Motif 1119 (n=49)

Position-wise Probabilities

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uniprot genes site source protein function
O60330 PCDHGA12 Y879 ochoa Protocadherin gamma-A12 (PCDH-gamma-A12) (Cadherin-21) (Fibroblast cadherin-3) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
P06213 INSR Y1149 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}.
P07949 RET Y864 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}.
P08581 MET Y1194 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}.
P52333 JAK3 Y939 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}.
Q04912 MST1R Y1198 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}.
Q9UN70 PCDHGC3 Y881 ochoa Protocadherin gamma-C3 (PCDH-gamma-C3) (Protocadherin-2) (Protocadherin-43) (PC-43) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9UN71 PCDHGB4 Y870 ochoa Protocadherin gamma-B4 (PCDH-gamma-B4) (Cadherin-20) (Fibroblast cadherin-2) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5F6 PCDHGC5 Y891 ochoa Protocadherin gamma-C5 (PCDH-gamma-C5) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5F7 PCDHGC4 Y885 ochoa Protocadherin gamma-C4 (PCDH-gamma-C4) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5F8 PCDHGB7 Y876 ochoa Protocadherin gamma-B7 (PCDH-gamma-B7) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5F9 PCDHGB6 Y877 ochoa Protocadherin gamma-B6 (PCDH-gamma-B6) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G0 PCDHGB5 Y870 ochoa Protocadherin gamma-B5 (PCDH-gamma-B5) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G1 PCDHGB3 Y876 ochoa Protocadherin gamma-B3 (PCDH-gamma-B3) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G2 PCDHGB2 Y878 ochoa Protocadherin gamma-B2 (PCDH-gamma-B2) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G3 PCDHGB1 Y874 ochoa Protocadherin gamma-B1 (PCDH-gamma-B1) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G4 PCDHGA9 Y879 ochoa Protocadherin gamma-A9 (PCDH-gamma-A9) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G5 PCDHGA8 Y879 ochoa Protocadherin gamma-A8 (PCDH-gamma-A8) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G6 PCDHGA7 Y879 ochoa Protocadherin gamma-A7 (PCDH-gamma-A7) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G7 PCDHGA6 Y879 ochoa Protocadherin gamma-A6 (PCDH-gamma-A6) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5G8 PCDHGA5 Y878 ochoa Protocadherin gamma-A5 (PCDH-gamma-A5) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5H0 PCDHGA3 Y879 ochoa Protocadherin gamma-A3 (PCDH-gamma-A3) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5H1 PCDHGA2 Y879 ochoa Protocadherin gamma-A2 (PCDH-gamma-A2) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5H2 PCDHGA11 Y882 ochoa Protocadherin gamma-A11 (PCDH-gamma-A11) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5H3 PCDHGA10 Y883 ochoa Protocadherin gamma-A10 (PCDH-gamma-A10) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Q9Y5H4 PCDHGA1 Y878 ochoa Protocadherin gamma-A1 (PCDH-gamma-A1) Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
O15146 MUSK Y715 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}.
P29322 EPHA8 Y750 Sugiyama Ephrin type-A receptor 8 (EC 2.7.10.1) (EPH- and ELK-related kinase) (EPH-like kinase 3) (EK3) (hEK3) (Tyrosine-protein kinase receptor EEK) Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system also plays a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity). {ECO:0000250}.
O60674 JAK2 Y966 SIGNOR 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}.
P00533 EGFR Y827 Sugiyama Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1) Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:Q01279, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11116146, ECO:0000269|PubMed:11483589, ECO:0000269|PubMed:11602604, ECO:0000269|PubMed:12297049, ECO:0000269|PubMed:12297050, ECO:0000269|PubMed:12620237, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15374980, ECO:0000269|PubMed:15590694, ECO:0000269|PubMed:15611079, ECO:0000269|PubMed:17115032, ECO:0000269|PubMed:17909029, ECO:0000269|PubMed:19560417, ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:20837704, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:27153536, ECO:0000269|PubMed:2790960, ECO:0000269|PubMed:35538033, ECO:0000269|PubMed:7679104, ECO:0000269|PubMed:8144591, ECO:0000269|PubMed:9419975}.; FUNCTION: Isoform 2 may act as an antagonist of EGF action.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.
P21802 FGFR2 Y616 Sugiyama 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 Y607 Sugiyama 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}.
P22455 FGFR4 Y602 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}.
P23458 JAK1 Y993 Sugiyama 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}.
P29317 EPHA2 Y729 Sugiyama Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}.
P29320 EPHA3 Y736 Sugiyama Ephrin type-A receptor 3 (EC 2.7.10.1) (EPH-like kinase 4) (EK4) (hEK4) (HEK) (Human embryo kinase) (Tyrosine-protein kinase TYRO4) (Tyrosine-protein kinase receptor ETK1) (Eph-like tyrosine kinase 1) Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}.
P54756 EPHA5 Y790 Sugiyama Ephrin type-A receptor 5 (EC 2.7.10.1) (Brain-specific kinase) (EPH homology kinase 1) (EHK-1) (EPH-like kinase 7) (EK7) (hEK7) Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion (By similarity). {ECO:0000250}.
P29323 EPHB2 Y736 Sugiyama Ephrin type-B receptor 2 (EC 2.7.10.1) (Developmentally-regulated Eph-related tyrosine kinase) (ELK-related tyrosine kinase) (EPH tyrosine kinase 3) (EPH-like kinase 5) (EK5) (hEK5) (Renal carcinoma antigen NY-REN-47) (Tyrosine-protein kinase TYRO5) (Tyrosine-protein kinase receptor EPH-3) [Cleaved into: EphB2/CTF1; EphB2/CTF2] 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874). {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:30213874}.
P41240 CSK Y304 SIGNOR|iPTMNet Tyrosine-protein kinase CSK (EC 2.7.10.2) (C-Src kinase) (Protein-tyrosine kinase CYL) Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs) including LCK, SRC, HCK, FYN, LYN, CSK or YES1. Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane. Suppresses signaling by various surface receptors, including T-cell receptor (TCR) and B-cell receptor (BCR) by phosphorylating and maintaining inactive several positive effectors such as FYN or LCK. {ECO:0000269|PubMed:1639064, ECO:0000269|PubMed:9281320}.
P42680 TEC Y479 Sugiyama Tyrosine-protein kinase Tec (EC 2.7.10.2) Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC also regulates FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation. {ECO:0000269|PubMed:10518561, ECO:0000269|PubMed:19883687, ECO:0000269|PubMed:20230531, ECO:0000269|PubMed:9753425}.
P42681 TXK Y380 Sugiyama Tyrosine-protein kinase TXK (EC 2.7.10.2) (Protein-tyrosine kinase 4) (Resting lymphocyte kinase) Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation leads to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Also contributes to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with PARP1 and EEF1A1 (PubMed:11859127, PubMed:17177976). Within the complex, phosphorylates both PARP1 and EEF1A1 (PubMed:17177976). Also phosphorylates key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor. {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:11564877, ECO:0000269|PubMed:11859127, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:9813138}.
P43405 SYK Y484 Sugiyama 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}.
