Motif 983 (n=60)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| 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}. |
| 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}. |
| 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}. |
| 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}. |
| P20794 | MAK | Y159 | psp | Serine/threonine-protein kinase MAK (EC 2.7.11.1) (Male germ cell-associated kinase) | Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors (By similarity). Phosphorylates FZR1 in a cell cycle-dependent manner. Plays a role in the transcriptional coactivation of AR. Could play an important function in spermatogenesis. May play a role in chromosomal stability in prostate cancer cells. {ECO:0000250, ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:21986944}. |
| P21709 | EPHA1 | T783 | ochoa | Ephrin type-A receptor 1 (hEpha1) (EC 2.7.10.1) (EPH tyrosine kinase) (EPH tyrosine kinase 1) (Erythropoietin-producing hepatoma receptor) (Tyrosine-protein kinase receptor EPH) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217, ECO:0000269|PubMed:20043122}. |
| 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}. |
| P29317 | EPHA2 | T773 | ochoa | Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}. |
| P29320 | EPHA3 | T780 | ochoa | Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) | Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}. |
| 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}. |
| P45983 | MAPK8 | Y185 | ochoa|psp | Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1) | Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:28943315, ECO:0000269|PubMed:34048572}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. |
| P45984 | MAPK9 | Y185 | ochoa|psp | Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2) | Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:10376527). In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (PubMed:15805466). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (PubMed:17525747, PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:19290929). Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels (PubMed:19290929). Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (PubMed:20595622). When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (PubMed:19675674). Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:10376527, ECO:0000269|PubMed:15805466, ECO:0000269|PubMed:17525747, ECO:0000269|PubMed:19675674, ECO:0000269|PubMed:20595622, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:34048572, ECO:0000303|PubMed:19290929}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it. |
| P49840 | GSK3A | Y279 | ochoa|psp | Glycogen synthase kinase-3 alpha (GSK-3 alpha) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3A) (EC 2.7.11.1) | Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions which activates KAT5/TIP60 acetyltransferase activity and promotes acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). {ECO:0000250|UniProtKB:P18265, ECO:0000250|UniProtKB:P49841, ECO:0000250|UniProtKB:Q2NL51, ECO:0000269|PubMed:10868943, ECO:0000269|PubMed:12761548, ECO:0000269|PubMed:17229088, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:30704899, ECO:0000303|PubMed:11749387, ECO:0000303|PubMed:17478001, ECO:0000303|PubMed:19366350}. |
| P49841 | GSK3B | Y216 | ochoa|psp | Glycogen synthase kinase-3 beta (GSK-3 beta) (EC 2.7.11.26) (Serine/threonine-protein kinase GSK3B) (EC 2.7.11.1) | Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1 (PubMed:11430833, PubMed:12554650, PubMed:14690523, PubMed:16484495, PubMed:1846781, PubMed:20937854, PubMed:9072970). Requires primed phosphorylation of the majority of its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:8397507). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:8397507). Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease (PubMed:14690523). Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854). Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (By similarity). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the establishment of neuronal polarity and axon outgrowth (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1 which enhances its antiviral activity (PubMed:22514281). Phosphorylates SNAI1, leading to its ubiquitination and proteasomal degradation (PubMed:15448698, PubMed:15647282, PubMed:25827072, PubMed:29059170). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex and proteasomal degradation (By similarity). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and BMAL1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, activating KAT5/TIP60 acetyltransferase activity and promoting acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110). Phosphorylates E2F1, promoting the interaction between E2F1 and USP11, stabilizing E2F1 and promoting its activity (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2 complex component RICTOR at 'Ser-1235' in response to endoplasmic stress, inhibiting mTORC2 (PubMed:21343617). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the proteasome (By similarity). Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20067585, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21343617, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25827072, ECO:0000269|PubMed:25897075, ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:29059170, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}. |
| 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}. |
| 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}. |
| P53779 | MAPK10 | Y223 | ochoa|psp | Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (MAP kinase p49 3F12) (Stress-activated protein kinase 1b) (SAPK1b) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3) | Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000269|PubMed:11718727, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692}. |
| P54646 | PRKAA2 | S173 | ochoa|psp | 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK subunit alpha-2) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:7959015). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (By similarity). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). Upon glucose starvation, promotes ARF6 activation in a kinase-independent manner leading to cell migration (PubMed:36017701). Upon glucose deprivation mediates the phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear localization signal of ACSS2, required for its interaction with KPNA1 and nuclear translocation (PubMed:28552616). Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:Q09137, ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36017701, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:7959015, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| P54756 | EPHA5 | T834 | ochoa | Ephrin type-A receptor 5 (EC 2.7.10.1) (Brain-specific kinase) (EPH homology kinase 1) (EHK-1) (EPH-like kinase 7) (EK7) (hEK7) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion (By similarity). {ECO:0000250}. |
