Motif 987 (n=79)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| O00192 | ARVCF | T284 | ochoa | Splicing regulator ARVCF (Armadillo repeat protein deleted in velo-cardio-facial syndrome) | Contributes to the regulation of alternative splicing of pre-mRNAs. {ECO:0000269|PubMed:24644279}. |
| O00311 | CDC7 | T376 | psp | Cell division cycle 7-related protein kinase (CDC7-related kinase) (HsCdc7) (huCdc7) (EC 2.7.11.1) | Kinase involved in initiation of DNA replication. Phosphorylates critical substrates that regulate the G1/S phase transition and initiation of DNA replication, such as MCM proteins and CLASPIN. {ECO:0000269|PubMed:12065429, ECO:0000269|PubMed:27401717}. |
| O15264 | MAPK13 | T185 | ochoa | Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}. |
| O15530 | PDPK1 | T245 | ochoa | 3-phosphoinositide-dependent protein kinase 1 (hPDK1) (EC 2.7.11.1) | Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9445477, PubMed:9707564, PubMed:9768361). Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), TSSK3, protein kinase PKN (PKN1 and PKN2) (PubMed:10226025, PubMed:10480933, PubMed:10995762, PubMed:12167717, PubMed:14585963, PubMed:14604990, PubMed:16207722, PubMed:16251192, PubMed:17327236, PubMed:17371830, PubMed:18835241, PubMed:9094314, PubMed:9368760, PubMed:9445476, PubMed:9707564, PubMed:9768361). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage (PubMed:10226025, PubMed:12167717, PubMed:9094314). Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta (PubMed:17327236). Activates PPARG transcriptional activity and promotes adipocyte differentiation (By similarity). Activates the NF-kappa-B pathway via phosphorylation of IKKB (PubMed:16207722). The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II (PubMed:14585963). Controls proliferation, survival, and growth of developing pancreatic cells (By similarity). Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells (By similarity). Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis (PubMed:17371830). Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response (By similarity). Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses (By similarity). Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages (By similarity). {ECO:0000250|UniProtKB:Q9Z2A0, ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10480933, ECO:0000269|PubMed:10995762, ECO:0000269|PubMed:12167717, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:14604990, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:16251192, ECO:0000269|PubMed:17327236, ECO:0000269|PubMed:17371830, ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9094314, ECO:0000269|PubMed:9368760, ECO:0000269|PubMed:9445476, ECO:0000269|PubMed:9445477, ECO:0000269|PubMed:9707564, ECO:0000269|PubMed:9768361}.; FUNCTION: [Isoform 3]: Catalytically inactive. {ECO:0000269|PubMed:9445477}. |
| O43318 | MAP3K7 | S192 | psp | Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). 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 MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}. |
| O76039 | CDKL5 | T174 | ochoa | Cyclin-dependent kinase-like 5 (EC 2.7.11.22) (Serine/threonine-protein kinase 9) | Mediates phosphorylation of MECP2 (PubMed:15917271, PubMed:16935860). May regulate ciliogenesis (PubMed:29420175). {ECO:0000269|PubMed:15917271, ECO:0000269|PubMed:16935860, ECO:0000269|PubMed:29420175}. |
| O94804 | STK10 | T195 | ochoa | Serine/threonine-protein kinase 10 (EC 2.7.11.1) (Lymphocyte-oriented kinase) | Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo. {ECO:0000269|PubMed:11903060, ECO:0000269|PubMed:12639966, ECO:0000269|PubMed:19255442}. |
| O95819 | MAP4K4 | T191 | psp | Mitogen-activated protein kinase kinase kinase kinase 4 (EC 2.7.11.1) (HPK/GCK-like kinase HGK) (MAPK/ERK kinase kinase kinase 4) (MEK kinase kinase 4) (MEKKK 4) (Nck-interacting kinase) | Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway (PubMed:9890973). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). Phosphorylates SMAD1 on Thr-322 (PubMed:21690388). {ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:9890973}. |
| O96013 | PAK4 | T478 | ochoa | Serine/threonine-protein kinase PAK 4 (EC 2.7.11.1) (p21-activated kinase 4) (PAK-4) | Serine/threonine-protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell adhesion turnover, cell migration, growth, proliferation or cell survival (PubMed:26598620). Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. Promotes kinase-independent stabilization of RHOU, thereby contributing to focal adhesion disassembly during cell migration (PubMed:26598620). {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26598620, ECO:0000269|PubMed:26607847}. |
| P19525 | EIF2AK2 | T451 | psp | Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) | IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. |
| P21127 | CDK11B | T600 | ochoa | Cyclin-dependent kinase 11B (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 1) (CLK-1) (Cell division protein kinase 11B) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L1) (p58 CLK-1) | Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:18216018, ECO:0000269|PubMed:2217177}. |
| P24941 | CDK2 | T165 | psp | Cyclin-dependent kinase 2 (EC 2.7.11.22) (Cell division protein kinase 2) (p33 protein kinase) | Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:29203878, ECO:0000303|PubMed:19238148, ECO:0000303|PubMed:19561645}. |
| P27361 | MAPK3 | T207 | ochoa|psp | Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}. |
| P28482 | MAPK1 | T190 | ochoa|psp | Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}. |
| P33981 | TTK | T686 | psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P36507 | MAP2K2 | T230 | ochoa | Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2) | Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}. |
| P41279 | MAP3K8 | T290 | psp | Mitogen-activated protein kinase kinase kinase 8 (EC 2.7.11.25) (Cancer Osaka thyroid oncogene) (Proto-oncogene c-Cot) (Serine/threonine-protein kinase cot) (Tumor progression locus 2) (TPL-2) | Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the pro-inflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. {ECO:0000269|PubMed:11342626, ECO:0000269|PubMed:12667451, ECO:0000269|PubMed:15169888, ECO:0000269|PubMed:16371247, ECO:0000269|PubMed:1833717, ECO:0000269|PubMed:19001140, ECO:0000269|PubMed:19808894}. |
| P45983 | MAPK8 | T188 | ochoa | 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 | T188 | ochoa | 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. |
| P49759 | CLK1 | T342 | ochoa | Dual specificity protein kinase CLK1 (EC 2.7.12.1) (CDC-like kinase 1) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1 (PubMed:10480872, PubMed:19168442). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (PubMed:19168442). {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442}. |
| P49840 | GSK3A | S282 | ochoa | 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 | S219 | ochoa | 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}. |
| P50613 | CDK7 | T175 | ochoa | Cyclin-dependent kinase 7 (EC 2.7.11.22) (EC 2.7.11.23) (39 kDa protein kinase) (p39 Mo15) (CDK-activating kinase 1) (Cell division protein kinase 7) (Serine/threonine-protein kinase 1) (TFIIH basal transcription factor complex kinase subunit) | Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription (PubMed:9852112, PubMed:19136461, PubMed:26257281, PubMed:28768201). Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201). Initiates transcription by RNA polymerase II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, PubMed:28768201). CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the CTD of POLR2A, allowing its escape from the promoter and elongation of the transcripts (PubMed:9852112). Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130, ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173, ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:28768201, ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}. |
| P51956 | NEK3 | T165 | psp | Serine/threonine-protein kinase Nek3 (EC 2.7.11.1) (HSPK 36) (Never in mitosis A-related kinase 3) (NimA-related protein kinase 3) | Protein kinase which influences neuronal morphogenesis and polarity through effects on microtubules. Regulates microtubule acetylation in neurons. Contributes to prolactin-mediated phosphorylation of PXN and VAV2. Implicated in prolactin-mediated cytoskeletal reorganization and motility of breast cancer cells through mechanisms involving RAC1 activation and phosphorylation of PXN and VAV2. {ECO:0000269|PubMed:15618286, ECO:0000269|PubMed:17297458}. |
| P53778 | MAPK12 | T188 | ochoa | Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}. |
| P53779 | MAPK10 | T226 | ochoa | 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}. |
| P78362 | SRPK2 | T547 | ochoa | SRSF protein kinase 2 (EC 2.7.11.1) (SFRS protein kinase 2) (Serine/arginine-rich protein-specific kinase 2) (SR-protein-specific kinase 2) [Cleaved into: SRSF protein kinase 2 N-terminal; SRSF protein kinase 2 C-terminal] | Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing (PubMed:18559500, PubMed:21056976, PubMed:9472028). Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression (PubMed:19592491). This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression (PubMed:21205200). Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation (PubMed:18559500). Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28 (PubMed:18425142). Probably by phosphorylating DDX23, leads to the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:28076779). Can mediate hepatitis B virus (HBV) core protein phosphorylation (PubMed:12134018). Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles (PubMed:16122776). {ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:18425142, ECO:0000269|PubMed:18559500, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21056976, ECO:0000269|PubMed:21205200, ECO:0000269|PubMed:28076779, ECO:0000269|PubMed:9472028}. |
| P80192 | MAP3K9 | T312 | psp | Mitogen-activated protein kinase kinase kinase 9 (EC 2.7.11.25) (Mixed lineage kinase 1) | 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. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Also plays a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. {ECO:0000269|PubMed:11416147, ECO:0000269|PubMed:15610029}. |
| Q02750 | MAP2K1 | T226 | ochoa | Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}. |
| Q13164 | MAPK7 | T224 | ochoa | Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) | Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}. |
| Q13523 | PRP4K | S852 | ochoa | Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) | Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}. |
| Q13873 | BMPR2 | T379 | ochoa | Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}. |
| Q14694 | USP10 | T82 | ochoa | Ubiquitin carboxyl-terminal hydrolase 10 (EC 3.4.19.12) (Deubiquitinating enzyme 10) (Ubiquitin thioesterase 10) (Ubiquitin-specific-processing protease 10) | Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}. |
| Q16539 | MAPK14 | T185 | ochoa|psp | Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}. |
