4 | T170 | psp | Serine/threonine-protein kinase PLK4 (EC 2.7.11.21) (Polo-like kinase 4) (PLK-4) (Serine/threonine-protein kinase 18) (Serine/threonine-protein kinase Sak) | Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:30804208}. |
O00506 | STK25 | T174 | ochoa|psp | Serine/threonine-protein kinase 25 (EC 2.7.11.1) (Ste20-like kinase) (Sterile 20/oxidant stress-response kinase 1) (SOK-1) (Ste20/oxidant stress response kinase 1) | Oxidant stress-activated serine/threonine kinase that may play a role in the response to environmental stress. Targets to the Golgi apparatus where it appears to regulate protein transport events, cell adhesion, and polarity complexes important for cell migration. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:15037601, ECO:0000269|PubMed:18782753}. |
O75582 | RPS6KA5 | T581 | psp | Ribosomal protein S6 kinase alpha-5 (S6K-alpha-5) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 5) (Nuclear mitogen- and stress-activated protein kinase 1) (RSK-like protein kinase) (RSKL) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:18511904, PubMed:9687510, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810). {ECO:0000250|UniProtKB:Q8C050, ECO:0000269|PubMed:11909979, ECO:0000269|PubMed:12569367, ECO:0000269|PubMed:12628924, ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:15010469, ECO:0000269|PubMed:18511904, ECO:0000269|PubMed:25851810, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9873047}. |
O75914 | PAK3 | T436 | ochoa|psp | Serine/threonine-protein kinase PAK 3 (EC 2.7.11.1) (Beta-PAK) (Oligophrenin-3) (p21-activated kinase 3) (PAK-3) | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as a downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). {ECO:0000250|UniProtKB:Q61036, ECO:0000269|PubMed:21177870}. |
O94804 | STK10 | S191 | ochoa | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
O95382 | MAP3K6 | T806 | psp | Mitogen-activated protein kinase kinase kinase 6 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 2) | Component of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways. {ECO:0000269|PubMed:17210579, ECO:0000269|PubMed:9875215}. |
O95819 | MAP4K4 | T187 | psp | Mitogen-activated protein kinase kinase kinase kinase 4 (EC 2.7.11.1) (HPK/GCK-like kinase HGK) (MAPK/ERK kinase kinase kinase 4) (MEK kinase kinase 4) (MEKKK 4) (Nck-interacting kinase) | Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway (PubMed:9890973). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). Phosphorylates SMAD1 on Thr-322 (PubMed:21690388). {ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:9890973}. |
O96013 | PAK4 | S474 | ochoa|psp | Serine/threonine-protein kinase PAK 4 (EC 2.7.11.1) (p21-activated kinase 4) (PAK-4) | Serine/threonine-protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell adhesion turnover, cell migration, growth, proliferation or cell survival (PubMed:26598620). Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Promotes kinase-independent stabilization of RHOU, thereby contributing to focal adhesion disassembly during cell migration (PubMed:26598620). {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26598620, ECO:0000269|PubMed:26607847}. |
P05129 | PRKCG | T514 | ochoa|psp | Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319, ECO:0000269|PubMed:16377624, ECO:0000269|PubMed:36040231}. |
P05771 | PRKCB | T500 | ochoa|psp | Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}. |
P17252 | PRKCA | T497 | ochoa|psp | Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13) | Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}. |
P23443 | RPS6KB1 | T252 | psp | Ribosomal protein S6 kinase beta-1 (S6K-beta-1) (S6K1) (EC 2.7.11.1) (70 kDa ribosomal protein S6 kinase 1) (P70S6K1) (p70-S6K 1) (Ribosomal protein S6 kinase I) (Serine/threonine-protein kinase 14A) (p70 ribosomal S6 kinase alpha) (p70 S6 kinase alpha) (p70 S6K-alpha) (p70 S6KA) | Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating MAPKAP1/SIN1, MTOR and RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (PubMed:15899889, PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (By similarity). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (PubMed:17936702). The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function (PubMed:17936702). Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (PubMed:17052453). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239). {ECO:0000250|UniProtKB:P67999, ECO:0000250|UniProtKB:Q8BSK8, ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500, ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:15899889, ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:28178239}. |
P24723 | PRKCH | T513 | psp | Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. {ECO:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}. |
P31749 | AKT1 | T308 | ochoa|psp | RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha) | AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:15526160, PubMed:15861136, PubMed:21432781, PubMed:21620960, PubMed:31204173). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960, PubMed:29343641, PubMed:31204173). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF1 (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (PubMed:30504268). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (PubMed:15861136). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (PubMed:31204173). {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10358075, ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941, ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:18507042, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20471940, ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:30504268, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058, ECO:0000269|PubMed:9829964, ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}. |
P31751 | AKT2 | T309 | ochoa|psp | RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-2) (Protein kinase B beta) (PKB beta) (RAC protein kinase beta) (RAC-PK-beta) | Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (PubMed:21432781, PubMed:21620960). In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth (PubMed:31204173). Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion (By similarity). Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation (PubMed:23444369). {ECO:0000250|UniProtKB:Q60823, ECO:0000269|PubMed:23444369, ECO:0000269|PubMed:31204173, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.; FUNCTION: Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity). {ECO:0000250|UniProtKB:Q60823}. |
P41743 | PRKCI | T412 | ochoa|psp | Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) | Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}. |
P51812 | RPS6KA3 | S227 | ochoa|psp | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
P51812 | RPS6KA3 | T577 | ochoa|psp | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
P53350 | PLK1 | T210 | ochoa|psp | Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13) | Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250|UniProtKB:P70032, ECO:0000250|UniProtKB:Q5F2C3, ECO:0000269|PubMed:11202906, ECO:0000269|PubMed:12207013, ECO:0000269|PubMed:12447691, ECO:0000269|PubMed:12524548, ECO:0000269|PubMed:12738781, ECO:0000269|PubMed:12852856, ECO:0000269|PubMed:12939256, ECO:0000269|PubMed:14532005, ECO:0000269|PubMed:14734534, ECO:0000269|PubMed:15070733, ECO:0000269|PubMed:15148369, ECO:0000269|PubMed:15469984, ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16198290, ECO:0000269|PubMed:16247472, ECO:0000269|PubMed:16980960, ECO:0000269|PubMed:17081991, ECO:0000269|PubMed:17218258, ECO:0000269|PubMed:17351640, ECO:0000269|PubMed:17376779, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:18331714, ECO:0000269|PubMed:18418051, ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:18521620, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:19160488, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19468300, ECO:0000269|PubMed:19468302, ECO:0000269|PubMed:19473992, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19597481, ECO:0000269|PubMed:20679239, ECO:0000269|PubMed:21857149, ECO:0000269|PubMed:21880710, ECO:0000269|PubMed:22325354, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23509069, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26811421, ECO:0000269|PubMed:27979967, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080, ECO:0000269|PubMed:8991084}. |