| P54764 | EPHA4 | T780 | ochoa | Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK) | Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (By similarity). {ECO:0000250|UniProtKB:Q03137, ECO:0000269|PubMed:17143272}. |
| 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}. |
| Q05397 | PTK2 | S580 | ochoa | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| 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}. |
| Q13131 | PRKAA1 | S184 | ochoa | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| Q14004 | CDK13 | T871 | ochoa | Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) | Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}. |
| 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}. |
| Q15375 | EPHA7 | T792 | ochoa | Ephrin type-A receptor 7 (EC 2.7.10.1) (EPH homology kinase 3) (EHK-3) (EPH-like kinase 11) (EK11) (hEK11) | Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 and MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269|PubMed:17726105}. |
| 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}. |
| 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}. |
| 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}. |
| 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}. |
| 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}. |
| 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}. |
| Q9NWZ3 | IRAK4 | T345 | ochoa|psp | Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}. |
| Q9NYV4 | CDK12 | T893 | ochoa | Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) | Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| 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}. |
| Q9UPZ9 | CILK1 | Y159 | ochoa | Serine/threonine-protein kinase ICK (EC 2.7.11.1) (Ciliogenesis associated kinase 1) (Intestinal cell kinase) (hICK) (Laryngeal cancer kinase 2) (LCK2) (MAK-related kinase) (MRK) | Required for ciliogenesis (PubMed:24797473). Phosphorylates KIF3A (By similarity). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (By similarity). May play a key role in the development of multiple organ systems and particularly in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity (By similarity). {ECO:0000250|UniProtKB:Q62726, ECO:0000250|UniProtKB:Q9JKV2, ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502}. |
| Q9UQ07 | MOK | Y161 | psp | MAPK/MAK/MRK overlapping kinase (EC 2.7.11.22) (MOK protein kinase) (Renal tumor antigen 1) (RAGE-1) | Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner. {ECO:0000250|UniProtKB:Q9WVS4}. |
| 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}. |
| O14733 | MAP2K7 | S277 | Sugiyama | Dual specificity mitogen-activated protein kinase kinase 7 (MAP kinase kinase 7) (MAPKK 7) (EC 2.7.12.2) (JNK-activating kinase 2) (MAPK/ERK kinase 7) (MEK 7) (Stress-activated protein kinase kinase 4) (SAPK kinase 4) (SAPKK-4) (SAPKK4) (c-Jun N-terminal kinase kinase 2) (JNK kinase 2) (JNKK 2) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074). {ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:9312068, ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, ECO:0000269|Ref.5}. |
| O43353 | RIPK2 | S180 | EPSD|PSP | Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. |
| P42680 | TEC | S523 | Sugiyama | Tyrosine-protein kinase Tec (EC 2.7.10.2) | Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC also regulates FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation. {ECO:0000269|PubMed:10518561, ECO:0000269|PubMed:19883687, ECO:0000269|PubMed:20230531, ECO:0000269|PubMed:9753425}. |
| 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-450294 | MAP kinase activation | 5.356871e-11 | 10.271 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.283397e-10 | 9.892 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.283397e-10 | 9.892 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.283397e-10 | 9.892 |
| R-HSA-448424 | Interleukin-17 signaling | 1.561223e-10 | 9.807 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 4.393705e-10 | 9.357 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 3.487195e-10 | 9.458 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 3.221499e-10 | 9.492 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 4.755873e-10 | 9.323 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 5.961563e-10 | 9.225 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 8.583414e-10 | 9.066 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 8.583414e-10 | 9.066 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 1.060870e-09 | 8.974 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 1.060870e-09 | 8.974 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 5.185072e-09 | 8.285 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 6.694589e-09 | 8.174 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 6.960332e-09 | 8.157 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 7.416049e-09 | 8.130 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 7.416049e-09 | 8.130 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.432029e-08 | 7.844 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 1.687042e-08 | 7.773 |
| R-HSA-418597 | G alpha (z) signalling events | 2.421913e-08 | 7.616 |
| R-HSA-422475 | Axon guidance | 5.731710e-08 | 7.242 |
| R-HSA-168898 | Toll-like Receptor Cascades | 6.197572e-08 | 7.208 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 1.212233e-07 | 6.916 |
| R-HSA-199920 | CREB phosphorylation | 1.212233e-07 | 6.916 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 1.358076e-07 | 6.867 |
| R-HSA-9675108 | Nervous system development | 1.295052e-07 | 6.888 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 1.842694e-07 | 6.735 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 1.970234e-07 | 6.705 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 2.453450e-07 | 6.610 |
| R-HSA-444257 | RSK activation | 2.685857e-07 | 6.571 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 2.828024e-07 | 6.549 |
| R-HSA-194138 | Signaling by VEGF | 3.638120e-07 | 6.439 |
| R-HSA-198693 | AKT phosphorylates targets in the nucleus | 3.790403e-07 | 6.421 |
| R-HSA-2682334 | EPH-Ephrin signaling | 6.102475e-07 | 6.214 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 7.423862e-07 | 6.129 |
| R-HSA-162582 | Signal Transduction | 8.576163e-07 | 6.067 |
| R-HSA-1227986 | Signaling by ERBB2 | 9.624029e-07 | 6.017 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 1.308520e-06 | 5.883 |
| R-HSA-1640170 | Cell Cycle | 1.407789e-06 | 5.851 |
| R-HSA-8953897 | Cellular responses to stimuli | 1.462530e-06 | 5.835 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 1.595611e-06 | 5.797 |
| R-HSA-212436 | Generic Transcription Pathway | 2.245862e-06 | 5.649 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 2.935652e-06 | 5.532 |
| R-HSA-69278 | Cell Cycle, Mitotic | 3.548626e-06 | 5.450 |
| R-HSA-211163 | AKT-mediated inactivation of FOXO1A | 3.563148e-06 | 5.448 |
| R-HSA-165159 | MTOR signalling | 4.438311e-06 | 5.353 |
| R-HSA-2559583 | Cellular Senescence | 4.857405e-06 | 5.314 |