| Q38SD2 | LRRK1 | T1427 | psp | Leucine-rich repeat serine/threonine-protein kinase 1 (EC 2.7.11.1) | Serine/threonine-protein kinase which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). Phosphorylates RAB7A; this activity is dependent on protein kinase C (PKC) activation (PubMed:36040231, PubMed:37558661, PubMed:37857821). Plays a role in the negative regulation of bone mass, acting through the maturation of osteoclasts (By similarity). {ECO:0000250|UniProtKB:Q3UHC2, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:37558661, ECO:0000269|PubMed:37857821}. |
| Q52WX2 | SBK1 | T211 | ochoa | Serine/threonine-protein kinase SBK1 (EC 2.7.11.1) (SH3 domain-binding kinase 1) | May be involved in signal-transduction pathways related to the control of brain development. {ECO:0000250}. |
| Q5S007 | LRRK2 | T2035 | psp | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q5VT25 | CDC42BPA | T240 | psp | Serine/threonine-protein kinase MRCK alpha (EC 2.7.11.1) (CDC42-binding protein kinase alpha) (DMPK-like alpha) (Myotonic dystrophy kinase-related CDC42-binding kinase alpha) (MRCK alpha) (Myotonic dystrophy protein kinase-like alpha) | Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration (PubMed:15723050, PubMed:9092543, PubMed:9418861). Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates: PPP1R12A, LIMK1 and LIMK2 (PubMed:11340065, PubMed:11399775). May play a role in TFRC-mediated iron uptake (PubMed:20188707). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). Triggers the formation of an extrusion apical actin ring required for epithelial extrusion of apoptotic cells (PubMed:29162624). {ECO:0000250|UniProtKB:Q3UU96, ECO:0000269|PubMed:11340065, ECO:0000269|PubMed:11399775, ECO:0000269|PubMed:15723050, ECO:0000269|PubMed:18854160, ECO:0000269|PubMed:20188707, ECO:0000269|PubMed:21457715, ECO:0000269|PubMed:29162624, ECO:0000269|PubMed:9092543, ECO:0000269|PubMed:9418861}. |
| Q6A1A2 | PDPK2P | T218 | ochoa | Putative 3-phosphoinositide-dependent protein kinase 2 (EC 2.7.11.1) (3-phosphoinositide-dependent protein kinase 2 pseudogene) | Phosphorylates and activates not only PKB/AKT, but also PKA, PKC-zeta, RPS6KA1 and RPS6KB1. May play a general role in signaling processes and in development (By similarity). {ECO:0000250}. |
| Q7L7X3 | TAOK1 | T185 | ochoa | Serine/threonine-protein kinase TAO1 (EC 2.7.11.1) (Kinase from chicken homolog B) (hKFC-B) (MARK Kinase) (MARKK) (Prostate-derived sterile 20-like kinase 2) (PSK-2) (PSK2) (Prostate-derived STE20-like kinase 2) (Thousand and one amino acid protein kinase 1) (TAOK1) (hTAOK1) | Serine/threonine-protein kinase involved in various processes such as p38/MAPK14 stress-activated MAPK cascade, DNA damage response and regulation of cytoskeleton stability. Phosphorylates MAP2K3, MAP2K6 and MARK2. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade by mediating phosphorylation and subsequent activation of the upstream MAP2K3 and MAP2K6 kinases. Involved in G-protein coupled receptor signaling to p38/MAPK14. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of MAP2K3 and MAP2K6. Acts as a regulator of cytoskeleton stability by phosphorylating 'Thr-208' of MARK2, leading to activate MARK2 kinase activity and subsequent phosphorylation and detachment of MAPT/TAU from microtubules. Also acts as a regulator of apoptosis: regulates apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation via activation of the MAPK8/JNK cascade. Plays an essential role in the regulation of neuronal development in the central nervous system (PubMed:33565190). Also plays a role in the regulation of neuronal migration to the cortical plate (By similarity). {ECO:0000250|UniProtKB:Q5F2E8, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16407310, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:17900936, ECO:0000269|PubMed:33565190}. |
| Q8N165 | PDIK1L | T221 | ochoa | Serine/threonine-protein kinase PDIK1L (EC 2.7.11.1) (PDLIM1-interacting kinase 1-like) | None |
| Q8N4C8 | MINK1 | T191 | ochoa|psp | Misshapen-like kinase 1 (EC 2.7.11.1) (GCK family kinase MiNK) (MAPK/ERK kinase kinase kinase 6) (MEK kinase kinase 6) (MEKKK 6) (Misshapen/NIK-related kinase) (Mitogen-activated protein kinase kinase kinase kinase 6) | Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking (PubMed:10708748, PubMed:16337592). Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons (By similarity). Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates TANC1 upon stimulation by RAP2A, MBP and SMAD1 (PubMed:18930710, PubMed:21690388). Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1 (By similarity). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000250|UniProtKB:F1LP90, ECO:0000250|UniProtKB:Q9JM52, ECO:0000269|PubMed:10708748, ECO:0000269|PubMed:16337592, ECO:0000269|PubMed:18930710, ECO:0000269|PubMed:21690388, ECO:0000269|PubMed:26437443}.; FUNCTION: Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration. |
| Q8NEV4 | MYO3A | T188 | psp | Myosin-IIIa (EC 2.7.11.1) | Actin-dependent motor protein with a protein kinase activity, playing an essential role in hearing (PubMed:12032315, PubMed:29880844, PubMed:34788109). Probably also plays a role in vision. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments (PubMed:29880844, PubMed:34788109). {ECO:0000250|UniProtKB:Q8K3H5, ECO:0000269|PubMed:12032315, ECO:0000269|PubMed:29880844, ECO:0000269|PubMed:34788109}. |
| Q8TD19 | NEK9 | T214 | ochoa | Serine/threonine-protein kinase Nek9 (EC 2.7.11.1) (Nercc1 kinase) (Never in mitosis A-related kinase 9) (NimA-related protein kinase 9) (NimA-related kinase 8) (Nek8) | Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation (PubMed:12101123, PubMed:12840024, PubMed:14660563, PubMed:19941817). Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2 (PubMed:11864968). Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues (PubMed:11864968). Important for G1/S transition and S phase progression (PubMed:12840024, PubMed:14660563, PubMed:19941817). Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively (PubMed:12840024, PubMed:14660563, PubMed:19941817, PubMed:26522158). {ECO:0000269|PubMed:11864968, ECO:0000269|PubMed:12101123, ECO:0000269|PubMed:12840024, ECO:0000269|PubMed:14660563, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158}. |
| Q92918 | MAP4K1 | T175 | psp | Mitogen-activated protein kinase kinase kinase kinase 1 (EC 2.7.11.1) (Hematopoietic progenitor kinase) (MAPK/ERK kinase kinase kinase 1) (MEK kinase kinase 1) (MEKKK 1) | Serine/threonine-protein kinase, which plays a role in the response to environmental stress (PubMed:24362026). Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:24362026, PubMed:8824585). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity). {ECO:0000250|UniProtKB:P70218, ECO:0000269|PubMed:24362026, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:8824585}. |
| Q96GD4 | AURKB | T236 | psp | Aurora kinase B (EC 2.7.11.1) (Aurora 1) (Aurora- and IPL1-like midbody-associated protein 1) (AIM-1) (Aurora/IPL1-related kinase 2) (ARK-2) (Aurora-related kinase 2) (STK-1) (Serine/threonine-protein kinase 12) (Serine/threonine-protein kinase 5) (Serine/threonine-protein kinase aurora-B) | Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:29449677). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (PubMed:11756469, PubMed:11784863, PubMed:11856369, PubMed:12689593, PubMed:14602875, PubMed:16103226, PubMed:21658950). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity). Phosphorylates ATXN10 which promotes phosphorylation of ATXN10 by PLK1 and may play a role in the regulation of cytokinesis and stimulating the proteasomal degradation of ATXN10 (PubMed:25666058). {ECO:0000250|UniProtKB:O70126, ECO:0000269|PubMed:11516652, ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:11784863, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12458200, ECO:0000269|PubMed:12686604, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14602875, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21658950, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:24814515, ECO:0000269|PubMed:25666058, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:29449677, ECO:0000269|PubMed:33542149}. |
| Q96SB4 | SRPK1 | T514 | ochoa | SRSF protein kinase 1 (EC 2.7.11.1) (SFRS protein kinase 1) (Serine/arginine-rich protein-specific kinase 1) (SR-protein-specific kinase 1) | Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. {ECO:0000269|PubMed:10049757, ECO:0000269|PubMed:10390541, ECO:0000269|PubMed:11509566, ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:15034300, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:16209947, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19240134, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675, ECO:0000269|PubMed:20708644, ECO:0000269|PubMed:8208298, ECO:0000269|PubMed:9237760}. |
| Q99558 | MAP3K14 | T559 | psp | Mitogen-activated protein kinase kinase kinase 14 (EC 2.7.11.25) (NF-kappa-beta-inducing kinase) (HsNIK) (Serine/threonine-protein kinase NIK) | Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Phosphorylates CHUK/IKKA, thereby promoting proteolytic processing of NFKB2/P100, which leads to NF-kappa-B activation via the non-canonical pathway (PubMed:25406581, PubMed:29230214). Has an essential role in the non-canonical NF-kappa-B signaling that regulates genes encoding molecules involved in B-cell survival, lymphoid organogenesis, and immune response (PubMed:25406581). Could act in a receptor-selective manner. {ECO:0000269|PubMed:15084608, ECO:0000269|PubMed:25406581}. |
| Q99683 | MAP3K5 | T842 | 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}. |
| Q99759 | MAP3K3 | T530 | psp | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q9C0D5 | TANC1 | T347 | ochoa | Protein TANC1 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 1) | May be a scaffold component in the postsynaptic density. {ECO:0000250}. |
| Q9H2G2 | SLK | T193 | ochoa|psp | STE20-like serine/threonine-protein kinase (STE20-like kinase) (hSLK) (EC 2.7.11.1) (CTCL tumor antigen se20-9) (STE20-related serine/threonine-protein kinase) (STE20-related kinase) (Serine/threonine-protein kinase 2) | Mediates apoptosis and actin stress fiber dissolution. {ECO:0000250}. |
| Q9H2K8 | TAOK3 | T181 | ochoa | Serine/threonine-protein kinase TAO3 (EC 2.7.11.1) (Cutaneous T-cell lymphoma-associated antigen HD-CL-09) (CTCL-associated antigen HD-CL-09) (Dendritic cell-derived protein kinase) (JNK/SAPK-inhibitory kinase) (Jun kinase-inhibitory kinase) (Kinase from chicken homolog A) (hKFC-A) (Thousand and one amino acid protein 3) | Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Inhibits basal activity of the MAPK8/JNK cascade and diminishes its activation in response to epidermal growth factor (EGF). Positively regulates canonical T cell receptor (TCR) signaling by preventing early PTPN6/SHP1-mediated inactivation of LCK, ensuring sustained TCR signaling that is required for optimal activation and differentiation of T cells (PubMed:30373850). Phosphorylates PTPN6/SHP1 on 'Thr-394', leading to its polyubiquitination and subsequent proteasomal degradation (PubMed:38166031). Required for cell surface expression of metalloprotease ADAM10 on type 1 transitional B cells which is necessary for their NOTCH-mediated development into marginal zone B cells (By similarity). Also required for the NOTCH-mediated terminal differentiation of splenic conventional type 2 dendritic cells (By similarity). Positively regulates osteoblast differentiation by acting as an upstream activator of the JNK pathway (PubMed:32807497). Promotes JNK signaling in hepatocytes and positively regulates hepatocyte lipid storage by inhibiting beta-oxidation and triacylglycerol secretion while enhancing lipid synthesis (PubMed:34634521). Restricts age-associated inflammation by negatively regulating differentiation of macrophages and their production of pro-inflammatory cytokines (By similarity). Plays a role in negatively regulating the abundance of regulatory T cells in white adipose tissue (By similarity). {ECO:0000250|UniProtKB:Q8BYC6, ECO:0000269|PubMed:10559204, ECO:0000269|PubMed:10924369, ECO:0000269|PubMed:17396146, ECO:0000269|PubMed:30373850, ECO:0000269|PubMed:32807497, ECO:0000269|PubMed:34634521, ECO:0000269|PubMed:38166031}. |