P54753 EPHB3 Y748 Sugiyama Ephrin type-B receptor 3 (EC 2.7.10.1) (EPH-like tyrosine kinase 2) (EPH-like kinase 2) (Embryonic kinase 2) (EK2) (hEK2) (Tyrosine-protein kinase TYRO6) 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. Generally has an overlapping and redundant function with EPHB2. Like EPHB2, functions in axon guidance during development regulating for instance the neurons forming the corpus callosum and the anterior commissure, 2 major interhemispheric connections between the temporal lobes of the cerebral cortex. 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 the formation of excitatory synapses. Controls other aspects of development through regulation of cell migration and positioning. This includes angiogenesis, palate development and thymic epithelium development for instance. Forward and reverse signaling through the EFNB2/EPHB3 complex also regulate migration and adhesion of cells that tubularize the urethra and septate the cloaca. Finally, plays an important role in intestinal epithelium differentiation segregating progenitor from differentiated cells in the crypt. {ECO:0000269|PubMed:15536074}.
P54760 EPHB4 Y730 Sugiyama Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11) 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. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. {ECO:0000269|PubMed:12734395, ECO:0000269|PubMed:16424904, ECO:0000269|PubMed:27400125, ECO:0000269|PubMed:30578106}.
P54764 EPHA4 Y736 Sugiyama Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK) Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (By similarity). {ECO:0000250|UniProtKB:Q03137, ECO:0000269|PubMed:17143272}.
Q06187 BTK Y511 Sugiyama Tyrosine-protein kinase BTK (EC 2.7.10.2) (Agammaglobulinemia tyrosine kinase) (ATK) (B-cell progenitor kinase) (BPK) (Bruton tyrosine kinase) Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling (PubMed:19290921). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (PubMed:19290921). After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members (PubMed:11606584). PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK (PubMed:11606584). BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways (PubMed:16517732, PubMed:17932028). Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway (PubMed:16517732). The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense (PubMed:16517732). Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells (PubMed:16517732, PubMed:17932028). Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation (PubMed:16415872). BTK also plays a critical role in transcription regulation (PubMed:19290921). Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes (PubMed:19290921). BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B (PubMed:19290921). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (PubMed:34554188). Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR (PubMed:9012831). GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression (PubMed:9012831). ARID3A and NFAT are other transcriptional target of BTK (PubMed:16738337). BTK is required for the formation of functional ARID3A DNA-binding complexes (PubMed:16738337). There is however no evidence that BTK itself binds directly to DNA (PubMed:16738337). BTK has a dual role in the regulation of apoptosis (PubMed:9751072). Plays a role in STING1-mediated induction of type I interferon (IFN) response by phosphorylating DDX41 (PubMed:25704810). {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:25704810, ECO:0000269|PubMed:34554188, ECO:0000269|PubMed:9012831, ECO:0000303|PubMed:19290921, ECO:0000303|PubMed:9751072}.
Q15303 ERBB4 Y833 Sugiyama Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis. {ECO:0000269|PubMed:10348342, ECO:0000269|PubMed:10353604, ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:10722704, ECO:0000269|PubMed:10867024, ECO:0000269|PubMed:11178955, ECO:0000269|PubMed:11390655, ECO:0000269|PubMed:12807903, ECO:0000269|PubMed:15534001, ECO:0000269|PubMed:15746097, ECO:0000269|PubMed:16251361, ECO:0000269|PubMed:16778220, ECO:0000269|PubMed:16837552, ECO:0000269|PubMed:17486069, ECO:0000269|PubMed:17638867, ECO:0000269|PubMed:19098003, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:8383326, ECO:0000269|PubMed:8617750, ECO:0000269|PubMed:9135143, ECO:0000269|PubMed:9168115, ECO:0000269|PubMed:9334263}.
Q15375 EPHA7 Y748 Sugiyama Ephrin type-A receptor 7 (EC 2.7.10.1) (EPH homology kinase 3) (EHK-3) (EPH-like kinase 11) (EK11) (hEK11) Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 and MAPK3 which are phosphorylated upon activation of EPHA7. {ECO:0000269|PubMed:17726105}.
Q9UM73 ALK Y1239 Sugiyama ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}.
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reactome_id name p -log10_p
R-HSA-5684996 MAPK1/MAPK3 signaling 2.142730e-14 13.669
R-HSA-5673001 RAF/MAP kinase cascade 1.498801e-14 13.824
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 1.357803e-13 12.867
R-HSA-5683057 MAPK family signaling cascades 2.328138e-13 12.633