| R-HSA-2262752 | Cellular responses to stress | 5.588543e-06 | 5.253 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 5.810279e-06 | 5.236 |
| R-HSA-438064 | Post NMDA receptor activation events | 6.866244e-06 | 5.163 |
| R-HSA-437239 | Recycling pathway of L1 | 7.018194e-06 | 5.154 |
| R-HSA-198753 | ERK/MAPK targets | 7.945957e-06 | 5.100 |
| R-HSA-73857 | RNA Polymerase II Transcription | 9.146759e-06 | 5.039 |
| R-HSA-6804115 | TP53 regulates transcription of additional cell cycle genes whose exact role in ... | 1.061173e-05 | 4.974 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.216738e-05 | 4.915 |
| R-HSA-449147 | Signaling by Interleukins | 9.899473e-06 | 5.004 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 1.577445e-05 | 4.802 |
| R-HSA-114516 | Disinhibition of SNARE formation | 1.627354e-05 | 4.789 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 1.627544e-05 | 4.788 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 1.714475e-05 | 4.766 |
| R-HSA-5633007 | Regulation of TP53 Activity | 2.262735e-05 | 4.645 |
| R-HSA-109581 | Apoptosis | 2.428566e-05 | 4.615 |
| R-HSA-1266738 | Developmental Biology | 2.456961e-05 | 4.610 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 2.793048e-05 | 4.554 |
| R-HSA-114452 | Activation of BH3-only proteins | 2.818229e-05 | 4.550 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 4.059412e-05 | 4.392 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 3.840447e-05 | 4.416 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 4.405269e-05 | 4.356 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 4.169826e-05 | 4.380 |
| R-HSA-8941332 | RUNX2 regulates genes involved in cell migration | 4.405269e-05 | 4.356 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 4.234635e-05 | 4.373 |
| R-HSA-112315 | Transmission across Chemical Synapses | 3.547475e-05 | 4.450 |
| R-HSA-68875 | Mitotic Prophase | 4.409852e-05 | 4.356 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 4.422076e-05 | 4.354 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 5.595113e-05 | 4.252 |
| R-HSA-416476 | G alpha (q) signalling events | 6.073259e-05 | 4.217 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 6.531351e-05 | 4.185 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 7.249814e-05 | 4.140 |
| R-HSA-6804759 | Regulation of TP53 Activity through Association with Co-factors | 7.807601e-05 | 4.107 |
| R-HSA-388396 | GPCR downstream signalling | 8.437779e-05 | 4.074 |
| R-HSA-74160 | Gene expression (Transcription) | 9.111943e-05 | 4.040 |
| R-HSA-5357801 | Programmed Cell Death | 9.785682e-05 | 4.009 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 1.082650e-04 | 3.966 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 1.082650e-04 | 3.966 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 1.238167e-04 | 3.907 |
| R-HSA-1489509 | DAG and IP3 signaling | 1.246175e-04 | 3.904 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 1.258478e-04 | 3.900 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 1.894639e-04 | 3.722 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 1.995141e-04 | 3.700 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.078214e-04 | 3.682 |
| R-HSA-372790 | Signaling by GPCR | 2.249599e-04 | 3.648 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 2.416699e-04 | 3.617 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 2.548057e-04 | 3.594 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 2.701466e-04 | 3.568 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 3.379601e-04 | 3.471 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 3.669270e-04 | 3.435 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 3.721507e-04 | 3.429 |
| R-HSA-373760 | L1CAM interactions | 3.936219e-04 | 3.405 |
| R-HSA-9711123 | Cellular response to chemical stress | 4.352874e-04 | 3.361 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 4.855523e-04 | 3.314 |
| R-HSA-168249 | Innate Immune System | 4.910078e-04 | 3.309 |
| R-HSA-112316 | Neuronal System | 4.982099e-04 | 3.303 |
| R-HSA-68877 | Mitotic Prometaphase | 5.178966e-04 | 3.286 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 5.409952e-04 | 3.267 |
| R-HSA-399719 | Trafficking of AMPA receptors | 7.522942e-04 | 3.124 |
| R-HSA-68886 | M Phase | 6.385550e-04 | 3.195 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 6.580734e-04 | 3.182 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 8.750715e-04 | 3.058 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 6.952755e-04 | 3.158 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 8.750715e-04 | 3.058 |
| R-HSA-210745 | Regulation of gene expression in beta cells | 6.410924e-04 | 3.193 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 8.122071e-04 | 3.090 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 6.045960e-04 | 3.219 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 6.952755e-04 | 3.158 |
| R-HSA-397795 | G-protein beta:gamma signalling | 8.750715e-04 | 3.058 |
| R-HSA-168256 | Immune System | 7.486383e-04 | 3.126 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 8.445415e-04 | 3.073 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 1.066050e-03 | 2.972 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 1.081933e-03 | 2.966 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 1.114866e-03 | 2.953 |
| R-HSA-111933 | Calmodulin induced events | 1.157158e-03 | 2.937 |
| R-HSA-111997 | CaM pathway | 1.157158e-03 | 2.937 |
| R-HSA-166520 | Signaling by NTRKs | 1.172098e-03 | 2.931 |
| R-HSA-8939246 | RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... | 1.285903e-03 | 2.891 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 1.525668e-03 | 2.817 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 1.582666e-03 | 2.801 |
| R-HSA-9607240 | FLT3 Signaling | 1.582666e-03 | 2.801 |
| R-HSA-111996 | Ca-dependent events | 1.776842e-03 | 2.750 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 2.094972e-03 | 2.679 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 2.094972e-03 | 2.679 |
| R-HSA-75153 | Apoptotic execution phase | 2.208359e-03 | 2.656 |
| R-HSA-389356 | Co-stimulation by CD28 | 2.446409e-03 | 2.611 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 2.660357e-03 | 2.575 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 2.679419e-03 | 2.572 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 2.903258e-03 | 2.537 |
| R-HSA-9683610 | Maturation of nucleoprotein | 3.015612e-03 | 2.521 |
| R-HSA-8948751 | Regulation of PTEN stability and activity | 3.109215e-03 | 2.507 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 3.722347e-03 | 2.429 |
| R-HSA-193639 | p75NTR signals via NF-kB | 3.744036e-03 | 2.427 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 3.796434e-03 | 2.421 |
| R-HSA-195721 | Signaling by WNT | 3.988309e-03 | 2.399 |
| R-HSA-186712 | Regulation of beta-cell development | 4.037668e-03 | 2.394 |
| R-HSA-112043 | PLC beta mediated events | 4.380638e-03 | 2.358 |
| R-HSA-109582 | Hemostasis | 4.527801e-03 | 2.344 |