| Q9H2X6 | HIPK2 | S364 | psp | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| Q9HAZ1 | CLK4 | T340 | ochoa | Dual specificity protein kinase CLK4 (EC 2.7.12.1) (CDC-like kinase 4) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:11170754, ECO:0000269|PubMed:19168442}. |
| Q9HC98 | NEK6 | T210 | psp | Serine/threonine-protein kinase Nek6 (EC 2.7.11.34) (Never in mitosis A-related kinase 6) (NimA-related protein kinase 6) (Protein kinase SID6-1512) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:11516946, PubMed:14563848). Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis (PubMed:19414596). Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3 (PubMed:12054534, PubMed:20873783). Phosphorylates KIF11 to promote mitotic spindle formation (PubMed:19001501). Involved in G2/M phase cell cycle arrest induced by DNA damage (PubMed:18728393). Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (PubMed:21099361). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). {ECO:0000269|PubMed:11516946, ECO:0000269|PubMed:12054534, ECO:0000269|PubMed:14563848, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21099361, ECO:0000269|PubMed:31409757}. |
| Q9NQU5 | PAK6 | T564 | ochoa | Serine/threonine-protein kinase PAK 6 (EC 2.7.11.1) (PAK-5) (p21-activated kinase 6) (PAK-6) | Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Also inhibits ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}. |
| Q9P286 | PAK5 | T606 | ochoa | Serine/threonine-protein kinase PAK 5 (EC 2.7.11.1) (p21-activated kinase 5) (PAK-5) (p21-activated kinase 7) (PAK-7) | Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions. {ECO:0000269|PubMed:12897128, ECO:0000269|PubMed:16014608, ECO:0000269|PubMed:16581795, ECO:0000269|PubMed:18465753, ECO:0000269|PubMed:20564219}. |
| Q9P289 | STK26 | T182 | ochoa | Serine/threonine-protein kinase 26 (EC 2.7.11.1) (MST3 and SOK1-related kinase) (Mammalian STE20-like protein kinase 4) (MST-4) (STE20-like kinase MST4) (Serine/threonine-protein kinase MASK) | Serine/threonine-protein kinase that acts as a mediator of cell growth (PubMed:11641781, PubMed:17360971). Modulates apoptosis (PubMed:11641781, PubMed:17360971). In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation (PubMed:27807006). Phosphorylates ATG4B at 'Ser-383', thereby increasing autophagic flux (PubMed:29232556). Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation (PubMed:18782753). {ECO:0000269|PubMed:11641781, ECO:0000269|PubMed:17360971, ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:27807006, ECO:0000269|PubMed:29232556}. |
| Q9UL54 | TAOK2 | T185 | ochoa | Serine/threonine-protein kinase TAO2 (EC 2.7.11.1) (Kinase from chicken homolog C) (hKFC-C) (Prostate-derived sterile 20-like kinase 1) (PSK-1) (PSK1) (Prostate-derived STE20-like kinase 1) (Thousand and one amino acid protein kinase 2) | Serine/threonine-protein kinase involved in different processes such as membrane blebbing and apoptotic bodies formation DNA damage response and MAPK14/p38 MAPK stress-activated MAPK cascade. Phosphorylates itself, MBP, activated MAPK8, MAP2K3, MAP2K6 and tubulins. Activates the MAPK14/p38 MAPK signaling pathway through the specific activation and phosphorylation of the upstream MAP2K3 and MAP2K6 kinases. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP2K3 and MAP2K6 kinases. Isoform 1, but not isoform 2, plays a role in apoptotic morphological changes, including cell contraction, membrane blebbing and apoptotic bodies formation. This function, which requires the activation of MAPK8/JNK and nuclear localization of C-terminally truncated isoform 1, may be linked to the mitochondrial CASP9-associated death pathway. Isoform 1 binds to microtubules and affects their organization and stability independently of its kinase activity. Prevents MAP3K7-mediated activation of CHUK, and thus NF-kappa-B activation, but not that of MAPK8/JNK. May play a role in the osmotic stress-MAPK8 pathway. Isoform 2, but not isoform 1, is required for PCDH8 endocytosis. Following homophilic interactions between PCDH8 extracellular domains, isoform 2 phosphorylates and activates MAPK14/p38 MAPK which in turn phosphorylates isoform 2. This process leads to PCDH8 endocytosis and CDH2 cointernalization. Both isoforms are involved in MAPK14 phosphorylation. {ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:12639963, ECO:0000269|PubMed:12665513, ECO:0000269|PubMed:13679851, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:17158878, ECO:0000269|PubMed:17396146}. |
| Q9UPE1 | SRPK3 | T426 | ochoa | SRSF protein kinase 3 (EC 2.7.11.1) (Muscle-specific serine kinase 1) (MSSK-1) (Serine/arginine-rich protein-specific kinase 3) (SR-protein-specific kinase 3) (Serine/threonine-protein kinase 23) | Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains. Phosphorylates the SR splicing factor SRSF1 and the lamin-B receptor (LBR) in vitro. Required for normal muscle development (By similarity). {ECO:0000250|UniProtKB:Q9Z0G2}. |
| Q9UQB9 | AURKC | T202 | psp | Aurora kinase C (EC 2.7.11.1) (Aurora 3) (Aurora/IPL1-related kinase 3) (ARK-3) (Aurora-related kinase 3) (Aurora/IPL1/Eg2 protein 2) (Serine/threonine-protein kinase 13) (Serine/threonine-protein kinase aurora-C) | Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Also plays a role in meiosis and more particularly in spermatogenesis. Has redundant cellular functions with AURKB and can rescue an AURKB knockdown. Like AURKB, AURKC phosphorylates histone H3 at 'Ser-10' and 'Ser-28'. AURKC phosphorylates the CPC complex subunits BIRC5/survivin and INCENP leading to increased AURKC activity. Phosphorylates TACC1, another protein involved in cell division, at 'Ser-228'. {ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:15499654, ECO:0000269|PubMed:15670791, ECO:0000269|PubMed:15938719, ECO:0000269|PubMed:21493633, ECO:0000269|PubMed:21531210, ECO:0000269|PubMed:27332895}. |
| Q9Y2U5 | MAP3K2 | T524 | psp | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| O75582 | RPS6KA5 | T216 | Sugiyama | 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}. |
| P51955 | NEK2 | T179 | 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}. |
| Q12851 | MAP4K2 | T174 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein) | Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Also mediates the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:11784851, ECO:0000269|PubMed:15456887, ECO:0000269|PubMed:17584736, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:7477268, ECO:0000269|PubMed:7515885, ECO:0000269|PubMed:9712898}. |
| Q8IVH8 | MAP4K3 | T174 | Sugiyama | Mitogen-activated protein kinase kinase kinase kinase 3 (EC 2.7.11.1) (Germinal center kinase-related protein kinase) (GLK) (MAPK/ERK kinase kinase kinase 3) (MEK kinase kinase 3) (MEKKK 3) | Serine/threonine kinase that plays a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway (PubMed:9275185). Activator of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. MAP4Ks act in parallel to and are partially redundant with STK3/MST2 and STK4/MST2 in the phosphorylation and activation of LATS1/2, and establish MAP4Ks as components of the expanded Hippo pathway (PubMed:26437443). {ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:9275185}. |
| Q13043 | STK4 | T187 | SIGNOR|EPSD | Serine/threonine-protein kinase 4 (EC 2.7.11.1) (Mammalian STE20-like protein kinase 1) (MST-1) (STE20-like kinase MST1) (Serine/threonine-protein kinase Krs-2) [Cleaved into: Serine/threonine-protein kinase 4 37kDa subunit (MST1/N); Serine/threonine-protein kinase 4 18kDa subunit (MST1/C)] | Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}. |
| Q13163 | MAP2K5 | T319 | Sugiyama | Dual specificity mitogen-activated protein kinase kinase 5 (MAP kinase kinase 5) (MAPKK 5) (EC 2.7.12.2) (MAPK/ERK kinase 5) (MEK 5) | Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). {ECO:0000250|UniProtKB:Q62862, ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}. |
| Q15569 | TESK1 | S220 | SIGNOR|iPTMNet|EPSD | Dual specificity testis-specific protein kinase 1 (EC 2.7.12.1) (Testicular protein kinase 1) | Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues (By similarity). Regulates the cellular cytoskeleton by enhancing actin stress fiber formation via phosphorylation of cofilin and by preventing microtubule breakdown via inhibition of TAOK1/MARKK kinase activity (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Positively regulates integrin-mediated cell spreading, via phosphorylation of cofilin (PubMed:15584898). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of ciliary vesicle directional trafficking to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity). {ECO:0000250|UniProtKB:O70146, ECO:0000250|UniProtKB:Q63572, ECO:0000269|PubMed:15584898, ECO:0000269|PubMed:25849865}. |
| Q15759 | MAPK11 | T185 | Sugiyama | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q86V86 | PIM3 | T207 | Sugiyama | Serine/threonine-protein kinase pim-3 (EC 2.7.11.1) | Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth. {ECO:0000269|PubMed:15540201, ECO:0000269|PubMed:16818649, ECO:0000269|PubMed:17270021, ECO:0000269|PubMed:17876606, ECO:0000269|PubMed:18593906}. |
| Q86Z02 | HIPK1 | S355 | Sugiyama | Homeodomain-interacting protein kinase 1 (EC 2.7.11.1) (Nuclear body-associated kinase 2) | Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:24559171). {ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:24559171}. |
| Q8TD08 | MAPK15 | T180 | Sugiyama | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| Q8TDX7 | NEK7 | T199 | Sugiyama | 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}. |
| Q9H422 | HIPK3 | S362 | Sugiyama | Homeodomain-interacting protein kinase 3 (EC 2.7.11.1) (Androgen receptor-interacting nuclear protein kinase) (ANPK) (Fas-interacting serine/threonine-protein kinase) (FIST) (Homolog of protein kinase YAK1) | Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}. |
