Motif 1126 (n=54)

Position-wise Probabilities
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uniprot genes site source protein function
A0A0A6YYL1 ST20-MTHFS Y59 ochoa 5-formyltetrahydrofolate cyclo-ligase (EC 6.3.3.2) None
A0A0B4J203 None Y609 ochoa receptor protein-tyrosine kinase (EC 2.7.10.1) None
O60674 JAK2 Y1007 psp Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2) Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}.
P04049 RAF1 S499 ochoa|psp RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1) Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. {ECO:0000269|PubMed:11427728, ECO:0000269|PubMed:11719507, ECO:0000269|PubMed:15385642, ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:15849194, ECO:0000269|PubMed:16892053, ECO:0000269|PubMed:16924233, ECO:0000269|PubMed:9360956}.
P04629 NTRK1 Y681 psp High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (TRK1-transforming tyrosine kinase protein) (Tropomyosin-related kinase A) (Tyrosine kinase receptor) (Tyrosine kinase receptor A) (Trk-A) (gp140trk) (p140-TrkA) Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269|PubMed:15488758}.
P05771 PRKCB T497 ochoa Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13) Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}.
P06213 INSR Y1190 ochoa|psp Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta] Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity). {ECO:0000250|UniProtKB:P15208, ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}.
P07333 CSF1R Y809 psp Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms) (CD antigen CD115) Tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of pro-inflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608). {ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, ECO:0000269|PubMed:30982608, ECO:0000269|PubMed:30982609, ECO:0000269|PubMed:7683918}.
P07949 RET Y905 psp Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment] Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) (PubMed:20064382, PubMed:20616503, PubMed:20702524, PubMed:21357690, PubMed:21454698, PubMed:24560924, PubMed:28846097, PubMed:28846099, PubMed:28953886, PubMed:31118272). In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation (PubMed:21994944, PubMed:23333276, PubMed:28846097, PubMed:28846099, PubMed:28953886). GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways (PubMed:21994944, PubMed:23333276, PubMed:24560924, PubMed:25242331, PubMed:28846097, PubMed:28846099, PubMed:28953886). Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF (PubMed:20616503, PubMed:21994944). Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846099, PubMed:28953886). Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner (PubMed:20702524, PubMed:21357690). Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage (PubMed:21357690). Triggers the differentiation of rapidly adapting (RA) mechanoreceptors (PubMed:20064382). Involved in the development of the neural crest (By similarity). Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 (PubMed:21454698). {ECO:0000250|UniProtKB:P35546, ECO:0000269|PubMed:20064382, ECO:0000269|PubMed:20616503, ECO:0000269|PubMed:20702524, ECO:0000269|PubMed:21357690, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:21994944, ECO:0000269|PubMed:23333276, ECO:0000269|PubMed:24560924, ECO:0000269|PubMed:25242331, ECO:0000269|PubMed:28846097, ECO:0000269|PubMed:28846099, ECO:0000269|PubMed:28953886, ECO:0000269|PubMed:31118272}.; FUNCTION: [Isoform 1]: Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. {ECO:0000269|PubMed:28846099}.
P08069 IGF1R Y1166 ochoa|psp Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain] Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.
P08581 MET Y1235 ochoa|psp Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}.
P09619 PDGFRB Y857 psp Platelet-derived growth factor receptor beta (PDGF-R-beta) (PDGFR-beta) (EC 2.7.10.1) (Beta platelet-derived growth factor receptor) (Beta-type platelet-derived growth factor receptor) (CD140 antigen-like family member B) (Platelet-derived growth factor receptor 1) (PDGFR-1) (CD antigen CD140b) Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Plays a role in the migration of vascular smooth muscle cells and the formation of neointima at vascular injury sites. Required for normal development of the cardiovascular system. Required for normal recruitment of pericytes (mesangial cells) in the kidney glomerulus, and for normal formation of a branched network of capillaries in kidney glomeruli. Promotes rearrangement of the actin cytoskeleton and the formation of membrane ruffles. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to the activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or of the C-terminus of PTPN11, creates a binding site for GRB2, resulting in the activation of HRAS, RAF1 and down-stream MAP kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and STAM. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11331881, ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:1653029, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:1846866, ECO:0000269|PubMed:20494825, ECO:0000269|PubMed:20529858, ECO:0000269|PubMed:21098708, ECO:0000269|PubMed:21679854, ECO:0000269|PubMed:21733313, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:26599395, ECO:0000269|PubMed:2835772, ECO:0000269|PubMed:2850496, ECO:0000269|PubMed:7685273, ECO:0000269|PubMed:7691811, ECO:0000269|PubMed:7692233, ECO:0000269|PubMed:8195171}.
P10721 KIT Y823 psp Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117) Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1. {ECO:0000269|PubMed:10397721, ECO:0000269|PubMed:12444928, ECO:0000269|PubMed:12511554, ECO:0000269|PubMed:12878163, ECO:0000269|PubMed:17904548, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:21640708, ECO:0000269|PubMed:7520444, ECO:0000269|PubMed:9528781}.
P11362 FGFR1 Y654 ochoa|psp Fibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD antigen CD331) Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. {ECO:0000250|UniProtKB:P16092, ECO:0000269|PubMed:10830168, ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19261810, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:20139426, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:8622701, ECO:0000269|PubMed:8663044}.
P12882 MYH1 T452 ochoa Myosin-1 (Myosin heavy chain 1) (Myosin heavy chain 2x) (MyHC-2x) (Myosin heavy chain IIx/d) (MyHC-IIx/d) (Myosin heavy chain, skeletal muscle, adult 1) Required for normal hearing. It plays a role in cochlear amplification of auditory stimuli, likely through the positive regulation of prestin (SLC26A5) activity and outer hair cell (OHC) electromotility. {ECO:0000250|UniProtKB:Q5SX40}.
P12883 MYH7 T449 ochoa Myosin-7 (Myosin heavy chain 7) (Myosin heavy chain slow isoform) (MyHC-slow) (Myosin heavy chain, cardiac muscle beta isoform) (MyHC-beta) Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. Forms regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. {ECO:0000305|PubMed:26150528, ECO:0000305|PubMed:26246073}.
P13533 MYH6 T450 ochoa Myosin-6 (Myosin heavy chain 6) (Myosin heavy chain, cardiac muscle alpha isoform) (MyHC-alpha) Muscle contraction.
P13535 MYH8 T452 ochoa Myosin-8 (Myosin heavy chain 8) (Myosin heavy chain, skeletal muscle, perinatal) (MyHC-perinatal) Muscle contraction.
P15056 BRAF S607 ochoa Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1) Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway (PubMed:21441910, PubMed:29433126). Phosphorylates PFKFB2 (PubMed:36402789). May play a role in the postsynaptic responses of hippocampal neurons (PubMed:1508179). {ECO:0000269|PubMed:1508179, ECO:0000269|PubMed:21441910, ECO:0000269|PubMed:29433126, ECO:0000269|PubMed:36402789, ECO:0000305}.
P16234 PDGFRA Y849 ochoa|psp Platelet-derived growth factor receptor alpha (PDGF-R-alpha) (PDGFR-alpha) (EC 2.7.10.1) (Alpha platelet-derived growth factor receptor) (Alpha-type platelet-derived growth factor receptor) (CD140 antigen-like family member A) (CD140a antigen) (Platelet-derived growth factor alpha receptor) (Platelet-derived growth factor receptor 2) (PDGFR-2) (CD antigen CD140a) Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:10734113, ECO:0000269|PubMed:10947961, ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:1646396, ECO:0000269|PubMed:17087943, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17141222, ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664, ECO:0000269|PubMed:8760137, ECO:0000269|PubMed:8943348}.
P17252 PRKCA T494 ochoa Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13) Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}.
P21709 EPHA1 T780 ochoa Ephrin type-A receptor 1 (hEpha1) (EC 2.7.10.1) (EPH tyrosine kinase) (EPH tyrosine kinase 1) (Erythropoietin-producing hepatoma receptor) (Tyrosine-protein kinase receptor EPH) Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis. {ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:19118217, ECO:0000269|PubMed:20043122}.
P21802 FGFR2 Y657 psp Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD antigen CD332) Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. {ECO:0000269|PubMed:12529371, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:15629145, ECO:0000269|PubMed:16384934, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19103595, ECO:0000269|PubMed:19387476, ECO:0000269|PubMed:19410646, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:8663044}.
P22607 FGFR3 Y648 psp Fibroblast growth factor receptor 3 (FGFR-3) (EC 2.7.10.1) (CD antigen CD333) Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14534538, ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:8663044}.
P23458 JAK1 Y1034 ochoa|psp Tyrosine-protein kinase JAK1 (EC 2.7.10.2) (Janus kinase 1) (JAK-1) Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16239216, ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:8232552}.
P24941 CDK2 T158 ochoa 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}.
P29597 TYK2 Y1054 psp Non-receptor tyrosine-protein kinase TYK2 (EC 2.7.10.2) Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862). {ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:10995743, ECO:0000269|PubMed:25762719, ECO:0000269|PubMed:29162862, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7638186, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:8232552}.
P30530 AXL Y703 ochoa Tyrosine-protein kinase receptor UFO (EC 2.7.10.1) (AXL oncogene) Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. {ECO:0000269|PubMed:10403904, ECO:0000269|PubMed:11484958, ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:12490074, ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:15733062, ECO:0000269|PubMed:1656220, ECO:0000269|PubMed:18840707}.; FUNCTION: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828, ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:25277499}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22673088}.; FUNCTION: (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes (PubMed:28076778, PubMed:29379210, PubMed:31311882). Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection (PubMed:28076778). Interferon signaling inhibition occurs via an SOCS1-dependent mechanism (PubMed:29379210). {ECO:0000269|PubMed:28076778, ECO:0000269|PubMed:29379210, ECO:0000269|PubMed:31311882}.
P33981 TTK S677 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}.
P35916 FLT4 Y1068 ochoa|psp Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4) Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}.
P35968 KDR Y1059 ochoa|psp Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309) Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC. {ECO:0000269|PubMed:10102632, ECO:0000269|PubMed:10368301, ECO:0000269|PubMed:10600473, ECO:0000269|PubMed:11387210, ECO:0000269|PubMed:12649282, ECO:0000269|PubMed:1417831, ECO:0000269|PubMed:15026417, ECO:0000269|PubMed:15215251, ECO:0000269|PubMed:15962004, ECO:0000269|PubMed:16966330, ECO:0000269|PubMed:17303569, ECO:0000269|PubMed:18529047, ECO:0000269|PubMed:19668192, ECO:0000269|PubMed:19834490, ECO:0000269|PubMed:20080685, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20705758, ECO:0000269|PubMed:21893193, ECO:0000269|PubMed:25825981, ECO:0000269|PubMed:7929439, ECO:0000269|PubMed:9160888, ECO:0000269|PubMed:9804796, ECO:0000269|PubMed:9837777}.