| R-HSA-2892247 | POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation | 4.545990e-03 | 2.342 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 4.740783e-03 | 2.324 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 4.740783e-03 | 2.324 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 4.740783e-03 | 2.324 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 5.041045e-03 | 2.297 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 5.313735e-03 | 2.275 |
| R-HSA-156711 | Polo-like kinase mediated events | 5.420064e-03 | 2.266 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 5.420064e-03 | 2.266 |
| R-HSA-112040 | G-protein mediated events | 5.513563e-03 | 2.259 |
| R-HSA-9694631 | Maturation of nucleoprotein | 5.883712e-03 | 2.230 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 6.139959e-03 | 2.212 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 6.357814e-03 | 2.197 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.580241e-03 | 2.182 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 6.580241e-03 | 2.182 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 6.807261e-03 | 2.167 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 6.807261e-03 | 2.167 |
| R-HSA-380287 | Centrosome maturation | 7.275176e-03 | 2.138 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 7.379035e-03 | 2.132 |
| R-HSA-8939211 | ESR-mediated signaling | 7.495891e-03 | 2.125 |
| R-HSA-4086400 | PCP/CE pathway | 8.012067e-03 | 2.096 |
| R-HSA-69242 | S Phase | 8.042901e-03 | 2.095 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 8.070483e-03 | 2.093 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 9.060820e-03 | 2.043 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 9.613922e-03 | 2.017 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 1.018636e-02 | 1.992 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 1.047987e-02 | 1.980 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 1.108154e-02 | 1.955 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 1.145548e-02 | 1.941 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 1.170286e-02 | 1.932 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 1.276530e-02 | 1.894 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 1.291362e-02 | 1.889 |
| R-HSA-68881 | Mitotic Metaphase/Anaphase Transition | 1.870369e-02 | 1.728 |
| R-HSA-5603037 | IRAK4 deficiency (TLR5) | 2.332541e-02 | 1.632 |
| R-HSA-165181 | Inhibition of TSC complex formation by PKB | 2.792565e-02 | 1.554 |
| R-HSA-111446 | Activation of BIM and translocation to mitochondria | 2.332541e-02 | 1.632 |
| R-HSA-139910 | Activation of BMF and translocation to mitochondria | 2.332541e-02 | 1.632 |
| R-HSA-354192 | Integrin signaling | 1.484619e-02 | 1.828 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 2.628482e-02 | 1.580 |
| R-HSA-373752 | Netrin-1 signaling | 2.537852e-02 | 1.596 |
| R-HSA-69275 | G2/M Transition | 1.631800e-02 | 1.787 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 1.684606e-02 | 1.774 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 2.022198e-02 | 1.694 |
| R-HSA-9007892 | Interleukin-38 signaling | 2.792565e-02 | 1.554 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 2.205367e-02 | 1.657 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 1.739131e-02 | 1.760 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 1.547541e-02 | 1.810 |
| R-HSA-9824272 | Somitogenesis | 2.628482e-02 | 1.580 |
| R-HSA-1433557 | Signaling by SCF-KIT | 2.448538e-02 | 1.611 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 1.861373e-02 | 1.730 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 1.630906e-02 | 1.788 |
| R-HSA-452723 | Transcriptional regulation of pluripotent stem cells | 1.941077e-02 | 1.712 |
| R-HSA-9683701 | Translation of Structural Proteins | 2.273913e-02 | 1.643 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 2.720412e-02 | 1.565 |
| R-HSA-389948 | Co-inhibition by PD-1 | 2.023972e-02 | 1.694 |
| R-HSA-111885 | Opioid Signalling | 1.739131e-02 | 1.760 |
| R-HSA-2672351 | Stimuli-sensing channels | 1.943410e-02 | 1.711 |
| R-HSA-9007101 | Rab regulation of trafficking | 2.437708e-02 | 1.613 |
| R-HSA-9614085 | FOXO-mediated transcription | 1.547541e-02 | 1.810 |
| R-HSA-1280218 | Adaptive Immune System | 2.821785e-02 | 1.549 |
| R-HSA-69206 | G1/S Transition | 2.888078e-02 | 1.539 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 3.008852e-02 | 1.522 |
| R-HSA-2514856 | The phototransduction cascade | 3.199105e-02 | 1.495 |
| R-HSA-165158 | Activation of AKT2 | 3.250450e-02 | 1.488 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 3.298555e-02 | 1.482 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 3.298555e-02 | 1.482 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 3.379602e-02 | 1.471 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 3.504119e-02 | 1.455 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 3.611168e-02 | 1.442 |
| R-HSA-176417 | Phosphorylation of Emi1 | 3.706207e-02 | 1.431 |
| R-HSA-109703 | PKB-mediated events | 3.706207e-02 | 1.431 |
| R-HSA-165160 | PDE3B signalling | 3.706207e-02 | 1.431 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 3.708287e-02 | 1.431 |
| R-HSA-6807070 | PTEN Regulation | 3.790099e-02 | 1.421 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 4.246317e-02 | 1.372 |
| R-HSA-69620 | Cell Cycle Checkpoints | 4.281708e-02 | 1.368 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 4.289082e-02 | 1.368 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 4.357244e-02 | 1.361 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 4.550365e-02 | 1.342 |
| R-HSA-446652 | Interleukin-1 family signaling | 4.683924e-02 | 1.329 |
| R-HSA-73887 | Death Receptor Signaling | 4.819416e-02 | 1.317 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 5.060803e-02 | 1.296 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 5.060803e-02 | 1.296 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 5.402638e-02 | 1.267 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 5.402638e-02 | 1.267 |
| R-HSA-9679506 | SARS-CoV Infections | 5.484231e-02 | 1.261 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 5.508143e-02 | 1.259 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 5.508143e-02 | 1.259 |
| R-HSA-9613354 | Lipophagy | 5.508143e-02 | 1.259 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 5.953402e-02 | 1.225 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 5.953402e-02 | 1.225 |
| R-HSA-9694635 | Translation of Structural Proteins | 6.143770e-02 | 1.212 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 6.270516e-02 | 1.203 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 6.270516e-02 | 1.203 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 6.356110e-02 | 1.197 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 6.396591e-02 | 1.194 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 6.396591e-02 | 1.194 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 6.396591e-02 | 1.194 |
| R-HSA-4839744 | Signaling by APC mutants | 6.396591e-02 | 1.194 |