| Q96J92 | WNK4 | T339 | Sugiyama | Serine/threonine-protein kinase WNK4 (EC 2.7.11.1) (Protein kinase lysine-deficient 4) (Protein kinase with no lysine 4) | Serine/threonine-protein kinase component of the WNK4-SPAK/OSR1 kinase cascade, which acts as a key regulator of ion transport in the distal nephron and blood pressure (By similarity). The WNK4-SPAK/OSR1 kinase cascade is composed of WNK4, which mediates phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:16832045). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:16832045, PubMed:22989884). Acts as a molecular switch that regulates the balance between renal salt reabsorption and K(+) secretion by modulating the activities of renal transporters and channels, including the Na-Cl cotransporter SLC12A3/NCC and the K(+) channel, KCNJ1/ROMK (By similarity). Regulates NaCl reabsorption in the distal nephron by activating the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney: activates SLC12A3/NCC in a OXSR1/OSR1- and STK39/SPAK-dependent process (By similarity). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels (CFTR, KCNJ1/ROMK, SLC4A4, SLC26A9 and TRPV4) by clathrin-dependent endocytosis (By similarity). Also inhibits the activity of the epithelial Na(+) channel (ENaC) SCNN1A, SCNN1B, SCNN1D in a inase-independent mechanism (By similarity). May also phosphorylate NEDD4L (PubMed:20525693). {ECO:0000250|UniProtKB:Q80UE6, ECO:0000269|PubMed:16832045, ECO:0000269|PubMed:20525693, ECO:0000269|PubMed:22989884}. |
| Q9H4A3 | WNK1 | T386 | Sugiyama | Serine/threonine-protein kinase WNK1 (EC 2.7.11.1) (Erythrocyte 65 kDa protein) (p65) (Kinase deficient protein) (Protein kinase lysine-deficient 1) (Protein kinase with no lysine 1) (hWNK1) | Serine/threonine-protein kinase component of the WNK1-SPAK/OSR1 kinase cascade, which acts as a key regulator of blood pressure and regulatory volume increase by promoting ion influx (PubMed:15883153, PubMed:17190791, PubMed:31656913, PubMed:34289367, PubMed:36318922). WNK1 mediates regulatory volume increase in response to hyperosmotic stress by acting as a molecular crowding sensor, which senses cell shrinkage and mediates formation of a membraneless compartment by undergoing liquid-liquid phase separation (PubMed:36318922). The membraneless compartment concentrates WNK1 with its substrates, OXSR1/OSR1 and STK39/SPAK, promoting WNK1-dependent phosphorylation and activation of downstream kinases OXSR1/OSR1 and STK39/SPAK (PubMed:15883153, PubMed:16263722, PubMed:17190791, PubMed:19739668, PubMed:21321328, PubMed:22989884, PubMed:25477473, PubMed:34289367, PubMed:36318922). Following activation, OXSR1/OSR1 and STK39/SPAK catalyze phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A5/KCC2 and SLC12A6/KCC3, regulating their activity (PubMed:16263722, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:19665974, PubMed:21321328). Also acts as a regulator of angiogenesis in endothelial cells via activation of OXSR1/OSR1 and STK39/SPAK: activation of OXSR1/OSR1 regulates chemotaxis and invasion, while STK39/SPAK regulates endothelial cell proliferation (PubMed:25362046). Also acts independently of the WNK1-SPAK/OSR1 kinase cascade by catalyzing phosphorylation of other substrates, such as SYT2, PCF11 and NEDD4L (PubMed:29196535). Mediates phosphorylation of SYT2, regulating SYT2 association with phospholipids and membrane-binding (By similarity). Regulates mRNA export in the nucleus by mediating phosphorylation of PCF11, thereby decreasing the association between PCF11 and POLR2A/RNA polymerase II and promoting mRNA export to the cytoplasm (PubMed:29196535). Acts as a negative regulator of autophagy (PubMed:27911840). Required for the abscission step during mitosis, independently of the WNK1-SPAK/OSR1 kinase cascade (PubMed:21220314). May also play a role in actin cytoskeletal reorganization (PubMed:10660600). Also acts as a scaffold protein independently of its protein kinase activity: negatively regulates cell membrane localization of various transporters and channels, such as SLC4A4, SLC26A6, SLC26A9, TRPV4 and CFTR (By similarity). Involved in the regulation of epithelial Na(+) channel (ENaC) by promoting activation of SGK1 in a kinase-independent manner: probably acts as a scaffold protein that promotes the recruitment of SGK1 to the mTORC2 complex in response to chloride, leading to mTORC2-dependent phosphorylation and activation of SGK1 (PubMed:36373794). Acts as an assembly factor for the ER membrane protein complex independently of its protein kinase activity: associates with EMC2 in the cytoplasm via its amphipathic alpha-helix, and prevents EMC2 ubiquitination and subsequent degradation, thereby promoting EMC2 stabilization (PubMed:33964204). {ECO:0000250|UniProtKB:P83741, ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:10660600, ECO:0000269|PubMed:15883153, ECO:0000269|PubMed:16263722, ECO:0000269|PubMed:17190791, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:19739668, ECO:0000269|PubMed:21220314, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22989884, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:25477473, ECO:0000269|PubMed:27911840, ECO:0000269|PubMed:29196535, ECO:0000269|PubMed:31656913, ECO:0000269|PubMed:33964204, ECO:0000269|PubMed:34289367, ECO:0000269|PubMed:36318922, ECO:0000269|PubMed:36373794}.; FUNCTION: [Isoform 3]: Kinase-defective isoform specifically expressed in kidney, which acts as a dominant-negative regulator of the longer isoform 1 (PubMed:14645531). Does not directly inhibit WNK4 and has no direct effect on sodium and chloride ion transport (By similarity). Down-regulates sodium-chloride cotransporter activity indirectly by inhibiting isoform 1, it associates with isoform 1 and attenuates its kinase activity (By similarity). In kidney, may play an important role regulating sodium and potassium balance (By similarity). {ECO:0000250|UniProtKB:Q9JIH7, ECO:0000269|PubMed:14645531}. |
| Q9UBE8 | NLK | T303 | Sugiyama | Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1) | Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-450294 | MAP kinase activation | 6.661338e-15 | 14.176 |
| R-HSA-448424 | Interleukin-17 signaling | 2.808864e-14 | 13.551 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 5.884182e-13 | 12.230 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 8.335554e-13 | 12.079 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.356359e-12 | 11.868 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.356359e-12 | 11.868 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.356359e-12 | 11.868 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.053580e-12 | 11.687 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 3.062661e-12 | 11.514 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 4.095280e-12 | 11.388 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 4.504064e-12 | 11.346 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 4.949596e-12 | 11.305 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 4.949596e-12 | 11.305 |
| R-HSA-2559583 | Cellular Senescence | 6.205925e-12 | 11.207 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 6.537326e-12 | 11.185 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 8.574919e-12 | 11.067 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 1.328337e-11 | 10.877 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 1.328337e-11 | 10.877 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 1.713085e-11 | 10.766 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 1.713085e-11 | 10.766 |
| R-HSA-187687 | Signalling to ERKs | 1.253558e-10 | 9.902 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 1.639989e-10 | 9.785 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 5.235991e-10 | 9.281 |
| R-HSA-168898 | Toll-like Receptor Cascades | 2.266516e-09 | 8.645 |
| R-HSA-166520 | Signaling by NTRKs | 2.437651e-09 | 8.613 |
| R-HSA-198753 | ERK/MAPK targets | 9.178972e-09 | 8.037 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 4.588359e-08 | 7.338 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 1.437963e-07 | 6.842 |
| R-HSA-1640170 | Cell Cycle | 2.334479e-06 | 5.632 |
| R-HSA-170968 | Frs2-mediated activation | 2.822954e-06 | 5.549 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 3.717284e-06 | 5.430 |
| R-HSA-171007 | p38MAPK events | 4.367802e-06 | 5.360 |
| R-HSA-169893 | Prolonged ERK activation events | 5.339973e-06 | 5.272 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 6.139121e-06 | 5.212 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 8.754556e-06 | 5.058 |
| R-HSA-9694631 | Maturation of nucleoprotein | 1.088801e-05 | 4.963 |
| R-HSA-445144 | Signal transduction by L1 | 1.276543e-05 | 4.894 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 1.487102e-05 | 4.828 |
| R-HSA-167044 | Signalling to RAS | 1.487102e-05 | 4.828 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 1.611511e-05 | 4.793 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 1.912526e-05 | 4.718 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 1.983464e-05 | 4.703 |
| R-HSA-69278 | Cell Cycle, Mitotic | 2.101626e-05 | 4.677 |
| R-HSA-444257 | RSK activation | 3.464067e-05 | 4.460 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 4.637553e-05 | 4.334 |
| R-HSA-2262752 | Cellular responses to stress | 4.960458e-05 | 4.304 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 5.083928e-05 | 4.294 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 5.428659e-05 | 4.265 |
| R-HSA-449147 | Signaling by Interleukins | 5.608766e-05 | 4.251 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 5.672419e-05 | 4.246 |
| R-HSA-8953897 | Cellular responses to stimuli | 6.106975e-05 | 4.214 |
| R-HSA-5633007 | Regulation of TP53 Activity | 6.294943e-05 | 4.201 |
| R-HSA-9635465 | Suppression of apoptosis | 7.056478e-05 | 4.151 |
| R-HSA-202670 | ERKs are inactivated | 8.644575e-05 | 4.063 |
| R-HSA-428540 | Activation of RAC1 | 8.644575e-05 | 4.063 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 8.699825e-05 | 4.060 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 1.130824e-04 | 3.947 |
| R-HSA-162582 | Signal Transduction | 1.207086e-04 | 3.918 |
| R-HSA-194138 | Signaling by VEGF | 1.354444e-04 | 3.868 |
| R-HSA-69620 | Cell Cycle Checkpoints | 1.609227e-04 | 3.793 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.703153e-04 | 3.769 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 1.703153e-04 | 3.769 |
| R-HSA-198765 | Signalling to ERK5 | 2.381755e-04 | 3.623 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 2.460004e-04 | 3.609 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 2.460004e-04 | 3.609 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 2.460004e-04 | 3.609 |
| R-HSA-6802949 | Signaling by RAS mutants | 2.460004e-04 | 3.609 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 2.292374e-04 | 3.640 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 2.292374e-04 | 3.640 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 2.430920e-04 | 3.614 |
| R-HSA-422475 | Axon guidance | 2.947474e-04 | 3.531 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 3.104560e-04 | 3.508 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 3.415977e-04 | 3.466 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 4.805994e-04 | 3.318 |
| R-HSA-9675108 | Nervous system development | 5.010081e-04 | 3.300 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 5.890422e-04 | 3.230 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 5.907836e-04 | 3.229 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 6.572334e-04 | 3.182 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 7.587462e-04 | 3.120 |
| R-HSA-525793 | Myogenesis | 7.843340e-04 | 3.105 |