P36888 FLT3 Y842 ochoa|psp Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135) Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways. {ECO:0000269|PubMed:10080542, ECO:0000269|PubMed:11090077, ECO:0000269|PubMed:14504097, ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:16627759, ECO:0000269|PubMed:18490735, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21067588, ECO:0000269|PubMed:21262971, ECO:0000269|PubMed:21516120, ECO:0000269|PubMed:7507245}.
P43403 ZAP70 Y492 ochoa|psp Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase) Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.
P43405 SYK Y525 ochoa|psp Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) (p72-Syk) Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:34634301, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.
P49914 MTHFS Y83 ochoa 5-formyltetrahydrofolate cyclo-ligase (EC 6.3.3.2) (5,10-methenyl-tetrahydrofolate synthetase) (MTHFS) (Methenyl-THF synthetase) Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate. {ECO:0000269|PubMed:8522195}.
P52333 JAK3 Y980 psp Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK) Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:20440074, ECO:0000269|PubMed:7662955, ECO:0000269|PubMed:8022485}.
P54762 EPHB1 Y778 psp Ephrin type-B receptor 1 (EC 2.7.10.1) (ELK) (EPH tyrosine kinase 2) (EPH-like kinase 6) (EK6) (hEK6) (Neuronally-expressed EPH-related tyrosine kinase) (NET) (Tyrosine-protein kinase receptor EPH-2) Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}.
Q00526 CDK3 T158 ochoa Cyclin-dependent kinase 3 (EC 2.7.11.22) (Cell division protein kinase 3) Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner. {ECO:0000269|PubMed:15084261, ECO:0000269|PubMed:18794154, ECO:0000269|PubMed:8846921}.
Q02763 TEK Y992 psp Angiopoietin-1 receptor (EC 2.7.10.1) (Endothelial tyrosine kinase) (Tunica interna endothelial cell kinase) (Tyrosine kinase with Ig and EGF homology domains-2) (Tyrosine-protein kinase receptor TEK) (Tyrosine-protein kinase receptor TIE-2) (hTIE2) (p140 TEK) (CD antigen CD202b) Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1. {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}.
Q04912 MST1R Y1239 ochoa|psp Macrophage-stimulating protein receptor (MSP receptor) (EC 2.7.10.1) (CDw136) (Protein-tyrosine kinase 8) (p185-Ron) (CD antigen CD136) [Cleaved into: Macrophage-stimulating protein receptor alpha chain; Macrophage-stimulating protein receptor beta chain] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}.
Q12866 MERTK Y754 psp Tyrosine-protein kinase Mer (EC 2.7.10.1) (Proto-oncogene c-Mer) (Receptor tyrosine kinase MerTK) Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment (PubMed:32640697). Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:32640697}.
Q16288 NTRK3 Y710 psp NT-3 growth factor receptor (EC 2.7.10.1) (GP145-TrkC) (Trk-C) (Neurotrophic tyrosine kinase receptor type 3) (TrkC tyrosine kinase) Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. {ECO:0000269|PubMed:25196463}.
Q16620 NTRK2 Y707 psp BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Tropomyosin-related kinase B) Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:15494731, PubMed:7574684). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}.
Q16832 DDR2 Y741 psp Discoidin domain-containing receptor 2 (Discoidin domain receptor 2) (EC 2.7.10.1) (CD167 antigen-like family member B) (Discoidin domain-containing receptor tyrosine kinase 2) (Neurotrophic tyrosine kinase, receptor-related 3) (Receptor protein-tyrosine kinase TKT) (Tyrosine-protein kinase TYRO10) (CD antigen CD167b) Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416, ECO:0000269|PubMed:9659899}.
Q9NWZ3 IRAK4 T342 ochoa|psp Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}.
Q9UKX2 MYH2 T452 ochoa Myosin-2 (Myosin heavy chain 2) (Myosin heavy chain 2a) (MyHC-2a) (Myosin heavy chain IIa) (MyHC-IIa) (Myosin heavy chain, skeletal muscle, adult 2) Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction. {ECO:0000250|UniProtKB:P12883}.
Q9UKX3 MYH13 T451 ochoa Myosin-13 (Myosin heavy chain 13) (Myosin heavy chain, skeletal muscle, extraocular) (MyHC-EO) (Myosin heavy chain, skeletal muscle, laryngeal) (MyHC-IIL) (Superfast myosin) Fast twitching myosin mediating the high-velocity and low-tension contractions of specific striated muscles. {ECO:0000269|PubMed:23908353}.
Q9UM73 ALK Y1283 psp ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}.
Q9Y623 MYH4 T452 ochoa Myosin-4 (Myosin heavy chain 2b) (MyHC-2b) (Myosin heavy chain 4) (Myosin heavy chain IIb) (MyHC-IIb) (Myosin heavy chain, skeletal muscle, fetal) Muscle contraction.
O15146 MUSK Y756 Sugiyama Muscle, skeletal receptor tyrosine-protein kinase (EC 2.7.10.1) (Muscle-specific tyrosine-protein kinase receptor) (MuSK) (Muscle-specific kinase receptor) Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:25537362}.
P17948 FLT1 Y1053 Sugiyama Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor) Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at 'Ser-473'. Promotes phosphorylation of PTK2/FAK1 (PubMed:16685275). {ECO:0000250|UniProtKB:P35969, ECO:0000269|PubMed:11141500, ECO:0000269|PubMed:11312102, ECO:0000269|PubMed:11811792, ECO:0000269|PubMed:12796773, ECO:0000269|PubMed:14633857, ECO:0000269|PubMed:15735759, ECO:0000269|PubMed:16685275, ECO:0000269|PubMed:18079407, ECO:0000269|PubMed:18515749, ECO:0000269|PubMed:18583712, ECO:0000269|PubMed:18593464, ECO:0000269|PubMed:20512933, ECO:0000269|PubMed:20551949, ECO:0000269|PubMed:21752276, ECO:0000269|PubMed:7824266, ECO:0000269|PubMed:8248162, ECO:0000269|PubMed:8605350, ECO:0000269|PubMed:9299537, ECO:0000269|Ref.11}.; FUNCTION: [Isoform 1]: Phosphorylates PLCG. {ECO:0000269|PubMed:9299537}.; FUNCTION: [Isoform 2]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 3]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 4]: May function as decoy receptor for VEGFA. {ECO:0000269|PubMed:21752276}.; FUNCTION: [Isoform 7]: Has a truncated kinase domain; it increases phosphorylation of SRC at 'Tyr-418' by unknown means and promotes tumor cell invasion. {ECO:0000269|PubMed:20512933}.
P22455 FGFR4 Y643 GPS6|SIGNOR|EPSD|Sugiyama Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (CD antigen CD334) Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling. {ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:18670643, ECO:0000269|PubMed:20018895, ECO:0000269|PubMed:20683963, ECO:0000269|PubMed:20798051, ECO:0000269|PubMed:20876804, ECO:0000269|PubMed:21653700, ECO:0000269|PubMed:7518429, ECO:0000269|PubMed:7680645, ECO:0000269|PubMed:8663044}.
P31749 AKT1 T305 Sugiyama RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha) AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:15526160, PubMed:15861136, PubMed:21432781, PubMed:21620960, PubMed:31204173). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960, PubMed:29343641, PubMed:31204173). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF1 (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (PubMed:30504268). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (PubMed:15861136). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (PubMed:31204173). {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10358075, ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941, ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:18507042, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20471940, ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:30504268, ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058, ECO:0000269|PubMed:9829964, ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:21432781, ECO:0000303|PubMed:21620960}.
Q08345 DDR1 Y797 Sugiyama Epithelial discoidin domain-containing receptor 1 (Epithelial discoidin domain receptor 1) (EC 2.7.10.1) (CD167 antigen-like family member A) (Cell adhesion kinase) (Discoidin receptor tyrosine kinase) (HGK2) (Mammary carcinoma kinase 10) (MCK-10) (Protein-tyrosine kinase 3A) (Protein-tyrosine kinase RTK-6) (TRK E) (Tyrosine kinase DDR) (Tyrosine-protein kinase CAK) (CD antigen CD167a) Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11. {ECO:0000250, ECO:0000269|PubMed:12065315, ECO:0000269|PubMed:16234985, ECO:0000269|PubMed:16337946, ECO:0000269|PubMed:19401332, ECO:0000269|PubMed:20093046, ECO:0000269|PubMed:20432435, ECO:0000269|PubMed:20884741, ECO:0000269|PubMed:21044884, ECO:0000269|PubMed:9659899}.