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 8.092416e-13 12.092
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 1.054379e-12 11.977
R-HSA-199418 Negative regulation of the PI3K/AKT network 1.557532e-12 11.808
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 2.980727e-12 11.526
R-HSA-1226099 Signaling by FGFR in disease 3.032685e-12 11.518
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 8.491541e-12 11.071
R-HSA-2219528 PI3K/AKT Signaling in Cancer 1.323186e-11 10.878
R-HSA-2682334 EPH-Ephrin signaling 6.605329e-10 9.180
R-HSA-74751 Insulin receptor signalling cascade 1.047967e-09 8.980
R-HSA-109704 PI3K Cascade 6.978559e-09 8.156
R-HSA-3928663 EPHA-mediated growth cone collapse 7.949377e-09 8.100
R-HSA-1257604 PIP3 activates AKT signaling 9.827618e-09 8.008
R-HSA-74752 Signaling by Insulin receptor 1.536635e-08 7.813
R-HSA-112399 IRS-mediated signalling 1.513287e-08 7.820
R-HSA-2428928 IRS-related events triggered by IGF1R 2.267873e-08 7.644
R-HSA-2428924 IGF1R signaling cascade 3.024219e-08 7.519
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) 3.319576e-08 7.479
R-HSA-1839126 FGFR2 mutant receptor activation 3.762753e-08 7.424
R-HSA-9006925 Intracellular signaling by second messengers 4.463753e-08 7.350
R-HSA-8851708 Signaling by FGFR2 IIIa TM 7.633561e-08 7.117
R-HSA-5655253 Signaling by FGFR2 in disease 2.154945e-07 6.667
R-HSA-190236 Signaling by FGFR 4.865608e-07 6.313
R-HSA-8847993 ERBB2 Activates PTK6 Signaling 1.273514e-06 5.895
R-HSA-6785631 ERBB2 Regulates Cell Motility 1.575897e-06 5.802
R-HSA-1963640 GRB2 events in ERBB2 signaling 2.336632e-06 5.631
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 2.749049e-06 5.561
R-HSA-5654221 Phospholipase C-mediated cascade; FGFR2 4.633129e-06 5.334
R-HSA-422475 Axon guidance 4.838009e-06 5.315
R-HSA-190241 FGFR2 ligand binding and activation 5.402669e-06 5.267
R-HSA-9675108 Nervous system development 9.142932e-06 5.039
R-HSA-9665686 Signaling by ERBB2 TMD/JMD mutants 9.453737e-06 5.024
R-HSA-5654695 PI-3K cascade:FGFR2 1.074401e-05 4.969
R-HSA-5654699 SHC-mediated cascade:FGFR2 1.370813e-05 4.863
R-HSA-5654700 FRS-mediated FGFR2 signaling 1.539713e-05 4.813
R-HSA-1253288 Downregulation of ERBB4 signaling 1.614607e-05 4.792
R-HSA-9664565 Signaling by ERBB2 KD Mutants 1.723447e-05 4.764
R-HSA-1250196 SHC1 events in ERBB2 signaling 1.922815e-05 4.716
R-HSA-1227990 Signaling by ERBB2 in Cancer 1.922815e-05 4.716
R-HSA-8863795 Downregulation of ERBB2 signaling 1.922815e-05 4.716
R-HSA-1236394 Signaling by ERBB4 2.934322e-05 4.532
R-HSA-5654727 Negative regulation of FGFR2 signaling 3.183272e-05 4.497
R-HSA-9020558 Interleukin-2 signaling 3.298190e-05 4.482
R-HSA-5654696 Downstream signaling of activated FGFR2 3.494122e-05 4.457
R-HSA-1251985 Nuclear signaling by ERBB4 5.391963e-05 4.268
R-HSA-451927 Interleukin-2 family signaling 5.391963e-05 4.268
R-HSA-2033514 FGFR3 mutant receptor activation 5.851174e-05 4.233
R-HSA-1839130 Signaling by activated point mutants of FGFR3 5.851174e-05 4.233
R-HSA-1250347 SHC1 events in ERBB4 signaling 1.089507e-04 3.963
R-HSA-1963642 PI3K events in ERBB2 signaling 1.248848e-04 3.903
R-HSA-3928664 Ephrin signaling 1.422640e-04 3.847
R-HSA-2033519 Activated point mutants of FGFR2 1.422640e-04 3.847
R-HSA-162582 Signal Transduction 2.134611e-04 3.671
R-HSA-1227986 Signaling by ERBB2 2.208444e-04 3.656
R-HSA-2023837 Signaling by FGFR2 amplification mutants 2.230672e-04 3.652
R-HSA-9705462 Inactivation of CSF3 (G-CSF) signaling 2.273441e-04 3.643
R-HSA-8848021 Signaling by PTK6 2.599575e-04 3.585
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 2.599575e-04 3.585
R-HSA-912526 Interleukin receptor SHC signaling 2.799808e-04 3.553
R-HSA-8854691 Interleukin-20 family signaling 2.799808e-04 3.553
R-HSA-9620244 Long-term potentiation 3.399084e-04 3.469
R-HSA-5655332 Signaling by FGFR3 in disease 4.075324e-04 3.390
R-HSA-9674555 Signaling by CSF3 (G-CSF) 4.832467e-04 3.316
R-HSA-5654738 Signaling by FGFR2 5.809314e-04 3.236
R-HSA-9679191 Potential therapeutics for SARS 7.980141e-04 3.098
R-HSA-9732724 IFNG signaling activates MAPKs 8.800068e-04 3.056
R-HSA-201556 Signaling by ALK 1.060835e-03 2.974
R-HSA-8985947 Interleukin-9 signaling 1.061868e-03 2.974
R-HSA-9020958 Interleukin-21 signaling 1.260223e-03 2.900
R-HSA-112411 MAPK1 (ERK2) activation 1.260223e-03 2.900
R-HSA-9020956 Interleukin-27 signaling 1.474930e-03 2.831
R-HSA-110056 MAPK3 (ERK1) activation 1.474930e-03 2.831
R-HSA-3928662 EPHB-mediated forward signaling 1.504655e-03 2.823
R-HSA-190377 FGFR2b ligand binding and activation 1.705850e-03 2.768
R-HSA-1250342 PI3K events in ERBB4 signaling 1.952846e-03 2.709
R-HSA-190375 FGFR2c ligand binding and activation 2.494513e-03 2.603
R-HSA-8983432 Interleukin-15 signaling 2.215779e-03 2.654
R-HSA-8984722 Interleukin-35 Signalling 2.215779e-03 2.654
R-HSA-6788467 IL-6-type cytokine receptor ligand interactions 2.494513e-03 2.603
R-HSA-1059683 Interleukin-6 signaling 2.494513e-03 2.603
R-HSA-877312 Regulation of IFNG signaling 2.215779e-03 2.654
R-HSA-2871809 FCERI mediated Ca+2 mobilization 2.352954e-03 2.628