P53667 | LIMK1 | T508 | psp | LIM domain kinase 1 (LIMK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11832213, PubMed:12807904, PubMed:15660133, PubMed:16230460, PubMed:18028908, PubMed:22328514, PubMed:23633677). Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop (PubMed:10436159). LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation (PubMed:11832213, PubMed:15660133, PubMed:16230460, PubMed:23633677). Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly (PubMed:18028908). Stimulates axonal outgrowth and may be involved in brain development (PubMed:18028908). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:23633677}.; FUNCTION: [Isoform 3]: Has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). {ECO:0000269|PubMed:10196227}. |
Q02156 | PRKCE | T566 | psp | Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067, ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566, ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639, ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:36040231}. |
Q04759 | PRKCQ | T538 | ochoa|psp | Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta) | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation (PubMed:21964608). Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (PubMed:23509302). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11342610, ECO:0000269|PubMed:14988727, ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:16252004, ECO:0000269|PubMed:16356855, ECO:0000269|PubMed:16709830, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:21964608, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:8657160}. |
Q05513 | PRKCZ | T410 | ochoa|psp | Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta) | Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro (PubMed:17313651). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9447975}.; FUNCTION: [Isoform 2]: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance. {ECO:0000250|UniProtKB:Q02956}. |
Q05655 | PRKCD | T507 | ochoa|psp | Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}. |
Q12851 | MAP4K2 | S170 | ochoa | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
Q13043 | STK4 | T183 | psp | Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. |
Q13153 | PAK1 | T423 | ochoa|psp | Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (Alpha-PAK) (p21-activated kinase 1) (PAK-1) (p65-PAK) | Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (PubMed:12624090). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}. |
Q13177 | PAK2 | T402 | ochoa|psp | Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}. |
Q13188 | STK3 | T180 | psp | Serine/threonine-protein kinase 3 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 2) (MST-2) (STE20-like kinase MST2) (Serine/threonine-protein kinase Krs-1) [Cleaved into: Serine/threonine-protein kinase 3 36kDa subunit (MST2/N); Serine/threonine-protein kinase 3 20kDa subunit (MST2/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation (PubMed:11278283, PubMed:8566796, PubMed:8816758). Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714, PubMed:29063833, PubMed:30622739). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714). STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250 (PubMed:21076410, PubMed:21723128). In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (PubMed:21104395). Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259' (PubMed:20212043). Phosphorylates MOBKL1A and RASSF2 (PubMed:19525978). Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 (PubMed:18328708, PubMed:18362890). {ECO:0000250|UniProtKB:Q9JI10, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:20212043, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:21723128, ECO:0000269|PubMed:23972470, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:8566796, ECO:0000269|PubMed:8816758}. |
Q15349 | RPS6KA2 | S218 | psp | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
Q15349 | RPS6KA2 | T570 | psp | Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}. |
Q15418 | RPS6KA1 | S221 | ochoa|psp | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
Q15418 | RPS6KA1 | T573 | ochoa|psp | Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}. |
Q16512 | PKN1 | T774 | ochoa|psp | Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) | PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}. |
Q16513 | PKN2 | T816 | ochoa|psp | 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}. |
Q6P5Z2 | PKN3 | T718 | ochoa|psp | Serine/threonine-protein kinase N3 (EC 2.7.11.13) (Protein kinase PKN-beta) (Protein-kinase C-related kinase 3) | Contributes to invasiveness in malignant prostate cancer. {ECO:0000269|PubMed:15282551}. |
Q6ZN16 | MAP3K15 | T808 | psp | Mitogen-activated protein kinase kinase kinase 15 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 3) (MAPK/ERK kinase kinase 15) (MEK kinase 15) (MEKK 15) | Serine/threonine kinase which acts as a component of the MAP kinase signal transduction pathway (PubMed:20362554, PubMed:26732173). Once activated, acts as an upstream activator of the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases (PubMed:20362554, PubMed:26732173). May function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis (PubMed:20362554). Involved in phosphorylation of WNK4 in response to osmotic stress or hypotonic low-chloride stimulation via the p38 MAPK signal transduction cascade (PubMed:26732173). {ECO:0000269|PubMed:20362554, ECO:0000269|PubMed:26732173}. |
Q7L7X3 | TAOK1 | S181 | ochoa|psp | Serine/threonine-protein kinase TAO1 (EC 2.7.11.1) (Kinase from chicken homolog B) (hKFC-B) (MARK Kinase) (MARKK) (Prostate-derived sterile 20-like kinase 2) (PSK-2) (PSK2) (Prostate-derived STE20-like kinase 2) (Thousand and one amino acid protein kinase 1) (TAOK1) (hTAOK1) | Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system (PubMed:33565190). Also plays a role in the regulation of neuronal migration to the cortical plate (By similarity). {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936, ECO:0000269|PubMed:33565190}. |
Q8IVH8 | MAP4K3 | S170 | ochoa|psp | Mitogen-activated protein kinase kinase kinase kinase 3 (EC 2.7.11.1) (Germinal center kinase-related protein kinase) (GLK) (MAPK/ERK kinase kinase kinase 3) (MEK kinase kinase 3) (MEKKK 3) | Serine/threonine kinase that plays a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway (PubMed:9275185). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:9275185}. |
Q8N4C8 | MINK1 | T187 | ochoa|psp | Misshapen-like kinase 1 (EC 2.7.11.1) (GCK family kinase MiNK) (MAPK/ERK kinase kinase kinase 6) (MEK kinase kinase 6) (MEKKK 6) (Misshapen/NIK-related kinase) (Mitogen-activated protein kinase kinase kinase kinase 6) | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking (PubMed:10708748, PubMed:16337592). Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons (By similarity). Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1 (PubMed:18930710, PubMed:21690388). Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1 (By similarity). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000250|UniProtKB:F1LP90, ECO:0000250|UniProtKB:Q9JM52, ECO:0000269|PubMed:10708748, ECO:0000269|PubMed:16337592, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. |
Q8NEV4 | MYO3A | T184 | psp | Myosin-IIIa (EC 2.7.11.1) | Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:29880844, PubMed:34788109). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315, ECO:0000269|PubMed:29880844, ECO:0000269|PubMed:34788109}. |
Q8TD19 | NEK9 | T210 | ochoa|psp | 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}. |
Q8TDX7 | NEK7 | S195 | ochoa|psp | Serine/threonine-protein kinase Nek7 (EC 2.7.11.34) (Never in mitosis A-related kinase 7) (NimA-related protein kinase 7) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:19941817, PubMed:31409757). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:19941817, PubMed:26522158, PubMed:31409757). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502, PubMed:39173637). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502, PubMed:39173637). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953). {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132, ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158, ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:31409757, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637}. |
Q92918 | MAP4K1 | S171 | ochoa|psp | Mitogen-activated protein kinase kinase kinase kinase 1 (EC 2.7.11.1) (Hematopoietic progenitor kinase) (MAPK/ERK kinase kinase kinase 1) (MEK kinase kinase 1) (MEKKK 1) | Serine/threonine-protein kinase, which plays a role in the response to environmental stress (PubMed:24362026). Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:24362026, PubMed:8824585). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity). {ECO:0000250|UniProtKB:P70218, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:8824585}. |