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reactome_id name p -log10_p
R-HSA-2219528 PI3K/AKT Signaling in Cancer 1.110223e-16 15.955
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 1.110223e-16 15.955
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 1.110223e-16 15.955
R-HSA-199418 Negative regulation of the PI3K/AKT network 1.110223e-16 15.955
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 1.110223e-16 15.955
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 1.110223e-16 15.955
R-HSA-5673001 RAF/MAP kinase cascade 1.110223e-16 15.955
R-HSA-5684996 MAPK1/MAPK3 signaling 1.110223e-16 15.955
R-HSA-1257604 PIP3 activates AKT signaling 1.110223e-16 15.955
R-HSA-5683057 MAPK family signaling cascades 1.110223e-16 15.955
R-HSA-9006925 Intracellular signaling by second messengers 1.110223e-16 15.955
R-HSA-1226099 Signaling by FGFR in disease 2.220446e-16 15.654
R-HSA-2428928 IRS-related events triggered by IGF1R 3.963496e-14 13.402
R-HSA-2428924 IGF1R signaling cascade 6.261658e-14 13.203
R-HSA-74751 Insulin receptor signalling cascade 6.261658e-14 13.203
R-HSA-162582 Signal Transduction 6.172840e-14 13.210
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 7.260859e-14 13.139
R-HSA-109704 PI3K Cascade 2.825518e-13 12.549
R-HSA-112399 IRS-mediated signalling 8.602008e-13 12.065
R-HSA-74752 Signaling by Insulin receptor 2.584599e-12 11.588
R-HSA-190236 Signaling by FGFR 1.283397e-10 9.892
R-HSA-1643685 Disease 6.698022e-10 9.174
R-HSA-1839126 FGFR2 mutant receptor activation 6.753238e-08 7.170
R-HSA-8851708 Signaling by FGFR2 IIIa TM 1.244028e-07 6.905
R-HSA-194138 Signaling by VEGF 3.638120e-07 6.439
R-HSA-5655253 Signaling by FGFR2 in disease 3.846159e-07 6.415
R-HSA-5654727 Negative regulation of FGFR2 signaling 1.700643e-06 5.769
R-HSA-5654221 Phospholipase C-mediated cascade; FGFR2 6.816515e-06 5.166
R-HSA-190241 FGFR2 ligand binding and activation 7.945957e-06 5.100
R-HSA-195399 VEGF binds to VEGFR leading to receptor dimerization 8.388813e-06 5.076
R-HSA-194313 VEGF ligand-receptor interactions 8.388813e-06 5.076
R-HSA-9705462 Inactivation of CSF3 (G-CSF) signaling 9.207856e-06 5.036
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 9.207856e-06 5.036
R-HSA-8854691 Interleukin-20 family signaling 1.216738e-05 4.915
R-HSA-187015 Activation of TRKA receptors 1.627354e-05 4.789
R-HSA-9732724 IFNG signaling activates MAPKs 1.627354e-05 4.789
R-HSA-5654695 PI-3K cascade:FGFR2 1.577445e-05 4.802
R-HSA-5654699 SHC-mediated cascade:FGFR2 2.011251e-05 4.697
R-HSA-5654700 FRS-mediated FGFR2 signaling 2.258281e-05 4.646
R-HSA-9674555 Signaling by CSF3 (G-CSF) 2.526890e-05 4.597
R-HSA-112411 MAPK1 (ERK2) activation 2.793048e-05 4.554
R-HSA-9020956 Interleukin-27 signaling 3.539089e-05 4.451
R-HSA-110056 MAPK3 (ERK1) activation 3.539089e-05 4.451
R-HSA-4420097 VEGFA-VEGFR2 Pathway 3.575976e-05 4.447
R-HSA-9020558 Interleukin-2 signaling 4.405269e-05 4.356
R-HSA-5654696 Downstream signaling of activated FGFR2 5.110684e-05 4.292
R-HSA-5654738 Signaling by FGFR2 6.521924e-05 4.186
R-HSA-8984722 Interleukin-35 Signalling 6.531351e-05 4.185
R-HSA-2033514 FGFR3 mutant receptor activation 7.807601e-05 4.107
R-HSA-1839130 Signaling by activated point mutants of FGFR3 7.807601e-05 4.107
R-HSA-451927 Interleukin-2 family signaling 7.873010e-05 4.104
R-HSA-6788467 IL-6-type cytokine receptor ligand interactions 7.807601e-05 4.107
R-HSA-1059683 Interleukin-6 signaling 7.807601e-05 4.107
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 9.976813e-05 4.001
R-HSA-169893 Prolonged ERK activation events 1.258478e-04 3.900
R-HSA-194306 Neurophilin interactions with VEGF and VEGFR 1.737132e-04 3.760
R-HSA-2033519 Activated point mutants of FGFR2 1.894639e-04 3.722
R-HSA-449836 Other interleukin signaling 2.145391e-04 3.668
R-HSA-1839120 Signaling by FGFR1 amplification mutants 2.705978e-04 3.568
R-HSA-2023837 Signaling by FGFR2 amplification mutants 2.705978e-04 3.568
R-HSA-187042 TRKA activation by NGF 2.705978e-04 3.568
R-HSA-112409 RAF-independent MAPK1/3 activation 3.360996e-04 3.474
R-HSA-9706374 FLT3 signaling through SRC family kinases 3.884712e-04 3.411
R-HSA-912526 Interleukin receptor SHC signaling 3.721507e-04 3.429
R-HSA-6783589 Interleukin-6 family signaling 4.106009e-04 3.387
R-HSA-5218921 VEGFR2 mediated cell proliferation 4.515156e-04 3.345
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 5.052777e-04 3.296
R-HSA-5655332 Signaling by FGFR3 in disease 5.409952e-04 3.267
R-HSA-5654732 Negative regulation of FGFR3 signaling 5.896858e-04 3.229
R-HSA-187024 NGF-independant TRKA activation 6.864067e-04 3.163
R-HSA-187706 Signalling to p38 via RIT and RIN 6.864067e-04 3.163
R-HSA-5674499 Negative feedback regulation of MAPK pathway 6.864067e-04 3.163
R-HSA-1839124 FGFR1 mutant receptor activation 8.750715e-04 3.058
R-HSA-5654726 Negative regulation of FGFR1 signaling 8.750715e-04 3.058
R-HSA-5673000 RAF activation 1.009879e-03 2.996
R-HSA-114516 Disinhibition of SNARE formation 1.065979e-03 2.972
R-HSA-9726840 SHOC2 M1731 mutant abolishes MRAS complex function 1.065979e-03 2.972
R-HSA-187687 Signalling to ERKs 1.081933e-03 2.966
R-HSA-9660537 Signaling by MRAS-complex mutants 1.285903e-03 2.891
R-HSA-9726842 Gain-of-function MRAS complexes activate RAF signaling 1.285903e-03 2.891
R-HSA-8985947 Interleukin-9 signaling 1.285903e-03 2.891
R-HSA-9020933 Interleukin-23 signaling 1.285903e-03 2.891
R-HSA-166520 Signaling by NTRKs 1.172098e-03 2.931
R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... 1.285903e-03 2.891
R-HSA-9679191 Potential therapeutics for SARS 1.235409e-03 2.908
R-HSA-201556 Signaling by ALK 1.402384e-03 2.853
R-HSA-170984 ARMS-mediated activation 1.525668e-03 2.817
R-HSA-9020958 Interleukin-21 signaling 1.525668e-03 2.817
R-HSA-9607240 FLT3 Signaling 1.582666e-03 2.801
R-HSA-9656223 Signaling by RAF1 mutants 1.677993e-03 2.775
R-HSA-5655302 Signaling by FGFR1 in disease 1.677993e-03 2.775
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 2.208359e-03 2.656
R-HSA-9649948 Signaling downstream of RAS mutants 2.208359e-03 2.656
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 2.208359e-03 2.656
R-HSA-1433557 Signaling by SCF-KIT 1.879257e-03 2.726
R-HSA-6802949 Signaling by RAS mutants 2.208359e-03 2.656
R-HSA-5654741 Signaling by FGFR3 2.094972e-03 2.679
R-HSA-190377 FGFR2b ligand binding and activation 2.063974e-03 2.685
R-HSA-1839122 Signaling by activated point mutants of FGFR1 2.362146e-03 2.627
R-HSA-9700206 Signaling by ALK in cancer 2.506418e-03 2.601
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 2.506418e-03 2.601
R-HSA-8983432 Interleukin-15 signaling 2.679419e-03 2.572
R-HSA-877312 Regulation of IFNG signaling 2.679419e-03 2.572
R-HSA-9702506 Drug resistance of FLT3 mutants 4.708643e-03 2.327
R-HSA-9669937 Drug resistance of KIT mutants 4.708643e-03 2.327
R-HSA-9700649 Drug resistance of ALK mutants 4.708643e-03 2.327
R-HSA-9674415 Drug resistance of PDGFR mutants 4.708643e-03 2.327
R-HSA-9669921 KIT mutants bind TKIs 4.708643e-03 2.327
R-HSA-9674428 PDGFR mutants bind TKIs 4.708643e-03 2.327
R-HSA-9702509 FLT3 mutants bind TKIs 4.708643e-03 2.327
R-HSA-9717319 brigatinib-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9674396 Imatinib-resistant PDGFR mutants 4.708643e-03 2.327
R-HSA-9702581 crenolanib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9717264 ASP-3026-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9717323 ceritinib-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9702614 ponatinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9669936 Sorafenib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9702577 semaxanib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9702620 quizartinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9702624 sorafenib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9674401 Sunitinib-resistant PDGFR mutants 4.708643e-03 2.327