| R-HSA-9635465 | Suppression of apoptosis | 6.396591e-02 | 1.194 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 6.396591e-02 | 1.194 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 6.526671e-02 | 1.185 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 6.837719e-02 | 1.165 |
| R-HSA-68884 | Mitotic Telophase/Cytokinesis | 6.837719e-02 | 1.165 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 6.837719e-02 | 1.165 |
| R-HSA-4839735 | Signaling by AXIN mutants | 6.837719e-02 | 1.165 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 7.076324e-02 | 1.150 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 7.276795e-02 | 1.138 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 7.276795e-02 | 1.138 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 7.276795e-02 | 1.138 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 7.276795e-02 | 1.138 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 7.276795e-02 | 1.138 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 7.450042e-02 | 1.128 |
| R-HSA-983712 | Ion channel transport | 7.576136e-02 | 1.121 |
| R-HSA-5617833 | Cilium Assembly | 7.660936e-02 | 1.116 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 7.713829e-02 | 1.113 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 7.738751e-02 | 1.111 |
| R-HSA-202424 | Downstream TCR signaling | 7.995419e-02 | 1.097 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 8.133676e-02 | 1.090 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 8.148829e-02 | 1.089 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 8.148829e-02 | 1.089 |
| R-HSA-1433559 | Regulation of KIT signaling | 8.148829e-02 | 1.089 |
| R-HSA-391160 | Signal regulatory protein family interactions | 8.148829e-02 | 1.089 |
| R-HSA-381070 | IRE1alpha activates chaperones | 8.272679e-02 | 1.082 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 8.412417e-02 | 1.075 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 8.581807e-02 | 1.066 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 8.581807e-02 | 1.066 |
| R-HSA-418885 | DCC mediated attractive signaling | 8.581807e-02 | 1.066 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 8.581807e-02 | 1.066 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 9.012770e-02 | 1.045 |
| R-HSA-176412 | Phosphorylation of the APC/C | 9.012770e-02 | 1.045 |
| R-HSA-9664420 | Killing mechanisms | 9.012770e-02 | 1.045 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 9.012770e-02 | 1.045 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 9.012770e-02 | 1.045 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 9.441728e-02 | 1.025 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 9.441728e-02 | 1.025 |
| R-HSA-9020702 | Interleukin-1 signaling | 9.848129e-02 | 1.007 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 9.868690e-02 | 1.006 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 9.868690e-02 | 1.006 |
| R-HSA-9856532 | Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1.071666e-01 | 0.970 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 1.089128e-01 | 0.963 |
| R-HSA-9700206 | Signaling by ALK in cancer | 1.089128e-01 | 0.963 |
| R-HSA-202403 | TCR signaling | 1.134707e-01 | 0.945 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 1.155676e-01 | 0.937 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 1.197388e-01 | 0.922 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 1.197388e-01 | 0.922 |
| R-HSA-166208 | mTORC1-mediated signalling | 1.238906e-01 | 0.907 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 1.242927e-01 | 0.906 |
| R-HSA-200425 | Carnitine shuttle | 1.280231e-01 | 0.893 |
| R-HSA-3000170 | Syndecan interactions | 1.280231e-01 | 0.893 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 1.321363e-01 | 0.879 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 1.337601e-01 | 0.874 |
| R-HSA-420029 | Tight junction interactions | 1.362303e-01 | 0.866 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1.369520e-01 | 0.863 |
| R-HSA-8874081 | MET activates PTK2 signaling | 1.403054e-01 | 0.853 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1.443614e-01 | 0.841 |
| R-HSA-9841251 | Mitochondrial unfolded protein response (UPRmt) | 1.443614e-01 | 0.841 |
| R-HSA-1474151 | Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation | 1.564165e-01 | 0.806 |
| R-HSA-163685 | Integration of energy metabolism | 1.630528e-01 | 0.788 |
| R-HSA-4791275 | Signaling by WNT in cancer | 1.643600e-01 | 0.784 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 1.680448e-01 | 0.775 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 1.683040e-01 | 0.774 |
| R-HSA-9824443 | Parasitic Infection Pathways | 1.701551e-01 | 0.769 |
| R-HSA-9658195 | Leishmania infection | 1.701551e-01 | 0.769 |
| R-HSA-1632852 | Macroautophagy | 1.713876e-01 | 0.766 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 1.761370e-01 | 0.754 |
| R-HSA-203615 | eNOS activation | 1.761370e-01 | 0.754 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 1.761370e-01 | 0.754 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 1.800262e-01 | 0.745 |
| R-HSA-2187338 | Visual phototransduction | 1.831733e-01 | 0.737 |
| R-HSA-114604 | GPVI-mediated activation cascade | 1.838972e-01 | 0.735 |
| R-HSA-8853659 | RET signaling | 1.838972e-01 | 0.735 |
| R-HSA-9758941 | Gastrulation | 1.865632e-01 | 0.729 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 1.877502e-01 | 0.726 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 1.877502e-01 | 0.726 |
| R-HSA-8875878 | MET promotes cell motility | 1.915853e-01 | 0.718 |
| R-HSA-202131 | Metabolism of nitric oxide: NOS3 activation and regulation | 1.915853e-01 | 0.718 |
| R-HSA-9648002 | RAS processing | 1.954025e-01 | 0.709 |
| R-HSA-9612973 | Autophagy | 1.984965e-01 | 0.702 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 1.992019e-01 | 0.701 |
| R-HSA-5260271 | Diseases of Immune System | 1.992019e-01 | 0.701 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 1.992019e-01 | 0.701 |
| R-HSA-5625886 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... | 2.029835e-01 | 0.693 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 2.067476e-01 | 0.685 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 2.067476e-01 | 0.685 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 2.104941e-01 | 0.677 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 2.142232e-01 | 0.669 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 2.179348e-01 | 0.662 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 2.216292e-01 | 0.654 |
| R-HSA-2299718 | Condensation of Prophase Chromosomes | 2.253064e-01 | 0.647 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 2.260907e-01 | 0.646 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 2.289664e-01 | 0.640 |
| R-HSA-9031628 | NGF-stimulated transcription | 2.326093e-01 | 0.633 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 2.330397e-01 | 0.633 |