R-HSA-5654227 Phospholipase C-mediated cascade; FGFR3 2.788911e-03 2.555
R-HSA-190239 FGFR3 ligand binding and activation 3.098838e-03 2.509
R-HSA-1643685 Disease 3.120213e-03 2.506
R-HSA-8866910 TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... 3.764745e-03 2.424
R-HSA-9700649 Drug resistance of ALK mutants 4.275881e-03 2.369
R-HSA-9717264 ASP-3026-resistant ALK mutants 4.275881e-03 2.369
R-HSA-9717301 NVP-TAE684-resistant ALK mutants 4.275881e-03 2.369
R-HSA-9717329 lorlatinib-resistant ALK mutants 4.275881e-03 2.369
R-HSA-9717316 alectinib-resistant ALK mutants 4.275881e-03 2.369
R-HSA-9717319 brigatinib-resistant ALK mutants 4.275881e-03 2.369
R-HSA-9717326 crizotinib-resistant ALK mutants 4.275881e-03 2.369
R-HSA-9717323 ceritinib-resistant ALK mutants 4.275881e-03 2.369
R-HSA-180292 GAB1 signalosome 4.491169e-03 2.348
R-HSA-5654710 PI-3K cascade:FGFR3 4.876746e-03 2.312
R-HSA-5654704 SHC-mediated cascade:FGFR3 5.691980e-03 2.245
R-HSA-5654706 FRS-mediated FGFR3 signaling 6.121378e-03 2.213
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 6.121378e-03 2.213
R-HSA-112409 RAF-independent MAPK1/3 activation 6.565128e-03 2.183
R-HSA-9734091 Drug-mediated inhibition of MET activation 8.533743e-03 2.069
R-HSA-9927432 Developmental Lineage of Mammary Gland Myoepithelial Cells 1.006263e-02 1.997
R-HSA-5654708 Downstream signaling of activated FGFR3 1.006263e-02 1.997
R-HSA-6783589 Interleukin-6 family signaling 7.495171e-03 2.125
R-HSA-2424491 DAP12 signaling 1.061668e-02 1.974
R-HSA-1266695 Interleukin-7 signaling 7.981214e-03 2.098
R-HSA-5654732 Negative regulation of FGFR3 signaling 9.521935e-03 2.021
R-HSA-9830364 Formation of the nephric duct 7.981214e-03 2.098
R-HSA-1266738 Developmental Biology 8.082243e-03 2.092
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 8.481105e-03 2.072
R-HSA-438064 Post NMDA receptor activation events 8.283358e-03 2.082
R-HSA-354192 Integrin signaling 1.235778e-02 1.908
R-HSA-1839128 FGFR4 mutant receptor activation 1.277366e-02 1.894
R-HSA-2033515 t(4;14) translocations of FGFR3 1.277366e-02 1.894
R-HSA-8853333 Signaling by FGFR2 fusions 1.277366e-02 1.894
R-HSA-8853334 Signaling by FGFR3 fusions in cancer 1.277366e-02 1.894
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 1.283289e-02 1.892
R-HSA-9768919 NPAS4 regulates expression of target genes 1.358310e-02 1.867
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 1.536033e-02 1.814
R-HSA-9607240 FLT3 Signaling 1.826401e-02 1.738
R-HSA-9656223 Signaling by RAF1 mutants 1.898100e-02 1.722
R-HSA-1433557 Signaling by SCF-KIT 2.045007e-02 1.689
R-HSA-8875513 MET interacts with TNS proteins 2.119996e-02 1.674
R-HSA-8865999 MET activates PTPN11 2.119996e-02 1.674
R-HSA-8875791 MET activates STAT3 2.119996e-02 1.674
R-HSA-2172127 DAP12 interactions 2.120194e-02 1.674
R-HSA-8864260 Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors 2.120194e-02 1.674
R-HSA-5654741 Signaling by FGFR3 2.196521e-02 1.658
R-HSA-76009 Platelet Aggregation (Plug Formation) 2.196521e-02 1.658
R-HSA-9824272 Somitogenesis 2.196521e-02 1.658
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 2.273978e-02 1.643
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 2.273978e-02 1.643
R-HSA-9649948 Signaling downstream of RAS mutants 2.273978e-02 1.643
R-HSA-6802949 Signaling by RAS mutants 2.273978e-02 1.643
R-HSA-1251932 PLCG1 events in ERBB2 signaling 2.538649e-02 1.595
R-HSA-1307965 betaKlotho-mediated ligand binding 2.538649e-02 1.595
R-HSA-9851151 MDK and PTN in ALK signaling 2.538649e-02 1.595
R-HSA-9706374 FLT3 signaling through SRC family kinases 2.538649e-02 1.595
R-HSA-9634815 Transcriptional Regulation by NPAS4 2.761850e-02 1.559
R-HSA-74713 IRS activation 2.955537e-02 1.529
R-HSA-177929 Signaling by EGFR 3.108358e-02 1.507
R-HSA-5638303 Inhibition of Signaling by Overexpressed EGFR 3.370668e-02 1.472
R-HSA-5638302 Signaling by Overexpressed Wild-Type EGFR in Cancer 3.370668e-02 1.472
R-HSA-8857538 PTK6 promotes HIF1A stabilization 3.784048e-02 1.422
R-HSA-9027283 Erythropoietin activates STAT5 3.784048e-02 1.422
R-HSA-8851907 MET activates PI3K/AKT signaling 4.195686e-02 1.377
R-HSA-190371 FGFR3b ligand binding and activation 4.195686e-02 1.377
R-HSA-212718 EGFR interacts with phospholipase C-gamma 4.605588e-02 1.337
R-HSA-8875656 MET receptor recycling 4.605588e-02 1.337
R-HSA-9700645 ALK mutants bind TKIs 5.013761e-02 1.300
R-HSA-8875555 MET activates RAP1 and RAC1 5.420213e-02 1.266
R-HSA-9027277 Erythropoietin activates Phospholipase C gamma (PLCG) 5.420213e-02 1.266
R-HSA-416550 Sema4D mediated inhibition of cell attachment and migration 6.227982e-02 1.206
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 3.946432e-02 1.404
R-HSA-383280 Nuclear Receptor transcription pathway 5.287885e-02 1.277
R-HSA-2586552 Signaling by Leptin 5.420213e-02 1.266
R-HSA-8852405 Signaling by MST1 3.370668e-02 1.472
R-HSA-9020933 Interleukin-23 signaling 4.605588e-02 1.337
R-HSA-6802957 Oncogenic MAPK signaling 6.068114e-02 1.217
R-HSA-6806942 MET Receptor Activation 3.784048e-02 1.422