Q96BR1 | SGK3 | T320 | psp | Serine/threonine-protein kinase Sgk3 (EC 2.7.11.1) (Cytokine-independent survival kinase) (Serum/glucocorticoid-regulated kinase 3) (Serum/glucocorticoid-regulated kinase-like) | Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes. {ECO:0000269|PubMed:12054501, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12632189, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16888620, ECO:0000269|PubMed:17167223, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:19293151, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:21865597}. |
Q99683 | MAP3K5 | T838 | psp | Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). {ECO:0000269|PubMed:10411906, ECO:0000269|PubMed:10688666, ECO:0000269|PubMed:10849426, ECO:0000269|PubMed:11029458, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11689443, ECO:0000269|PubMed:11920685, ECO:0000269|PubMed:14688258, ECO:0000269|PubMed:14749717, ECO:0000269|PubMed:15023544, ECO:0000269|PubMed:16129676, ECO:0000269|PubMed:17220297, ECO:0000269|PubMed:23102700, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:8940179, ECO:0000269|PubMed:8974401, ECO:0000269|PubMed:9564042, ECO:0000269|PubMed:9774977}. |
Q9H2G2 | SLK | S189 | ochoa|psp | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
Q9H2K8 | TAOK3 | S177 | ochoa | Serine/threonine-protein kinase TAO3 (EC 2.7.11.1) (Cutaneous T-cell lymphoma-associated antigen HD-CL-09) (CTCL-associated antigen HD-CL-09) (Dendritic cell-derived protein kinase) (JNK/SAPK-inhibitory kinase) (Jun kinase-inhibitory kinase) (Kinase from chicken homolog A) (hKFC-A) (Thousand and one amino acid protein 3) | Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of the MAPK8/JNK cascade and diminishes its activation in response to epidermal growth factor (EGF). Positively regulates canonical T cell receptor (TCR) signaling by preventing early PTPN6/SHP1-mediated inactivation of LCK, ensuring sustained TCR signaling that is required for optimal activation and differentiation of T cells (PubMed:30373850). Phosphorylates PTPN6/SHP1 on 'Thr-394', leading to its polyubiquitination and subsequent proteasomal degradation (PubMed:38166031). Required for cell surface expression of metalloprotease ADAM10 on type 1 transitional B cells which is necessary for their NOTCH-mediated development into marginal zone B cells (By similarity). Also required for the NOTCH-mediated terminal differentiation of splenic conventional type 2 dendritic cells (By similarity). Positively regulates osteoblast differentiation by acting as an upstream activator of the JNK pathway (PubMed:32807497). Promotes JNK signaling in hepatocytes and positively regulates hepatocyte lipid storage by inhibiting beta-oxidation and triacylglycerol secretion while enhancing lipid synthesis (PubMed:34634521). Restricts age-associated inflammation by negatively regulating differentiation of macrophages and their production of pro-inflammatory cytokines (By similarity). Plays a role in negatively regulating the abundance of regulatory T cells in white adipose tissue (By similarity). {ECO:0000250|UniProtKB:Q8BYC6, ECO:0000269|PubMed:10559204, ECO:0000269|PubMed:10924369, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:30373850, ECO:0000269|PubMed:32807497, ECO:0000269|PubMed:34634521, ECO:0000269|PubMed:38166031}. |
Q9H4B4 | PLK3 | T219 | psp | Serine/threonine-protein kinase PLK3 (EC 2.7.11.21) (Cytokine-inducible serine/threonine-protein kinase) (FGF-inducible kinase) (Polo-like kinase 3) (PLK-3) (Proliferation-related kinase) | Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1. {ECO:0000269|PubMed:10557092, ECO:0000269|PubMed:11156373, ECO:0000269|PubMed:11447225, ECO:0000269|PubMed:11551930, ECO:0000269|PubMed:11971976, ECO:0000269|PubMed:12242661, ECO:0000269|PubMed:14968113, ECO:0000269|PubMed:14980500, ECO:0000269|PubMed:15021912, ECO:0000269|PubMed:16478733, ECO:0000269|PubMed:16481012, ECO:0000269|PubMed:17264206, ECO:0000269|PubMed:17804415, ECO:0000269|PubMed:18062778, ECO:0000269|PubMed:18650425, ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:19490146, ECO:0000269|PubMed:20889502, ECO:0000269|PubMed:20940307, ECO:0000269|PubMed:20951827, ECO:0000269|PubMed:21098032, ECO:0000269|PubMed:21264284, ECO:0000269|PubMed:21376736, ECO:0000269|PubMed:21840391, ECO:0000269|PubMed:9353331}. |
Q9HBY8 | SGK2 | T193 | psp | Serine/threonine-protein kinase Sgk2 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 2) | Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, survival and proliferation. Up-regulates Na(+) channels: SCNN1A/ENAC, K(+) channels: KCNA3/Kv1.3, KCNE1 and KCNQ1, amino acid transporter: SLC6A19, glutamate transporter: SLC1A6/EAAT4, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. {ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12632189, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:21865597}. |
Q9HC98 | NEK6 | S206 | ochoa|psp | Serine/threonine-protein kinase Nek6 (EC 2.7.11.34) (Never in mitosis A-related kinase 6) (NimA-related protein kinase 6) (Protein kinase SID6-1512) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:11516946, PubMed:14563848). Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis (PubMed:19414596). Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3 (PubMed:12054534, PubMed:20873783). Phosphorylates KIF11 to promote mitotic spindle formation (PubMed:19001501). Involved in G2/M phase cell cycle arrest induced by DNA damage (PubMed:18728393). Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (PubMed:21099361). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). {ECO:0000269|PubMed:11516946, ECO:0000269|PubMed:12054534, ECO:0000269|PubMed:14563848, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21099361, ECO:0000269|PubMed:31409757}. |
Q9NQU5 | PAK6 | S560 | ochoa|psp | Serine/threonine-protein kinase PAK 6 (EC 2.7.11.1) (PAK-5) (p21-activated kinase 6) (PAK-6) | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Also inhibits ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}. |
Q9NRP7 | STK36 | S159 | ochoa | Serine/threonine-protein kinase 36 (EC 2.7.11.1) (Fused homolog) | Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur (PubMed:10806483). Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia. {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:28543983}. |
Q9P286 | PAK5 | S602 | ochoa|psp | Serine/threonine-protein kinase PAK 5 (EC 2.7.11.1) (p21-activated kinase 5) (PAK-5) (p21-activated kinase 7) (PAK-7) | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions. {ECO:0000269|PubMed:12897128, ECO:0000269|PubMed:16014608, ECO:0000269|PubMed:16581795, ECO:0000269|PubMed:18465753, ECO:0000269|PubMed:20564219}. |
Q9P289 | STK26 | T178 | ochoa|psp | Serine/threonine-protein kinase 26 (EC 2.7.11.1) (MST3 and SOK1-related kinase) (Mammalian STE20-like protein kinase 4) (MST-4) (STE20-like kinase MST4) (Serine/threonine-protein kinase MASK) | Serine/threonine-protein kinase that acts as a mediator of cell growth (PubMed:11641781, PubMed:17360971). Modulates apoptosis (PubMed:11641781, PubMed:17360971). In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Phosphorylates ATG4B at 'Ser-383', thereby increasing autophagic flux (PubMed:29232556). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:11641781, ECO:0000269|PubMed:17360971, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:27807006, ECO:0000269|PubMed:29232556}. |
Q9UBS0 | RPS6KB2 | T228 | psp | Ribosomal protein S6 kinase beta-2 (S6K-beta-2) (S6K2) (EC 2.7.11.1) (70 kDa ribosomal protein S6 kinase 2) (P70S6K2) (p70-S6K 2) (S6 kinase-related kinase) (SRK) (Serine/threonine-protein kinase 14B) (p70 ribosomal S6 kinase beta) (S6K-beta) (p70 S6 kinase beta) (p70 S6K-beta) (p70 S6KB) (p70-beta) | Phosphorylates specifically ribosomal protein S6 (PubMed:29750193). Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7 (PubMed:29750193). {ECO:0000269|PubMed:29750193}. |
Q9UK32 | RPS6KA6 | S232 | ochoa|psp | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
Q9UK32 | RPS6KA6 | T581 | psp | Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) | Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}. |