| R-HSA-109704 | PI3K Cascade | 2.398443e-01 | 0.620 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 2.434365e-01 | 0.614 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 2.470120e-01 | 0.607 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 2.505707e-01 | 0.601 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 2.505707e-01 | 0.601 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.505707e-01 | 0.601 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 2.576386e-01 | 0.589 |
| R-HSA-193648 | NRAGE signals death through JNK | 2.611478e-01 | 0.583 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 2.626950e-01 | 0.581 |
| R-HSA-112399 | IRS-mediated signalling | 2.646406e-01 | 0.577 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 2.715775e-01 | 0.566 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 2.784498e-01 | 0.555 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 2.784498e-01 | 0.555 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 2.818619e-01 | 0.550 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 2.818619e-01 | 0.550 |
| R-HSA-8848021 | Signaling by PTK6 | 2.852581e-01 | 0.545 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 2.852581e-01 | 0.545 |
| R-HSA-373755 | Semaphorin interactions | 2.852581e-01 | 0.545 |
| R-HSA-5663205 | Infectious disease | 2.865516e-01 | 0.543 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 2.886384e-01 | 0.540 |
| R-HSA-2428924 | IGF1R signaling cascade | 2.886384e-01 | 0.540 |
| R-HSA-74751 | Insulin receptor signalling cascade | 2.886384e-01 | 0.540 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 2.920030e-01 | 0.535 |
| R-HSA-5693606 | DNA Double Strand Break Response | 2.986850e-01 | 0.525 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 3.085916e-01 | 0.511 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 3.085916e-01 | 0.511 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 3.118630e-01 | 0.506 |
| R-HSA-8978934 | Metabolism of cofactors | 3.118630e-01 | 0.506 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 3.183601e-01 | 0.497 |
| R-HSA-4086398 | Ca2+ pathway | 3.183601e-01 | 0.497 |
| R-HSA-9013694 | Signaling by NOTCH4 | 3.215859e-01 | 0.493 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 3.247966e-01 | 0.488 |
| R-HSA-418594 | G alpha (i) signalling events | 3.287930e-01 | 0.483 |
| R-HSA-9925561 | Developmental Lineage of Pancreatic Acinar Cells | 3.374902e-01 | 0.472 |
| R-HSA-6806834 | Signaling by MET | 3.406266e-01 | 0.468 |
| R-HSA-157118 | Signaling by NOTCH | 3.478057e-01 | 0.459 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 3.591398e-01 | 0.445 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 3.591398e-01 | 0.445 |
| R-HSA-9663891 | Selective autophagy | 3.682031e-01 | 0.434 |
| R-HSA-1912408 | Pre-NOTCH Transcription and Translation | 3.771399e-01 | 0.423 |
| R-HSA-74752 | Signaling by Insulin receptor | 3.830283e-01 | 0.417 |
| R-HSA-199991 | Membrane Trafficking | 3.887117e-01 | 0.410 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 3.975101e-01 | 0.401 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 4.003659e-01 | 0.398 |
| R-HSA-422356 | Regulation of insulin secretion | 4.032084e-01 | 0.394 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 4.088535e-01 | 0.388 |
| R-HSA-5610787 | Hedgehog 'off' state | 4.088535e-01 | 0.388 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 4.144460e-01 | 0.383 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 4.296478e-01 | 0.367 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 4.409248e-01 | 0.356 |
| R-HSA-1912422 | Pre-NOTCH Expression and Processing | 4.469207e-01 | 0.350 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 4.573455e-01 | 0.340 |
| R-HSA-9824446 | Viral Infection Pathways | 4.596406e-01 | 0.338 |
| R-HSA-1592230 | Mitochondrial biogenesis | 4.624849e-01 | 0.335 |
| R-HSA-1500931 | Cell-Cell communication | 4.724721e-01 | 0.326 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 4.726201e-01 | 0.325 |
| R-HSA-3371556 | Cellular response to heat stress | 4.726201e-01 | 0.325 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 4.726201e-01 | 0.325 |
| R-HSA-5683057 | MAPK family signaling cascades | 5.192436e-01 | 0.285 |
| R-HSA-5358351 | Signaling by Hedgehog | 5.205349e-01 | 0.284 |
| R-HSA-9664417 | Leishmania phagocytosis | 5.250833e-01 | 0.280 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 5.250833e-01 | 0.280 |
| R-HSA-9664407 | Parasite infection | 5.250833e-01 | 0.280 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 5.273414e-01 | 0.278 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 5.318261e-01 | 0.274 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 5.362687e-01 | 0.271 |
| R-HSA-9820448 | Developmental Cell Lineages of the Exocrine Pancreas | 5.536269e-01 | 0.257 |
| R-HSA-5653656 | Vesicle-mediated transport | 5.540856e-01 | 0.256 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 5.557511e-01 | 0.255 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 5.662233e-01 | 0.247 |
| R-HSA-877300 | Interferon gamma signaling | 5.682883e-01 | 0.245 |
| R-HSA-9006936 | Signaling by TGFB family members | 5.703436e-01 | 0.244 |
| R-HSA-2467813 | Separation of Sister Chromatids | 5.784688e-01 | 0.238 |
| R-HSA-9824439 | Bacterial Infection Pathways | 5.808319e-01 | 0.236 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 5.981242e-01 | 0.223 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 5.981242e-01 | 0.223 |
| R-HSA-1643685 | Disease | 6.028853e-01 | 0.220 |
| R-HSA-376176 | Signaling by ROBO receptors | 6.518231e-01 | 0.186 |
| R-HSA-6798695 | Neutrophil degranulation | 6.633363e-01 | 0.178 |
| R-HSA-68882 | Mitotic Anaphase | 6.743957e-01 | 0.171 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 6.759516e-01 | 0.170 |
| R-HSA-421270 | Cell-cell junction organization | 7.247020e-01 | 0.140 |
| R-HSA-5688426 | Deubiquitination | 7.299384e-01 | 0.137 |
| R-HSA-9734767 | Developmental Cell Lineages | 7.401180e-01 | 0.131 |
| R-HSA-446728 | Cell junction organization | 7.581947e-01 | 0.120 |
| R-HSA-8953854 | Metabolism of RNA | 7.756591e-01 | 0.110 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 8.053045e-01 | 0.094 |
| R-HSA-1474244 | Extracellular matrix organization | 8.126744e-01 | 0.090 |
| R-HSA-73894 | DNA Repair | 8.371547e-01 | 0.077 |
| R-HSA-196854 | Metabolism of vitamins and cofactors | 8.402734e-01 | 0.076 |
| R-HSA-913531 | Interferon Signaling | 8.550044e-01 | 0.068 |
| R-HSA-382551 | Transport of small molecules | 8.591318e-01 | 0.066 |
| R-HSA-8978868 | Fatty acid metabolism | 8.709204e-01 | 0.060 |
| R-HSA-9709957 | Sensory Perception | 9.846264e-01 | 0.007 |
| R-HSA-556833 | Metabolism of lipids | 9.994346e-01 | 0.000 |
| R-HSA-597592 | Post-translational protein modification | 9.997692e-01 | 0.000 |
| R-HSA-392499 | Metabolism of proteins | 9.999960e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 9.999995e-01 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
PDK1 |
0.674 | 0.325 | 1 | 0.750 |
MST3 |
0.671 | 0.132 | 2 | 0.567 |
TAO3 |
0.670 | 0.173 | 1 | 0.628 |
TAK1 |
0.670 | 0.183 | 1 | 0.650 |
NEK11 |
0.663 | 0.136 | 1 | 0.705 |
PKN3 |
0.660 | 0.255 | -3 | 0.782 |
MAP3K15 |
0.660 | 0.112 | 1 | 0.673 |