R-HSA-9669924 Masitinib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9717329 lorlatinib-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9702600 midostaurin-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9717316 alectinib-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9669929 Regorafenib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9702605 pexidartinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9717301 NVP-TAE684-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9669917 Imatinib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9702636 tandutinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9703009 tamatinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9702569 KW2449-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9702998 linifanib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9669934 Sunitinib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9674404 Sorafenib-resistant PDGFR mutants 4.708643e-03 2.327
R-HSA-9669914 Dasatinib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9702632 sunitinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9717326 crizotinib-resistant ALK mutants 4.708643e-03 2.327
R-HSA-9702590 gilteritinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9669926 Nilotinib-resistant KIT mutants 4.708643e-03 2.327
R-HSA-9702596 lestaurtinib-resistant FLT3 mutants 4.708643e-03 2.327
R-HSA-9674403 Regorafenib-resistant PDGFR mutants 4.708643e-03 2.327
R-HSA-190375 FGFR2c ligand binding and activation 3.015612e-03 2.521
R-HSA-1433559 Regulation of KIT signaling 3.370544e-03 2.472
R-HSA-5654227 Phospholipase C-mediated cascade; FGFR3 3.370544e-03 2.472
R-HSA-170968 Frs2-mediated activation 3.015612e-03 2.521
R-HSA-5654736 Signaling by FGFR1 3.554859e-03 2.449
R-HSA-190239 FGFR3 ligand binding and activation 3.744036e-03 2.427
R-HSA-449147 Signaling by Interleukins 3.380986e-03 2.471
R-HSA-5099900 WNT5A-dependent internalization of FZD4 4.135911e-03 2.383
R-HSA-2892247 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation 4.545990e-03 2.342
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 4.545990e-03 2.342
R-HSA-187037 Signaling by NTRK1 (TRKA) 4.802321e-03 2.319
R-HSA-5654219 Phospholipase C-mediated cascade: FGFR1 4.974100e-03 2.303
R-HSA-9730414 MITF-M-regulated melanocyte development 5.007536e-03 2.300
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 5.118348e-03 2.291
R-HSA-190242 FGFR1 ligand binding and activation 5.420064e-03 2.266
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors 5.420064e-03 2.266
R-HSA-4419969 Depolymerization of the Nuclear Lamina 5.420064e-03 2.266
R-HSA-5654710 PI-3K cascade:FGFR3 5.883712e-03 2.230
R-HSA-389513 Co-inhibition by CTLA4 6.364869e-03 2.196
R-HSA-5654704 SHC-mediated cascade:FGFR3 6.863367e-03 2.163
R-HSA-9013695 NOTCH4 Intracellular Domain Regulates Transcription 6.863367e-03 2.163
R-HSA-9013694 Signaling by NOTCH4 7.038898e-03 2.152
R-HSA-3000171 Non-integrin membrane-ECM interactions 7.275176e-03 2.138
R-HSA-5654706 FRS-mediated FGFR3 signaling 7.379035e-03 2.132
R-HSA-9671555 Signaling by PDGFR in disease 7.379035e-03 2.132
R-HSA-9020591 Interleukin-12 signaling 7.516116e-03 2.124
R-HSA-9669938 Signaling by KIT in disease 7.911704e-03 2.102
R-HSA-9670439 Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... 7.911704e-03 2.102
R-HSA-5654689 PI-3K cascade:FGFR1 7.911704e-03 2.102
R-HSA-912694 Regulation of IFNA/IFNB signaling 7.911704e-03 2.102
R-HSA-9856651 MITF-M-dependent gene expression 8.378529e-03 2.077
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 8.461208e-03 2.073
R-HSA-392451 G beta:gamma signalling through PI3Kgamma 8.461208e-03 2.073
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 8.526917e-03 2.069
R-HSA-5654688 SHC-mediated cascade:FGFR1 9.027381e-03 2.044
R-HSA-9734091 Drug-mediated inhibition of MET activation 9.395406e-03 2.027
R-HSA-1839128 FGFR4 mutant receptor activation 1.406039e-02 1.852
R-HSA-9603505 NTRK3 as a dependence receptor 1.406039e-02 1.852
R-HSA-9680187 Signaling by extracellular domain mutants of KIT 1.406039e-02 1.852
R-HSA-8853334 Signaling by FGFR3 fusions in cancer 1.406039e-02 1.852
R-HSA-2033515 t(4;14) translocations of FGFR3 1.406039e-02 1.852
R-HSA-9669935 Signaling by juxtamembrane domain KIT mutants 1.406039e-02 1.852
R-HSA-8853333 Signaling by FGFR2 fusions 1.406039e-02 1.852
R-HSA-9669933 Signaling by kinase domain mutants of KIT 1.406039e-02 1.852
R-HSA-5654693 FRS-mediated FGFR1 signaling 9.610058e-03 2.017
R-HSA-186763 Downstream signal transduction 1.344361e-02 1.871
R-HSA-5654708 Downstream signaling of activated FGFR3 1.210254e-02 1.917
R-HSA-6802957 Oncogenic MAPK signaling 9.897715e-03 2.004
R-HSA-389357 CD28 dependent PI3K/Akt signaling 1.082427e-02 1.966
R-HSA-399719 Trafficking of AMPA receptors 1.344361e-02 1.871
R-HSA-1280215 Cytokine Signaling in Immune system 1.356777e-02 1.867
R-HSA-1266695 Interleukin-7 signaling 9.610058e-03 2.017
R-HSA-447115 Interleukin-12 family signaling 1.077826e-02 1.967
R-HSA-5654733 Negative regulation of FGFR4 signaling 1.210254e-02 1.917
R-HSA-76002 Platelet activation, signaling and aggregation 1.285110e-02 1.891
R-HSA-9830364 Formation of the nephric duct 9.610058e-03 2.017
R-HSA-109582 Hemostasis 1.347077e-02 1.871
R-HSA-9833109 Evasion by RSV of host interferon responses 1.344361e-02 1.871
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 1.020907e-02 1.991
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 1.484619e-02 1.828
R-HSA-354192 Integrin signaling 1.484619e-02 1.828
R-HSA-397795 G-protein beta:gamma signalling 1.484619e-02 1.828
R-HSA-390522 Striated Muscle Contraction 1.557017e-02 1.808
R-HSA-9927426 Developmental Lineage of Mammary Gland Alveolar Cells 1.630906e-02 1.788
R-HSA-9768919 NPAS4 regulates expression of target genes 1.630906e-02 1.788
R-HSA-5654687 Downstream signaling of activated FGFR1 1.706272e-02 1.768
R-HSA-9860931 Response of endothelial cells to shear stress 1.739131e-02 1.760
R-HSA-8853659 RET signaling 1.783099e-02 1.749
R-HSA-6804757 Regulation of TP53 Degradation 1.783099e-02 1.749
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 1.861373e-02 1.730
R-HSA-9026357 NTF4 activates NTRK2 (TRKB) signaling 1.870369e-02 1.728
R-HSA-9025046 NTF3 activates NTRK2 (TRKB) signaling 1.870369e-02 1.728
R-HSA-9024909 BDNF activates NTRK2 (TRKB) signaling 1.870369e-02 1.728
R-HSA-9034013 NTF3 activates NTRK3 signaling 1.870369e-02 1.728
R-HSA-452723 Transcriptional regulation of pluripotent stem cells 1.941077e-02 1.712
R-HSA-6806003 Regulation of TP53 Expression and Degradation 2.022198e-02 1.694
R-HSA-5218920 VEGFR2 mediated vascular permeability 2.188631e-02 1.660
R-HSA-8853884 Transcriptional Regulation by VENTX 2.188631e-02 1.660
R-HSA-9855142 Cellular responses to mechanical stimuli 2.205367e-02 1.657
R-HSA-5674135 MAP2K and MAPK activation 2.273913e-02 1.643
R-HSA-5675221 Negative regulation of MAPK pathway 2.273913e-02 1.643
R-HSA-9034793 Activated NTRK3 signals through PLCG1 2.332541e-02 1.632
R-HSA-167021 PLC-gamma1 signalling 2.332541e-02 1.632
R-HSA-8875513 MET interacts with TNS proteins 2.332541e-02 1.632
R-HSA-8853336 Signaling by plasma membrane FGFR1 fusions 2.332541e-02 1.632
R-HSA-5603037 IRAK4 deficiency (TLR5) 2.332541e-02 1.632
R-HSA-8865999 MET activates PTPN11 2.332541e-02 1.632
R-HSA-198745 Signalling to STAT3 2.332541e-02 1.632
R-HSA-8875791 MET activates STAT3 2.332541e-02 1.632
R-HSA-9927418 Developmental Lineage of Mammary Gland Luminal Epithelial Cells 2.360554e-02 1.627
R-HSA-5654743 Signaling by FGFR4 2.448538e-02 1.611
R-HSA-69236 G1 Phase 2.537852e-02 1.596
R-HSA-69231 Cyclin D associated events in G1 2.537852e-02 1.596
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 2.537852e-02 1.596
R-HSA-1474244 Extracellular matrix organization 2.539963e-02 1.595
R-HSA-76009 Platelet Aggregation (Plug Formation) 2.628482e-02 1.580
R-HSA-9026527 Activated NTRK2 signals through PLCG1 2.792565e-02 1.554
R-HSA-1307965 betaKlotho-mediated ligand binding 2.792565e-02 1.554
R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... 2.792565e-02 1.554
R-HSA-9851151 MDK and PTN in ALK signaling 2.792565e-02 1.554
R-HSA-211163 AKT-mediated inactivation of FOXO1A 2.792565e-02 1.554
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 2.813631e-02 1.551
R-HSA-389356 Co-stimulation by CD28 2.908123e-02 1.536
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 2.908123e-02 1.536
R-HSA-74713 IRS activation 3.250450e-02 1.488
R-HSA-190374 FGFR1c and Klotho ligand binding and activation 3.250450e-02 1.488
R-HSA-68911 G2 Phase 3.250450e-02 1.488
R-HSA-9032759 NTRK2 activates RAC1 3.250450e-02 1.488
R-HSA-9673768 Signaling by membrane-tethered fusions of PDGFRA or PDGFRB 3.250450e-02 1.488