R-HSA-2179392 EGFR Transactivation by Gastrin 5.420213e-02 1.266
R-HSA-447115 Interleukin-12 family signaling 6.413913e-02 1.193
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 6.233499e-02 1.205
R-HSA-9924644 Developmental Lineages of the Mammary Gland 4.650572e-02 1.332
R-HSA-9020591 Interleukin-12 signaling 5.072116e-02 1.295
R-HSA-74749 Signal attenuation 5.420213e-02 1.266
R-HSA-9830369 Kidney development 4.143118e-02 1.383
R-HSA-9793380 Formation of paraxial mesoderm 3.564263e-02 1.448
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 4.242829e-02 1.372
R-HSA-8851805 MET activates RAS signaling 6.629313e-02 1.179
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 6.629313e-02 1.179
R-HSA-179812 GRB2 events in EGFR signaling 6.629313e-02 1.179
R-HSA-8986944 Transcriptional Regulation by MECP2 6.885092e-02 1.162
R-HSA-190322 FGFR4 ligand binding and activation 7.028951e-02 1.153
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 7.245781e-02 1.140
R-HSA-5655291 Signaling by FGFR4 in disease 7.426904e-02 1.129
R-HSA-1170546 Prolactin receptor signaling 7.426904e-02 1.129
R-HSA-190372 FGFR3c ligand binding and activation 7.426904e-02 1.129
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 7.787686e-02 1.109
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 7.823177e-02 1.107
R-HSA-9027284 Erythropoietin activates RAS 7.823177e-02 1.107
R-HSA-180336 SHC1 events in EGFR signaling 7.823177e-02 1.107
R-HSA-5654228 Phospholipase C-mediated cascade; FGFR4 7.823177e-02 1.107
R-HSA-8964315 G beta:gamma signalling through BTK 7.823177e-02 1.107
R-HSA-9706369 Negative regulation of FLT3 8.217779e-02 1.085
R-HSA-5637812 Signaling by EGFRvIII in Cancer 9.001995e-02 1.046
R-HSA-5637810 Constitutive Signaling by EGFRvIII 9.001995e-02 1.046
R-HSA-9665348 Signaling by ERBB2 ECD mutants 9.391623e-02 1.027
R-HSA-9734779 Developmental Cell Lineages of the Integumentary System 9.397507e-02 1.027
R-HSA-912631 Regulation of signaling by CBL 9.779606e-02 1.010
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 9.779606e-02 1.010
R-HSA-449836 Other interleukin signaling 9.779606e-02 1.010
R-HSA-8939211 ESR-mediated signaling 9.836168e-02 1.007
R-HSA-9679506 SARS-CoV Infections 1.009154e-01 0.996
R-HSA-6807004 Negative regulation of MET activity 1.016595e-01 0.993
R-HSA-5654720 PI-3K cascade:FGFR4 1.016595e-01 0.993
R-HSA-445144 Signal transduction by L1 1.016595e-01 0.993
R-HSA-5602498 MyD88 deficiency (TLR2/4) 1.055067e-01 0.977
R-HSA-5637815 Signaling by Ligand-Responsive EGFR Variants in Cancer 1.055067e-01 0.977
R-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants 1.055067e-01 0.977
R-HSA-9931295 PD-L1(CD274) glycosylation and translocation to plasma membrane 1.055067e-01 0.977
R-HSA-373760 L1CAM interactions 1.073907e-01 0.969
R-HSA-5654719 SHC-mediated cascade:FGFR4 1.093376e-01 0.961
R-HSA-5603041 IRAK4 deficiency (TLR2/4) 1.093376e-01 0.961
R-HSA-8876384 Listeria monocytogenes entry into host cells 1.093376e-01 0.961
R-HSA-5654712 FRS-mediated FGFR4 signaling 1.131524e-01 0.946
R-HSA-912694 Regulation of IFNA/IFNB signaling 1.131524e-01 0.946
R-HSA-9670439 Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... 1.131524e-01 0.946
R-HSA-9669938 Signaling by KIT in disease 1.131524e-01 0.946
R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus 1.131524e-01 0.946
R-HSA-982772 Growth hormone receptor signaling 1.169510e-01 0.932
R-HSA-9830674 Formation of the ureteric bud 1.169510e-01 0.932
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 1.169510e-01 0.932
R-HSA-400685 Sema4D in semaphorin signaling 1.245003e-01 0.905
R-HSA-8874081 MET activates PTK2 signaling 1.282510e-01 0.892
R-HSA-1643713 Signaling by EGFR in Cancer 1.282510e-01 0.892
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains 1.319859e-01 0.879
R-HSA-212436 Generic Transcription Pathway 1.330970e-01 0.876
R-HSA-77387 Insulin receptor recycling 1.357050e-01 0.867
R-HSA-9006335 Signaling by Erythropoietin 1.394084e-01 0.856
R-HSA-5654733 Negative regulation of FGFR4 signaling 1.394084e-01 0.856
R-HSA-9018519 Estrogen-dependent gene expression 1.399601e-01 0.854
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 1.414221e-01 0.849
R-HSA-5654716 Downstream signaling of activated FGFR4 1.430962e-01 0.844
R-HSA-449147 Signaling by Interleukins 1.434553e-01 0.843
R-HSA-9664407 Parasite infection 1.458280e-01 0.836
R-HSA-9664422 FCGR3A-mediated phagocytosis 1.458280e-01 0.836
R-HSA-9664417 Leishmania phagocytosis 1.458280e-01 0.836
R-HSA-182971 EGFR downregulation 1.467684e-01 0.833
R-HSA-9820960 Respiratory syncytial virus (RSV) attachment and entry 1.467684e-01 0.833
R-HSA-9833109 Evasion by RSV of host interferon responses 1.467684e-01 0.833
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 1.473032e-01 0.832
R-HSA-397795 G-protein beta:gamma signalling 1.540664e-01 0.812
R-HSA-9758941 Gastrulation 1.607143e-01 0.794
R-HSA-5673000 RAF activation 1.613028e-01 0.792
R-HSA-9856651 MITF-M-dependent gene expression 1.622185e-01 0.790
R-HSA-8853659 RET signaling 1.684783e-01 0.773