HPK1 |
0.660 | 0.074 | 1 | 0.650 |
GAK |
0.660 | 0.086 | 1 | 0.524 |
GCK |
0.659 | 0.076 | 1 | 0.638 |
GRK1 |
0.659 | 0.257 | -2 | 0.623 |
GRK7 |
0.659 | 0.181 | 1 | 0.527 |
ANKRD3 |
0.659 | 0.139 | 1 | 0.677 |
NEK8 |
0.658 | 0.108 | 2 | 0.538 |
PKN2 |
0.658 | 0.184 | -3 | 0.788 |
MEKK3 |
0.658 | 0.111 | 1 | 0.639 |
PKR |
0.658 | 0.099 | 1 | 0.557 |
SGK3 |
0.657 | 0.198 | -3 | 0.758 |
MINK |
0.657 | 0.062 | 1 | 0.648 |
MEKK1 |
0.657 | 0.099 | 1 | 0.632 |
ZAK |
0.656 | 0.094 | 1 | 0.676 |
BRAF |
0.656 | 0.081 | -4 | 0.729 |
TNIK |
0.656 | 0.053 | 3 | 0.409 |
DLK |
0.655 | 0.102 | 1 | 0.638 |
MST4 |
0.655 | 0.147 | 2 | 0.577 |
NIK |
0.655 | 0.095 | -3 | 0.771 |
KHS1 |
0.655 | 0.056 | 1 | 0.635 |
ASK1 |
0.655 | 0.102 | 1 | 0.668 |
MEKK2 |
0.655 | 0.037 | 2 | 0.517 |
OSR1 |
0.655 | 0.090 | 2 | 0.518 |
RAF1 |
0.655 | 0.144 | 1 | 0.639 |
KHS2 |
0.655 | 0.058 | 1 | 0.645 |
MLK1 |
0.654 | 0.122 | 2 | 0.539 |
TAO2 |
0.654 | 0.055 | 2 | 0.551 |
YSK1 |
0.654 | 0.066 | 2 | 0.555 |
DRAK1 |
0.654 | 0.150 | 1 | 0.678 |
PASK |
0.654 | 0.103 | -3 | 0.757 |
YSK4 |
0.653 | 0.083 | 1 | 0.634 |
MOS |
0.653 | 0.129 | 1 | 0.509 |
GSK3B |
0.652 | 0.202 | 4 | 0.544 |
NEK5 |
0.652 | 0.057 | 1 | 0.591 |
NLK |
0.651 | 0.059 | 1 | 0.558 |
P70S6KB |
0.651 | 0.188 | -3 | 0.771 |
VRK1 |
0.651 | 0.139 | 2 | 0.592 |
MEK5 |
0.651 | 0.015 | 2 | 0.507 |
MLK3 |
0.650 | 0.079 | 2 | 0.510 |
DAPK2 |
0.650 | 0.066 | -3 | 0.786 |
ROCK2 |
0.650 | 0.127 | -3 | 0.759 |
MLK4 |
0.650 | 0.080 | 2 | 0.478 |
PKCA |
0.650 | 0.117 | 2 | 0.510 |
COT |
0.649 | 0.191 | 2 | 0.561 |
MEKK6 |
0.649 | -0.002 | 1 | 0.581 |
SKMLCK |
0.649 | 0.099 | -2 | 0.634 |
VRK2 |
0.649 | 0.019 | 1 | 0.585 |
CAMK1B |
0.648 | 0.100 | -3 | 0.790 |
AKT1 |
0.648 | 0.152 | -3 | 0.739 |
HGK |
0.648 | 0.011 | 3 | 0.412 |
CAMLCK |
0.648 | 0.046 | -2 | 0.604 |
LRRK2 |
0.647 | 0.009 | 2 | 0.550 |
AKT2 |
0.647 | 0.144 | -3 | 0.732 |
NEK9 |
0.647 | 0.095 | 2 | 0.558 |
RIPK3 |
0.647 | 0.089 | 3 | 0.384 |
MEK1 |
0.647 | 0.004 | 2 | 0.481 |
MLK2 |
0.647 | 0.081 | 2 | 0.520 |
MST1 |
0.646 | 0.005 | 1 | 0.627 |
PKCD |
0.646 | 0.112 | 2 | 0.520 |
TAO1 |
0.646 | 0.074 | 1 | 0.627 |
MYO3A |
0.646 | -0.000 | 1 | 0.581 |
PKCH |
0.646 | 0.109 | 2 | 0.520 |
EEF2K |
0.646 | -0.001 | 3 | 0.391 |
NEK1 |
0.645 | 0.020 | 1 | 0.595 |
MST2 |
0.645 | 0.011 | 1 | 0.621 |
GSK3A |
0.645 | 0.187 | 4 | 0.541 |
SLK |
0.645 | 0.051 | -2 | 0.479 |
LOK |
0.645 | 0.046 | -2 | 0.528 |
ICK |
0.645 | 0.084 | -3 | 0.782 |
CDKL1 |
0.645 | 0.081 | -3 | 0.765 |
DCAMKL1 |
0.644 | 0.163 | -3 | 0.769 |
PKCE |
0.644 | 0.108 | 2 | 0.527 |
MPSK1 |
0.644 | 0.056 | 1 | 0.493 |
PRPK |
0.644 | 0.071 | -1 | 0.764 |
NEK4 |
0.644 | -0.009 | 1 | 0.604 |
CAMKK2 |
0.643 | 0.007 | -2 | 0.527 |
CAMKK1 |
0.643 | 0.001 | -2 | 0.527 |
RIPK1 |
0.643 | 0.076 | 1 | 0.624 |
SGK1 |
0.643 | 0.155 | -3 | 0.673 |
PLK1 |
0.643 | 0.131 | -2 | 0.447 |
PKCZ |
0.643 | 0.099 | 2 | 0.546 |
WNK1 |
0.642 | 0.060 | -2 | 0.639 |
PKCB |
0.642 | 0.088 | 2 | 0.527 |
LATS1 |
0.642 | 0.082 | -3 | 0.730 |
BMPR2 |
0.642 | -0.029 | -2 | 0.570 |
DAPK1 |
0.642 | 0.080 | -3 | 0.769 |
GRK6 |
0.642 | 0.084 | 1 | 0.583 |
JNK3 |
0.642 | 0.029 | 1 | 0.415 |
LKB1 |
0.641 | 0.026 | -3 | 0.704 |
SMMLCK |
0.641 | 0.038 | -3 | 0.790 |
CAMK2G |
0.641 | 0.125 | 2 | 0.425 |
MYO3B |
0.641 | -0.002 | 2 | 0.549 |
NEK2 |
0.641 | 0.042 | 2 | 0.550 |
PKCG |
0.640 | 0.091 | 2 | 0.528 |
MRCKB |
0.640 | 0.105 | -3 | 0.758 |
NEK7 |
0.640 | 0.115 | -3 | 0.690 |
GRK5 |
0.640 | 0.086 | -3 | 0.684 |
NEK6 |
0.640 | 0.156 | -2 | 0.530 |
PKCI |
0.640 | 0.092 | 2 | 0.547 |
IKKB |
0.640 | 0.177 | -2 | 0.535 |
CHAK2 |
0.639 | 0.051 | -1 | 0.805 |
CHAK1 |
0.639 | 0.029 | 2 | 0.512 |
JNK2 |
0.639 | 0.027 | 1 | 0.405 |
DSTYK |
0.639 | 0.074 | 2 | 0.532 |
DAPK3 |
0.638 | 0.049 | -3 | 0.771 |
WNK4 |
0.638 | 0.014 | -2 | 0.621 |
IRAK4 |
0.638 | 0.004 | 1 | 0.555 |
ROCK1 |
0.638 | 0.094 | -3 | 0.758 |
MTOR |
0.638 | 0.118 | 1 | 0.604 |
DCAMKL2 |
0.638 | 0.135 | -3 | 0.780 |
ALPHAK3 |
0.637 | 0.055 | -1 | 0.797 |
ALK4 |
0.637 | 0.005 | -2 | 0.521 |
ATR |
0.637 | -0.021 | 1 | 0.537 |
DMPK1 |
0.637 | 0.069 | -3 | 0.765 |
MASTL |
0.636 | 0.084 | -2 | 0.543 |
HASPIN |
0.636 | 0.050 | -1 | 0.675 |
STLK3 |
0.636 | 0.004 | 1 | 0.630 |
AKT3 |
0.636 | 0.142 | -3 | 0.691 |
PKN1 |
0.635 | 0.180 | -3 | 0.766 |
TTBK2 |
0.635 | 0.076 | 2 | 0.463 |
PHKG1 |
0.635 | 0.177 | -3 | 0.775 |
CAMK4 |
0.635 | 0.152 | -3 | 0.783 |
AURA |
0.635 | 0.099 | -2 | 0.443 |
PKACG |
0.635 | 0.132 | -2 | 0.547 |
ULK2 |
0.635 | 0.101 | 2 | 0.504 |
P70S6K |
0.635 | 0.157 | -3 | 0.746 |
GRK4 |
0.635 | 0.151 | -2 | 0.597 |
HIPK1 |
0.635 | 0.053 | 1 | 0.430 |
CAMK2D |
0.635 | 0.159 | -3 | 0.784 |
PERK |
0.634 | 0.060 | -2 | 0.523 |
PKCT |
0.634 | 0.092 | 2 | 0.523 |
BMPR1B |
0.634 | 0.023 | 1 | 0.502 |
GRK2 |
0.634 | 0.045 | -2 | 0.536 |
PIM1 |
0.634 | 0.098 | -3 | 0.752 |
PAK1 |
0.634 | 0.076 | -2 | 0.580 |
MAK |
0.634 | 0.078 | -2 | 0.531 |
TBK1 |
0.633 | 0.104 | 1 | 0.661 |
CLK3 |
0.633 | 0.073 | 1 | 0.484 |
PIM3 |
0.633 | 0.086 | -3 | 0.752 |
PKG2 |
0.633 | 0.103 | -2 | 0.502 |
PLK4 |
0.633 | 0.129 | 2 | 0.418 |
NUAK2 |
0.633 | 0.074 | -3 | 0.787 |
RIPK2 |
0.633 | 0.023 | 1 | 0.699 |
HRI |
0.633 | 0.001 | -2 | 0.526 |
PBK |
0.632 | 0.001 | 1 | 0.454 |
IKKE |
0.632 | 0.094 | 1 | 0.658 |
CAMK2A |
0.632 | 0.131 | 2 | 0.414 |
RSK4 |
0.632 | 0.122 | -3 | 0.730 |
CLK4 |
0.632 | 0.093 | -3 | 0.765 |
ERK5 |
0.632 | -0.017 | 1 | 0.486 |
IKKA |
0.632 | 0.140 | -2 | 0.516 |
P38A |
0.631 | -0.015 | 1 | 0.439 |
MEK2 |
0.631 | -0.019 | 2 | 0.497 |
HUNK |
0.631 | 0.020 | 2 | 0.501 |
AMPKA1 |
0.631 | 0.064 | -3 | 0.783 |
TTK |
0.631 | -0.066 | -2 | 0.475 |
TLK2 |
0.630 | 0.018 | 1 | 0.553 |
MYLK4 |
0.630 | 0.051 | -2 | 0.579 |
CHK2 |
0.630 | 0.101 | -3 | 0.715 |
TGFBR1 |
0.630 | 0.027 | -2 | 0.499 |
CLK1 |
0.630 | 0.104 | -3 | 0.768 |
JNK1 |
0.629 | 0.015 | 1 | 0.374 |
MELK |
0.629 | 0.107 | -3 | 0.783 |
HIPK3 |
0.629 | 0.039 | 1 | 0.458 |
MRCKA |
0.629 | 0.078 | -3 | 0.753 |
IRE1 |
0.629 | -0.016 | 1 | 0.516 |
WNK3 |
0.629 | -0.026 | 1 | 0.609 |
NEK3 |
0.628 | 0.033 | 1 | 0.628 |
CDKL5 |
0.628 | 0.058 | -3 | 0.764 |
P38G |
0.628 | 0.003 | 1 | 0.334 |
ULK1 |
0.628 | 0.085 | -3 | 0.683 |
RSK2 |
0.628 | 0.115 | -3 | 0.756 |
PDHK4 |
0.628 | -0.024 | 1 | 0.617 |
AURC |
0.628 | 0.105 | -2 | 0.479 |
CAMK2B |
0.628 | 0.126 | 2 | 0.390 |
AURB |
0.627 | 0.071 | -2 | 0.471 |
ERK1 |
0.627 | 0.002 | 1 | 0.395 |
MSK1 |
0.627 | 0.117 | -3 | 0.742 |
PDHK1 |
0.627 | -0.009 | 1 | 0.640 |
ACVR2B |
0.627 | -0.011 | -2 | 0.483 |
CDK1 |
0.627 | 0.000 | 1 | 0.379 |
IRAK1 |
0.627 | -0.035 | -1 | 0.639 |
CRIK |
0.626 | 0.084 | -3 | 0.730 |
NDR1 |
0.626 | 0.094 | -3 | 0.764 |
DYRK2 |
0.626 | 0.049 | 1 | 0.415 |
STK33 |
0.626 | -0.012 | 2 | 0.379 |
PLK2 |
0.626 | 0.088 | -3 | 0.536 |
TGFBR2 |
0.626 | 0.021 | -2 | 0.464 |
PAK3 |
0.626 | 0.044 | -2 | 0.578 |
PLK3 |
0.626 | 0.096 | 2 | 0.409 |
P38B |
0.626 | -0.019 | 1 | 0.386 |
CDK5 |
0.626 | -0.014 | 1 | 0.408 |
PAK2 |
0.626 | 0.029 | -2 | 0.560 |
RSK3 |
0.625 | 0.105 | -3 | 0.754 |
MNK1 |
0.625 | 0.116 | -2 | 0.567 |
ALK2 |
0.625 | -0.032 | -2 | 0.520 |
HIPK2 |
0.625 | 0.062 | 1 | 0.351 |