R-HSA-9706377 FLT3 signaling by CBL mutants 3.250450e-02 1.488
R-HSA-8849470 PTK6 Regulates Cell Cycle 3.706207e-02 1.431
R-HSA-9027283 Erythropoietin activates STAT5 4.159845e-02 1.381
R-HSA-9645135 STAT5 Activation 4.159845e-02 1.381
R-HSA-9032845 Activated NTRK2 signals through CDK5 4.611374e-02 1.336
R-HSA-8851907 MET activates PI3K/AKT signaling 4.611374e-02 1.336
R-HSA-9603381 Activated NTRK3 signals through PI3K 4.611374e-02 1.336
R-HSA-190371 FGFR3b ligand binding and activation 4.611374e-02 1.336
R-HSA-9032500 Activated NTRK2 signals through FYN 5.060803e-02 1.296
R-HSA-9028335 Activated NTRK2 signals through PI3K 5.060803e-02 1.296
R-HSA-8875656 MET receptor recycling 5.060803e-02 1.296
R-HSA-190370 FGFR1b ligand binding and activation 5.060803e-02 1.296
R-HSA-198693 AKT phosphorylates targets in the nucleus 5.508143e-02 1.259
R-HSA-9700645 ALK mutants bind TKIs 5.508143e-02 1.259
R-HSA-8875555 MET activates RAP1 and RAC1 5.953402e-02 1.225
R-HSA-9027277 Erythropoietin activates Phospholipase C gamma (PLCG) 5.953402e-02 1.225
R-HSA-198203 PI3K/AKT activation 5.953402e-02 1.225
R-HSA-2586552 Signaling by Leptin 5.953402e-02 1.225
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 5.523801e-02 1.258
R-HSA-186797 Signaling by PDGF 4.357244e-02 1.361
R-HSA-8852405 Signaling by MST1 3.706207e-02 1.431
R-HSA-69202 Cyclin E associated events during G1/S transition 5.282445e-02 1.277
R-HSA-877300 Interferon gamma signaling 5.166535e-02 1.287
R-HSA-6806942 MET Receptor Activation 4.159845e-02 1.381
R-HSA-6783783 Interleukin-10 signaling 6.270516e-02 1.203
R-HSA-9010642 ROBO receptors bind AKAP5 5.060803e-02 1.296
R-HSA-2179392 EGFR Transactivation by Gastrin 5.953402e-02 1.225
R-HSA-422475 Axon guidance 5.119457e-02 1.291
R-HSA-453279 Mitotic G1 phase and G1/S transition 4.289082e-02 1.368
R-HSA-8849469 PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 5.060803e-02 1.296
R-HSA-9924644 Developmental Lineages of the Mammary Gland 5.523801e-02 1.258
R-HSA-418597 G alpha (z) signalling events 3.604091e-02 1.443
R-HSA-430116 GP1b-IX-V activation signalling 5.508143e-02 1.259
R-HSA-9758919 Epithelial-Mesenchymal Transition (EMT) during gastrulation 3.706207e-02 1.431
R-HSA-2980766 Nuclear Envelope Breakdown 3.813637e-02 1.419
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 5.508143e-02 1.259
R-HSA-74749 Signal attenuation 5.953402e-02 1.225
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 5.523801e-02 1.258
R-HSA-1266738 Developmental Biology 4.039693e-02 1.394
R-HSA-9830369 Kidney development 4.927805e-02 1.307
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 4.469250e-02 1.350
R-HSA-8848021 Signaling by PTK6 4.469250e-02 1.350
R-HSA-9634815 Transcriptional Regulation by NPAS4 3.298555e-02 1.482
R-HSA-1227986 Signaling by ERBB2 4.136480e-02 1.383
R-HSA-4086400 PCP/CE pathway 6.270516e-02 1.203
R-HSA-9679506 SARS-CoV Infections 5.484231e-02 1.261
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 3.670313e-02 1.435
R-HSA-9034864 Activated NTRK3 signals through RAS 6.396591e-02 1.194
R-HSA-9614399 Regulation of localization of FOXO transcription factors 6.396591e-02 1.194
R-HSA-8941332 RUNX2 regulates genes involved in cell migration 6.396591e-02 1.194
R-HSA-212436 Generic Transcription Pathway 6.459229e-02 1.190
R-HSA-9675108 Nervous system development 6.546918e-02 1.184
R-HSA-416550 Sema4D mediated inhibition of cell attachment and migration 6.837719e-02 1.165
R-HSA-9026519 Activated NTRK2 signals through RAS 6.837719e-02 1.165
R-HSA-8851805 MET activates RAS signaling 7.276795e-02 1.138
R-HSA-198323 AKT phosphorylates targets in the cytosol 7.276795e-02 1.138
R-HSA-9028731 Activated NTRK2 signals through FRS2 and FRS3 7.276795e-02 1.138
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 7.276795e-02 1.138
R-HSA-2428933 SHC-related events triggered by IGF1R 7.276795e-02 1.138
R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling 7.276795e-02 1.138
R-HSA-190322 FGFR4 ligand binding and activation 7.713829e-02 1.113
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 7.713829e-02 1.113
R-HSA-190373 FGFR1c ligand binding and activation 7.713829e-02 1.113
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 7.713829e-02 1.113
R-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors 7.713829e-02 1.113
R-HSA-8986944 Transcriptional Regulation by MECP2 8.133676e-02 1.090
R-HSA-5655291 Signaling by FGFR4 in disease 8.148829e-02 1.089
R-HSA-1170546 Prolactin receptor signaling 8.148829e-02 1.089
R-HSA-177504 Retrograde neurotrophin signalling 8.148829e-02 1.089
R-HSA-190372 FGFR3c ligand binding and activation 8.148829e-02 1.089
R-HSA-2682334 EPH-Ephrin signaling 8.412417e-02 1.075
R-HSA-9027284 Erythropoietin activates RAS 8.581807e-02 1.066
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 8.581807e-02 1.066
R-HSA-9673767 Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants 8.581807e-02 1.066
R-HSA-9673770 Signaling by PDGFRA extracellular domain mutants 8.581807e-02 1.066
R-HSA-5654228 Phospholipase C-mediated cascade; FGFR4 8.581807e-02 1.066
R-HSA-9755779 SARS-CoV-2 targets host intracellular signalling and regulatory pathways 8.581807e-02 1.066
R-HSA-111447 Activation of BAD and translocation to mitochondria 8.581807e-02 1.066
R-HSA-1295596 Spry regulation of FGF signaling 8.581807e-02 1.066
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA 8.581807e-02 1.066
R-HSA-9706369 Negative regulation of FLT3 9.012770e-02 1.045
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 9.012770e-02 1.045
R-HSA-388844 Receptor-type tyrosine-protein phosphatases 9.012770e-02 1.045
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest 9.012770e-02 1.045
R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling 9.441728e-02 1.025
R-HSA-9702518 STAT5 activation downstream of FLT3 ITD mutants 9.441728e-02 1.025
R-HSA-399997 Acetylcholine regulates insulin secretion 9.441728e-02 1.025
R-HSA-9009391 Extra-nuclear estrogen signaling 9.848129e-02 1.007
R-HSA-210993 Tie2 Signaling 1.029367e-01 0.987
R-HSA-3928664 Ephrin signaling 1.029367e-01 0.987
R-HSA-9833110 RSV-host interactions 1.044062e-01 0.981
R-HSA-73857 RNA Polymerase II Transcription 1.064973e-01 0.973
R-HSA-912631 Regulation of signaling by CBL 1.071666e-01 0.970
R-HSA-9856532 Mechanical load activates signaling by PIEZO1 and integrins in osteocytes 1.071666e-01 0.970
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 1.071666e-01 0.970
R-HSA-392517 Rap1 signalling 1.071666e-01 0.970
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 1.104265e-01 0.957
R-HSA-6807004 Negative regulation of MET activity 1.113769e-01 0.953
R-HSA-5654720 PI-3K cascade:FGFR4 1.113769e-01 0.953
R-HSA-445144 Signal transduction by L1 1.113769e-01 0.953
R-HSA-9705683 SARS-CoV-2-host interactions 1.127932e-01 0.948
R-HSA-167044 Signalling to RAS 1.155676e-01 0.937
R-HSA-9931295 PD-L1(CD274) glycosylation and translocation to plasma membrane 1.155676e-01 0.937
R-HSA-9034015 Signaling by NTRK3 (TRKC) 1.197388e-01 0.922
R-HSA-5654719 SHC-mediated cascade:FGFR4 1.197388e-01 0.922
R-HSA-5603041 IRAK4 deficiency (TLR2/4) 1.197388e-01 0.922
R-HSA-8876384 Listeria monocytogenes entry into host cells 1.197388e-01 0.922
R-HSA-5654712 FRS-mediated FGFR4 signaling 1.238906e-01 0.907
R-HSA-913531 Interferon Signaling 1.240429e-01 0.906
R-HSA-909733 Interferon alpha/beta signaling 1.242927e-01 0.906
R-HSA-157118 Signaling by NOTCH 1.250419e-01 0.903
R-HSA-982772 Growth hormone receptor signaling 1.280231e-01 0.893
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 1.280231e-01 0.893
R-HSA-9830674 Formation of the ureteric bud 1.280231e-01 0.893
R-HSA-3000170 Syndecan interactions 1.280231e-01 0.893
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 1.321363e-01 0.879
R-HSA-9703648 Signaling by FLT3 ITD and TKD mutants 1.321363e-01 0.879
R-HSA-5621575 CD209 (DC-SIGN) signaling 1.321363e-01 0.879
R-HSA-68875 Mitotic Prophase 1.321707e-01 0.879
R-HSA-400685 Sema4D in semaphorin signaling 1.362303e-01 0.866
R-HSA-8874081 MET activates PTK2 signaling 1.403054e-01 0.853
R-HSA-69206 G1/S Transition 1.417716e-01 0.848
R-HSA-388841 Regulation of T cell activation by CD28 family 1.420861e-01 0.847
R-HSA-69278 Cell Cycle, Mitotic 1.441910e-01 0.841
R-HSA-9006115 Signaling by NTRK2 (TRKB) 1.443614e-01 0.841