| R-HSA-373760 | L1CAM interactions | 8.111773e-04 | 3.091 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 8.567733e-04 | 3.067 |
| R-HSA-68875 | Mitotic Prophase | 9.277942e-04 | 3.033 |
| R-HSA-168249 | Innate Immune System | 1.070874e-03 | 2.970 |
| R-HSA-68877 | Mitotic Prometaphase | 1.191242e-03 | 2.924 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 1.456862e-03 | 2.837 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1.380907e-03 | 2.860 |
| R-HSA-9842640 | Signaling by LTK in cancer | 1.184299e-03 | 2.927 |
| R-HSA-9694635 | Translation of Structural Proteins | 1.326488e-03 | 2.877 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 1.632807e-03 | 2.787 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 1.704304e-03 | 2.768 |
| R-HSA-68886 | M Phase | 1.798017e-03 | 2.745 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.838494e-03 | 2.736 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 1.915445e-03 | 2.718 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 2.082890e-03 | 2.681 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 2.082890e-03 | 2.681 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 2.435758e-03 | 2.613 |
| R-HSA-74749 | Signal attenuation | 2.435758e-03 | 2.613 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 2.435758e-03 | 2.613 |
| R-HSA-111458 | Formation of apoptosome | 2.435758e-03 | 2.613 |
| R-HSA-9772573 | Late SARS-CoV-2 Infection Events | 2.562368e-03 | 2.591 |
| R-HSA-446652 | Interleukin-1 family signaling | 2.612494e-03 | 2.583 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 2.895682e-03 | 2.538 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 2.944537e-03 | 2.531 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 3.219729e-03 | 2.492 |
| R-HSA-9020702 | Interleukin-1 signaling | 3.573049e-03 | 2.447 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 3.650248e-03 | 2.438 |
| R-HSA-198323 | AKT phosphorylates targets in the cytosol | 3.650248e-03 | 2.438 |
| R-HSA-389356 | Co-stimulation by CD28 | 3.821885e-03 | 2.418 |
| R-HSA-9683610 | Maturation of nucleoprotein | 4.106071e-03 | 2.387 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 4.106071e-03 | 2.387 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 4.423021e-03 | 2.354 |
| R-HSA-9700206 | Signaling by ALK in cancer | 4.423021e-03 | 2.354 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 4.586914e-03 | 2.338 |
| R-HSA-5578768 | Physiological factors | 4.586914e-03 | 2.338 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 4.586914e-03 | 2.338 |
| R-HSA-1502540 | Signaling by Activin | 5.092491e-03 | 2.293 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 5.092491e-03 | 2.293 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 5.527467e-03 | 2.257 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 5.562013e-03 | 2.255 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 5.622524e-03 | 2.250 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 5.767827e-03 | 2.239 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 9.799410e-03 | 2.009 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 9.799410e-03 | 2.009 |
| R-HSA-74751 | Insulin receptor signalling cascade | 7.625752e-03 | 2.118 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 9.799410e-03 | 2.009 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 6.754839e-03 | 2.170 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 7.063210e-03 | 2.151 |
| R-HSA-1181150 | Signaling by NODAL | 8.629824e-03 | 2.064 |
| R-HSA-111471 | Apoptotic factor-mediated response | 7.356571e-03 | 2.133 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 9.994343e-03 | 2.000 |
| R-HSA-4086398 | Ca2+ pathway | 1.047993e-02 | 1.980 |
| R-HSA-169131 | Inhibition of PKR | 1.099365e-02 | 1.959 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.144801e-02 | 1.941 |
| R-HSA-982772 | Growth hormone receptor signaling | 1.144801e-02 | 1.941 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 1.545866e-02 | 1.811 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 1.545866e-02 | 1.811 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 1.632330e-02 | 1.787 |
| R-HSA-5683057 | MAPK family signaling cascades | 1.633787e-02 | 1.787 |
| R-HSA-438064 | Post NMDA receptor activation events | 1.644965e-02 | 1.784 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 1.673407e-02 | 1.776 |
| R-HSA-68962 | Activation of the pre-replicative complex | 1.720820e-02 | 1.764 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 1.720820e-02 | 1.764 |
| R-HSA-109581 | Apoptosis | 1.799255e-02 | 1.745 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 1.875673e-02 | 1.727 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 1.903780e-02 | 1.720 |
| R-HSA-74752 | Signaling by Insulin receptor | 1.927287e-02 | 1.715 |
| R-HSA-176187 | Activation of ATR in response to replication stress | 1.998202e-02 | 1.699 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 1.998202e-02 | 1.699 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 1.998202e-02 | 1.699 |
| R-HSA-69273 | Cyclin A/B1/B2 associated events during G2/M transition | 1.998202e-02 | 1.699 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 2.143705e-02 | 1.669 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 2.181782e-02 | 1.661 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 2.192809e-02 | 1.659 |
| R-HSA-5673000 | RAF activation | 2.192809e-02 | 1.659 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 2.192809e-02 | 1.659 |
| R-HSA-2559585 | Oncogene Induced Senescence | 2.292948e-02 | 1.640 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 2.394946e-02 | 1.621 |
| R-HSA-8941326 | RUNX2 regulates bone development | 2.394946e-02 | 1.621 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 2.453800e-02 | 1.610 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 2.498780e-02 | 1.602 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 2.510306e-02 | 1.600 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 2.510306e-02 | 1.600 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 2.711864e-02 | 1.567 |
| R-HSA-8953750 | Transcriptional Regulation by E2F6 | 2.711864e-02 | 1.567 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 2.711864e-02 | 1.567 |
| R-HSA-139910 | Activation of BMF and translocation to mitochondria | 2.726043e-02 | 1.564 |
| R-HSA-111446 | Activation of BIM and translocation to mitochondria | 2.726043e-02 | 1.564 |
| R-HSA-69275 | G2/M Transition | 2.731777e-02 | 1.564 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 2.816784e-02 | 1.550 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 2.869455e-02 | 1.542 |
| R-HSA-5218920 | VEGFR2 mediated vascular permeability | 2.932021e-02 | 1.533 |
| R-HSA-9683701 | Translation of Structural Proteins | 3.044696e-02 | 1.516 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 3.080115e-02 | 1.511 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 3.116149e-02 | 1.506 |
| R-HSA-69200 | Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... | 3.262369e-02 | 1.486 |
| R-HSA-68911 | G2 Phase | 3.795770e-02 | 1.421 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 4.326262e-02 | 1.364 |
| R-HSA-9652817 | Signaling by MAPK mutants | 4.326262e-02 | 1.364 |
| R-HSA-165158 | Activation of AKT2 | 3.795770e-02 | 1.421 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 4.853863e-02 | 1.314 |
| R-HSA-199920 | CREB phosphorylation | 4.853863e-02 | 1.314 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 6.419464e-02 | 1.193 |
| R-HSA-111995 | phospho-PLA2 pathway | 5.900448e-02 | 1.229 |
| R-HSA-69206 | G1/S Transition | 4.298465e-02 | 1.367 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 6.298511e-02 | 1.201 |
| R-HSA-9007892 | Interleukin-38 signaling | 3.262369e-02 | 1.486 |
| R-HSA-446388 | Regulation of cytoskeletal remodeling and cell spreading by IPP complex componen... | 4.326262e-02 | 1.364 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 5.335601e-02 | 1.273 |
| R-HSA-437239 | Recycling pathway of L1 | 3.755726e-02 | 1.425 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 3.716354e-02 | 1.430 |
| R-HSA-69236 | G1 Phase | 3.392843e-02 | 1.469 |
| R-HSA-69231 | Cyclin D associated events in G1 | 3.392843e-02 | 1.469 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 5.917174e-02 | 1.228 |
| R-HSA-8848021 | Signaling by PTK6 | 5.917174e-02 | 1.228 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 3.879863e-02 | 1.411 |
| R-HSA-168256 | Immune System | 4.939967e-02 | 1.306 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 5.066836e-02 | 1.295 |
| R-HSA-373755 | Semaphorin interactions | 5.917174e-02 | 1.228 |
| R-HSA-3371556 | Cellular response to heat stress | 3.929556e-02 | 1.406 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 5.484940e-02 | 1.261 |
| R-HSA-5654743 | Signaling by FGFR4 | 3.275129e-02 | 1.485 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 5.484940e-02 | 1.261 |
| R-HSA-5654741 | Signaling by FGFR3 | 3.512195e-02 | 1.454 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 4.391740e-02 | 1.357 |
| R-HSA-5654736 | Signaling by FGFR1 | 4.927183e-02 | 1.307 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 3.929556e-02 | 1.406 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 4.927183e-02 | 1.307 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 3.786739e-02 | 1.422 |
| R-HSA-1266738 | Developmental Biology | 4.041045e-02 | 1.394 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 4.391740e-02 | 1.357 |
| R-HSA-1592230 | Mitochondrial biogenesis | 3.646653e-02 | 1.438 |
| R-HSA-5357801 | Programmed Cell Death | 3.652922e-02 | 1.437 |
| R-HSA-69242 | S Phase | 6.481726e-02 | 1.188 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 6.667395e-02 | 1.176 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 6.935649e-02 | 1.159 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 6.969135e-02 | 1.157 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 6.969135e-02 | 1.157 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 7.280227e-02 | 1.138 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 7.280227e-02 | 1.138 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 7.437443e-02 | 1.129 |
| R-HSA-5467337 | APC truncation mutants have impaired AXIN binding | 7.449018e-02 | 1.128 |
| R-HSA-5467348 | Truncations of AMER1 destabilize the destruction complex | 7.449018e-02 | 1.128 |
| R-HSA-5467340 | AXIN missense mutants destabilize the destruction complex | 7.449018e-02 | 1.128 |
| R-HSA-4839744 | Signaling by APC mutants | 7.449018e-02 | 1.128 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 7.449018e-02 | 1.128 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 7.449018e-02 | 1.128 |
| R-HSA-9006936 | Signaling by TGFB family members | 7.631787e-02 | 1.117 |
| R-HSA-380287 | Centrosome maturation | 7.755131e-02 | 1.110 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 7.755131e-02 | 1.110 |
| R-HSA-9824439 | Bacterial Infection Pathways | 7.789465e-02 | 1.108 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 7.915571e-02 | 1.102 |
| R-HSA-5339716 | Signaling by GSK3beta mutants | 7.959588e-02 | 1.099 |
| R-HSA-4839748 | Signaling by AMER1 mutants | 7.959588e-02 | 1.099 |
| R-HSA-4839735 | Signaling by AXIN mutants | 7.959588e-02 | 1.099 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 8.049249e-02 | 1.094 |