R-HSA-114604 GPVI-mediated activation cascade 1.684783e-01 0.773
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 1.720432e-01 0.764
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 1.743427e-01 0.759
R-HSA-8875878 MET promotes cell motility 1.755932e-01 0.755
R-HSA-877300 Interferon gamma signaling 1.758689e-01 0.755
R-HSA-112315 Transmission across Chemical Synapses 1.821548e-01 0.740
R-HSA-5260271 Diseases of Immune System 1.826481e-01 0.738
R-HSA-5602358 Diseases associated with the TLR signaling cascade 1.826481e-01 0.738
R-HSA-5674135 MAP2K and MAPK activation 1.896435e-01 0.722
R-HSA-73857 RNA Polymerase II Transcription 1.958892e-01 0.708
R-HSA-5654743 Signaling by FGFR4 1.965799e-01 0.706
R-HSA-69231 Cyclin D associated events in G1 2.000261e-01 0.699
R-HSA-69236 G1 Phase 2.000261e-01 0.699
R-HSA-3214858 RMTs methylate histone arginines 2.000261e-01 0.699
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 2.005566e-01 0.698
R-HSA-9006931 Signaling by Nuclear Receptors 2.261720e-01 0.646
R-HSA-9012852 Signaling by NOTCH3 2.369862e-01 0.625
R-HSA-389948 Co-inhibition by PD-1 2.414318e-01 0.617
R-HSA-5621480 Dectin-2 family 2.435230e-01 0.613
R-HSA-373755 Semaphorin interactions 2.628042e-01 0.580
R-HSA-9730414 MITF-M-regulated melanocyte development 2.636363e-01 0.579
R-HSA-8878171 Transcriptional regulation by RUNX1 2.842767e-01 0.546
R-HSA-3000178 ECM proteoglycans 2.877608e-01 0.541
R-HSA-1169408 ISG15 antiviral mechanism 2.999250e-01 0.523
R-HSA-6783783 Interleukin-10 signaling 3.089135e-01 0.510
R-HSA-416482 G alpha (12/13) signalling events 3.089135e-01 0.510
R-HSA-6806834 Signaling by MET 3.148426e-01 0.502
R-HSA-1280215 Cytokine Signaling in Immune system 3.281737e-01 0.484
R-HSA-388841 Regulation of T cell activation by CD28 family 3.316551e-01 0.479
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 3.323307e-01 0.478
R-HSA-9734767 Developmental Cell Lineages 3.426080e-01 0.465
R-HSA-1236974 ER-Phagosome pathway 3.437443e-01 0.464
R-HSA-416476 G alpha (q) signalling events 3.441685e-01 0.463
R-HSA-74160 Gene expression (Transcription) 3.461401e-01 0.461
R-HSA-112316 Neuronal System 3.494854e-01 0.457
R-HSA-2029481 FCGR activation 3.577412e-01 0.446
R-HSA-76002 Platelet activation, signaling and aggregation 3.597089e-01 0.444
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization 3.687265e-01 0.433
R-HSA-5607764 CLEC7A (Dectin-1) signaling 3.687265e-01 0.433
R-HSA-9824446 Viral Infection Pathways 3.692284e-01 0.433
R-HSA-9824443 Parasitic Infection Pathways 3.705112e-01 0.431
R-HSA-9658195 Leishmania infection 3.705112e-01 0.431
R-HSA-9009391 Extra-nuclear estrogen signaling 3.821980e-01 0.418
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis 3.901445e-01 0.409
R-HSA-9833110 RSV-host interactions 3.927709e-01 0.406
R-HSA-9700206 Signaling by ALK in cancer 4.005834e-01 0.397
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 4.005834e-01 0.397
R-HSA-1236975 Antigen processing-Cross presentation 4.031655e-01 0.395
R-HSA-202403 TCR signaling 4.082968e-01 0.389
R-HSA-2871796 FCERI mediated MAPK activation 4.133846e-01 0.384
R-HSA-909733 Interferon alpha/beta signaling 4.259163e-01 0.371
R-HSA-2029485 Role of phospholipids in phagocytosis 4.259163e-01 0.371
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 4.357514e-01 0.361
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 4.357514e-01 0.361
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 4.430185e-01 0.354
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 4.430185e-01 0.354
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 4.549260e-01 0.342
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 4.979298e-01 0.303
R-HSA-8856828 Clathrin-mediated endocytosis 5.000981e-01 0.301
R-HSA-453279 Mitotic G1 phase and G1/S transition 5.065477e-01 0.295
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 5.108019e-01 0.292
R-HSA-913531 Interferon Signaling 5.192005e-01 0.285
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 5.233486e-01 0.281
R-HSA-5621481 C-type lectin receptors (CLRs) 5.591167e-01 0.252
R-HSA-9909648 Regulation of PD-L1(CD274) expression 5.610244e-01 0.251
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 5.629238e-01 0.250
R-HSA-9664433 Leishmania parasite growth and survival 5.629238e-01 0.250
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 5.666986e-01 0.247
R-HSA-168898 Toll-like Receptor Cascades 5.957619e-01 0.225
R-HSA-9609690 HCMV Early Events 6.044438e-01 0.219
R-HSA-5663205 Infectious disease 6.097098e-01 0.215
R-HSA-9705683 SARS-CoV-2-host interactions 6.573093e-01 0.182
R-HSA-3247509 Chromatin modifying enzymes 6.661434e-01 0.176
R-HSA-157118 Signaling by NOTCH 6.747529e-01 0.171
R-HSA-109582 Hemostasis 6.767057e-01 0.170
R-HSA-1280218 Adaptive Immune System 6.785887e-01 0.168
R-HSA-4839726 Chromatin organization 6.872585e-01 0.163
R-HSA-9609646 HCMV Infection 6.886184e-01 0.162
R-HSA-1474244 Extracellular matrix organization 7.814279e-01 0.107
R-HSA-9694516 SARS-CoV-2 Infection 7.980088e-01 0.098