GRK3 |
0.625 | 0.080 | -2 | 0.521 |
CDC7 |
0.625 | 0.008 | 1 | 0.506 |
CAMK1G |
0.624 | 0.082 | -3 | 0.781 |
SRPK3 |
0.624 | 0.059 | -3 | 0.730 |
HIPK4 |
0.624 | 0.061 | 1 | 0.472 |
PIM2 |
0.624 | 0.051 | -3 | 0.758 |
CDK14 |
0.623 | -0.010 | 1 | 0.401 |
TLK1 |
0.623 | -0.047 | -2 | 0.544 |
ACVR2A |
0.623 | -0.026 | -2 | 0.453 |
CK1A2 |
0.623 | 0.077 | -3 | 0.433 |
PRP4 |
0.622 | -0.037 | -3 | 0.545 |
DNAPK |
0.622 | 0.007 | 1 | 0.557 |
GCN2 |
0.622 | 0.155 | 2 | 0.495 |
PRKD3 |
0.622 | 0.081 | -3 | 0.784 |
PINK1 |
0.622 | -0.069 | 1 | 0.508 |
AMPKA2 |
0.622 | 0.071 | -3 | 0.776 |
PKACB |
0.622 | 0.104 | -2 | 0.488 |
SRPK1 |
0.622 | 0.078 | -3 | 0.742 |
BUB1 |
0.622 | -0.001 | -5 | 0.517 |
P90RSK |
0.622 | 0.098 | -3 | 0.753 |
ERK2 |
0.622 | -0.031 | 1 | 0.406 |
ERK7 |
0.622 | 0.019 | 2 | 0.403 |
MSK2 |
0.621 | 0.099 | -3 | 0.746 |
YANK3 |
0.621 | 0.011 | 2 | 0.213 |
CDK10 |
0.621 | 0.015 | 1 | 0.389 |
DYRK1A |
0.620 | 0.041 | 1 | 0.467 |
MNK2 |
0.620 | 0.101 | -2 | 0.553 |
PHKG2 |
0.620 | 0.120 | -3 | 0.792 |
CLK2 |
0.620 | 0.108 | -3 | 0.737 |
MOK |
0.619 | 0.049 | 1 | 0.400 |
CDK6 |
0.619 | -0.022 | 1 | 0.390 |
PKACA |
0.619 | 0.107 | -2 | 0.460 |
BMPR1A |
0.619 | -0.015 | 1 | 0.496 |
P38D |
0.619 | -0.009 | 1 | 0.326 |
PAK6 |
0.618 | 0.086 | -2 | 0.509 |
MAPKAPK3 |
0.617 | 0.089 | -3 | 0.765 |
CK1E |
0.617 | 0.093 | -3 | 0.454 |
ATM |
0.617 | -0.010 | 1 | 0.498 |
BIKE |
0.617 | -0.029 | 1 | 0.419 |
IRE2 |
0.617 | -0.080 | 2 | 0.518 |
CK1D |
0.617 | 0.077 | -3 | 0.420 |
PRKX |
0.616 | 0.139 | -3 | 0.694 |
TTBK1 |
0.616 | 0.017 | 2 | 0.412 |
NDR2 |
0.616 | 0.111 | -3 | 0.750 |
PAK5 |
0.616 | 0.102 | -2 | 0.457 |
TSSK1 |
0.615 | 0.001 | -3 | 0.784 |
PRKD2 |
0.615 | 0.104 | -3 | 0.769 |
YANK2 |
0.615 | -0.000 | 2 | 0.210 |
DYRK3 |
0.615 | 0.047 | 1 | 0.438 |
PRKD1 |
0.615 | 0.092 | -3 | 0.793 |
QIK |
0.615 | -0.038 | -3 | 0.784 |
CDK3 |
0.614 | -0.009 | 1 | 0.332 |
CDK4 |
0.614 | -0.019 | 1 | 0.368 |
TSSK2 |
0.614 | -0.046 | -5 | 0.531 |
CDK17 |
0.613 | -0.023 | 1 | 0.331 |
DYRK1B |
0.613 | 0.016 | 1 | 0.377 |
CDK8 |
0.613 | -0.002 | 1 | 0.431 |
CAMK1A |
0.613 | 0.090 | -3 | 0.727 |
CAMK1D |
0.613 | 0.073 | -3 | 0.728 |
CDK18 |
0.612 | -0.014 | 1 | 0.355 |
CDK2 |
0.611 | -0.054 | 1 | 0.450 |
NIM1 |
0.611 | -0.026 | 3 | 0.350 |
PAK4 |
0.610 | 0.097 | -2 | 0.451 |
MARK4 |
0.610 | -0.076 | 4 | 0.467 |
DYRK4 |
0.610 | 0.025 | 1 | 0.369 |
SRPK2 |
0.609 | 0.076 | -3 | 0.707 |
NUAK1 |
0.609 | 0.047 | -3 | 0.769 |
SNRK |
0.609 | -0.013 | 2 | 0.382 |
MAPKAPK5 |
0.608 | 0.072 | -3 | 0.750 |
SIK |
0.608 | 0.014 | -3 | 0.768 |
QSK |
0.607 | -0.026 | 4 | 0.449 |
CDK12 |
0.607 | -0.029 | 1 | 0.387 |
LATS2 |
0.606 | 0.065 | -5 | 0.550 |
SMG1 |
0.605 | -0.073 | 1 | 0.489 |
CDK16 |
0.605 | -0.029 | 1 | 0.325 |
BCKDK |
0.605 | -0.038 | -1 | 0.626 |
CDK13 |
0.605 | -0.039 | 1 | 0.392 |
CHK1 |
0.604 | -0.015 | -3 | 0.722 |
CDK7 |
0.604 | -0.032 | 1 | 0.411 |
CDK9 |
0.604 | -0.034 | 1 | 0.408 |
BRSK2 |
0.603 | 0.031 | -3 | 0.783 |
MARK2 |
0.603 | -0.066 | 4 | 0.392 |
BRSK1 |
0.602 | 0.037 | -3 | 0.777 |
CK2A2 |
0.602 | 0.016 | 1 | 0.406 |
SSTK |
0.602 | -0.050 | 4 | 0.448 |
MARK3 |
0.601 | -0.050 | 4 | 0.418 |
AAK1 |
0.601 | -0.024 | 1 | 0.338 |
CDK19 |
0.600 | -0.012 | 1 | 0.402 |
MARK1 |
0.600 | -0.072 | 4 | 0.423 |
MAPKAPK2 |
0.599 | 0.071 | -3 | 0.726 |
CK2A1 |
0.598 | 0.030 | 1 | 0.400 |
PKG1 |
0.597 | 0.071 | -2 | 0.451 |
SBK |
0.597 | 0.065 | -3 | 0.667 |
CK1G2 |
0.595 | 0.084 | -3 | 0.375 |
CK1G1 |
0.595 | 0.080 | -3 | 0.430 |
BMPR2_TYR |
0.595 | 0.088 | -1 | 0.789 |
MAP2K4_TYR |
0.591 | 0.089 | -1 | 0.745 |
JAK1 |
0.590 | 0.102 | 1 | 0.654 |
KIS |
0.588 | 0.008 | 1 | 0.434 |
PINK1_TYR |
0.587 | 0.038 | 1 | 0.580 |
CK1G3 |
0.587 | 0.057 | -3 | 0.309 |
ABL2 |
0.587 | 0.091 | -1 | 0.719 |
PKMYT1_TYR |
0.587 | -0.012 | 3 | 0.429 |
PDHK3_TYR |
0.586 | 0.016 | 4 | 0.532 |
MAP2K6_TYR |
0.586 | 0.013 | -1 | 0.768 |
CSF1R |
0.586 | 0.038 | 3 | 0.367 |
CK1A |
0.586 | 0.099 | -3 | 0.343 |
PDHK1_TYR |
0.585 | 0.014 | -1 | 0.777 |
KDR |
0.584 | 0.008 | 3 | 0.347 |
JAK3 |
0.584 | 0.055 | 1 | 0.631 |
LIMK2_TYR |
0.583 | 0.004 | -3 | 0.749 |
ABL1 |
0.583 | 0.062 | -1 | 0.690 |
JAK2 |
0.583 | 0.023 | 1 | 0.633 |
MAP2K7_TYR |
0.583 | -0.052 | 2 | 0.491 |
FLT1 |
0.582 | 0.057 | -1 | 0.781 |
TESK1_TYR |
0.582 | -0.058 | 3 | 0.423 |
RET |
0.582 | 0.009 | 1 | 0.612 |
MST1R |
0.581 | 0.005 | 3 | 0.384 |
PDHK4_TYR |
0.581 | -0.012 | 2 | 0.476 |
WEE1_TYR |
0.580 | 0.031 | -1 | 0.720 |
NEK10_TYR |
0.580 | 0.084 | 1 | 0.589 |
KIT |
0.580 | 0.027 | 3 | 0.361 |
TYK2 |
0.579 | -0.014 | 1 | 0.613 |
ROS1 |
0.579 | -0.050 | 3 | 0.373 |
LIMK1_TYR |
0.579 | -0.058 | 2 | 0.523 |
EPHA6 |
0.578 | -0.040 | -1 | 0.760 |
MET |
0.576 | 0.005 | 3 | 0.359 |
FLT3 |
0.575 | -0.005 | 3 | 0.364 |
INSRR |
0.575 | -0.028 | 3 | 0.346 |
EPHB4 |
0.575 | -0.043 | -1 | 0.714 |
FAM20C |
0.574 | -0.047 | 2 | 0.235 |
FLT4 |
0.574 | 0.008 | 3 | 0.376 |
DDR1 |
0.574 | -0.055 | 4 | 0.473 |
PDGFRB |
0.574 | -0.038 | 3 | 0.373 |
TNK1 |
0.573 | -0.008 | 3 | 0.372 |
BMX |
0.573 | 0.024 | -1 | 0.683 |
FGR |
0.572 | -0.057 | 1 | 0.537 |
SYK |
0.571 | 0.081 | -1 | 0.764 |
NTRK1 |
0.571 | 0.017 | -1 | 0.724 |
FGFR2 |
0.571 | -0.045 | 3 | 0.373 |
NTRK3 |
0.571 | 0.034 | -1 | 0.723 |
TYRO3 |
0.571 | -0.107 | 3 | 0.378 |
TXK |
0.570 | -0.017 | 1 | 0.524 |
TNNI3K_TYR |
0.570 | -0.033 | 1 | 0.584 |
ERBB2 |
0.570 | -0.024 | 1 | 0.586 |
ALK |
0.569 | -0.054 | 3 | 0.345 |
TNK2 |
0.569 | -0.076 | 3 | 0.363 |
BLK |
0.568 | -0.018 | -1 | 0.671 |
EGFR |
0.568 | 0.023 | 1 | 0.533 |
NTRK2 |
0.568 | -0.024 | 3 | 0.360 |
FGFR4 |
0.568 | 0.032 | -1 | 0.737 |
LCK |
0.567 | -0.036 | -1 | 0.679 |
PDGFRA |
0.567 | -0.040 | 3 | 0.389 |
ITK |
0.567 | -0.067 | -1 | 0.654 |
HCK |
0.567 | -0.056 | -1 | 0.662 |
ZAP70 |
0.567 | 0.074 | -1 | 0.776 |
FGFR3 |
0.567 | -0.034 | 3 | 0.350 |
INSR |
0.566 | -0.022 | 3 | 0.339 |
MATK |
0.566 | 0.004 | -1 | 0.740 |
EPHA4 |
0.565 | -0.062 | 2 | 0.386 |
LTK |
0.565 | -0.050 | 3 | 0.367 |
FER |
0.565 | -0.112 | 1 | 0.524 |
CSK |
0.565 | -0.021 | 2 | 0.396 |
PTK6 |
0.564 | 0.004 | -1 | 0.641 |
EPHB1 |
0.564 | -0.091 | 1 | 0.571 |
FYN |
0.564 | -0.003 | -1 | 0.662 |
FGFR1 |
0.564 | -0.068 | 3 | 0.354 |
SRMS |
0.563 | -0.074 | 1 | 0.540 |
MUSK |
0.563 | -0.000 | 1 | 0.502 |
DDR2 |
0.563 | -0.045 | 3 | 0.354 |
YES1 |
0.562 | -0.103 | -1 | 0.646 |
MERTK |
0.562 | -0.075 | 3 | 0.355 |
BTK |
0.560 | -0.105 | -1 | 0.598 |
EPHA7 |
0.559 | -0.087 | 2 | 0.408 |
TEC |
0.559 | -0.083 | -1 | 0.573 |
TEK |
0.559 | -0.131 | 3 | 0.339 |
EPHB2 |
0.559 | -0.089 | -1 | 0.687 |
IGF1R |
0.558 | -0.020 | 3 | 0.308 |
EPHB3 |
0.558 | -0.106 | -1 | 0.688 |
AXL |
0.557 | -0.118 | 3 | 0.352 |
PTK2 |
0.557 | -0.004 | -1 | 0.717 |
FRK |
0.557 | -0.080 | -1 | 0.669 |
SRC |
0.557 | -0.050 | -1 | 0.638 |
EPHA8 |
0.556 | -0.053 | -1 | 0.726 |
ERBB4 |
0.555 | -0.025 | 1 | 0.486 |
EPHA3 |
0.555 | -0.097 | 2 | 0.376 |
LYN |
0.554 | -0.085 | 3 | 0.352 |
EPHA2 |
0.550 | -0.053 | -1 | 0.736 |
EPHA5 |
0.549 | -0.087 | 2 | 0.366 |
EPHA1 |
0.547 | -0.143 | 3 | 0.331 |
PTK2B |
0.544 | -0.110 | -1 | 0.588 |
FES |
0.544 | -0.048 | -1 | 0.656 |