| R-HSA-73864 | RNA Polymerase I Transcription | 8.239560e-02 | 1.084 |
| R-HSA-4839743 | Signaling by CTNNB1 phospho-site mutants | 8.467372e-02 | 1.072 |
| R-HSA-5358749 | CTNNB1 S37 mutants aren't phosphorylated | 8.467372e-02 | 1.072 |
| R-HSA-5358752 | CTNNB1 T41 mutants aren't phosphorylated | 8.467372e-02 | 1.072 |
| R-HSA-5358751 | CTNNB1 S45 mutants aren't phosphorylated | 8.467372e-02 | 1.072 |
| R-HSA-5358747 | CTNNB1 S33 mutants aren't phosphorylated | 8.467372e-02 | 1.072 |
| R-HSA-5654738 | Signaling by FGFR2 | 8.567590e-02 | 1.067 |
| R-HSA-9658195 | Leishmania infection | 8.597883e-02 | 1.066 |
| R-HSA-9824443 | Parasitic Infection Pathways | 8.597883e-02 | 1.066 |
| R-HSA-5663205 | Infectious disease | 8.744469e-02 | 1.058 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 8.972386e-02 | 1.047 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 8.972386e-02 | 1.047 |
| R-HSA-5676594 | TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway | 8.972386e-02 | 1.047 |
| R-HSA-212436 | Generic Transcription Pathway | 9.198530e-02 | 1.036 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 9.294170e-02 | 1.032 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 9.474645e-02 | 1.023 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 9.474645e-02 | 1.023 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 9.474645e-02 | 1.023 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 9.574679e-02 | 1.019 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 9.574679e-02 | 1.019 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 9.574679e-02 | 1.019 |
| R-HSA-381038 | XBP1(S) activates chaperone genes | 9.745721e-02 | 1.011 |
| R-HSA-196299 | Beta-catenin phosphorylation cascade | 9.974164e-02 | 1.001 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 9.974164e-02 | 1.001 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 9.974164e-02 | 1.001 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 9.974164e-02 | 1.001 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 9.974164e-02 | 1.001 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 9.974164e-02 | 1.001 |
| R-HSA-9679506 | SARS-CoV Infections | 9.977688e-02 | 1.001 |
| R-HSA-195721 | Signaling by WNT | 1.000412e-01 | 1.000 |
| R-HSA-202424 | Downstream TCR signaling | 1.043848e-01 | 0.981 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 1.047096e-01 | 0.980 |
| R-HSA-9664420 | Killing mechanisms | 1.047096e-01 | 0.980 |
| R-HSA-6804116 | TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest | 1.047096e-01 | 0.980 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 1.061374e-01 | 0.974 |
| R-HSA-381070 | IRE1alpha activates chaperones | 1.078981e-01 | 0.967 |
| R-HSA-2028269 | Signaling by Hippo | 1.145643e-01 | 0.941 |
| R-HSA-432142 | Platelet sensitization by LDL | 1.194513e-01 | 0.923 |
| R-HSA-3928664 | Ephrin signaling | 1.194513e-01 | 0.923 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 1.197191e-01 | 0.922 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 1.204356e-01 | 0.919 |
| R-HSA-190236 | Signaling by FGFR | 1.222555e-01 | 0.913 |
| R-HSA-376176 | Signaling by ROBO receptors | 1.252220e-01 | 0.902 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 1.259156e-01 | 0.900 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 1.339530e-01 | 0.873 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 1.376212e-01 | 0.861 |
| R-HSA-2672351 | Stimuli-sensing channels | 1.426961e-01 | 0.846 |
| R-HSA-69002 | DNA Replication Pre-Initiation | 1.445895e-01 | 0.840 |
| R-HSA-202403 | TCR signaling | 1.464883e-01 | 0.834 |
| R-HSA-77075 | RNA Pol II CTD phosphorylation and interaction with CE | 1.482185e-01 | 0.829 |
| R-HSA-167160 | RNA Pol II CTD phosphorylation and interaction with CE during HIV infection | 1.482185e-01 | 0.829 |
| R-HSA-392451 | G beta:gamma signalling through PI3Kgamma | 1.482185e-01 | 0.829 |
| R-HSA-73857 | RNA Polymerase II Transcription | 1.496108e-01 | 0.825 |
| R-HSA-9821993 | Replacement of protamines by nucleosomes in the male pronucleus | 1.529218e-01 | 0.816 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 1.529218e-01 | 0.816 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 1.529218e-01 | 0.816 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 1.575994e-01 | 0.802 |
| R-HSA-73894 | DNA Repair | 1.593477e-01 | 0.798 |
| R-HSA-909733 | Interferon alpha/beta signaling | 1.599198e-01 | 0.796 |
| R-HSA-4641262 | Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1.668783e-01 | 0.778 |
| R-HSA-73863 | RNA Polymerase I Transcription Termination | 1.668783e-01 | 0.778 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 1.668783e-01 | 0.778 |
| R-HSA-201451 | Signaling by BMP | 1.668783e-01 | 0.778 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 1.668783e-01 | 0.778 |
| R-HSA-8939211 | ESR-mediated signaling | 1.703101e-01 | 0.769 |
| R-HSA-113418 | Formation of the Early Elongation Complex | 1.714797e-01 | 0.766 |
| R-HSA-171319 | Telomere Extension By Telomerase | 1.714797e-01 | 0.766 |
| R-HSA-167158 | Formation of the HIV-1 Early Elongation Complex | 1.714797e-01 | 0.766 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 1.716082e-01 | 0.765 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1.755361e-01 | 0.756 |
| R-HSA-72086 | mRNA Capping | 1.760560e-01 | 0.754 |
| R-HSA-5656169 | Termination of translesion DNA synthesis | 1.760560e-01 | 0.754 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 1.806073e-01 | 0.743 |
| R-HSA-114452 | Activation of BH3-only proteins | 1.806073e-01 | 0.743 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 1.851338e-01 | 0.733 |
| R-HSA-913531 | Interferon Signaling | 1.851866e-01 | 0.732 |
| R-HSA-69481 | G2/M Checkpoints | 1.854179e-01 | 0.732 |
| R-HSA-4791275 | Signaling by WNT in cancer | 1.896355e-01 | 0.722 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 1.896355e-01 | 0.722 |
| R-HSA-1538133 | G0 and Early G1 | 1.896355e-01 | 0.722 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.896355e-01 | 0.722 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 1.913857e-01 | 0.718 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 1.941127e-01 | 0.712 |
| R-HSA-397795 | G-protein beta:gamma signalling | 1.941127e-01 | 0.712 |
| R-HSA-354192 | Integrin signaling | 1.941127e-01 | 0.712 |
| R-HSA-5576891 | Cardiac conduction | 1.953787e-01 | 0.709 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 2.029937e-01 | 0.693 |
| R-HSA-392518 | Signal amplification | 2.029937e-01 | 0.693 |
| R-HSA-416476 | G alpha (q) signalling events | 2.078331e-01 | 0.682 |
| R-HSA-114604 | GPVI-mediated activation cascade | 2.117780e-01 | 0.674 |
| R-HSA-8853659 | RET signaling | 2.117780e-01 | 0.674 |
| R-HSA-6807070 | PTEN Regulation | 2.134710e-01 | 0.671 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 2.134710e-01 | 0.671 |
| R-HSA-9664417 | Leishmania phagocytosis | 2.154920e-01 | 0.667 |
| R-HSA-9664407 | Parasite infection | 2.154920e-01 | 0.667 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 2.154920e-01 | 0.667 |
| R-HSA-9762114 | GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 | 2.161341e-01 | 0.665 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 2.175149e-01 | 0.663 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 2.247752e-01 | 0.648 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 2.247752e-01 | 0.648 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 2.256232e-01 | 0.647 |
| R-HSA-446728 | Cell junction organization | 2.279870e-01 | 0.642 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 2.290603e-01 | 0.640 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 2.290603e-01 | 0.640 |
| R-HSA-167169 | HIV Transcription Elongation | 2.290603e-01 | 0.640 |
| R-HSA-5696395 | Formation of Incision Complex in GG-NER | 2.290603e-01 | 0.640 |
| R-HSA-73779 | RNA Polymerase II Transcription Pre-Initiation And Promoter Opening | 2.290603e-01 | 0.640 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 2.333220e-01 | 0.632 |
| R-HSA-110313 | Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... | 2.333220e-01 | 0.632 |
| R-HSA-167162 | RNA Polymerase II HIV Promoter Escape | 2.375604e-01 | 0.624 |
| R-HSA-167161 | HIV Transcription Initiation | 2.375604e-01 | 0.624 |
| R-HSA-75953 | RNA Polymerase II Transcription Initiation | 2.375604e-01 | 0.624 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 2.375604e-01 | 0.624 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 2.375604e-01 | 0.624 |
| R-HSA-73762 | RNA Polymerase I Transcription Initiation | 2.417756e-01 | 0.617 |
| R-HSA-111996 | Ca-dependent events | 2.417756e-01 | 0.617 |
| R-HSA-69306 | DNA Replication | 2.439446e-01 | 0.613 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 2.439446e-01 | 0.613 |
| R-HSA-73776 | RNA Polymerase II Promoter Escape | 2.459678e-01 | 0.609 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 2.459852e-01 | 0.609 |
| R-HSA-73887 | Death Receptor Signaling | 2.459852e-01 | 0.609 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 2.501371e-01 | 0.602 |
| R-HSA-76042 | RNA Polymerase II Transcription Initiation And Promoter Clearance | 2.542836e-01 | 0.595 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 2.542836e-01 | 0.595 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 2.542836e-01 | 0.595 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 2.542836e-01 | 0.595 |
| R-HSA-877300 | Interferon gamma signaling | 2.561977e-01 | 0.591 |
| R-HSA-6781823 | Formation of TC-NER Pre-Incision Complex | 2.584074e-01 | 0.588 |
| R-HSA-75153 | Apoptotic execution phase | 2.584074e-01 | 0.588 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 2.625087e-01 | 0.581 |
| R-HSA-2467813 | Separation of Sister Chromatids | 2.664198e-01 | 0.574 |
| R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint | 2.706440e-01 | 0.568 |
| R-HSA-69563 | p53-Dependent G1 DNA Damage Response | 2.706440e-01 | 0.568 |
| R-HSA-73893 | DNA Damage Bypass | 2.706440e-01 | 0.568 |
| R-HSA-109704 | PI3K Cascade | 2.746784e-01 | 0.561 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 2.786906e-01 | 0.555 |
| R-HSA-912446 | Meiotic recombination | 2.786906e-01 | 0.555 |
| R-HSA-73772 | RNA Polymerase I Promoter Escape | 2.826810e-01 | 0.549 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 2.826810e-01 | 0.549 |
| R-HSA-68949 | Orc1 removal from chromatin | 2.826810e-01 | 0.549 |
| R-HSA-1500931 | Cell-Cell communication | 2.842795e-01 | 0.546 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 2.848185e-01 | 0.545 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 2.866495e-01 | 0.543 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 2.866495e-01 | 0.543 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 2.866495e-01 | 0.543 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.866495e-01 | 0.543 |
| R-HSA-5689880 | Ub-specific processing proteases | 2.868612e-01 | 0.542 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 2.868612e-01 | 0.542 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 2.868612e-01 | 0.542 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 2.889034e-01 | 0.539 |
| R-HSA-69017 | CDK-mediated phosphorylation and removal of Cdc6 | 2.905962e-01 | 0.537 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 2.945214e-01 | 0.531 |