Q9UKE5 | TNIK | T187 | ochoa | TRAF2 and NCK-interacting protein kinase (EC 2.7.11.1) | Serine/threonine kinase that acts as an essential activator of the Wnt signaling pathway. Recruited to promoters of Wnt target genes and required to activate their expression. May act by phosphorylating TCF4/TCF7L2. Appears to act upstream of the JUN N-terminal pathway. May play a role in the response to environmental stress. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. More generally, it may play a role in cytoskeletal rearrangements and regulate cell spreading. Phosphorylates SMAD1 on Thr-322. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:10521462, ECO:0000269|PubMed:15342639, ECO:0000269|PubMed:19061864, ECO:0000269|PubMed:19816403, ECO:0000269|PubMed:20159449, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}. |
Q9UL54 | TAOK2 | S181 | ochoa|psp | Serine/threonine-protein kinase TAO2 (EC 2.7.11.1) (Kinase from chicken homolog C) (hKFC-C) (Prostate-derived sterile 20-like kinase 1) (PSK-1) (PSK1) (Prostate-derived STE20-like kinase 1) (Thousand and one amino acid protein kinase 2) | Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17396146}. |
Q9Y243 | AKT3 | T305 | ochoa|psp | RAC-gamma serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-3) (Protein kinase B gamma) (PKB gamma) (RAC-PK-gamma) (STK-2) | AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. {ECO:0000269|PubMed:18524868, ECO:0000269|PubMed:21191416}. |
Q9Y6E0 | STK24 | T190 | ochoa|psp | Serine/threonine-protein kinase 24 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 3) (MST-3) (STE20-like kinase MST3) [Cleaved into: Serine/threonine-protein kinase 24 36 kDa subunit (Mammalian STE20-like protein kinase 3 N-terminal) (MST3/N); Serine/threonine-protein kinase 24 12 kDa subunit (Mammalian STE20-like protein kinase 3 C-terminal) (MST3/C)] | Serine/threonine-protein kinase that acts on both serine and threonine residues and promotes apoptosis in response to stress stimuli and caspase activation. Mediates oxidative-stress-induced cell death by modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11, MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a staurosporine-induced caspase-independent apoptotic pathway by regulating the nuclear translocation of AIFM1 and ENDOG and the DNase activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and stimulates its kinase activity. In association with STK26 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Also regulates cellular migration with alteration of PTPN12 activity and PXN phosphorylation: phosphorylates PTPN12 and inhibits its activity and may regulate PXN phosphorylation through PTPN12. May act as a key regulator of axon regeneration in the optic nerve and radial nerve. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:16314523, ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:19782762, ECO:0000269|PubMed:19855390, ECO:0000269|PubMed:27807006}. |
P51955 | NEK2 | T175 | GPS6|SIGNOR|EPSD|PSP | Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) | Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856, ECO:0000269|PubMed:30404835}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}. |
Q9NYY3 | PLK2 | T239 | Sugiyama | Serine/threonine-protein kinase PLK2 (EC 2.7.11.21) (Polo-like kinase 2) (PLK-2) (hPlk2) (Serine/threonine-protein kinase SNK) (hSNK) (Serum-inducible kinase) | Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CPAP, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CPAP and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress. {ECO:0000269|PubMed:15242618, ECO:0000269|PubMed:19001868, ECO:0000269|PubMed:20352051, ECO:0000269|PubMed:20531387}. |
Download
reactome_id | name | p | -log10_p |
---|---|---|---|
R-HSA-428540 | Activation of RAC1 | 1.146282e-10 | 9.941 |
R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 4.902748e-10 | 9.310 |
R-HSA-194138 | Signaling by VEGF | 1.067832e-09 | 8.971 |
R-HSA-162582 | Signal Transduction | 7.316653e-09 | 8.136 |
R-HSA-418597 | G alpha (z) signalling events | 2.007285e-08 | 7.697 |
R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 2.532331e-08 | 7.596 |
R-HSA-2559583 | Cellular Senescence | 2.902541e-08 | 7.537 |
R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 1.088153e-07 | 6.963 |
R-HSA-199920 | CREB phosphorylation | 1.088153e-07 | 6.963 |
R-HSA-5218920 | VEGFR2 mediated vascular permeability | 1.092328e-07 | 6.962 |
R-HSA-444257 | RSK activation | 2.411420e-07 | 6.618 |
R-HSA-389356 | Co-stimulation by CD28 | 2.675920e-07 | 6.573 |
R-HSA-422475 | Axon guidance | 2.733894e-07 | 6.563 |
R-HSA-198693 | AKT phosphorylates targets in the nucleus | 3.403443e-07 | 6.468 |
R-HSA-9675108 | Nervous system development | 5.815314e-07 | 6.235 |
R-HSA-2980766 | Nuclear Envelope Breakdown | 6.334281e-07 | 6.198 |
R-HSA-1227986 | Signaling by ERBB2 | 8.214140e-07 | 6.085 |
R-HSA-1640170 | Cell Cycle | 9.848160e-07 | 6.007 |
R-HSA-2559580 | Oxidative Stress Induced Senescence | 9.994298e-07 | 6.000 |
R-HSA-109581 | Apoptosis | 1.905768e-06 | 5.720 |
R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 2.087619e-06 | 5.680 |
R-HSA-69278 | Cell Cycle, Mitotic | 2.602831e-06 | 5.585 |
R-HSA-211163 | AKT-mediated inactivation of FOXO1A | 3.287432e-06 | 5.483 |
R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 5.223308e-06 | 5.282 |
R-HSA-75153 | Apoptotic execution phase | 5.634691e-06 | 5.249 |
R-HSA-198753 | ERK/MAPK targets | 7.144644e-06 | 5.146 |
R-HSA-437239 | Recycling pathway of L1 | 6.154154e-06 | 5.211 |
R-HSA-76002 | Platelet activation, signaling and aggregation | 8.538863e-06 | 5.069 |
R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 9.543473e-06 | 5.020 |
R-HSA-5357801 | Programmed Cell Death | 9.639489e-06 | 5.016 |
R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 1.094360e-05 | 4.961 |
R-HSA-5621575 | CD209 (DC-SIGN) signaling | 1.248956e-05 | 4.903 |
R-HSA-114516 | Disinhibition of SNARE formation | 1.501988e-05 | 4.823 |
R-HSA-5218921 | VEGFR2 mediated cell proliferation | 1.419067e-05 | 4.848 |
R-HSA-388396 | GPCR downstream signalling | 1.403064e-05 | 4.853 |
R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 2.274082e-05 | 4.643 |
R-HSA-111465 | Apoptotic cleavage of cellular proteins | 3.127183e-05 | 4.505 |
R-HSA-373760 | L1CAM interactions | 3.205862e-05 | 4.494 |
R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 3.457582e-05 | 4.461 |
R-HSA-397795 | G-protein beta:gamma signalling | 3.457582e-05 | 4.461 |
R-HSA-68875 | Mitotic Prophase | 3.790068e-05 | 4.421 |
R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 4.067408e-05 | 4.391 |
R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 3.665829e-05 | 4.436 |
R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 4.067408e-05 | 4.391 |
R-HSA-114508 | Effects of PIP2 hydrolysis | 3.812848e-05 | 4.419 |
R-HSA-372790 | Signaling by GPCR | 4.181371e-05 | 4.379 |
R-HSA-9006925 | Intracellular signaling by second messengers | 4.333424e-05 | 4.363 |
R-HSA-416476 | G alpha (q) signalling events | 5.007905e-05 | 4.300 |
R-HSA-6804757 | Regulation of TP53 Degradation | 5.039303e-05 | 4.298 |
R-HSA-68877 | Mitotic Prometaphase | 5.704232e-05 | 4.244 |
R-HSA-198323 | AKT phosphorylates targets in the cytosol | 6.031547e-05 | 4.220 |
R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 6.031547e-05 | 4.220 |
R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 6.531554e-05 | 4.185 |
R-HSA-2262752 | Cellular responses to stress | 6.632223e-05 | 4.178 |
R-HSA-8953897 | Cellular responses to stimuli | 6.635607e-05 | 4.178 |
R-HSA-389359 | CD28 dependent Vav1 pathway | 7.210801e-05 | 4.142 |
R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 7.210801e-05 | 4.142 |
R-HSA-376176 | Signaling by ROBO receptors | 7.595103e-05 | 4.119 |
R-HSA-68886 | M Phase | 9.798461e-05 | 4.009 |
R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 1.000079e-04 | 4.000 |
R-HSA-111447 | Activation of BAD and translocation to mitochondria | 1.000079e-04 | 4.000 |
R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 1.162605e-04 | 3.935 |
R-HSA-1489509 | DAG and IP3 signaling | 1.123485e-04 | 3.949 |
R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 9.970059e-05 | 4.001 |
R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 1.750787e-04 | 3.757 |
R-HSA-3928664 | Ephrin signaling | 1.750787e-04 | 3.757 |
R-HSA-389513 | Co-inhibition by CTLA4 | 2.233620e-04 | 3.651 |
R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 2.438358e-04 | 3.613 |
R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 2.508486e-04 | 3.601 |
R-HSA-388841 | Regulation of T cell activation by CD28 family | 2.865749e-04 | 3.543 |
R-HSA-450294 | MAP kinase activation | 3.053788e-04 | 3.515 |
R-HSA-373755 | Semaphorin interactions | 3.399977e-04 | 3.469 |
R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 3.440850e-04 | 3.463 |