R-HSA-983169 Class I MHC mediated antigen processing & presentation 8.267798e-01 0.083
R-HSA-9824439 Bacterial Infection Pathways 8.320291e-01 0.080
R-HSA-168249 Innate Immune System 8.404399e-01 0.075
R-HSA-388396 GPCR downstream signalling 8.606862e-01 0.065
R-HSA-372790 Signaling by GPCR 8.959991e-01 0.048
R-HSA-69278 Cell Cycle, Mitotic 9.228678e-01 0.035
R-HSA-168256 Immune System 9.287113e-01 0.032
R-HSA-199991 Membrane Trafficking 9.464885e-01 0.024
R-HSA-1640170 Cell Cycle 9.590998e-01 0.018
R-HSA-5653656 Vesicle-mediated transport 9.739280e-01 0.011
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
NEK10_TYRNEK10_TYR 0.457 0.102 1 0.239
LIMK2_TYRLIMK2_TYR 0.451 0.084 -3 0.289
PDHK3_TYRPDHK3_TYR 0.448 0.082 4 0.428
TNNI3K_TYRTNNI3K_TYR 0.447 0.032 1 0.184
TESK1_TYRTESK1_TYR 0.446 0.027 3 0.490
TNK1TNK1 0.444 0.098 3 0.346
LIMK1_TYRLIMK1_TYR 0.442 0.028 2 0.396
RETRET 0.440 -0.002 1 0.214
PKMYT1_TYRPKMYT1_TYR 0.439 -0.001 3 0.422
MAP2K7_TYRMAP2K7_TYR 0.438 -0.031 2 0.397
TYK2TYK2 0.438 0.008 1 0.240
MAP2K4_TYRMAP2K4_TYR 0.438 -0.024 -1 0.408
PDHK4_TYRPDHK4_TYR 0.437 -0.049 2 0.421
JAK1JAK1 0.434 0.034 1 0.245
MAP2K6_TYRMAP2K6_TYR 0.434 -0.076 -1 0.424
PINK1_TYRPINK1_TYR 0.432 -0.119 1 0.186
PDHK1_TYRPDHK1_TYR 0.432 -0.081 -1 0.435
ABL2ABL2 0.431 -0.029 -1 0.347
TNK2TNK2 0.431 0.030 3 0.293
ROS1ROS1 0.431 -0.021 3 0.347
FGRFGR 0.430 -0.025 1 0.280
DDR1DDR1 0.428 -0.037 4 0.509
JAK2JAK2 0.428 -0.044 1 0.223
BMPR2_TYRBMPR2_TYR 0.427 -0.098 -1 0.396
MST1RMST1R 0.427 -0.065 3 0.355
ABL1ABL1 0.426 -0.044 -1 0.331
BLKBLK 0.426 -0.005 -1 0.309
YES1YES1 0.425 -0.039 -1 0.317
LCKLCK 0.425 -0.014 -1 0.278
JAK3JAK3 0.424 -0.084 1 0.153
EPHA6EPHA6 0.422 -0.077 -1 0.380
HCKHCK 0.422 -0.042 -1 0.273
CSF1RCSF1R 0.420 -0.082 3 0.329
TYRO3TYRO3 0.420 -0.109 3 0.373
EPHB4EPHB4 0.418 -0.101 -1 0.343
FERFER 0.415 -0.125 1 0.200
WEE1_TYRWEE1_TYR 0.414 -0.079 -1 0.328
PDGFRAPDGFRA 0.413 -0.104 3 0.342
AXLAXL 0.412 -0.093 3 0.350
TXKTXK 0.411 -0.115 1 0.155
PDGFRBPDGFRB 0.411 -0.152 3 0.361
ITKITK 0.410 -0.126 -1 0.275
KDRKDR 0.410 -0.121 3 0.308
PTK6PTK6 0.410 -0.111 -1 0.245
EPHA1EPHA1 0.410 -0.078 3 0.308
FLT3FLT3 0.409 -0.148 3 0.356
ALKALK 0.409 -0.094 3 0.285
INSRRINSRR 0.409 -0.138 3 0.324
EPHB3EPHB3 0.409 -0.114 -1 0.318
BTKBTK 0.409 -0.133 -1 0.250
FGFR1FGFR1 0.409 -0.135 3 0.355
DDR2DDR2 0.408 -0.085 3 0.292
FGFR2FGFR2 0.408 -0.148 3 0.361
KITKIT 0.408 -0.132 3 0.332
FYNFYN 0.408 -0.067 -1 0.244
MERTKMERTK 0.407 -0.109 3 0.345
TEKTEK 0.407 -0.133 3 0.299
SRMSSRMS 0.407 -0.143 1 0.170
LYNLYN 0.406 -0.083 3 0.279
LTKLTK 0.406 -0.110 3 0.297
ERBB2ERBB2 0.405 -0.119 1 0.182
METMET 0.405 -0.131 3 0.325
FRKFRK 0.405 -0.107 -1 0.333
EGFREGFR 0.404 -0.093 1 0.107
SRCSRC 0.403 -0.073 -1 0.250
BMXBMX 0.403 -0.113 -1 0.234
EPHB2EPHB2 0.402 -0.148 -1 0.318
INSRINSR 0.402 -0.132 3 0.300
EPHA4EPHA4 0.402 -0.136 2 0.351
TECTEC 0.402 -0.133 -1 0.243
MATKMATK 0.400 -0.116 -1 0.372
MUSKMUSK 0.400 -0.097 1 0.145
EPHB1EPHB1 0.399 -0.176 1 0.157
EPHA7EPHA7 0.398 -0.126 2 0.335
NTRK3NTRK3 0.397 -0.128 -1 0.291
NTRK1NTRK1 0.397 -0.169 -1 0.326
CSKCSK 0.397 -0.125 2 0.341
FLT4FLT4 0.397 -0.159 3 0.311
FLT1FLT1 0.397 -0.172 -1 0.384
EPHA3EPHA3 0.396 -0.132 2 0.317
NTRK2NTRK2 0.396 -0.177 3 0.322
FGFR3FGFR3 0.394 -0.171 3 0.334
FGFR4FGFR4 0.392 -0.122 -1 0.321
AAK1AAK1 0.391 0.257 1 0.570
EPHA8EPHA8 0.389 -0.140 -1 0.312
PTK2BPTK2B 0.388 -0.138 -1 0.275
EPHA5EPHA5 0.388 -0.153 2 0.327
IGF1RIGF1R 0.384 -0.143 3 0.259
BIKEBIKE 0.384 0.251 1 0.531
SYKSYK 0.383 -0.150 -1 0.304
ERBB4ERBB4 0.381 -0.121 1 0.111
PTK2PTK2 0.380 -0.130 -1 0.299
ZAP70ZAP70 0.377 -0.113 -1 0.267
EPHA2EPHA2 0.377 -0.153 -1 0.285
PBKPBK 0.375 0.232 1 0.485
PRKD1PRKD1 0.373 0.133 -3 0.261
FESFES 0.372 -0.144 -1 0.211
LKB1LKB1 0.370 0.203 -3 0.334
KHS1KHS1 0.370 0.208 1 0.365
CAMKK2CAMKK2 0.369 0.187 -2 0.319
TSSK1TSSK1 0.368 0.119 -3 0.264
NEK2NEK2 0.367 0.170 2 0.368
PRP4PRP4 0.367 0.222 -3 0.582
PRKD2PRKD2 0.366 0.092 -3 0.204
KHS2KHS2 0.366 0.173 1 0.368
AURCAURC 0.366 0.091 -2 0.119
TNIKTNIK 0.365 0.154 3 0.447
HUNKHUNK 0.365 0.171 2 0.343
CHAK1CHAK1 0.363 0.157 2 0.401
NEK5NEK5 0.362 0.176 1 0.263
CAMKK1CAMKK1 0.362 0.159 -2 0.317
MPSK1MPSK1 0.361 0.141 1 0.369
HASPINHASPIN 0.361 0.202 -1 0.742
NEK4NEK4 0.361 0.185 1 0.315
TBK1TBK1 0.360 0.189 1 0.343
DYRK1BDYRK1B 0.360 0.049 1 0.155
SSTKSSTK 0.360 0.098 4 0.530
IKKEIKKE 0.359 0.204 1 0.353
CHAK2CHAK2 0.359 0.148 -1 0.607
AMPKA1AMPKA1 0.359 0.074 -3 0.235
TSSK2TSSK2 0.359 0.078 -5 0.302
HGKHGK 0.359 0.133 3 0.441
GAKGAK 0.359 0.173 1 0.412
NEK3NEK3 0.359 0.137 1 0.237
MINKMINK 0.358 0.149 1 0.338
PINK1PINK1 0.357 0.123 1 0.255
AMPKA2AMPKA2 0.357 0.056 -3 0.214
NEK1NEK1 0.357 0.134 1 0.262
GCKGCK 0.357 0.143 1 0.327
NEK6NEK6 0.356 0.067 -2 0.243
LOKLOK 0.356 0.107 -2 0.227
MARK4MARK4 0.355 0.071 4 0.448
PKRPKR 0.355 0.116 1 0.234
SRPK1SRPK1 0.354 0.040 -3 0.190
P38AP38A 0.354 0.044 1 0.201
JNK2JNK2 0.354 0.028 1 0.159
PIM1PIM1 0.354 0.049 -3 0.178
MYO3BMYO3B 0.354 0.096 2 0.382
HIPK2HIPK2 0.354 0.037 1 0.124
QSKQSK 0.354 0.051 4 0.456
HPK1HPK1 0.354 0.136 1 0.349
NEK9NEK9 0.353 0.106 2 0.371
IRAK4IRAK4 0.353 0.134 1 0.229