R-HSA-3928663 EPHA-mediated growth cone collapse 1.443614e-01 0.841
R-HSA-9841251 Mitochondrial unfolded protein response (UPRmt) 1.443614e-01 0.841
R-HSA-77387 Insulin receptor recycling 1.483985e-01 0.829
R-HSA-171319 Telomere Extension By Telomerase 1.483985e-01 0.829
R-HSA-9006335 Signaling by Erythropoietin 1.524169e-01 0.817
R-HSA-210745 Regulation of gene expression in beta cells 1.524169e-01 0.817
R-HSA-5654716 Downstream signaling of activated FGFR4 1.564165e-01 0.806
R-HSA-68962 Activation of the pre-replicative complex 1.564165e-01 0.806
R-HSA-2424491 DAP12 signaling 1.564165e-01 0.806
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 1.564165e-01 0.806
R-HSA-1250196 SHC1 events in ERBB2 signaling 1.564165e-01 0.806
R-HSA-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation 1.564165e-01 0.806
R-HSA-8863795 Downregulation of ERBB2 signaling 1.564165e-01 0.806
R-HSA-114452 Activation of BH3-only proteins 1.564165e-01 0.806
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 1.564412e-01 0.806
R-HSA-9820960 Respiratory syncytial virus (RSV) attachment and entry 1.603976e-01 0.795
R-HSA-3858494 Beta-catenin independent WNT signaling 1.630528e-01 0.788
R-HSA-9675126 Diseases of mitotic cell cycle 1.643600e-01 0.784
R-HSA-1538133 G0 and Early G1 1.643600e-01 0.784
R-HSA-176187 Activation of ATR in response to replication stress 1.683040e-01 0.774
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 1.683040e-01 0.774
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 1.683040e-01 0.774
R-HSA-9664422 FCGR3A-mediated phagocytosis 1.697147e-01 0.770
R-HSA-9664417 Leishmania phagocytosis 1.697147e-01 0.770
R-HSA-9664407 Parasite infection 1.697147e-01 0.770
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 1.713876e-01 0.766
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 1.747417e-01 0.758
R-HSA-9680350 Signaling by CSF1 (M-CSF) in myeloid cells 1.761370e-01 0.754
R-HSA-203615 eNOS activation 1.761370e-01 0.754
R-HSA-9682385 FLT3 signaling in disease 1.838972e-01 0.735
R-HSA-114604 GPVI-mediated activation cascade 1.838972e-01 0.735
R-HSA-111933 Calmodulin induced events 1.838972e-01 0.735
R-HSA-111997 CaM pathway 1.838972e-01 0.735
R-HSA-69242 S Phase 1.848671e-01 0.733
R-HSA-3769402 Deactivation of the beta-catenin transactivating complex 1.877502e-01 0.726
R-HSA-196757 Metabolism of folate and pterines 1.877502e-01 0.726
R-HSA-195721 Signaling by WNT 1.900967e-01 0.721
R-HSA-8875878 MET promotes cell motility 1.915853e-01 0.718
R-HSA-202131 Metabolism of nitric oxide: NOS3 activation and regulation 1.915853e-01 0.718
R-HSA-202433 Generation of second messenger molecules 1.992019e-01 0.701
R-HSA-9604323 Negative regulation of NOTCH4 signaling 1.992019e-01 0.701
R-HSA-5602358 Diseases associated with the TLR signaling cascade 1.992019e-01 0.701
R-HSA-5260271 Diseases of Immune System 1.992019e-01 0.701
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 2.019239e-01 0.695
R-HSA-5633007 Regulation of TP53 Activity 2.053583e-01 0.687
R-HSA-111996 Ca-dependent events 2.104941e-01 0.677
R-HSA-165159 MTOR signalling 2.104941e-01 0.677
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 2.179348e-01 0.662
R-HSA-3928662 EPHB-mediated forward signaling 2.179348e-01 0.662
R-HSA-2172127 DAP12 interactions 2.179348e-01 0.662
R-HSA-3214858 RMTs methylate histone arginines 2.179348e-01 0.662
R-HSA-1489509 DAG and IP3 signaling 2.216292e-01 0.654
R-HSA-74160 Gene expression (Transcription) 2.250178e-01 0.648
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 2.253064e-01 0.647
R-HSA-5621481 C-type lectin receptors (CLRs) 2.260907e-01 0.646
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 2.313011e-01 0.636
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 2.330397e-01 0.633
R-HSA-69563 p53-Dependent G1 DNA Damage Response 2.362352e-01 0.627
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 2.362352e-01 0.627
R-HSA-1280218 Adaptive Immune System 2.380650e-01 0.623
R-HSA-1169091 Activation of NF-kappaB in B cells 2.434365e-01 0.614
R-HSA-912446 Meiotic recombination 2.434365e-01 0.614
R-HSA-2514856 The phototransduction cascade 2.434365e-01 0.614
R-HSA-68949 Orc1 removal from chromatin 2.470120e-01 0.607
R-HSA-8948751 Regulation of PTEN stability and activity 2.505707e-01 0.601
R-HSA-9694516 SARS-CoV-2 Infection 2.529657e-01 0.597
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 2.541129e-01 0.595
R-HSA-1640170 Cell Cycle 2.608987e-01 0.584
R-HSA-109606 Intrinsic Pathway for Apoptosis 2.611478e-01 0.583
R-HSA-5621480 Dectin-2 family 2.646406e-01 0.577
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 2.646406e-01 0.577
R-HSA-180786 Extension of Telomeres 2.715775e-01 0.566
R-HSA-186712 Regulation of beta-cell development 2.715775e-01 0.566
R-HSA-112043 PLC beta mediated events 2.784498e-01 0.555
R-HSA-9793380 Formation of paraxial mesoderm 2.784498e-01 0.555
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 2.818619e-01 0.550
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 2.818619e-01 0.550
R-HSA-375165 NCAM signaling for neurite out-growth 2.818619e-01 0.550
R-HSA-9616222 Transcriptional regulation of granulopoiesis 2.818619e-01 0.550
R-HSA-373755 Semaphorin interactions 2.852581e-01 0.545
R-HSA-69615 G1/S DNA Damage Checkpoints 2.852581e-01 0.545
R-HSA-9824446 Viral Infection Pathways 2.976566e-01 0.526
R-HSA-112040 G-protein mediated events 2.986850e-01 0.525
R-HSA-397014 Muscle contraction 2.993691e-01 0.524
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 2.993691e-01 0.524
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 3.085916e-01 0.511
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 3.118630e-01 0.506
R-HSA-8978934 Metabolism of cofactors 3.118630e-01 0.506
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 3.118630e-01 0.506
R-HSA-453276 Regulation of mitotic cell cycle 3.118630e-01 0.506
R-HSA-3000178 ECM proteoglycans 3.118630e-01 0.506
R-HSA-69052 Switching of origins to a post-replicative state 3.183601e-01 0.497
R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane 3.183601e-01 0.497
R-HSA-4086398 Ca2+ pathway 3.183601e-01 0.497
R-HSA-8878171 Transcriptional regulation by RUNX1 3.236890e-01 0.490
R-HSA-1169408 ISG15 antiviral mechanism 3.247966e-01 0.488
R-HSA-216083 Integrin cell surface interactions 3.343390e-01 0.476
R-HSA-168256 Immune System 3.347872e-01 0.475
R-HSA-6806834 Signaling by MET 3.406266e-01 0.468
R-HSA-202733 Cell surface interactions at the vascular wall 3.426588e-01 0.465
R-HSA-8939211 ESR-mediated signaling 3.426588e-01 0.465
R-HSA-5693607 Processing of DNA double-strand break ends 3.437484e-01 0.464
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 3.468556e-01 0.460
R-HSA-1500620 Meiosis 3.560903e-01 0.448
R-HSA-6794362 Protein-protein interactions at synapses 3.560903e-01 0.448
R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs 3.591398e-01 0.445
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 3.591398e-01 0.445
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 3.621751e-01 0.441
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 3.859519e-01 0.413
R-HSA-2029481 FCGR activation 3.859519e-01 0.413
R-HSA-9734767 Developmental Cell Lineages 3.867968e-01 0.413
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization 3.975101e-01 0.401
R-HSA-5607764 CLEC7A (Dectin-1) signaling 3.975101e-01 0.401
R-HSA-157579 Telomere Maintenance 4.003659e-01 0.398
R-HSA-975871 MyD88 cascade initiated on plasma membrane 4.032084e-01 0.394
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 4.032084e-01 0.394
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 4.032084e-01 0.394
R-HSA-422356 Regulation of insulin secretion 4.032084e-01 0.394
R-HSA-9614085 FOXO-mediated transcription 4.060376e-01 0.391
R-HSA-112316 Neuronal System 4.073015e-01 0.390
R-HSA-9020702 Interleukin-1 signaling 4.116563e-01 0.385
R-HSA-9658195 Leishmania infection 4.166193e-01 0.380
R-HSA-9824443 Parasitic Infection Pathways 4.166193e-01 0.380
R-HSA-5663205 Infectious disease 4.191157e-01 0.378
R-HSA-111885 Opioid Signalling 4.199862e-01 0.377
R-HSA-69239 Synthesis of DNA 4.309119e-01 0.366
R-HSA-2672351 Stimuli-sensing channels 4.336114e-01 0.363
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 4.336114e-01 0.363
R-HSA-975155 MyD88 dependent cascade initiated on endosome 4.362983e-01 0.360