| R-HSA-112315 | Transmission across Chemical Synapses | 2.948124e-01 | 0.530 |
| R-HSA-6782210 | Gap-filling DNA repair synthesis and ligation in TC-NER | 2.984252e-01 | 0.525 |
| R-HSA-193648 | NRAGE signals death through JNK | 2.984252e-01 | 0.525 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 2.984252e-01 | 0.525 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 2.984252e-01 | 0.525 |
| R-HSA-75893 | TNF signaling | 2.984252e-01 | 0.525 |
| R-HSA-9824446 | Viral Infection Pathways | 3.010825e-01 | 0.521 |
| R-HSA-112399 | IRS-mediated signalling | 3.023075e-01 | 0.520 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 3.023075e-01 | 0.520 |
| R-HSA-74160 | Gene expression (Transcription) | 3.035190e-01 | 0.518 |
| R-HSA-6782135 | Dual incision in TC-NER | 3.061686e-01 | 0.514 |
| R-HSA-180786 | Extension of Telomeres | 3.100086e-01 | 0.509 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 3.100086e-01 | 0.509 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 3.176257e-01 | 0.498 |
| R-HSA-8939902 | Regulation of RUNX2 expression and activity | 3.176257e-01 | 0.498 |
| R-HSA-112043 | PLC beta mediated events | 3.176257e-01 | 0.498 |
| R-HSA-983712 | Ion channel transport | 3.194358e-01 | 0.496 |
| R-HSA-176408 | Regulation of APC/C activators between G1/S and early anaphase | 3.214029e-01 | 0.493 |
| R-HSA-2559586 | DNA Damage/Telomere Stress Induced Senescence | 3.214029e-01 | 0.493 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 3.214029e-01 | 0.493 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 3.251596e-01 | 0.488 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 3.251596e-01 | 0.488 |
| R-HSA-2428924 | IGF1R signaling cascade | 3.288956e-01 | 0.483 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 3.326112e-01 | 0.478 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 3.335906e-01 | 0.477 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 3.363064e-01 | 0.473 |
| R-HSA-112040 | G-protein mediated events | 3.399815e-01 | 0.469 |
| R-HSA-5693606 | DNA Double Strand Break Response | 3.399815e-01 | 0.469 |
| R-HSA-389948 | Co-inhibition by PD-1 | 3.416434e-01 | 0.466 |
| R-HSA-167172 | Transcription of the HIV genome | 3.436364e-01 | 0.464 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 3.436364e-01 | 0.464 |
| R-HSA-195253 | Degradation of beta-catenin by the destruction complex | 3.508862e-01 | 0.455 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 3.508862e-01 | 0.455 |
| R-HSA-427413 | NoRC negatively regulates rRNA expression | 3.544814e-01 | 0.450 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 3.544814e-01 | 0.450 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 3.552751e-01 | 0.449 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 3.616128e-01 | 0.442 |
| R-HSA-69052 | Switching of origins to a post-replicative state | 3.616128e-01 | 0.442 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 3.651492e-01 | 0.438 |
| R-HSA-397014 | Muscle contraction | 3.675998e-01 | 0.435 |
| R-HSA-6781827 | Transcription-Coupled Nucleotide Excision Repair (TC-NER) | 3.686663e-01 | 0.433 |
| R-HSA-68882 | Mitotic Anaphase | 3.755112e-01 | 0.425 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 3.774830e-01 | 0.423 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 3.791023e-01 | 0.421 |
| R-HSA-418990 | Adherens junctions interactions | 3.794523e-01 | 0.421 |
| R-HSA-9659379 | Sensory processing of sound | 3.825429e-01 | 0.417 |
| R-HSA-9833482 | PKR-mediated signaling | 3.859647e-01 | 0.413 |
| R-HSA-5250941 | Negative epigenetic regulation of rRNA expression | 3.859647e-01 | 0.413 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 3.859647e-01 | 0.413 |
| R-HSA-5693607 | Processing of DNA double-strand break ends | 3.893677e-01 | 0.410 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 3.951131e-01 | 0.403 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 3.961179e-01 | 0.402 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 3.990012e-01 | 0.399 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 3.994652e-01 | 0.399 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 3.994652e-01 | 0.399 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 3.994652e-01 | 0.399 |
| R-HSA-1500620 | Meiosis | 4.027943e-01 | 0.395 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 4.027943e-01 | 0.395 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 4.093977e-01 | 0.388 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 4.159289e-01 | 0.381 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 4.223886e-01 | 0.374 |
| R-HSA-2682334 | EPH-Ephrin signaling | 4.319461e-01 | 0.365 |
| R-HSA-421270 | Cell-cell junction organization | 4.428504e-01 | 0.354 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 4.475288e-01 | 0.349 |
| R-HSA-5688426 | Deubiquitination | 4.503016e-01 | 0.346 |
| R-HSA-157579 | Telomere Maintenance | 4.505943e-01 | 0.346 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 4.566748e-01 | 0.340 |
| R-HSA-5610787 | Hedgehog 'off' state | 4.596901e-01 | 0.338 |
| R-HSA-109582 | Hemostasis | 4.604088e-01 | 0.337 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 4.715866e-01 | 0.326 |
| R-HSA-111885 | Opioid Signalling | 4.715866e-01 | 0.326 |
| R-HSA-9833110 | RSV-host interactions | 4.745200e-01 | 0.324 |
| R-HSA-5696398 | Nucleotide Excision Repair | 4.774373e-01 | 0.321 |
| R-HSA-418346 | Platelet homeostasis | 4.803386e-01 | 0.318 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 4.803386e-01 | 0.318 |
| R-HSA-69239 | Synthesis of DNA | 4.832240e-01 | 0.316 |
| R-HSA-6798695 | Neutrophil degranulation | 4.944332e-01 | 0.306 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 5.029829e-01 | 0.298 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 5.029829e-01 | 0.298 |
| R-HSA-112316 | Neuronal System | 5.096807e-01 | 0.293 |
| R-HSA-1643685 | Disease | 5.183098e-01 | 0.285 |
| R-HSA-5693538 | Homology Directed Repair | 5.193232e-01 | 0.285 |
| R-HSA-73886 | Chromosome Maintenance | 5.272930e-01 | 0.278 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 5.272930e-01 | 0.278 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 5.325334e-01 | 0.274 |
| R-HSA-1280218 | Adaptive Immune System | 5.427124e-01 | 0.265 |
| R-HSA-1474165 | Reproduction | 5.554135e-01 | 0.255 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 5.677836e-01 | 0.246 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 5.748196e-01 | 0.240 |
| R-HSA-5358351 | Signaling by Hedgehog | 5.771857e-01 | 0.239 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 5.888223e-01 | 0.230 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 5.888223e-01 | 0.230 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 6.089757e-01 | 0.215 |
| R-HSA-162587 | HIV Life Cycle | 6.218654e-01 | 0.206 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 6.239725e-01 | 0.205 |
| R-HSA-388396 | GPCR downstream signalling | 6.456606e-01 | 0.190 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 6.561486e-01 | 0.183 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 6.561486e-01 | 0.183 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 6.599742e-01 | 0.180 |
| R-HSA-168255 | Influenza Infection | 6.674995e-01 | 0.176 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 6.748600e-01 | 0.171 |
| R-HSA-5617833 | Cilium Assembly | 6.873553e-01 | 0.163 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 6.942811e-01 | 0.158 |
| R-HSA-8953854 | Metabolism of RNA | 7.025314e-01 | 0.153 |
| R-HSA-72172 | mRNA Splicing | 7.125544e-01 | 0.147 |
| R-HSA-372790 | Signaling by GPCR | 7.213917e-01 | 0.142 |
| R-HSA-162906 | HIV Infection | 7.473443e-01 | 0.126 |
| R-HSA-9711123 | Cellular response to chemical stress | 7.993432e-01 | 0.097 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 8.113919e-01 | 0.091 |
| R-HSA-418594 | G alpha (i) signalling events | 9.090574e-01 | 0.041 |
| R-HSA-597592 | Post-translational protein modification | 9.617836e-01 | 0.017 |
| R-HSA-382551 | Transport of small molecules | 9.773016e-01 | 0.010 |
| R-HSA-392499 | Metabolism of proteins | 9.984717e-01 | 0.001 |
| R-HSA-9709957 | Sensory Perception | 9.992823e-01 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
PINK1 |
0.619 | 0.271 | 1 | 0.602 |
ERK2 |
0.614 | 0.269 | 1 | 0.699 |
P38D |
0.612 | 0.262 | 1 | 0.690 |
JNK3 |
0.612 | 0.253 | 1 | 0.697 |
P38B |
0.611 | 0.247 | 1 | 0.701 |
ERK1 |
0.609 | 0.258 | 1 | 0.702 |
P38G |
0.608 | 0.266 | 1 | 0.668 |
JNK1 |
0.607 | 0.244 | 1 | 0.670 |
MEKK2 |
0.607 | 0.155 | 2 | 0.748 |
P38A |
0.607 | 0.239 | 1 | 0.700 |
JNK2 |
0.606 | 0.241 | 1 | 0.691 |
MEKK6 |
0.603 | 0.162 | 1 | 0.425 |
MAP3K15 |
0.603 | 0.143 | 1 | 0.402 |
ASK1 |
0.602 | 0.128 | 1 | 0.395 |
VRK2 |
0.602 | 0.118 | 1 | 0.540 |
HIPK1 |
0.600 | 0.213 | 1 | 0.782 |
MEK5 |
0.600 | 0.114 | 2 | 0.757 |
CDK4 |
0.599 | 0.242 | 1 | 0.698 |
MEKK3 |
0.598 | 0.122 | 1 | 0.417 |
MOK |
0.598 | 0.182 | 1 | 0.799 |
HIPK3 |
0.597 | 0.213 | 1 | 0.763 |
PRP4 |
0.595 | 0.120 | -3 | 0.493 |
LKB1 |
0.595 | 0.040 | -3 | 0.636 |
CDK6 |
0.593 | 0.226 | 1 | 0.679 |
MPSK1 |
0.593 | 0.094 | 1 | 0.503 |
PDK1 |
0.593 | 0.037 | 1 | 0.441 |
NEK4 |
0.592 | 0.060 | 1 | 0.446 |
CDK14 |
0.592 | 0.258 | 1 | 0.679 |
BRAF |
0.592 | 0.000 | -4 | 0.597 |
NLK |
0.592 | 0.198 | 1 | 0.648 |
DYRK2 |
0.591 | 0.226 | 1 | 0.801 |
MYO3A |
0.591 | 0.069 | 1 | 0.496 |
CDK16 |
0.591 | 0.261 | 1 | 0.664 |
MEK2 |
0.591 | 0.031 | 2 | 0.743 |
PKR |
0.591 | 0.015 | 1 | 0.519 |
GAK |
0.590 | -0.030 | 1 | 0.421 |
NIM1 |
0.590 | 0.302 | 3 | 0.531 |
LRRK2 |
0.590 | 0.014 | 2 | 0.721 |
CDK5 |
0.589 | 0.221 | 1 | 0.680 |
MINK |
0.589 | 0.020 | 1 | 0.422 |
NEK1 |
0.588 | 0.034 | 1 | 0.444 |
HIPK2 |
0.588 | 0.219 | 1 | 0.788 |
CDK1 |
0.588 | 0.218 | 1 | 0.675 |
MYO3B |
0.587 | 0.067 | 2 | 0.666 |
MEKK1 |
0.587 | 0.032 | 1 | 0.438 |
CDK17 |
0.587 | 0.251 | 1 | 0.659 |
ERK5 |
0.587 | 0.132 | 1 | 0.601 |
NEK8 |
0.587 | -0.008 | 2 | 0.709 |
NEK11 |
0.586 | 0.047 | 1 | 0.414 |
TTK |
0.586 | -0.014 | -2 | 0.458 |
MEK1 |
0.586 | -0.013 | 2 | 0.733 |
TNIK |
0.586 | 0.028 | 3 | 0.365 |
HGK |
0.586 | 0.020 | 3 | 0.367 |
ZAK |
0.586 | 0.035 | 1 | 0.401 |
RIPK1 |
0.585 | 0.147 | 1 | 0.480 |
YSK1 |
0.585 | 0.060 | 2 | 0.666 |
CAMKK1 |
0.584 | -0.050 | -2 | 0.502 |
STK33 |
0.584 | 0.099 | 2 | 0.776 |
MST3 |
0.584 | 0.066 | 2 | 0.631 |
CDK9 |
0.584 | 0.231 | 1 | 0.696 |
TAO2 |
0.584 | 0.003 | 2 | 0.683 |
HIPK4 |
0.583 | 0.185 | 1 | 0.764 |
EEF2K |
0.583 | -0.019 | 3 | 0.338 |
CDK8 |
0.583 | 0.242 | 1 | 0.679 |
VRK1 |
0.583 | -0.027 | 2 | 0.654 |
DYRK3 |
0.583 | 0.172 | 1 | 0.812 |
PERK |
0.583 | 0.000 | -2 | 0.514 |
BMPR2 |
0.583 | -0.062 | -2 | 0.549 |
PRPK |
0.583 | 0.029 | -1 | 0.400 |
NEK5 |
0.582 | -0.029 | 1 | 0.446 |
MAK |
0.582 | 0.128 | -2 | 0.472 |
KHS2 |
0.582 | 0.028 | 1 | 0.443 |
WNK4 |
0.582 | 0.063 | -2 | 0.546 |
HASPIN |
0.582 | 0.033 | -1 | 0.282 |
KHS1 |
0.581 | 0.011 | 1 | 0.447 |
CDK12 |
0.581 | 0.225 | 1 | 0.696 |
ATR |
0.581 | 0.022 | 1 | 0.450 |
IRAK1 |
0.581 | 0.064 | -1 | 0.294 |
CDK13 |
0.580 | 0.220 | 1 | 0.695 |
TLK2 |
0.580 | -0.012 | 1 | 0.459 |
CDK7 |
0.580 | 0.240 | 1 | 0.691 |
IRE1 |
0.580 | 0.137 | 1 | 0.522 |
ANKRD3 |
0.579 | -0.046 | 1 | 0.456 |
CAMLCK |
0.579 | -0.009 | -2 | 0.524 |
TAK1 |
0.579 | -0.110 | 1 | 0.411 |
HPK1 |
0.579 | 0.012 | 1 | 0.423 |
TAO3 |
0.579 | 0.007 | 1 | 0.419 |
DYRK1B |
0.579 | 0.191 | 1 | 0.721 |