R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 3.440850e-04 | 3.463 |
R-HSA-1266738 | Developmental Biology | 4.370541e-04 | 3.359 |
R-HSA-448424 | Interleukin-17 signaling | 4.834220e-04 | 3.316 |
R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 5.003800e-04 | 3.301 |
R-HSA-187037 | Signaling by NTRK1 (TRKA) | 5.349308e-04 | 3.272 |
R-HSA-210745 | Regulation of gene expression in beta cells | 5.930715e-04 | 3.227 |
R-HSA-1250196 | SHC1 events in ERBB2 signaling | 6.432550e-04 | 3.192 |
R-HSA-8863795 | Downregulation of ERBB2 signaling | 6.432550e-04 | 3.192 |
R-HSA-114452 | Activation of BH3-only proteins | 6.432550e-04 | 3.192 |
R-HSA-399719 | Trafficking of AMPA receptors | 6.960715e-04 | 3.157 |
R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 1.001533e-03 | 2.999 |
R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 8.098215e-04 | 3.092 |
R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 8.098215e-04 | 3.092 |
R-HSA-112315 | Transmission across Chemical Synapses | 1.028847e-03 | 2.988 |
R-HSA-166520 | Signaling by NTRKs | 1.039446e-03 | 2.983 |
R-HSA-438064 | Post NMDA receptor activation events | 1.042516e-03 | 2.982 |
R-HSA-111933 | Calmodulin induced events | 1.071267e-03 | 2.970 |
R-HSA-111997 | CaM pathway | 1.071267e-03 | 2.970 |
R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.124831e-03 | 2.949 |
R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 1.219781e-03 | 2.914 |
R-HSA-2682334 | EPH-Ephrin signaling | 1.301447e-03 | 2.886 |
R-HSA-202433 | Generation of second messenger molecules | 1.380659e-03 | 2.860 |
R-HSA-5633007 | Regulation of TP53 Activity | 1.412330e-03 | 2.850 |
R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 1.447336e-03 | 2.839 |
R-HSA-9607240 | FLT3 Signaling | 1.465860e-03 | 2.834 |
R-HSA-165159 | MTOR signalling | 1.646006e-03 | 2.784 |
R-HSA-111996 | Ca-dependent events | 1.646006e-03 | 2.784 |
R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.656808e-03 | 2.781 |
R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.656808e-03 | 2.781 |
R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.656808e-03 | 2.781 |
R-HSA-3700989 | Transcriptional Regulation by TP53 | 1.763045e-03 | 2.754 |
R-HSA-9009391 | Extra-nuclear estrogen signaling | 1.827923e-03 | 2.738 |
R-HSA-5621481 | C-type lectin receptors (CLRs) | 1.875832e-03 | 2.727 |
R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 1.887585e-03 | 2.724 |
R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 2.139762e-03 | 2.670 |
R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 2.343531e-03 | 2.630 |
R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 2.414323e-03 | 2.617 |
R-HSA-202403 | TCR signaling | 2.486576e-03 | 2.604 |
R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 2.486576e-03 | 2.604 |
R-HSA-166166 | MyD88-independent TLR4 cascade | 2.486576e-03 | 2.604 |
R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 2.712243e-03 | 2.567 |
R-HSA-8948751 | Regulation of PTEN stability and activity | 2.883156e-03 | 2.540 |
R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 2.951591e-03 | 2.530 |
R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 3.292694e-03 | 2.482 |
R-HSA-109606 | Intrinsic Pathway for Apoptosis | 3.297296e-03 | 2.482 |
R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 3.381992e-03 | 2.471 |
R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 3.381992e-03 | 2.471 |
R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 3.659767e-03 | 2.437 |
R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 3.659767e-03 | 2.437 |
R-HSA-186712 | Regulation of beta-cell development | 3.746142e-03 | 2.426 |
R-HSA-112043 | PLC beta mediated events | 4.065084e-03 | 2.391 |
R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 4.400083e-03 | 2.357 |
R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 4.400083e-03 | 2.357 |
R-HSA-9730414 | MITF-M-regulated melanocyte development | 4.470574e-03 | 2.350 |
R-HSA-2028269 | Signaling by Hippo | 4.722577e-03 | 2.326 |
R-HSA-8854518 | AURKA Activation by TPX2 | 4.933196e-03 | 2.307 |
R-HSA-112040 | G-protein mediated events | 5.119175e-03 | 2.291 |
R-HSA-156711 | Polo-like kinase mediated events | 5.146411e-03 | 2.288 |
R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 5.146411e-03 | 2.288 |
R-HSA-211728 | Regulation of PAK-2p34 activity by PS-GAP/RHG10 | 9.149293e-03 | 2.039 |
R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 6.323751e-03 | 2.199 |
R-HSA-380287 | Centrosome maturation | 6.759647e-03 | 2.170 |
R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 1.030921e-02 | 1.987 |
R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 8.939880e-03 | 2.049 |
R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.112306e-03 | 2.214 |
R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 7.008754e-03 | 2.154 |
R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 8.424048e-03 | 2.074 |
R-HSA-5687128 | MAPK6/MAPK4 signaling | 9.204600e-03 | 2.036 |
R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 7.330508e-03 | 2.135 |
R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 6.112306e-03 | 2.214 |
R-HSA-69202 | Cyclin E associated events during G1/S transition | 5.702306e-03 | 2.244 |
R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 9.473877e-03 | 2.023 |
R-HSA-4086400 | PCP/CE pathway | 7.446327e-03 | 2.128 |
R-HSA-112316 | Neuronal System | 7.260378e-03 | 2.139 |
R-HSA-449147 | Signaling by Interleukins | 9.595985e-03 | 2.018 |
R-HSA-9711123 | Cellular response to chemical stress | 1.063257e-02 | 1.973 |
R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 1.088916e-02 | 1.963 |
R-HSA-1280215 | Cytokine Signaling in Immune system | 1.120362e-02 | 1.951 |
R-HSA-109582 | Hemostasis | 1.141588e-02 | 1.942 |
R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 1.221607e-02 | 1.913 |
R-HSA-9614085 | FOXO-mediated transcription | 1.441352e-02 | 1.841 |
R-HSA-69275 | G2/M Transition | 1.492736e-02 | 1.826 |
R-HSA-1257604 | PIP3 activates AKT signaling | 1.514164e-02 | 1.820 |
R-HSA-453274 | Mitotic G2-G2/M phases | 1.541331e-02 | 1.812 |
R-HSA-9768919 | NPAS4 regulates expression of target genes | 1.550820e-02 | 1.809 |
R-HSA-195721 | Signaling by WNT | 1.571085e-02 | 1.804 |
R-HSA-168898 | Toll-like Receptor Cascades | 1.616082e-02 | 1.792 |
R-HSA-111885 | Opioid Signalling | 1.620513e-02 | 1.790 |
R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 1.770395e-02 | 1.752 |
R-HSA-2672351 | Stimuli-sensing channels | 1.811660e-02 | 1.742 |
R-HSA-211736 | Stimulation of the cell death response by PAK-2p34 | 1.821600e-02 | 1.740 |
R-HSA-68881 | Mitotic Metaphase/Anaphase Transition | 1.821600e-02 | 1.740 |
R-HSA-168249 | Innate Immune System | 1.979305e-02 | 1.703 |
R-HSA-5628897 | TP53 Regulates Metabolic Genes | 2.142575e-02 | 1.669 |
R-HSA-9007101 | Rab regulation of trafficking | 2.274650e-02 | 1.643 |
R-HSA-8878166 | Transcriptional regulation by RUNX2 | 2.365122e-02 | 1.626 |
R-HSA-3928662 | EPHB-mediated forward signaling | 2.415354e-02 | 1.617 |
R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 2.501808e-02 | 1.602 |
R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 2.501808e-02 | 1.602 |
R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 2.589514e-02 | 1.587 |
R-HSA-212436 | Generic Transcription Pathway | 2.631693e-02 | 1.580 |
R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.693526e-02 | 1.570 |
R-HSA-69206 | G1/S Transition | 2.697020e-02 | 1.569 |
R-HSA-165181 | Inhibition of TSC complex formation by PKB | 2.720085e-02 | 1.565 |
R-HSA-199418 | Negative regulation of the PI3K/AKT network | 2.948586e-02 | 1.530 |
R-HSA-2514856 | The phototransduction cascade | 3.046382e-02 | 1.516 |
R-HSA-8939211 | ESR-mediated signaling | 3.091489e-02 | 1.510 |
R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 3.141334e-02 | 1.503 |
R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 3.158505e-02 | 1.501 |
R-HSA-165158 | Activation of AKT2 | 3.166281e-02 | 1.499 |
R-HSA-445355 | Smooth Muscle Contraction | 3.237449e-02 | 1.490 |
R-HSA-3858494 | Beta-catenin independent WNT signaling | 3.376096e-02 | 1.472 |
R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 3.532653e-02 | 1.452 |
R-HSA-6807070 | PTEN Regulation | 3.544301e-02 | 1.450 |
R-HSA-109703 | PKB-mediated events | 3.610458e-02 | 1.442 |
R-HSA-176417 | Phosphorylation of Emi1 | 3.610458e-02 | 1.442 |
R-HSA-165160 | PDE3B signalling | 3.610458e-02 | 1.442 |
R-HSA-69620 | Cell Cycle Checkpoints | 3.943291e-02 | 1.404 |
R-HSA-453279 | Mitotic G1 phase and G1/S transition | 4.013700e-02 | 1.396 |
R-HSA-164944 | Nef and signal transduction | 4.052624e-02 | 1.392 |