R-HSA-69002 DNA Replication Pre-Initiation 4.362983e-01 0.360
R-HSA-202403 TCR signaling 4.389726e-01 0.358
R-HSA-2871796 FCERI mediated MAPK activation 4.442838e-01 0.352
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 4.469207e-01 0.350
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 4.495453e-01 0.347
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 4.547576e-01 0.342
R-HSA-5628897 TP53 Regulates Metabolic Genes 4.547576e-01 0.342
R-HSA-2029485 Role of phospholipids in phagocytosis 4.573455e-01 0.340
R-HSA-2871809 FCERI mediated Ca+2 mobilization 4.573455e-01 0.340
R-HSA-373760 L1CAM interactions 4.599212e-01 0.337
R-HSA-9007101 Rab regulation of trafficking 4.624849e-01 0.335
R-HSA-5693538 Homology Directed Repair 4.650366e-01 0.333
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 4.675763e-01 0.330
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 4.675763e-01 0.330
R-HSA-8878166 Transcriptional regulation by RUNX2 4.675763e-01 0.330
R-HSA-73886 Chromosome Maintenance 4.726201e-01 0.325
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 4.751243e-01 0.323
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 4.751243e-01 0.323
R-HSA-112315 Transmission across Chemical Synapses 4.832663e-01 0.316
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 4.874703e-01 0.312
R-HSA-69481 G2/M Checkpoints 4.899049e-01 0.310
R-HSA-1474165 Reproduction 4.995296e-01 0.301
R-HSA-163685 Integration of energy metabolism 5.159436e-01 0.287
R-HSA-388396 GPCR downstream signalling 5.206035e-01 0.283
R-HSA-6807070 PTEN Regulation 5.228144e-01 0.282
R-HSA-9006931 Signaling by Nuclear Receptors 5.423076e-01 0.266
R-HSA-2187338 Visual phototransduction 5.428547e-01 0.265
R-HSA-196854 Metabolism of vitamins and cofactors 5.437240e-01 0.265
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 5.450295e-01 0.264
R-HSA-9758941 Gastrulation 5.471940e-01 0.262
R-HSA-9755511 KEAP1-NFE2L2 pathway 5.514927e-01 0.258
R-HSA-446652 Interleukin-1 family signaling 5.536269e-01 0.257
R-HSA-69306 DNA Replication 5.557511e-01 0.255
R-HSA-5693532 DNA Double-Strand Break Repair 5.557511e-01 0.255
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 5.578653e-01 0.253
R-HSA-68886 M Phase 5.700666e-01 0.244
R-HSA-109581 Apoptosis 5.744253e-01 0.241
R-HSA-9909648 Regulation of PD-L1(CD274) expression 5.962000e-01 0.225
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 5.981242e-01 0.223
R-HSA-9664433 Leishmania parasite growth and survival 5.981242e-01 0.223
R-HSA-372790 Signaling by GPCR 6.001583e-01 0.222
R-HSA-2559583 Cellular Senescence 6.113420e-01 0.214
R-HSA-201681 TCF dependent signaling in response to WNT 6.168746e-01 0.210
R-HSA-69275 G2/M Transition 6.223294e-01 0.206
R-HSA-453274 Mitotic G2-G2/M phases 6.259233e-01 0.203
R-HSA-983712 Ion channel transport 6.277076e-01 0.202
R-HSA-168898 Toll-like Receptor Cascades 6.312510e-01 0.200
R-HSA-389948 Co-inhibition by PD-1 6.467888e-01 0.189
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 6.518231e-01 0.186
R-HSA-376176 Signaling by ROBO receptors 6.518231e-01 0.186
R-HSA-5357801 Programmed Cell Death 6.567865e-01 0.183
R-HSA-3700989 Transcriptional Regulation by TP53 6.722807e-01 0.172
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors 6.955229e-01 0.158
R-HSA-3247509 Chromatin modifying enzymes 7.013067e-01 0.154
R-HSA-4839726 Chromatin organization 7.220463e-01 0.141
R-HSA-69620 Cell Cycle Checkpoints 7.338010e-01 0.134
R-HSA-416476 G alpha (q) signalling events 7.413636e-01 0.130
R-HSA-9711123 Cellular response to chemical stress 7.462870e-01 0.127
R-HSA-8953897 Cellular responses to stimuli 8.092042e-01 0.092
R-HSA-73894 DNA Repair 8.371547e-01 0.077
R-HSA-9824439 Bacterial Infection Pathways 8.598366e-01 0.066
R-HSA-418594 G alpha (i) signalling events 8.709204e-01 0.060
R-HSA-168249 Innate Immune System 8.896188e-01 0.051
R-HSA-8953854 Metabolism of RNA 9.170826e-01 0.038
R-HSA-199991 Membrane Trafficking 9.602397e-01 0.018
R-HSA-2262752 Cellular responses to stress 9.607478e-01 0.017
R-HSA-5653656 Vesicle-mediated transport 9.819908e-01 0.008
R-HSA-382551 Transport of small molecules 9.924226e-01 0.003
R-HSA-9709957 Sensory Perception 9.979338e-01 0.001
R-HSA-1430728 Metabolism 9.999995e-01 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
WEE1_TYRWEE1_TYR 0.697 0.335 -1 0.666
KDRKDR 0.689 0.202 3 0.548
ABL2ABL2 0.689 0.215 -1 0.669
BMPR2_TYRBMPR2_TYR 0.688 0.182 -1 0.707
METMET 0.688 0.222 3 0.598
MUSKMUSK 0.687 0.234 1 0.598
FLT3FLT3 0.687 0.190 3 0.640
MATKMATK 0.686 0.239 -1 0.755
EGFREGFR 0.686 0.234 1 0.622
KITKIT 0.686 0.201 3 0.608
EPHB4EPHB4 0.686 0.158 -1 0.701
FLT1FLT1 0.684 0.179 -1 0.731
CSF1RCSF1R 0.684 0.135 3 0.614
JAK3JAK3 0.683 0.127 1 0.559
ZAP70ZAP70 0.683 0.255 -1 0.769
ABL1ABL1 0.682 0.158 -1 0.637
EPHA6EPHA6 0.682 0.111 -1 0.703
RETRET 0.681 0.100 1 0.589
BMXBMX 0.680 0.214 -1 0.654
MST1RMST1R 0.680 0.138 3 0.622
PDGFRBPDGFRB 0.680 0.101 3 0.628
PINK1_TYRPINK1_TYR 0.680 0.087 1 0.580
ROS1ROS1 0.679 0.091 3 0.626
TNNI3K_TYRTNNI3K_TYR 0.679 0.137 1 0.628
ITKITK 0.679 0.111 -1 0.532
FLT4FLT4 0.678 0.143 3 0.540
PKMYT1_TYRPKMYT1_TYR 0.678 0.078 3 0.656
LIMK1_TYRLIMK1_TYR 0.677 0.094 2 0.658
PDHK4_TYRPDHK4_TYR 0.677 0.051 2 0.590
MAP2K6_TYRMAP2K6_TYR 0.677 0.086 -1 0.672
PDHK3_TYRPDHK3_TYR 0.677 0.016 4 0.603
TYK2TYK2 0.677 0.078 1 0.570
PDHK1_TYRPDHK1_TYR 0.677 0.073 -1 0.680
MAP2K4_TYRMAP2K4_TYR 0.677 0.091 -1 0.672
LIMK2_TYRLIMK2_TYR 0.677 0.076 -3 0.665
TESK1_TYRTESK1_TYR 0.676 0.013 3 0.696
JAK1JAK1 0.676 0.112 1 0.518
INSRRINSRR 0.675 0.101 3 0.552
SYKSYK 0.675 0.162 -1 0.710
JAK2JAK2 0.675 0.063 1 0.554
NTRK3NTRK3 0.674 0.208 -1 0.766
TXKTXK 0.674 0.085 1 0.485
PDGFRAPDGFRA 0.674 0.061 3 0.647
FGFR2FGFR2 0.673 0.090 3 0.562
ERBB2ERBB2 0.673 0.122 1 0.626
EPHB2EPHB2 0.672 0.093 -1 0.697
TYRO3TYRO3 0.672 0.013 3 0.654
MAP2K7_TYRMAP2K7_TYR 0.672 -0.048 2 0.607
TTKTTK 0.670 0.339 -2 0.707
EEF2KEEF2K 0.670 0.251 3 0.700
NTRK1NTRK1 0.670 0.132 -1 0.732
FGRFGR 0.669 0.019 1 0.530
NTRK2NTRK2 0.669 0.124 3 0.550
ALKALK 0.669 0.081 3 0.549
FGFR4FGFR4 0.668 0.171 -1 0.764
MLK4MLK4 0.668 0.308 2 0.645
INSRINSR 0.667 0.086 3 0.542
EPHB1EPHB1 0.667 0.034 1 0.541
FGFR1FGFR1 0.667 0.045 3 0.558
YES1YES1 0.666 0.010 -1 0.531
OSR1OSR1 0.666 0.244 2 0.607
EPHB3EPHB3 0.665 0.018 -1 0.670
FGFR3FGFR3 0.665 0.082 3 0.526
FERFER 0.665 0.056 1 0.525
EPHA4EPHA4 0.665 0.020 2 0.472
LCKLCK 0.665 0.030 -1 0.548
TECTEC 0.664 0.027 -1 0.501
PKRPKR 0.664 0.256 1 0.654
EPHA8EPHA8 0.664 0.069 -1 0.679
FRKFRK 0.663 0.030 -1 0.564
MLK3MLK3 0.663 0.282 2 0.687
IGF1RIGF1R 0.662 0.116 3 0.479
TEKTEK 0.662 -0.008 3 0.577
LTKLTK 0.662 0.065 3 0.552
VRK1VRK1 0.662 0.220 2 0.708
MYO3AMYO3A 0.661 0.242 1 0.629
COTCOT 0.661 0.324 2 0.674
PTK6PTK6 0.661 0.051 -1 0.555
TNK1TNK1 0.661 -0.032 3 0.623
MYO3BMYO3B 0.661 0.239 2 0.684
EPHA7EPHA7 0.661 0.010 2 0.501
BLKBLK 0.660 0.018 -1 0.551
EPHA5EPHA5 0.660 0.060 2 0.467
HRIHRI 0.660 0.303 -2 0.686
ERBB4ERBB4 0.659 0.102 1 0.625
BTKBTK 0.659 -0.028 -1 0.468
MLK1MLK1 0.659 0.274 2 0.700
ALPHAK3ALPHAK3 0.659 0.303 -1 0.756
DDR1DDR1 0.659 -0.100 4 0.538
DSTYKDSTYK 0.659 0.303 2 0.672
EPHA2EPHA2 0.659 0.093 -1 0.732
TAO3TAO3 0.658 0.206 1 0.537
EPHA3EPHA3 0.658 0.020 2 0.469
MST1MST1 0.658 0.188 1 0.540
HCKHCK 0.658 -0.033 -1 0.534
FYNFYN 0.658 0.037 -1 0.534
CSKCSK 0.658 0.062 2 0.508
MERTKMERTK 0.657 -0.010 3 0.570
TNIKTNIK 0.656 0.181 3 0.752
TNK2TNK2 0.656 -0.054 3 0.564
NEK8NEK8 0.656 0.177 2 0.694
DDR2DDR2 0.655 -0.027 3 0.523
MST2MST2 0.654 0.168 1 0.519
PERKPERK 0.654 0.245 -2 0.703
NEK10_TYRNEK10_TYR 0.654 -0.076 1 0.410
SRMSSRMS 0.653 -0.062 1 0.544
MEKK2MEKK2 0.653 0.154 2 0.649
MST3MST3 0.653 0.151 2 0.697
ZAKZAK 0.653 0.134 1 0.601
MEKK1MEKK1 0.652 0.140 1 0.583
PTK2PTK2 0.652 0.027 -1 0.627
NEK6NEK6 0.652 0.265 -2 0.676
HASPINHASPIN 0.652 0.171 -1 0.494
TAO2TAO2 0.651 0.142 2 0.702
NEK5NEK5 0.651 0.108 1 0.575
SRCSRC 0.651 0.010 -1 0.533
AXLAXL 0.650 -0.105 3 0.570
BMPR2BMPR2 0.649 0.240 -2 0.658
PKCAPKCA 0.649 0.200 2 0.699
EPHA1EPHA1 0.649 -0.075 3 0.579
PRPKPRPK 0.649 0.243 -1 0.683
HGKHGK 0.649 0.114 3 0.745
IRE2IRE2 0.648 0.184 2 0.702
PKCBPKCB 0.648 0.193 2 0.707
MINKMINK 0.648 0.091 1 0.525
GRK7GRK7 0.647 0.192 1 0.575
LYNLYN 0.647 -0.038 3 0.534
YSK4YSK4 0.647 0.120 1 0.511
ANKRD3ANKRD3 0.647 0.105 1 0.581