ICK |
0.578 | 0.063 | -3 | 0.552 |
MOS |
0.578 | -0.001 | 1 | 0.460 |
GCK |
0.577 | -0.035 | 1 | 0.411 |
ALPHAK3 |
0.576 | -0.052 | -1 | 0.296 |
DYRK1A |
0.576 | 0.141 | 1 | 0.709 |
CDK18 |
0.576 | 0.237 | 1 | 0.675 |
NIK |
0.576 | -0.054 | -3 | 0.617 |
CDKL1 |
0.576 | 0.048 | -3 | 0.558 |
IRAK4 |
0.575 | 0.047 | 1 | 0.490 |
PBK |
0.575 | -0.024 | 1 | 0.380 |
CDK19 |
0.575 | 0.241 | 1 | 0.677 |
RAF1 |
0.575 | 0.046 | 1 | 0.434 |
CDK2 |
0.575 | 0.149 | 1 | 0.647 |
NEK3 |
0.574 | 0.015 | 1 | 0.432 |
TLK1 |
0.574 | -0.021 | -2 | 0.488 |
HUNK |
0.574 | 0.081 | 2 | 0.766 |
MLK4 |
0.574 | 0.052 | 2 | 0.727 |
CDK3 |
0.574 | 0.183 | 1 | 0.666 |
DYRK4 |
0.573 | 0.193 | 1 | 0.755 |
PDHK4 |
0.573 | 0.068 | 1 | 0.483 |
PDHK1 |
0.573 | 0.034 | 1 | 0.485 |
GSK3A |
0.573 | 0.036 | 4 | 0.135 |
DLK |
0.573 | -0.106 | 1 | 0.408 |
IRE2 |
0.573 | 0.100 | 2 | 0.686 |
STLK3 |
0.572 | -0.075 | 1 | 0.383 |
MASTL |
0.572 | 0.038 | -2 | 0.484 |
CAMKK2 |
0.572 | -0.120 | -2 | 0.487 |
MLK1 |
0.571 | 0.022 | 2 | 0.680 |
HRI |
0.571 | -0.042 | -2 | 0.522 |
OSR1 |
0.571 | -0.066 | 2 | 0.706 |
ALK4 |
0.571 | -0.093 | -2 | 0.525 |
MTOR |
0.570 | 0.207 | 1 | 0.514 |
CHAK1 |
0.569 | 0.022 | 2 | 0.762 |
MST2 |
0.569 | -0.104 | 1 | 0.409 |
KIS |
0.569 | 0.247 | 1 | 0.713 |
ERK7 |
0.569 | 0.065 | 2 | 0.424 |
MARK4 |
0.568 | 0.093 | 4 | 0.407 |
DNAPK |
0.568 | 0.021 | 1 | 0.419 |
TTBK2 |
0.568 | 0.044 | 2 | 0.769 |
CAMK1B |
0.567 | -0.045 | -3 | 0.591 |
MLK3 |
0.567 | 0.034 | 2 | 0.658 |
TAO1 |
0.567 | -0.019 | 1 | 0.402 |
ACVR2A |
0.567 | -0.060 | -2 | 0.489 |
CDK10 |
0.566 | 0.206 | 1 | 0.680 |
BIKE |
0.566 | -0.059 | 1 | 0.364 |
PLK4 |
0.566 | 0.107 | 2 | 0.795 |
WNK1 |
0.566 | 0.034 | -2 | 0.553 |
ALK2 |
0.565 | -0.090 | -2 | 0.497 |
LOK |
0.565 | -0.065 | -2 | 0.449 |
RIPK2 |
0.565 | 0.005 | 1 | 0.371 |
DAPK2 |
0.565 | -0.118 | -3 | 0.601 |
MST1 |
0.565 | -0.122 | 1 | 0.410 |
NEK2 |
0.565 | -0.007 | 2 | 0.679 |
BMPR1A |
0.565 | -0.031 | 1 | 0.302 |
GRK5 |
0.565 | -0.042 | -3 | 0.681 |
SMG1 |
0.565 | -0.010 | 1 | 0.439 |
NEK9 |
0.564 | -0.040 | 2 | 0.707 |
ACVR2B |
0.563 | -0.071 | -2 | 0.498 |
WNK3 |
0.563 | 0.017 | 1 | 0.447 |
RIPK3 |
0.563 | -0.002 | 3 | 0.490 |
PAK2 |
0.563 | 0.009 | -2 | 0.485 |
MARK2 |
0.562 | 0.059 | 4 | 0.404 |
SRPK3 |
0.562 | 0.050 | -3 | 0.523 |
MLK2 |
0.562 | -0.092 | 2 | 0.736 |
ULK2 |
0.562 | 0.026 | 2 | 0.782 |
YANK2 |
0.562 | 0.055 | 2 | 0.561 |
GRK2 |
0.562 | -0.016 | -2 | 0.456 |
TTBK1 |
0.562 | 0.044 | 2 | 0.727 |
QIK |
0.562 | 0.090 | -3 | 0.582 |
BMPR1B |
0.562 | -0.048 | 1 | 0.327 |
GSK3B |
0.561 | -0.028 | 4 | 0.134 |
CK1G3 |
0.561 | 0.101 | -3 | 0.225 |
CDKL5 |
0.561 | 0.039 | -3 | 0.524 |
NEK7 |
0.561 | -0.025 | -3 | 0.720 |
CHAK2 |
0.560 | -0.047 | -1 | 0.307 |
SNRK |
0.560 | 0.113 | 2 | 0.778 |
SMMLCK |
0.560 | -0.062 | -3 | 0.568 |
BUB1 |
0.560 | 0.033 | -5 | 0.587 |
TGFBR1 |
0.559 | -0.096 | -2 | 0.497 |
GRK6 |
0.559 | -0.088 | 1 | 0.385 |
GRK4 |
0.558 | -0.010 | -2 | 0.504 |
PASK |
0.558 | -0.105 | -3 | 0.570 |
CAMK2G |
0.558 | -0.069 | 2 | 0.730 |
YSK4 |
0.558 | -0.137 | 1 | 0.393 |
DMPK1 |
0.557 | -0.032 | -3 | 0.450 |
AMPKA1 |
0.557 | 0.016 | -3 | 0.523 |
TSSK2 |
0.557 | -0.014 | -5 | 0.613 |
DSTYK |
0.556 | -0.057 | 2 | 0.684 |
SLK |
0.556 | -0.083 | -2 | 0.407 |
MARK1 |
0.555 | 0.041 | 4 | 0.410 |
PLK1 |
0.555 | -0.120 | -2 | 0.460 |
SKMLCK |
0.554 | -0.073 | -2 | 0.505 |
ROCK2 |
0.554 | -0.044 | -3 | 0.449 |
PLK3 |
0.554 | -0.068 | 2 | 0.757 |
MARK3 |
0.554 | 0.050 | 4 | 0.396 |
NUAK2 |
0.554 | 0.028 | -3 | 0.520 |
GRK7 |
0.553 | -0.040 | 1 | 0.361 |
CK1A2 |
0.553 | 0.048 | -3 | 0.294 |
ATM |
0.553 | -0.039 | 1 | 0.401 |
SSTK |
0.553 | 0.012 | 4 | 0.437 |
CK1D |
0.553 | 0.041 | -3 | 0.298 |
CK1G1 |
0.552 | 0.102 | -3 | 0.380 |
MST4 |
0.552 | 0.023 | 2 | 0.609 |
TBK1 |
0.551 | -0.044 | 1 | 0.384 |
ROCK1 |
0.551 | -0.027 | -3 | 0.441 |
CDC7 |
0.551 | -0.043 | 1 | 0.381 |
PAK1 |
0.551 | -0.006 | -2 | 0.494 |
AAK1 |
0.551 | -0.050 | 1 | 0.322 |
ULK1 |
0.551 | -0.001 | -3 | 0.663 |
BCKDK |
0.551 | -0.006 | -1 | 0.396 |
PAK3 |
0.550 | -0.007 | -2 | 0.499 |
PKCA |
0.550 | 0.050 | 2 | 0.628 |
PKCD |
0.550 | -0.009 | 2 | 0.676 |
PKCH |
0.550 | 0.021 | 2 | 0.656 |
MRCKB |
0.550 | -0.027 | -3 | 0.458 |
DAPK3 |
0.549 | -0.094 | -3 | 0.489 |
CLK4 |
0.549 | 0.039 | -3 | 0.458 |
DCAMKL1 |
0.549 | -0.019 | -3 | 0.437 |
NEK6 |
0.549 | -0.053 | -2 | 0.485 |
IKKE |
0.548 | -0.042 | 1 | 0.390 |
PLK2 |
0.548 | -0.040 | -3 | 0.624 |
PKCI |
0.548 | 0.021 | 2 | 0.628 |
GRK3 |
0.547 | -0.003 | -2 | 0.422 |
DCAMKL2 |
0.547 | -0.017 | -3 | 0.476 |
YANK3 |
0.547 | 0.031 | 2 | 0.545 |
PKCZ |
0.547 | -0.008 | 2 | 0.674 |
QSK |
0.547 | 0.047 | 4 | 0.422 |
DRAK1 |
0.547 | -0.079 | 1 | 0.278 |
GCN2 |
0.546 | 0.014 | 2 | 0.816 |
AMPKA2 |
0.546 | 0.006 | -3 | 0.485 |
TGFBR2 |
0.546 | -0.079 | -2 | 0.463 |
PKCE |
0.545 | 0.026 | 2 | 0.625 |
CK1E |
0.545 | 0.039 | -3 | 0.328 |
SRPK1 |
0.544 | 0.047 | -3 | 0.481 |
TSSK1 |
0.544 | -0.022 | -3 | 0.524 |
COT |
0.544 | -0.069 | 2 | 0.667 |
PKN3 |
0.544 | -0.065 | -3 | 0.557 |
SIK |
0.544 | 0.054 | -3 | 0.485 |
PKCT |
0.543 | 0.020 | 2 | 0.666 |
PKN2 |
0.543 | -0.025 | -3 | 0.551 |
CRIK |
0.543 | -0.041 | -3 | 0.395 |
MYLK4 |
0.542 | -0.049 | -2 | 0.466 |
BRSK2 |
0.542 | 0.044 | -3 | 0.513 |
IKKB |
0.542 | -0.060 | -2 | 0.524 |
CLK3 |
0.541 | 0.017 | 1 | 0.581 |
CAMK1G |
0.541 | -0.004 | -3 | 0.505 |
CK1G2 |
0.541 | 0.066 | -3 | 0.313 |
PKCG |
0.541 | 0.021 | 2 | 0.645 |
PIM2 |
0.541 | -0.041 | -3 | 0.459 |
BRSK1 |
0.540 | 0.040 | -3 | 0.503 |
DAPK1 |
0.540 | -0.094 | -3 | 0.494 |
GRK1 |
0.539 | -0.073 | -2 | 0.499 |
MRCKA |
0.535 | -0.064 | -3 | 0.452 |
AKT2 |
0.534 | -0.038 | -3 | 0.409 |
LATS1 |
0.534 | -0.155 | -3 | 0.509 |
PKCB |
0.534 | -0.012 | 2 | 0.602 |
NDR1 |
0.533 | -0.028 | -3 | 0.507 |
MNK1 |
0.533 | -0.017 | -2 | 0.467 |
CLK1 |
0.533 | 0.033 | -3 | 0.445 |
AURA |
0.532 | -0.031 | -2 | 0.333 |
CHK2 |
0.532 | -0.041 | -3 | 0.350 |
SGK3 |
0.532 | -0.049 | -3 | 0.459 |
P70S6KB |
0.530 | -0.096 | -3 | 0.507 |
SGK1 |
0.530 | -0.028 | -3 | 0.329 |
P90RSK |
0.529 | -0.049 | -3 | 0.471 |
AKT1 |
0.529 | -0.036 | -3 | 0.398 |
AURB |
0.529 | -0.059 | -2 | 0.361 |
MELK |
0.528 | -0.077 | -3 | 0.482 |
NUAK1 |
0.527 | -0.014 | -3 | 0.489 |
PIM1 |
0.527 | -0.091 | -3 | 0.450 |
IKKA |
0.527 | -0.093 | -2 | 0.493 |
PIM3 |
0.527 | -0.128 | -3 | 0.521 |
RSK2 |
0.526 | -0.049 | -3 | 0.463 |
CK2A1 |
0.526 | -0.059 | 1 | 0.246 |
MNK2 |
0.525 | -0.039 | -2 | 0.454 |
CAMK1D |
0.525 | -0.066 | -3 | 0.398 |
CK1A |
0.524 | 0.073 | -3 | 0.238 |
CK2A2 |
0.524 | -0.069 | 1 | 0.263 |
PHKG2 |
0.524 | -0.011 | -3 | 0.496 |
SRPK2 |
0.524 | 0.013 | -3 | 0.423 |
PHKG1 |
0.523 | -0.054 | -3 | 0.496 |
PKACG |
0.523 | -0.060 | -2 | 0.404 |
CAMK4 |
0.522 | -0.129 | -3 | 0.509 |
CLK2 |
0.520 | 0.038 | -3 | 0.428 |
CAMK2D |
0.520 | -0.154 | -3 | 0.564 |
RSK4 |
0.520 | -0.046 | -3 | 0.423 |
RSK3 |
0.520 | -0.056 | -3 | 0.491 |
PRKD3 |
0.519 | -0.084 | -3 | 0.475 |
PKMYT1_TYR |
0.518 | 0.325 | 3 | 0.500 |
PKN1 |
0.518 | -0.033 | -3 | 0.447 |
MSK2 |
0.518 | -0.075 | -3 | 0.471 |
PKG2 |
0.517 | -0.070 | -2 | 0.381 |
SBK |
0.516 | -0.032 | -3 | 0.306 |
CHK1 |
0.515 | -0.184 | -3 | 0.472 |
FLT3 |
0.515 | 0.155 | 3 | 0.499 |
P70S6K |
0.515 | -0.081 | -3 | 0.459 |
PAK6 |
0.514 | -0.049 | -2 | 0.456 |
FAM20C |
0.513 | -0.021 | 2 | 0.497 |
CAMK1A |
0.512 | -0.066 | -3 | 0.387 |
MAPKAPK5 |
0.512 | -0.094 | -3 | 0.482 |
ERBB2 |
0.512 | 0.105 | 1 | 0.369 |
TEK |
0.511 | 0.142 | 3 | 0.541 |
NDR2 |
0.510 | -0.069 | -3 | 0.515 |
MAP2K7_TYR |
0.509 | 0.189 | 2 | 0.788 |
AKT3 |
0.509 | -0.045 | -3 | 0.334 |
LYN |
0.509 | 0.115 | 3 | 0.588 |
PKACB |
0.508 | -0.052 | -2 | 0.369 |
MSK1 |
0.508 | -0.099 | -3 | 0.467 |
AURC |
0.508 | -0.067 | -2 | 0.368 |
LIMK1_TYR |
0.507 | 0.157 | 2 | 0.759 |
PAK5 |
0.507 | -0.062 | -2 | 0.372 |
HCK |
0.506 | 0.081 | -1 | 0.341 |
WEE1_TYR |
0.505 | 0.112 | -1 | 0.295 |
JAK2 |
0.505 | 0.066 | 1 | 0.455 |
CAMK2B |
0.505 | -0.156 | 2 | 0.699 |
ABL1 |
0.505 | 0.062 | -1 | 0.334 |
TESK1_TYR |
0.504 | 0.074 | 3 | 0.438 |
YES1 |
0.504 | 0.087 | -1 | 0.360 |
ROS1 |
0.503 | 0.070 | 3 | 0.483 |
KDR |
0.503 | 0.078 | 3 | 0.468 |
MAP2K6_TYR |
0.502 | 0.051 | -1 | 0.399 |
FLT4 |
0.502 | 0.084 | 3 | 0.536 |
TYK2 |
0.502 | 0.045 | 1 | 0.454 |
SRC |
0.502 | 0.088 | -1 | 0.347 |
PDHK1_TYR |
0.501 | 0.011 | -1 | 0.383 |
PINK1_TYR |
0.501 | 0.059 | 1 | 0.461 |
PRKD1 |
0.501 | -0.137 | -3 | 0.492 |
FRK |
0.501 | 0.051 | -1 | 0.328 |
CSF1R |
0.501 | 0.047 | 3 | 0.459 |
FGFR1 |
0.501 | 0.038 | 3 | 0.471 |
KIT |
0.501 | 0.042 | 3 | 0.477 |
FYN |
0.501 | 0.068 | -1 | 0.344 |
FER |
0.501 | 0.022 | 1 | 0.385 |
PKACA |
0.501 | -0.060 | -2 | 0.338 |
CSK |
0.500 | 0.074 | 2 | 0.774 |
MAP2K4_TYR |
0.500 | 0.058 | -1 | 0.415 |
TNK1 |
0.500 | 0.103 | 3 | 0.541 |
BLK |
0.500 | 0.046 | -1 | 0.347 |
IGF1R |
0.500 | 0.074 | 3 | 0.599 |
MST1R |
0.500 | 0.012 | 3 | 0.462 |
LTK |
0.500 | 0.032 | 3 | 0.476 |
TYRO3 |
0.500 | 0.031 | 3 | 0.484 |
INSR |
0.500 | 0.046 | 3 | 0.546 |
LCK |
0.499 | 0.032 | -1 | 0.346 |
FGR |
0.499 | 0.056 | 1 | 0.375 |
ABL2 |
0.499 | 0.018 | -1 | 0.327 |
TNNI3K_TYR |
0.499 | 0.060 | 1 | 0.508 |
FGFR2 |
0.499 | 0.027 | 3 | 0.465 |
PAK4 |
0.499 | -0.061 | -2 | 0.360 |
BMPR2_TYR |
0.498 | 0.015 | -1 | 0.391 |
MAPKAPK3 |
0.498 | -0.165 | -3 | 0.448 |
RET |
0.498 | -0.005 | 1 | 0.459 |
PKG1 |
0.498 | -0.056 | -2 | 0.363 |
FGFR3 |
0.498 | 0.035 | 3 | 0.475 |
ALK |
0.497 | 0.014 | 3 | 0.458 |
PDGFRA |
0.497 | 0.038 | 3 | 0.463 |
FLT1 |
0.497 | 0.052 | -1 | 0.297 |
BTK |
0.497 | 0.024 | -1 | 0.288 |
CAMK2A |
0.496 | -0.163 | 2 | 0.684 |
LATS2 |
0.496 | -0.130 | -5 | 0.605 |
PDGFRB |
0.496 | 0.006 | 3 | 0.460 |
PDHK4_TYR |
0.495 | -0.015 | 2 | 0.752 |
MATK |
0.495 | 0.033 | -1 | 0.288 |
FGFR4 |
0.495 | 0.031 | -1 | 0.281 |
INSRR |
0.495 | -0.007 | 3 | 0.495 |
TEC |
0.495 | 0.004 | -1 | 0.281 |
PDHK3_TYR |
0.495 | -0.086 | 4 | 0.336 |
MET |
0.494 | -0.004 | 3 | 0.464 |
LIMK2_TYR |
0.494 | 0.040 | -3 | 0.611 |
ERBB4 |
0.492 | 0.031 | 1 | 0.303 |
NTRK2 |
0.492 | -0.014 | 3 | 0.500 |
PTK6 |
0.491 | -0.004 | -1 | 0.263 |
EPHA6 |
0.491 | -0.058 | -1 | 0.318 |
MERTK |
0.491 | 0.005 | 3 | 0.506 |
PRKD2 |
0.490 | -0.130 | -3 | 0.429 |
EPHA3 |
0.490 | -0.013 | 2 | 0.777 |
ITK |
0.489 | -0.018 | -1 | 0.311 |
JAK1 |
0.489 | 0.000 | 1 | 0.415 |
NTRK1 |
0.488 | -0.033 | -1 | 0.321 |
FES |
0.488 | 0.027 | -1 | 0.263 |
JAK3 |
0.488 | -0.053 | 1 | 0.412 |
EPHA7 |
0.488 | -0.016 | 2 | 0.761 |
EPHA4 |
0.487 | -0.038 | 2 | 0.730 |
PTK2B |
0.487 | -0.010 | -1 | 0.333 |
DDR1 |
0.486 | -0.083 | 4 | 0.343 |
TNK2 |
0.486 | -0.041 | 3 | 0.444 |
EPHA1 |
0.486 | -0.031 | 3 | 0.453 |
EPHB1 |
0.486 | -0.072 | 1 | 0.374 |
SRMS |
0.486 | -0.065 | 1 | 0.365 |
EPHB2 |
0.486 | -0.063 | -1 | 0.290 |
EPHB4 |
0.486 | -0.090 | -1 | 0.296 |
BMX |
0.485 | -0.038 | -1 | 0.263 |
EPHA8 |
0.485 | -0.020 | -1 | 0.267 |
NTRK3 |
0.485 | -0.033 | -1 | 0.290 |
AXL |
0.484 | -0.041 | 3 | 0.467 |
PRKX |
0.484 | -0.062 | -3 | 0.329 |
EPHB3 |
0.482 | -0.079 | -1 | 0.280 |
SYK |
0.482 | -0.007 | -1 | 0.272 |
EGFR |
0.481 | -0.026 | 1 | 0.303 |
TXK |
0.481 | -0.062 | 1 | 0.322 |
ZAP70 |
0.480 | 0.014 | -1 | 0.267 |
EPHA5 |
0.477 | -0.061 | 2 | 0.759 |
PTK2 |
0.477 | -0.012 | -1 | 0.287 |
EPHA2 |
0.476 | -0.043 | -1 | 0.241 |
NEK10_TYR |
0.476 | -0.086 | 1 | 0.380 |
MUSK |
0.475 | -0.038 | 1 | 0.297 |
MAPKAPK2 |
0.473 | -0.163 | -3 | 0.389 |
DDR2 |
0.470 | -0.078 | 3 | 0.429 |