R-HSA-69242 | S Phase | 4.135754e-02 | 1.383 |
R-HSA-9856651 | MITF-M-dependent gene expression | 4.259676e-02 | 1.371 |
R-HSA-69615 | G1/S DNA Damage Checkpoints | 4.259920e-02 | 1.371 |
R-HSA-8950505 | Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... | 4.477175e-02 | 1.349 |
R-HSA-168256 | Immune System | 4.597994e-02 | 1.337 |
R-HSA-73857 | RNA Polymerase II Transcription | 4.798785e-02 | 1.319 |
R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 4.810602e-02 | 1.318 |
R-HSA-9010642 | ROBO receptors bind AKAP5 | 4.930964e-02 | 1.307 |
R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 4.930964e-02 | 1.307 |
R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 5.152813e-02 | 1.288 |
R-HSA-453276 | Regulation of mitotic cell cycle | 5.152813e-02 | 1.288 |
R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 5.152813e-02 | 1.288 |
R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 5.367154e-02 | 1.270 |
R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 5.385687e-02 | 1.269 |
R-HSA-1280218 | Adaptive Immune System | 5.548646e-02 | 1.256 |
R-HSA-9020591 | Interleukin-12 signaling | 5.741883e-02 | 1.241 |
R-HSA-2179392 | EGFR Transactivation by Gastrin | 5.801370e-02 | 1.236 |
R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 6.229222e-02 | 1.206 |
R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 6.233620e-02 | 1.205 |
R-HSA-68884 | Mitotic Telophase/Cytokinesis | 6.663914e-02 | 1.176 |
R-HSA-141424 | Amplification of signal from the kinetochores | 6.985488e-02 | 1.156 |
R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 6.985488e-02 | 1.156 |
R-HSA-209543 | p75NTR recruits signalling complexes | 7.092260e-02 | 1.149 |
R-HSA-983712 | Ion channel transport | 7.116356e-02 | 1.148 |
R-HSA-5617833 | Cilium Assembly | 7.196615e-02 | 1.143 |
R-HSA-447115 | Interleukin-12 family signaling | 7.243994e-02 | 1.140 |
R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 7.518666e-02 | 1.124 |
R-HSA-8986944 | Transcriptional Regulation by MECP2 | 7.770164e-02 | 1.110 |
R-HSA-1433559 | Regulation of KIT signaling | 7.943141e-02 | 1.100 |
R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 8.276744e-02 | 1.082 |
R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 8.365695e-02 | 1.077 |
R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 8.365695e-02 | 1.077 |
R-HSA-193639 | p75NTR signals via NF-kB | 8.365695e-02 | 1.077 |
R-HSA-176412 | Phosphorylation of the APC/C | 8.786335e-02 | 1.056 |
R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 8.786335e-02 | 1.056 |
R-HSA-5683057 | MAPK family signaling cascades | 8.892708e-02 | 1.051 |
R-HSA-8964616 | G beta:gamma signalling through CDC42 | 9.205070e-02 | 1.036 |
R-HSA-399997 | Acetylcholine regulates insulin secretion | 9.205070e-02 | 1.036 |
R-HSA-69618 | Mitotic Spindle Checkpoint | 9.275753e-02 | 1.033 |
R-HSA-9860931 | Response of endothelial cells to shear stress | 9.842856e-02 | 1.007 |
R-HSA-9006931 | Signaling by Nuclear Receptors | 1.000242e-01 | 1.000 |
R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1.044993e-01 | 0.981 |
R-HSA-9705683 | SARS-CoV-2-host interactions | 1.063012e-01 | 0.973 |
R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 1.086113e-01 | 0.964 |
R-HSA-445144 | Signal transduction by L1 | 1.086113e-01 | 0.964 |
R-HSA-2871796 | FCERI mediated MAPK activation | 1.115311e-01 | 0.953 |
R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 1.127047e-01 | 0.948 |
R-HSA-9855142 | Cellular responses to mechanical stimuli | 1.145028e-01 | 0.941 |
R-HSA-2029485 | Role of phospholipids in phagocytosis | 1.189985e-01 | 0.924 |
R-HSA-74160 | Gene expression (Transcription) | 1.204415e-01 | 0.919 |
R-HSA-166208 | mTORC1-mediated signalling | 1.208359e-01 | 0.918 |
R-HSA-3000170 | Syndecan interactions | 1.248739e-01 | 0.904 |
R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 1.248739e-01 | 0.904 |
R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 1.281198e-01 | 0.892 |
R-HSA-420029 | Tight junction interactions | 1.328950e-01 | 0.876 |
R-HSA-400685 | Sema4D in semaphorin signaling | 1.328950e-01 | 0.876 |
R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 1.408437e-01 | 0.851 |
R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 1.526320e-01 | 0.816 |
R-HSA-211733 | Regulation of activated PAK-2p34 by proteasome mediated degradation | 1.565259e-01 | 0.805 |
R-HSA-354192 | Integrin signaling | 1.642608e-01 | 0.784 |
R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 1.642608e-01 | 0.784 |
R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 1.644385e-01 | 0.784 |
R-HSA-203615 | eNOS activation | 1.719257e-01 | 0.765 |
R-HSA-169911 | Regulation of Apoptosis | 1.757321e-01 | 0.755 |
R-HSA-2187338 | Visual phototransduction | 1.758355e-01 | 0.755 |
R-HSA-114604 | GPVI-mediated activation cascade | 1.795212e-01 | 0.746 |
R-HSA-8853659 | RET signaling | 1.795212e-01 | 0.746 |
R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 1.870480e-01 | 0.728 |
R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 1.907858e-01 | 0.719 |
R-HSA-9648002 | RAS processing | 1.907858e-01 | 0.719 |
R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 1.945067e-01 | 0.711 |
R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 1.982107e-01 | 0.703 |
R-HSA-2467813 | Separation of Sister Chromatids | 2.039926e-01 | 0.690 |
R-HSA-1852241 | Organelle biogenesis and maintenance | 2.057694e-01 | 0.687 |
R-HSA-1433557 | Signaling by SCF-KIT | 2.092221e-01 | 0.679 |
R-HSA-373752 | Netrin-1 signaling | 2.128594e-01 | 0.672 |
R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 2.164801e-01 | 0.665 |
R-HSA-76009 | Platelet Aggregation (Plug Formation) | 2.164801e-01 | 0.665 |
R-HSA-2299718 | Condensation of Prophase Chromosomes | 2.200844e-01 | 0.657 |
R-HSA-9031628 | NGF-stimulated transcription | 2.272439e-01 | 0.644 |
R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 2.326072e-01 | 0.633 |
R-HSA-109704 | PI3K Cascade | 2.343387e-01 | 0.630 |
R-HSA-201681 | TCF dependent signaling in response to WNT | 2.377063e-01 | 0.624 |
R-HSA-1169091 | Activation of NF-kappaB in B cells | 2.378619e-01 | 0.624 |
R-HSA-9694516 | SARS-CoV-2 Infection | 2.406947e-01 | 0.619 |
R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 2.448605e-01 | 0.611 |
R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 2.448605e-01 | 0.611 |
R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 2.517956e-01 | 0.599 |
R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 2.529921e-01 | 0.597 |
R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 2.552396e-01 | 0.593 |
R-HSA-112399 | IRS-mediated signalling | 2.586679e-01 | 0.587 |
R-HSA-2428928 | IRS-related events triggered by IGF1R | 2.722262e-01 | 0.565 |
R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 2.755774e-01 | 0.560 |
R-HSA-375165 | NCAM signaling for neurite out-growth | 2.755774e-01 | 0.560 |
R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 2.755774e-01 | 0.560 |
R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 2.789134e-01 | 0.555 |
R-HSA-8848021 | Signaling by PTK6 | 2.789134e-01 | 0.555 |
R-HSA-2428924 | IGF1R signaling cascade | 2.822342e-01 | 0.549 |
R-HSA-74751 | Insulin receptor signalling cascade | 2.822342e-01 | 0.549 |
R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 2.855399e-01 | 0.544 |
R-HSA-397014 | Muscle contraction | 2.887251e-01 | 0.540 |
R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 2.953672e-01 | 0.530 |
R-HSA-68882 | Mitotic Anaphase | 2.955216e-01 | 0.529 |
R-HSA-2555396 | Mitotic Metaphase and Anaphase | 2.972196e-01 | 0.527 |
R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 3.018445e-01 | 0.520 |
R-HSA-8978934 | Metabolism of cofactors | 3.050611e-01 | 0.516 |
R-HSA-4086398 | Ca2+ pathway | 3.114505e-01 | 0.507 |
R-HSA-418594 | G alpha (i) signalling events | 3.142102e-01 | 0.503 |
R-HSA-9013694 | Signaling by NOTCH4 | 3.146235e-01 | 0.502 |
R-HSA-3000171 | Non-integrin membrane-ECM interactions | 3.177820e-01 | 0.498 |
R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 3.302731e-01 | 0.481 |
R-HSA-9659379 | Sensory processing of sound | 3.302731e-01 | 0.481 |
R-HSA-157118 | Signaling by NOTCH | 3.360645e-01 | 0.474 |
R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 3.515918e-01 | 0.454 |
R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 3.545822e-01 | 0.450 |
R-HSA-202424 | Downstream TCR signaling | 3.664083e-01 | 0.436 |
R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 3.693313e-01 | 0.433 |
R-HSA-74752 | Signaling by Insulin receptor | 3.751373e-01 | 0.426 |
R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 3.894228e-01 | 0.410 |