TLK1TLK1 0.647 0.205 -2 0.668
CHAK1CHAK1 0.646 0.130 2 0.628
NEK9NEK9 0.646 0.134 2 0.670
GCKGCK 0.646 0.071 1 0.505
PKCDPKCD 0.646 0.150 2 0.705
YSK1YSK1 0.646 0.109 2 0.682
CHAK2CHAK2 0.645 0.094 -1 0.559
PTK2BPTK2B 0.645 -0.041 -1 0.528
LRRK2LRRK2 0.645 0.073 2 0.656
MEKK3MEKK3 0.644 0.088 1 0.562
PLK1PLK1 0.644 0.160 -2 0.667
NIKNIK 0.644 0.038 -3 0.647
NEK7NEK7 0.643 0.165 -3 0.629
VRK2VRK2 0.643 -0.008 1 0.632
CAMKK1CAMKK1 0.643 0.047 -2 0.505
BRAFBRAF 0.643 0.039 -4 0.784
MLK2MLK2 0.643 0.085 2 0.662
DLKDLK 0.643 0.040 1 0.608
TGFBR2TGFBR2 0.643 0.183 -2 0.703
NEK1NEK1 0.642 0.053 1 0.588
PKCHPKCH 0.642 0.143 2 0.696
FESFES 0.642 0.100 -1 0.648
PKCGPKCG 0.642 0.169 2 0.699
ALK4ALK4 0.641 0.062 -2 0.653
IRE1IRE1 0.641 0.158 1 0.667
MEK5MEK5 0.641 0.006 2 0.624
MOSMOS 0.641 0.084 1 0.508
MAP3K15MAP3K15 0.641 0.020 1 0.546
ACVR2AACVR2A 0.640 0.163 -2 0.699
IRAK4IRAK4 0.640 0.100 1 0.649
ULK2ULK2 0.639 0.082 2 0.625
KHS1KHS1 0.639 0.044 1 0.507
CLK3CLK3 0.638 0.118 1 0.546
CDK5CDK5 0.638 0.068 1 0.369
ACVR2BACVR2B 0.638 0.145 -2 0.698
CDKL1CDKL1 0.638 0.036 -3 0.576
KHS2KHS2 0.638 0.053 1 0.508
MST4MST4 0.638 0.130 2 0.668
PRP4PRP4 0.638 0.070 -3 0.634
NEK4NEK4 0.638 0.016 1 0.556
PKCZPKCZ 0.637 0.115 2 0.687
TGFBR1TGFBR1 0.637 0.077 -2 0.640
TAO1TAO1 0.637 0.098 1 0.506
BUB1BUB1 0.637 0.151 -5 0.658
GCN2GCN2 0.636 0.173 2 0.560
BMPR1BBMPR1B 0.636 0.098 1 0.477
CDK2CDK2 0.636 0.101 1 0.472
TLK2TLK2 0.636 0.106 1 0.585
CDK1CDK1 0.636 0.067 1 0.362
LATS1LATS1 0.636 0.037 -3 0.650
TAK1TAK1 0.636 -0.005 1 0.502
MEKK6MEKK6 0.635 -0.020 1 0.537
NEK11NEK11 0.634 -0.041 1 0.526
RAF1RAF1 0.633 -0.015 1 0.530
STLK3STLK3 0.633 0.024 1 0.560
ASK1ASK1 0.633 -0.024 1 0.542
NLKNLK 0.633 -0.008 1 0.514
PKN2PKN2 0.633 0.063 -3 0.578
PKCEPKCE 0.633 0.140 2 0.706
GAKGAK 0.632 -0.058 1 0.502
LOKLOK 0.632 0.043 -2 0.467
ALK2ALK2 0.632 0.047 -2 0.661
TTBK2TTBK2 0.631 0.060 2 0.533
CAMKK2CAMKK2 0.630 -0.046 -2 0.494
MPSK1MPSK1 0.630 0.016 1 0.526
HPK1HPK1 0.629 -0.014 1 0.497
CAMLCKCAMLCK 0.629 -0.066 -2 0.537
ULK1ULK1 0.628 0.003 -3 0.626
NEK2NEK2 0.628 -0.009 2 0.662
CAMK1BCAMK1B 0.627 -0.065 -3 0.623
PDK1PDK1 0.627 -0.041 1 0.517
ATRATR 0.626 -0.046 1 0.522
PKCTPKCT 0.626 0.086 2 0.695
PASKPASK 0.626 -0.017 -3 0.612
MEK1MEK1 0.626 -0.154 2 0.574
PINK1PINK1 0.626 0.040 1 0.580
PKN3PKN3 0.625 -0.021 -3 0.581
CDK3CDK3 0.625 0.083 1 0.297
SRPK3SRPK3 0.625 0.069 -3 0.511
BMPR1ABMPR1A 0.624 0.066 1 0.470
GRK5GRK5 0.624 -0.020 -3 0.648
LKB1LKB1 0.624 -0.080 -3 0.628
ICKICK 0.624 -0.022 -3 0.607
SLKSLK 0.624 0.011 -2 0.446
GRK6GRK6 0.624 0.014 1 0.605
P38GP38G 0.624 -0.002 1 0.288
RIPK3RIPK3 0.624 -0.025 3 0.526
WNK1WNK1 0.623 -0.025 -2 0.548
NEK3NEK3 0.623 -0.002 1 0.530
CDKL5CDKL5 0.622 0.017 -3 0.566
DAPK2DAPK2 0.622 -0.137 -3 0.632
PLK3PLK3 0.622 0.068 2 0.475
MTORMTOR 0.622 -0.040 1 0.505
P38AP38A 0.621 -0.016 1 0.358
WNK4WNK4 0.621 -0.059 -2 0.558
P70S6KBP70S6KB 0.621 -0.003 -3 0.560
ERK7ERK7 0.620 0.052 2 0.535
CDK16CDK16 0.620 0.043 1 0.309
TBK1TBK1 0.620 -0.044 1 0.465
JNK3JNK3 0.620 -0.025 1 0.346
GRK4GRK4 0.620 0.060 -2 0.635
SMMLCKSMMLCK 0.620 -0.052 -3 0.576
SRPK1SRPK1 0.619 0.043 -3 0.534
PIM3PIM3 0.619 -0.017 -3 0.605
CAMK2GCAMK2G 0.619 -0.076 2 0.499
GRK2GRK2 0.619 0.000 -2 0.521
PKCIPKCI 0.618 0.062 2 0.688
RIPK1RIPK1 0.618 -0.096 1 0.646
ROCK2ROCK2 0.618 -0.016 -3 0.535
HIPK1HIPK1 0.618 -0.004 1 0.498
STK33STK33 0.617 -0.004 2 0.445
ERK5ERK5 0.617 -0.052 1 0.402
PDHK4PDHK4 0.617 -0.206 1 0.559
CDK6CDK6 0.617 0.016 1 0.324
PDHK1PDHK1 0.617 -0.139 1 0.557
GRK1GRK1 0.617 0.029 -2 0.579
CDK18CDK18 0.616 0.024 1 0.320
SRPK2SRPK2 0.616 0.057 -3 0.467
ATMATM 0.615 0.026 1 0.462
PLK2PLK2 0.615 0.086 -3 0.620
DRAK1DRAK1 0.615 -0.053 1 0.483
ROCK1ROCK1 0.615 -0.004 -3 0.506
BIKEBIKE 0.615 -0.049 1 0.386
P38BP38B 0.614 -0.025 1 0.311
GSK3AGSK3A 0.613 0.020 4 0.277
CDK14CDK14 0.613 -0.009 1 0.367
SKMLCKSKMLCK 0.613 -0.109 -2 0.538
CDK17CDK17 0.612 -0.005 1 0.301
PIM1PIM1 0.612 -0.028 -3 0.542
MEK2MEK2 0.612 -0.172 2 0.574
DYRK2DYRK2 0.612 -0.015 1 0.485
IKKEIKKE 0.612 -0.068 1 0.466
ERK2ERK2 0.611 -0.048 1 0.374
JNK2JNK2 0.611 -0.047 1 0.307
WNK3WNK3 0.611 -0.151 1 0.569
MOKMOK 0.611 0.033 1 0.515
DMPK1DMPK1 0.610 -0.035 -3 0.512
TSSK2TSSK2 0.610 -0.095 -5 0.642
NUAK2NUAK2 0.610 -0.051 -3 0.577
CDK8CDK8 0.610 -0.018 1 0.385
PHKG1PHKG1 0.609 -0.006 -3 0.589
CAMK1GCAMK1G 0.609 -0.010 -3 0.526
CLK1CLK1 0.609 0.003 -3 0.501
AKT2AKT2 0.609 -0.013 -3 0.454
KISKIS 0.609 0.067 1 0.376
DAPK3DAPK3 0.609 -0.082 -3 0.563
DCAMKL1DCAMKL1 0.608 -0.075 -3 0.532
AMPKA1AMPKA1 0.608 -0.105 -3 0.594
HUNKHUNK 0.608 -0.153 2 0.583
HIPK4HIPK4 0.608 0.009 1 0.585
PBKPBK 0.608 -0.099 1 0.391
CLK4CLK4 0.608 -0.026 -3 0.526
GRK3GRK3 0.607 0.038 -2 0.503
AKT1AKT1 0.607 -0.011 -3 0.466
PLK4PLK4 0.607 -0.031 2 0.444
P38DP38D 0.607 -0.013 1 0.245
NDR1NDR1 0.606 -0.062 -3 0.595
RSK2RSK2 0.606 -0.031 -3 0.544
PIM2PIM2 0.606 -0.031 -3 0.506
MAPKAPK3MAPKAPK3 0.606 -0.046 -3 0.541
PAK1PAK1 0.606 -0.073 -2 0.458
CLK2CLK2 0.606 0.019 -3 0.522
CDK4CDK4 0.606 -0.024 1 0.328
SGK3SGK3 0.605 -0.050 -3 0.503
MASTLMASTL 0.605 -0.289 -2 0.535
ERK1ERK1 0.605 -0.034 1 0.288
MNK1MNK1 0.605 -0.036 -2 0.473
GSK3BGSK3B 0.605 -0.032 4 0.265
RSK3RSK3 0.604 -0.029 -3 0.535
HIPK2HIPK2 0.604 -0.004 1 0.400
CDK10CDK10 0.604 0.003 1 0.350
IKKBIKKB 0.604 -0.079 -2 0.469
BCKDKBCKDK 0.603 -0.076 -1 0.614
CDC7CDC7 0.603 -0.153 1 0.461
CDK13CDK13 0.602 -0.046 1 0.336
MELKMELK 0.602 -0.082 -3 0.554
DYRK3DYRK3 0.602 -0.022 1 0.537
CDK19CDK19 0.602 -0.021 1 0.353
JNK1JNK1 0.601 -0.024 1 0.324
AAK1AAK1 0.601 -0.041 1 0.287
DCAMKL2DCAMKL2 0.601 -0.104 -3 0.561
HIPK3HIPK3 0.601 -0.053 1 0.448
MNK2MNK2 0.601 -0.059 -2 0.451
CDK12CDK12 0.601 -0.042 1 0.324
MAKMAK 0.600 0.001 -2 0.549
PKG2PKG2 0.600 -0.035 -2 0.393
IRAK1IRAK1 0.600 -0.141 -1 0.467
P90RSKP90RSK 0.599 -0.071 -3 0.554
DYRK1ADYRK1A 0.599 -0.054 1 0.444
PKACGPKACG 0.599 -0.065 -2 0.444
PAK2PAK2 0.599 -0.116 -2 0.442
RSK4RSK4 0.599 -0.036 -3 0.512
RIPK2RIPK2 0.599 -0.135 1 0.510
PAK3PAK3 0.598 -0.110 -2 0.442
CAMK4CAMK4 0.598 -0.133 -3 0.566
TTBK1TTBK1 0.598 -0.062 2 0.486
TSSK1TSSK1 0.598 -0.117 -3 0.612
MRCKBMRCKB 0.598 -0.052 -3 0.495
IKKAIKKA 0.597 -0.053 -2 0.494
PRKD3PRKD3 0.597 -0.049 -3 0.498
PRKD2PRKD2 0.597 -0.024 -3 0.531
MAPKAPK2MAPKAPK2 0.597 -0.022 -3 0.512
CHK2CHK2 0.597 -0.047 -3 0.405
PHKG2PHKG2 0.596 -0.006 -3 0.541
AMPKA2AMPKA2 0.596 -0.112 -3 0.563
NDR2NDR2 0.596 -0.069 -3 0.604
DYRK1BDYRK1B 0.596 -0.058 1 0.421
MYLK4MYLK4 0.596 -0.089 -2 0.442
MARK4MARK4 0.596 -0.163 4 0.501
MRCKAMRCKA 0.595 -0.078 -3 0.521
DAPK1DAPK1 0.595 -0.101 -3 0.542
MSK2MSK2 0.594 -0.076 -3 0.522
AURAAURA 0.594 -0.049 -2 0.349
AURBAURB 0.594 -0.072 -2 0.366
QIKQIK 0.594 -0.143 -3 0.586
CK1ECK1E 0.593 -0.009 -3 0.380
FAM20CFAM20C 0.593 0.006 2 0.340
CAMK2BCAMK2B 0.593 -0.084 2 0.429
PKACBPKACB 0.592 -0.039 -2 0.381
NIM1NIM1 0.592 -0.148 3 0.562
CK1DCK1D 0.591 -0.011 -3 0.346
SGK1SGK1 0.591 -0.045 -3 0.391
P70S6KP70S6K 0.591 -0.048 -3 0.475
CDK7CDK7 0.590 -0.074 1 0.344
NUAK1NUAK1 0.590 -0.087 -3 0.547
CK1A2CK1A2 0.590 -0.009 -3 0.334
AKT3AKT3 0.590 -0.020 -3 0.406
CHK1CHK1 0.590 -0.163 -3 0.584
CAMK2ACAMK2A 0.590 -0.089 2 0.452
CAMK2DCAMK2D 0.590 -0.176 -3 0.609
LATS2LATS2 0.588 -0.093 -5 0.636
AURCAURC 0.588 -0.058 -2 0.375
CAMK1DCAMK1D 0.588 -0.083 -3 0.457
CDK9CDK9 0.588 -0.087 1 0.344
DNAPKDNAPK 0.588 -0.141 1 0.373
SNRKSNRK 0.587 -0.156 2 0.528
SMG1SMG1 0.587 -0.136 1 0.488
PRKXPRKX 0.586 -0.014 -3 0.437
PKN1PKN1 0.586 -0.048 -3 0.483
MAPKAPK5MAPKAPK5 0.586 -0.085 -3 0.497
DYRK4DYRK4 0.585 -0.058 1 0.379
PRKD1PRKD1 0.585 -0.114 -3 0.579
SIKSIK 0.583 -0.105 -3 0.526
SSTKSSTK 0.583 -0.127 4 0.500
CAMK1ACAMK1A 0.582 -0.061 -3 0.429
CRIKCRIK 0.581 -0.083 -3 0.470
CK2A2CK2A2 0.580 -0.009 1 0.352
MARK3MARK3 0.580 -0.138 4 0.444
QSKQSK 0.579 -0.150 4 0.481
MARK2MARK2 0.579 -0.164 4 0.395
MSK1MSK1 0.579 -0.110 -3 0.519
PKACAPKACA 0.578 -0.059 -2 0.348
MARK1MARK1 0.578 -0.169 4 0.471
YANK3YANK3 0.577 -0.066 2 0.245
PAK6PAK6 0.576 -0.090 -2 0.379
BRSK2BRSK2 0.574 -0.158 -3 0.574
BRSK1BRSK1 0.574 -0.122 -3 0.547
YANK2YANK2 0.573 -0.053 2 0.268
CK2A1CK2A1 0.570 -0.034 1 0.346
CK1G1CK1G1 0.569 -0.024 -3 0.424
PAK5PAK5 0.569 -0.097 -2 0.329
CK1G2CK1G2 0.561 0.025 -3 0.336
PKG1PKG1 0.558 -0.080 -2 0.318
PAK4PAK4 0.556 -0.110 -2 0.335
SBKSBK 0.555 -0.100 -3 0.366
CK1G3CK1G3 0.548 -0.038 -3 0.249
CK1ACK1A 0.545 -0.017 -3 0.283