R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 3.922410e-01 | 0.406 |
R-HSA-422356 | Regulation of insulin secretion | 3.950463e-01 | 0.403 |
R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.978389e-01 | 0.400 |
R-HSA-1912422 | Pre-NOTCH Expression and Processing | 4.382331e-01 | 0.358 |
R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 4.686134e-01 | 0.329 |
R-HSA-162909 | Host Interactions of HIV factors | 4.710707e-01 | 0.327 |
R-HSA-9679506 | SARS-CoV Infections | 4.962195e-01 | 0.304 |
R-HSA-163685 | Integration of energy metabolism | 5.066124e-01 | 0.295 |
R-HSA-2871837 | FCERI mediated NF-kB activation | 5.267955e-01 | 0.278 |
R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 5.440508e-01 | 0.264 |
R-HSA-73887 | Death Receptor Signaling | 5.482667e-01 | 0.261 |
R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 5.565835e-01 | 0.254 |
R-HSA-877300 | Interferon gamma signaling | 5.586390e-01 | 0.253 |
R-HSA-9006936 | Signaling by TGFB family members | 5.606851e-01 | 0.251 |
R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 5.864478e-01 | 0.232 |
R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 5.883667e-01 | 0.230 |
R-HSA-9664433 | Leishmania parasite growth and survival | 5.883667e-01 | 0.230 |
R-HSA-199991 | Membrane Trafficking | 5.982402e-01 | 0.223 |
R-HSA-389948 | Co-inhibition by PD-1 | 6.369819e-01 | 0.196 |
R-HSA-6798695 | Neutrophil degranulation | 6.490026e-01 | 0.188 |
R-HSA-162906 | HIV Infection | 6.814142e-01 | 0.167 |
R-HSA-421270 | Cell-cell junction organization | 7.151966e-01 | 0.146 |
R-HSA-9734767 | Developmental Cell Lineages | 7.307369e-01 | 0.136 |
R-HSA-5653656 | Vesicle-mediated transport | 7.403172e-01 | 0.131 |
R-HSA-446728 | Cell junction organization | 7.489904e-01 | 0.126 |
R-HSA-9824443 | Parasitic Infection Pathways | 7.524918e-01 | 0.123 |
R-HSA-9658195 | Leishmania infection | 7.524918e-01 | 0.123 |
R-HSA-8953854 | Metabolism of RNA | 7.599810e-01 | 0.119 |
R-HSA-5673001 | RAF/MAP kinase cascade | 7.615951e-01 | 0.118 |
R-HSA-5684996 | MAPK1/MAPK3 signaling | 7.692890e-01 | 0.114 |
R-HSA-9824446 | Viral Infection Pathways | 7.820184e-01 | 0.107 |
R-HSA-1500931 | Cell-Cell communication | 7.899473e-01 | 0.102 |
R-HSA-1474244 | Extracellular matrix organization | 8.042331e-01 | 0.095 |
R-HSA-196854 | Metabolism of vitamins and cofactors | 8.323742e-01 | 0.080 |
R-HSA-382551 | Transport of small molecules | 8.466133e-01 | 0.072 |
R-HSA-913531 | Interferon Signaling | 8.474457e-01 | 0.072 |
R-HSA-5663205 | Infectious disease | 9.053684e-01 | 0.043 |
R-HSA-9709957 | Sensory Perception | 9.351642e-01 | 0.029 |
R-HSA-1643685 | Disease | 9.942267e-01 | 0.003 |
R-HSA-1430728 | Metabolism | 9.999999e-01 | 0.000 |
Download
kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
---|---|---|---|---|
SGK1 |
0.589 | 0.261 | -3 | 0.693 |
SGK3 |
0.589 | 0.312 | -3 | 0.734 |
AKT1 |
0.589 | 0.283 | -3 | 0.755 |
PDK1 |
0.588 | 0.388 | 1 | 0.658 |
ROCK2 |
0.582 | 0.264 | -3 | 0.745 |
AKT2 |
0.578 | 0.250 | -3 | 0.740 |
MRCKB |
0.578 | 0.244 | -3 | 0.749 |
AURA |
0.577 | 0.274 | -2 | 0.660 |
GSK3B |
0.577 | 0.268 | 4 | 0.563 |
PKN3 |
0.576 | 0.325 | -3 | 0.704 |
ROCK1 |
0.576 | 0.238 | -3 | 0.746 |
PKG2 |
0.576 | 0.267 | -2 | 0.641 |
PAK4 |
0.576 | 0.293 | -2 | 0.644 |
AKT3 |
0.575 | 0.249 | -3 | 0.710 |
DCAMKL2 |
0.575 | 0.253 | -3 | 0.779 |
P70S6KB |
0.574 | 0.280 | -3 | 0.737 |
DAPK1 |
0.573 | 0.225 | -3 | 0.739 |
PAK6 |
0.573 | 0.276 | -2 | 0.676 |
DCAMKL1 |
0.573 | 0.274 | -3 | 0.767 |
CLK4 |
0.572 | 0.234 | -3 | 0.751 |
MRCKA |
0.572 | 0.239 | -3 | 0.747 |
PAK5 |
0.572 | 0.293 | -2 | 0.634 |
PKN1 |
0.570 | 0.262 | -3 | 0.749 |
MSK1 |
0.570 | 0.271 | -3 | 0.696 |
AURB |
0.569 | 0.258 | -2 | 0.663 |
PKACA |
0.569 | 0.269 | -2 | 0.652 |
DMPK1 |
0.569 | 0.219 | -3 | 0.773 |
PKN2 |
0.569 | 0.252 | -3 | 0.720 |
PAK1 |
0.569 | 0.254 | -2 | 0.657 |
PKACG |
0.569 | 0.286 | -2 | 0.631 |
CAMLCK |
0.567 | 0.220 | -2 | 0.632 |
CAMK4 |
0.567 | 0.321 | -3 | 0.743 |
P70S6K |
0.567 | 0.243 | -3 | 0.715 |
DAPK3 |
0.567 | 0.202 | -3 | 0.750 |
CRIK |
0.566 | 0.193 | -3 | 0.740 |
MYLK4 |
0.566 | 0.219 | -2 | 0.682 |
SKMLCK |
0.566 | 0.238 | -2 | 0.638 |
MNK1 |
0.565 | 0.280 | -2 | 0.641 |
GSK3A |
0.565 | 0.243 | 4 | 0.559 |
CLK1 |
0.565 | 0.209 | -3 | 0.770 |
PAK2 |
0.565 | 0.225 | -2 | 0.648 |
CHK2 |
0.564 | 0.185 | -3 | 0.740 |
SMMLCK |
0.564 | 0.181 | -3 | 0.723 |
MNK2 |
0.564 | 0.285 | -2 | 0.643 |
PAK3 |
0.563 | 0.236 | -2 | 0.656 |
DAPK2 |
0.563 | 0.211 | -3 | 0.703 |
CAMK1B |
0.563 | 0.226 | -3 | 0.718 |
PKACB |
0.562 | 0.262 | -2 | 0.655 |
MELK |
0.561 | 0.232 | -3 | 0.756 |
AURC |
0.560 | 0.266 | -2 | 0.666 |
ICK |
0.560 | 0.152 | -3 | 0.711 |
LATS1 |
0.559 | 0.175 | -3 | 0.686 |
MSK2 |
0.559 | 0.238 | -3 | 0.692 |
TAO3 |
0.558 | 0.127 | 1 | 0.462 |
NIK |
0.558 | 0.181 | -3 | 0.678 |
RIPK1 |
0.558 | 0.169 | 1 | 0.453 |
PKCI |
0.558 | 0.162 | 2 | 0.315 |
DYRK3 |
0.558 | 0.175 | 1 | 0.366 |
NEK11 |
0.558 | 0.108 | 1 | 0.562 |
RSK4 |
0.557 | 0.222 | -3 | 0.737 |
PKCD |
0.557 | 0.170 | 2 | 0.299 |
CAMK1A |
0.557 | 0.211 | -3 | 0.737 |
PLK4 |
0.557 | 0.177 | 2 | 0.395 |
VRK1 |
0.557 | 0.177 | 2 | 0.481 |
PRKX |
0.557 | 0.276 | -3 | 0.755 |
NLK |
0.556 | 0.094 | 1 | 0.452 |
BRAF |
0.556 | 0.082 | -4 | 0.708 |
CAMK1D |
0.556 | 0.202 | -3 | 0.753 |
RIPK3 |
0.556 | 0.158 | 3 | 0.198 |
PKCE |
0.556 | 0.156 | 2 | 0.279 |
PKCH |
0.556 | 0.156 | 2 | 0.300 |
ANKRD3 |
0.555 | 0.123 | 1 | 0.496 |
AMPKA1 |
0.555 | 0.179 | -3 | 0.732 |
WNK4 |
0.555 | 0.089 | -2 | 0.539 |
MST3 |
0.554 | 0.071 | 2 | 0.281 |
PKG1 |
0.554 | 0.229 | -2 | 0.615 |
RIPK2 |
0.554 | 0.091 | 1 | 0.550 |
RSK2 |
0.553 | 0.221 | -3 | 0.743 |
MST4 |
0.553 | 0.146 | 2 | 0.287 |
MAP3K15 |
0.553 | 0.083 | 1 | 0.519 |
HIPK1 |
0.553 | 0.111 | 1 | 0.359 |
TAK1 |
0.553 | 0.095 | 1 | 0.462 |
CLK2 |
0.553 | 0.207 | -3 | 0.737 |
WNK1 |
0.553 | 0.141 | -2 | 0.566 |
HPK1 |
0.552 | 0.071 | 1 | 0.504 |
PKCT |
0.552 | 0.159 | 2 | 0.308 |
MAK |
0.552 | 0.113 | -2 | 0.470 |
RAF1 |
0.552 | 0.142 | 1 | 0.465 |
KHS2 |
0.552 | 0.064 | 1 | 0.503 |
RSK3 |
0.552 | 0.213 | -3 | 0.720 |
P90RSK |
0.552 | 0.204 | -3 | 0.726 |
CAMK1G |
0.552 | 0.185 | -3 | 0.742 |
PLK1 |
0.552 | 0.157 | -2 | 0.365 |
DYRK1A |
0.552 | 0.117 | 1 | 0.409 |
PKCZ |
0.552 | 0.153 | 2 | 0.323 |
VRK2 |
0.552 | 0.080 | 1 | 0.413 |
PRKD3 |
0.552 | 0.173 | -3 | 0.758 |
AMPKA2 |
0.551 | 0.186 | -3 | 0.748 |
LOK |
0.551 | 0.084 | -2 | 0.492 |
NEK8 |
0.551 | 0.083 | 2 | 0.321 |
TAO1 |
0.551 | 0.072 | 1 | 0.514 |
KHS1 |
0.551 | 0.061 | 1 | 0.510 |
CAMK2A |
0.551 | 0.200 | 2 | 0.223 |
CAMK2D |
0.551 | 0.239 | -3 | 0.706 |
JNK2 |
0.551 | 0.061 | 1 | 0.385 |
PASK |
0.550 | 0.105 | -3 | 0.691 |
HIPK3 |
0.550 | 0.099 | 1 | 0.431 |
MEKK1 |
0.550 | 0.037 | 1 | 0.467 |
TAO2 |
0.550 | 0.044 | 2 | 0.330 |
PKR |
0.550 | 0.069 | 1 | 0.361 |
CAMK2B |
0.550 | 0.194 | 2 | 0.235 |
JNK3 |
0.549 | 0.056 | 1 | 0.386 |
DYRK2 |
0.549 | 0.117 | 1 | 0.350 |
DRAK1 |
0.549 | 0.140 | 1 | 0.449 |
IRAK4 |
0.549 | 0.047 | 1 | 0.384 |
NEK1 |
0.548 | 0.051 | 1 | 0.436 |
PKCA |
0.548 | 0.125 | 2 | 0.266 |
MINK |
0.548 | 0.029 | 1 | 0.492 |
PHKG1 |
0.548 | 0.222 | -3 | 0.734 |
PIM1 |
0.548 | 0.168 | -3 | 0.727 |
NEK5 |
0.548 | 0.039 | 1 | 0.419 |
GCK |
0.548 | 0.050 | 1 | 0.471 |
ASK1 |
0.547 | 0.064 | 1 | 0.520 |
ZAK |
0.547 | 0.034 | 1 | 0.487 |
CDKL1 |
0.547 | 0.100 | -3 | 0.695 |
MEKK3 |
0.547 | 0.046 | 1 | 0.457 |
DLK |
0.546 | 0.062 | 1 | 0.426 |
DYRK1B |
0.546 | 0.099 | 1 | 0.342 |
SLK |
0.546 | 0.072 | -2 | 0.407 |
PHKG2 |
0.546 | 0.202 | -3 | 0.773 |
PRKD2 |
0.546 | 0.205 | -3 | 0.761 |
NEK4 |
0.546 | 0.000 | 1 | 0.457 |
YSK1 |
0.545 | 0.032 | 2 | 0.298 |
GAK |
0.545 | 0.054 | 1 | 0.316 |
JNK1 |
0.545 | 0.051 | 1 | 0.345 |
GRK6 |
0.545 | 0.096 | 1 | 0.354 |
NUAK2 |
0.545 | 0.134 | -3 | 0.756 |
MASTL |
0.545 | 0.156 | -2 | 0.436 |
NEK2 |
0.545 | 0.051 | 2 | 0.318 |
GRK7 |
0.545 | 0.114 | 1 | 0.331 |
CAMKK2 |
0.545 | 0.030 | -2 | 0.485 |
IRAK1 |
0.545 | 0.033 | -1 | 0.641 |
CAMK2G |
0.545 | 0.152 | 2 | 0.275 |
MEK5 |
0.545 | -0.000 | 2 | 0.313 |
DYRK4 |
0.545 | 0.098 | 1 | 0.330 |
LRRK2 |
0.544 | 0.018 | 2 | 0.339 |
HIPK2 |
0.544 | 0.109 | 1 | 0.319 |
GRK1 |
0.544 | 0.159 | -2 | 0.449 |
MEK1 |
0.544 | 0.012 | 2 | 0.318 |
NEK9 |
0.544 | 0.064 | 2 | 0.343 |
TNIK |
0.543 | 0.004 | 3 | 0.205 |
TBK1 |
0.543 | 0.133 | 1 | 0.571 |
CDK14 |
0.543 | 0.045 | 1 | 0.359 |
WNK3 |
0.543 | 0.080 | 1 | 0.456 |
NDR1 |
0.542 | 0.189 | -3 | 0.722 |
IKKE |
0.542 | 0.113 | 1 | 0.567 |
SBK |
0.542 | 0.152 | -3 | 0.706 |
TSSK1 |
0.541 | 0.107 | -3 | 0.732 |
PRKD1 |
0.541 | 0.183 | -3 | 0.719 |
MEKK2 |
0.541 | -0.041 | 2 | 0.320 |
HUNK |
0.540 | 0.062 | 2 | 0.389 |
MEK2 |
0.540 | 0.023 | 2 | 0.354 |
PIM2 |
0.540 | 0.123 | -3 | 0.746 |
YSK4 |
0.540 | 0.031 | 1 | 0.475 |
PKCG |
0.540 | 0.105 | 2 | 0.283 |
MAPKAPK3 |
0.540 | 0.176 | -3 | 0.733 |
PKCB |
0.539 | 0.091 | 2 | 0.269 |
LKB1 |
0.539 | 0.041 | -3 | 0.562 |
TSSK2 |
0.539 | 0.065 | -5 | 0.659 |
CAMKK1 |
0.539 | -0.022 | -2 | 0.472 |
NEK3 |
0.539 | 0.046 | 1 | 0.514 |
HGK |
0.539 | -0.020 | 3 | 0.192 |
MEKK6 |
0.538 | -0.033 | 1 | 0.408 |
CLK3 |
0.538 | 0.130 | 1 | 0.331 |
SNRK |
0.537 | 0.095 | 2 | 0.289 |
PBK |
0.537 | 0.030 | 1 | 0.283 |
STK33 |
0.537 | 0.017 | 2 | 0.258 |
NIM1 |
0.537 | 0.062 | 3 | 0.171 |
HASPIN |
0.537 | 0.038 | -1 | 0.627 |
CDK4 |
0.537 | 0.027 | 1 | 0.350 |
MLK2 |
0.537 | 0.046 | 2 | 0.291 |
MPSK1 |
0.536 | 0.021 | 1 | 0.302 |
CHAK2 |
0.536 | 0.043 | -1 | 0.801 |
CHK1 |
0.536 | 0.119 | -3 | 0.687 |
CHAK1 |
0.536 | 0.011 | 2 | 0.313 |
YANK3 |
0.536 | 0.021 | 2 | 0.131 |
PIM3 |
0.536 | 0.139 | -3 | 0.708 |
ULK2 |
0.536 | 0.090 | 2 | 0.359 |
MOS |
0.536 | 0.045 | 1 | 0.297 |
DNAPK |
0.536 | 0.031 | 1 | 0.475 |
IKKB |
0.536 | 0.144 | -2 | 0.421 |
SSTK |
0.536 | 0.044 | 4 | 0.144 |
PLK3 |
0.535 | 0.119 | 2 | 0.284 |
MOK |
0.535 | 0.087 | 1 | 0.302 |
COT |
0.535 | 0.121 | 2 | 0.377 |
SRPK1 |
0.535 | 0.113 | -3 | 0.704 |
ERK5 |
0.535 | -0.000 | 1 | 0.344 |
PRPK |
0.535 | -0.004 | -1 | 0.692 |
P38A |
0.534 | 0.007 | 1 | 0.373 |
MLK1 |
0.534 | 0.017 | 2 | 0.293 |
HIPK4 |
0.534 | 0.089 | 1 | 0.353 |
NEK7 |
0.533 | 0.060 | -3 | 0.543 |
P38G |
0.533 | 0.029 | 1 | 0.313 |
ERK2 |
0.533 | 0.007 | 1 | 0.373 |
MYO3A |
0.533 | -0.050 | 1 | 0.438 |
SRPK3 |
0.533 | 0.076 | -3 | 0.670 |
GRK5 |
0.533 | 0.072 | -3 | 0.530 |
BMPR2 |
0.533 | -0.096 | -2 | 0.450 |
MST1 |
0.533 | -0.033 | 1 | 0.464 |
BUB1 |
0.532 | 0.032 | -5 | 0.599 |
ULK1 |
0.532 | 0.079 | -3 | 0.500 |
ALK4 |
0.532 | -0.012 | -2 | 0.399 |
MAPKAPK5 |
0.532 | 0.134 | -3 | 0.676 |
HRI |
0.531 | -0.011 | -2 | 0.421 |
PERK |
0.531 | 0.038 | -2 | 0.414 |
EEF2K |
0.531 | -0.052 | 3 | 0.186 |
CDK10 |
0.531 | 0.055 | 1 | 0.349 |
CDKL5 |
0.531 | 0.067 | -3 | 0.704 |
PDHK1 |
0.530 | 0.024 | 1 | 0.492 |
NUAK1 |
0.530 | 0.125 | -3 | 0.751 |
QIK |
0.530 | 0.032 | -3 | 0.722 |
GRK4 |
0.530 | 0.098 | -2 | 0.428 |
MYO3B |
0.530 | -0.037 | 2 | 0.294 |
P38B |
0.530 | 0.004 | 1 | 0.345 |
MST2 |
0.530 | -0.039 | 1 | 0.454 |
TTBK2 |
0.530 | 0.030 | 2 | 0.316 |
OSR1 |
0.529 | -0.007 | 2 | 0.298 |
ATR |
0.529 | -0.017 | 1 | 0.343 |
MTOR |
0.529 | 0.103 | 1 | 0.508 |
SIK |
0.529 | 0.083 | -3 | 0.742 |
BRSK2 |
0.529 | 0.109 | -3 | 0.741 |
STLK3 |
0.529 | -0.035 | 1 | 0.460 |
IKKA |
0.529 | 0.097 | -2 | 0.379 |
IRE1 |
0.528 | -0.022 | 1 | 0.323 |
NEK6 |
0.528 | 0.081 | -2 | 0.427 |
PDHK4 |
0.528 | 0.025 | 1 | 0.469 |
ALPHAK3 |
0.528 | -0.021 | -1 | 0.678 |
TGFBR1 |
0.528 | 0.008 | -2 | 0.370 |
PLK2 |
0.527 | 0.074 | -3 | 0.394 |
PRP4 |
0.527 | -0.022 | -3 | 0.419 |
ERK1 |
0.527 | 0.012 | 1 | 0.370 |
LATS2 |
0.527 | 0.148 | -5 | 0.581 |
SRPK2 |
0.527 | 0.113 | -3 | 0.685 |
P38D |
0.526 | 0.019 | 1 | 0.320 |
BRSK1 |
0.526 | 0.099 | -3 | 0.740 |
NDR2 |
0.526 | 0.175 | -3 | 0.703 |
TLK2 |
0.526 | -0.004 | 1 | 0.369 |
QSK |
0.526 | 0.033 | 4 | 0.152 |
CDK6 |
0.525 | -0.005 | 1 | 0.369 |
CDK9 |
0.525 | 0.022 | 1 | 0.381 |
MAPKAPK2 |
0.524 | 0.143 | -3 | 0.723 |
MLK4 |
0.524 | -0.033 | 2 | 0.255 |
MLK3 |
0.524 | -0.024 | 2 | 0.250 |
CDK5 |
0.524 | -0.005 | 1 | 0.337 |
CDK12 |
0.524 | 0.020 | 1 | 0.371 |
TGFBR2 |
0.523 | 0.015 | -2 | 0.376 |
BIKE |
0.523 | -0.019 | 1 | 0.254 |
TTBK1 |
0.522 | 0.018 | 2 | 0.297 |
MARK1 |
0.521 | -0.015 | 4 | 0.153 |
MARK2 |
0.521 | -0.023 | 4 | 0.126 |
MARK4 |
0.521 | -0.026 | 4 | 0.175 |
TLK1 |
0.520 | -0.070 | -2 | 0.397 |
TTK |
0.520 | -0.097 | -2 | 0.378 |
GCN2 |
0.519 | 0.140 | 2 | 0.308 |
ATM |
0.519 | -0.021 | 1 | 0.321 |
IRE2 |
0.519 | -0.071 | 2 | 0.378 |
CDK13 |
0.518 | 0.006 | 1 | 0.362 |
DSTYK |
0.518 | -0.044 | 2 | 0.283 |
CDK1 |
0.518 | 0.000 | 1 | 0.315 |
CDK7 |
0.518 | 0.016 | 1 | 0.356 |
MARK3 |
0.518 | -0.010 | 4 | 0.146 |
CK1A2 |
0.517 | 0.033 | -3 | 0.311 |
ERK7 |
0.517 | -0.015 | 2 | 0.150 |
GRK2 |
0.517 | -0.019 | -2 | 0.373 |
CDC7 |
0.517 | -0.005 | 1 | 0.275 |
CDK3 |
0.516 | 0.000 | 1 | 0.296 |
BCKDK |
0.516 | 0.031 | -1 | 0.717 |
ALK2 |
0.516 | -0.069 | -2 | 0.395 |
YANK2 |
0.515 | -0.014 | 2 | 0.125 |
CDK17 |
0.515 | -0.000 | 1 | 0.301 |
PINK1 |
0.513 | -0.098 | 1 | 0.342 |
CDK18 |
0.512 | 0.001 | 1 | 0.315 |
GRK3 |
0.512 | 0.020 | -2 | 0.353 |
CDK8 |
0.511 | 0.010 | 1 | 0.377 |
AAK1 |
0.511 | -0.015 | 1 | 0.200 |
ACVR2B |
0.510 | -0.067 | -2 | 0.364 |
CDK2 |
0.510 | -0.048 | 1 | 0.349 |
ACVR2A |
0.509 | -0.075 | -2 | 0.344 |
SMG1 |
0.505 | -0.064 | 1 | 0.314 |
BMPR1B |
0.504 | -0.077 | 1 | 0.219 |
CDK16 |
0.504 | -0.021 | 1 | 0.298 |
CK1D |
0.504 | 0.008 | -3 | 0.295 |
CK1E |
0.503 | 0.019 | -3 | 0.328 |
CDK19 |
0.501 | 0.003 | 1 | 0.364 |
BMPR1A |
0.498 | -0.080 | 1 | 0.219 |
CK2A1 |
0.495 | 0.009 | 1 | 0.130 |
CK1G3 |
0.495 | 0.025 | -3 | 0.198 |
CK1G1 |
0.494 | 0.039 | -3 | 0.298 |
CK2A2 |
0.493 | -0.018 | 1 | 0.136 |
CK1G2 |
0.488 | 0.030 | -3 | 0.249 |
KIS |
0.487 | 0.002 | 1 | 0.384 |
FAM20C |
0.481 | -0.031 | 2 | 0.117 |
CK1A |
0.472 | 0.035 | -3 | 0.225 |
TNK1 |
0.453 | 0.072 | 3 | 0.202 |
NEK10_TYR |
0.451 | 0.120 | 1 | 0.515 |
DDR2 |
0.449 | 0.055 | 3 | 0.135 |
LIMK2_TYR |
0.448 | 0.068 | -3 | 0.648 |
DDR1 |
0.448 | 0.062 | 4 | 0.206 |
RET |
0.447 | 0.040 | 1 | 0.465 |
PDHK3_TYR |
0.447 | 0.056 | 4 | 0.260 |
JAK1 |
0.446 | 0.046 | 1 | 0.551 |
JAK2 |
0.445 | 0.001 | 1 | 0.503 |
MST1R |
0.445 | 0.002 | 3 | 0.205 |
CSF1R |
0.443 | -0.012 | 3 | 0.183 |
MAP2K7_TYR |
0.443 | -0.009 | 2 | 0.311 |
PKMYT1_TYR |
0.442 | -0.035 | 3 | 0.229 |
MAP2K4_TYR |
0.442 | 0.012 | -1 | 0.690 |
PINK1_TYR |
0.442 | 0.023 | 1 | 0.398 |
KDR |
0.441 | -0.021 | 3 | 0.163 |
BMPR2_TYR |
0.441 | 0.006 | -1 | 0.725 |
TYK2 |
0.441 | -0.024 | 1 | 0.476 |
ROS1 |
0.441 | -0.063 | 3 | 0.189 |
TESK1_TYR |
0.440 | -0.031 | 3 | 0.213 |
FLT4 |
0.439 | 0.006 | 3 | 0.201 |
LIMK1_TYR |
0.439 | -0.033 | 2 | 0.345 |
INSRR |
0.439 | -0.031 | 3 | 0.158 |
JAK3 |
0.439 | 0.014 | 1 | 0.481 |
PDGFRB |
0.438 | -0.031 | 3 | 0.179 |
PDGFRA |
0.438 | -0.001 | 3 | 0.196 |
NTRK1 |
0.438 | 0.011 | -1 | 0.699 |
ABL2 |
0.437 | 0.007 | -1 | 0.661 |
PDHK4_TYR |
0.437 | -0.015 | 2 | 0.271 |
FGFR1 |
0.437 | -0.039 | 3 | 0.166 |
MAP2K6_TYR |
0.437 | -0.049 | -1 | 0.714 |
FGFR2 |
0.437 | -0.041 | 3 | 0.165 |
INSR |
0.436 | -0.027 | 3 | 0.176 |
EPHB4 |
0.436 | -0.056 | -1 | 0.721 |
EPHA6 |
0.436 | -0.060 | -1 | 0.735 |
FLT3 |
0.436 | -0.027 | 3 | 0.177 |
TYRO3 |
0.435 | -0.091 | 3 | 0.187 |
ABL1 |
0.434 | -0.007 | -1 | 0.637 |
NTRK2 |
0.434 | -0.025 | 3 | 0.181 |
MUSK |
0.433 | -0.001 | 1 | 0.348 |
TNK2 |
0.433 | -0.063 | 3 | 0.164 |
ALK |
0.432 | -0.073 | 3 | 0.154 |
KIT |
0.432 | -0.047 | 3 | 0.174 |
PDHK1_TYR |
0.432 | -0.084 | -1 | 0.721 |
LTK |
0.432 | -0.050 | 3 | 0.183 |
WEE1_TYR |
0.431 | -0.027 | -1 | 0.671 |
FGFR3 |
0.431 | -0.047 | 3 | 0.153 |
AXL |
0.431 | -0.070 | 3 | 0.169 |
MERTK |
0.430 | -0.075 | 3 | 0.189 |
EPHB1 |
0.429 | -0.084 | 1 | 0.345 |
FLT1 |
0.428 | -0.007 | -1 | 0.719 |
TEK |
0.428 | -0.123 | 3 | 0.154 |
TNNI3K_TYR |
0.428 | -0.056 | 1 | 0.411 |
ERBB2 |
0.427 | -0.068 | 1 | 0.414 |
NTRK3 |
0.427 | -0.027 | -1 | 0.679 |
EPHB3 |
0.425 | -0.090 | -1 | 0.716 |
FGFR4 |
0.425 | -0.030 | -1 | 0.657 |
EPHA4 |
0.425 | -0.079 | 2 | 0.251 |
IGF1R |
0.424 | -0.048 | 3 | 0.154 |
EPHB2 |
0.424 | -0.090 | -1 | 0.700 |
EPHA7 |
0.423 | -0.093 | 2 | 0.280 |
MET |
0.423 | -0.086 | 3 | 0.175 |
EGFR |
0.420 | -0.031 | 1 | 0.373 |
EPHA1 |
0.420 | -0.111 | 3 | 0.168 |
EPHA3 |
0.420 | -0.095 | 2 | 0.259 |
HCK |
0.419 | -0.116 | -1 | 0.617 |
BMX |
0.418 | -0.071 | -1 | 0.610 |
ITK |
0.418 | -0.128 | -1 | 0.627 |
YES1 |
0.417 | -0.124 | -1 | 0.606 |
PTK6 |
0.417 | -0.057 | -1 | 0.582 |
EPHA5 |
0.417 | -0.086 | 2 | 0.253 |
CSK |
0.417 | -0.070 | 2 | 0.266 |
BTK |
0.416 | -0.126 | -1 | 0.596 |
FRK |
0.415 | -0.117 | -1 | 0.644 |
SRMS |
0.415 | -0.126 | 1 | 0.304 |
FER |
0.414 | -0.190 | 1 | 0.303 |
EPHA2 |
0.414 | -0.083 | -1 | 0.708 |
EPHA8 |
0.414 | -0.090 | -1 | 0.712 |
ERBB4 |
0.412 | -0.068 | 1 | 0.301 |
FGR |
0.412 | -0.152 | 1 | 0.310 |
TXK |
0.412 | -0.110 | 1 | 0.255 |
LCK |
0.411 | -0.119 | -1 | 0.624 |
BLK |
0.411 | -0.108 | -1 | 0.624 |
MATK |
0.410 | -0.087 | -1 | 0.658 |
TEC |
0.410 | -0.135 | -1 | 0.559 |
SYK |
0.409 | -0.023 | -1 | 0.674 |
FYN |
0.407 | -0.081 | -1 | 0.589 |
PTK2B |
0.406 | -0.120 | -1 | 0.571 |
LYN |
0.404 | -0.142 | 3 | 0.192 |
SRC |
0.403 | -0.110 | -1 | 0.572 |
ZAP70 |
0.402 | -0.027 | -1 | 0.653 |
FES |
0.400 | -0.108 | -1 | 0.580 |
PTK2 |
0.399 | -0.069 | -1 | 0.659 |