HIPK1HIPK1 0.353 0.043 1 0.165
WNK1WNK1 0.353 0.095 -2 0.258
MNK2MNK2 0.352 0.077 -2 0.202
PIM3PIM3 0.352 0.045 -3 0.222
CDK9CDK9 0.352 0.047 1 0.180
HIPK4HIPK4 0.351 0.056 1 0.153
PRKD3PRKD3 0.351 0.036 -3 0.170
RAF1RAF1 0.350 0.121 1 0.297
BUB1BUB1 0.350 0.065 -5 0.217
MAPKAPK3MAPKAPK3 0.350 0.029 -3 0.213
DSTYKDSTYK 0.350 0.042 2 0.424
CHK1CHK1 0.350 0.021 -3 0.220
MST4MST4 0.350 0.059 2 0.411
WNK4WNK4 0.349 0.096 -2 0.266
AURBAURB 0.349 0.046 -2 0.111
DCAMKL1DCAMKL1 0.349 0.043 -3 0.205
MARK3MARK3 0.349 0.047 4 0.422
CLK1CLK1 0.349 0.048 -3 0.162
PAK6PAK6 0.349 0.054 -2 0.172
LRRK2LRRK2 0.349 0.088 2 0.372
MST1MST1 0.349 0.080 1 0.307
DNAPKDNAPK 0.348 0.059 1 0.265
IKKAIKKA 0.348 0.051 -2 0.226
IKKBIKKB 0.348 0.057 -2 0.233
CDK18CDK18 0.348 0.035 1 0.167
P38GP38G 0.348 0.018 1 0.124
DYRK2DYRK2 0.347 0.027 1 0.136
NIKNIK 0.347 0.043 -3 0.242
MEKK1MEKK1 0.347 0.078 1 0.240
PKCZPKCZ 0.347 0.067 2 0.314
CLK3CLK3 0.347 0.021 1 0.172
MAKMAK 0.347 0.020 -2 0.180
ERK1ERK1 0.347 0.021 1 0.181
YSK1YSK1 0.346 0.054 2 0.356
NLKNLK 0.346 0.042 1 0.222
CDK16CDK16 0.346 0.025 1 0.148
ULK2ULK2 0.346 0.037 2 0.320
BRSK1BRSK1 0.345 0.027 -3 0.204
MOKMOK 0.345 0.018 1 0.176
ROCK2ROCK2 0.345 0.037 -3 0.205
CDK7CDK7 0.345 0.027 1 0.172
NUAK2NUAK2 0.345 0.007 -3 0.207
TAO1TAO1 0.345 0.062 1 0.246
LATS2LATS2 0.345 0.011 -5 0.293
CDK12CDK12 0.345 0.040 1 0.155
HIPK3HIPK3 0.345 0.030 1 0.183
PIM2PIM2 0.345 0.024 -3 0.165
MLK2MLK2 0.345 0.041 2 0.369
MELKMELK 0.345 0.021 -3 0.221
MARK2MARK2 0.344 0.033 4 0.395
CDK19CDK19 0.344 0.014 1 0.157
MST3MST3 0.344 0.045 2 0.372
TAO3TAO3 0.344 0.033 1 0.239
MARK1MARK1 0.344 0.027 4 0.450
PDHK1PDHK1 0.344 0.077 1 0.295
MEKK6MEKK6 0.344 0.060 1 0.233
CDK13CDK13 0.343 0.025 1 0.170
P38DP38D 0.343 0.014 1 0.162
TAO2TAO2 0.343 0.034 2 0.374
MAPKAPK2MAPKAPK2 0.343 -0.001 -3 0.171
CDKL5CDKL5 0.342 0.004 -3 0.203
MTORMTOR 0.342 0.022 1 0.232
PRKXPRKX 0.342 0.014 -3 0.140
CDK6CDK6 0.342 0.026 1 0.209
QIKQIK 0.342 0.019 -3 0.217
SRPK2SRPK2 0.342 0.009 -3 0.144
NUAK1NUAK1 0.342 0.007 -3 0.175
ERK5ERK5 0.342 0.023 1 0.238
YSK4YSK4 0.342 0.036 1 0.279
JNK3JNK3 0.341 -0.000 1 0.149
LATS1LATS1 0.341 -0.000 -3 0.230
MAP3K15MAP3K15 0.341 0.050 1 0.211
DYRK1ADYRK1A 0.341 0.013 1 0.159
CDC7CDC7 0.341 0.009 1 0.142
PKACBPKACB 0.341 0.005 -2 0.131
NIM1NIM1 0.341 0.025 3 0.411
IRE1IRE1 0.341 0.045 1 0.210
P38BP38B 0.341 0.002 1 0.162
COTCOT 0.341 -0.012 2 0.380
CDK8CDK8 0.341 0.004 1 0.153
CDK4CDK4 0.341 0.015 1 0.158
MEKK2MEKK2 0.341 0.017 2 0.332
NEK11NEK11 0.341 0.058 1 0.251
CDK5CDK5 0.340 0.010 1 0.183
CLK2CLK2 0.340 0.010 -3 0.187
DYRK3DYRK3 0.340 0.013 1 0.151
SGK3SGK3 0.340 0.014 -3 0.195
ICKICK 0.340 -0.012 -3 0.219
ASK1ASK1 0.340 0.030 1 0.200
PAK5PAK5 0.340 0.026 -2 0.130
BMPR2BMPR2 0.340 -0.054 -2 0.222
FAM20CFAM20C 0.340 0.076 2 0.471
NEK7NEK7 0.340 -0.022 -3 0.229
BRSK2BRSK2 0.340 0.013 -3 0.223
MST2MST2 0.339 0.014 1 0.298
BCKDKBCKDK 0.339 0.055 -1 0.345
SLKSLK 0.339 0.033 -2 0.170
NDR1NDR1 0.339 -0.009 -3 0.215
CLK4CLK4 0.339 0.009 -3 0.175
PDHK4PDHK4 0.339 0.022 1 0.254
ROCK1ROCK1 0.339 0.017 -3 0.184
CDKL1CDKL1 0.339 -0.017 -3 0.194
SIKSIK 0.339 -0.002 -3 0.165
PAK1PAK1 0.339 0.008 -2 0.181
MRCKBMRCKB 0.339 0.014 -3 0.163
PKCBPKCB 0.339 0.017 2 0.267
CDK10CDK10 0.339 0.023 1 0.193
SKMLCKSKMLCK 0.339 0.006 -2 0.249
ULK1ULK1 0.338 0.005 -3 0.235
CAMK1BCAMK1B 0.338 -0.031 -3 0.213
PRPKPRPK 0.338 -0.045 -1 0.402
CAMK2DCAMK2D 0.338 0.003 -3 0.245
PKCDPKCD 0.338 0.000 2 0.295
CAMK1DCAMK1D 0.338 -0.008 -3 0.143
MYO3AMYO3A 0.338 0.031 1 0.283
PDK1PDK1 0.338 0.010 1 0.220
PKCAPKCA 0.337 0.029 2 0.261
PAK3PAK3 0.337 0.007 -2 0.202
PKN3PKN3 0.337 -0.028 -3 0.229
DAPK2DAPK2 0.337 -0.020 -3 0.236
PKACGPKACG 0.337 0.001 -2 0.154
MNK1MNK1 0.337 0.033 -2 0.192
AKT2AKT2 0.336 -0.013 -3 0.140
DMPK1DMPK1 0.336 0.003 -3 0.157
AKT1AKT1 0.336 -0.008 -3 0.159
CDK14CDK14 0.336 0.012 1 0.203
SRPK3SRPK3 0.336 -0.003 -3 0.156
HRIHRI 0.336 -0.020 -2 0.223
WNK3WNK3 0.336 0.005 1 0.257
SBKSBK 0.336 -0.006 -3 0.096
MOSMOS 0.335 -0.039 1 0.186
VRK2VRK2 0.335 -0.032 1 0.209
PKG2PKG2 0.335 -0.003 -2 0.124
NDR2NDR2 0.335 -0.032 -3 0.220
NEK8NEK8 0.335 -0.024 2 0.327
IRAK1IRAK1 0.335 0.041 -1 0.404
PHKG2PHKG2 0.335 0.023 -3 0.194
PHKG1PHKG1 0.334 0.005 -3 0.230
CAMLCKCAMLCK 0.334 -0.041 -2 0.226
CDK17CDK17 0.334 -0.002 1 0.132
RSK3RSK3 0.334 -0.020 -3 0.192
BMPR1BBMPR1B 0.334 -0.042 1 0.120
PKCIPKCI 0.333 0.024 2 0.272
PKCGPKCG 0.333 0.020 2 0.251
MEK5MEK5 0.333 -0.043 2 0.360
SMG1SMG1 0.333 -0.004 1 0.181
MRCKAMRCKA 0.333 -0.001 -3 0.165
PKN2PKN2 0.333 -0.019 -3 0.223
TAK1TAK1 0.333 -0.019 1 0.262
PKACAPKACA 0.333 -0.011 -2 0.116
CDK3CDK3 0.333 -0.002 1 0.141
ERK2ERK2 0.333 -0.011 1 0.164
PAK4PAK4 0.332 0.023 -2 0.125
DYRK4DYRK4 0.332 -0.002 1 0.123
CRIKCRIK 0.332 -0.005 -3 0.147
CDK1CDK1 0.332 -0.016 1 0.130
BRAFBRAF 0.332 -0.060 -4 0.476
AKT3AKT3 0.332 -0.014 -3 0.130
ALK2ALK2 0.331 -0.042 -2 0.195
MEK2MEK2 0.331 -0.017 2 0.371
PERKPERK 0.331 -0.048 -2 0.215
MASTLMASTL 0.331 -0.040 -2 0.228
CHK2CHK2 0.331 -0.005 -3 0.127
ANKRD3ANKRD3 0.331 -0.042 1 0.249
PKCTPKCT 0.331 0.001 2 0.251
ATRATR 0.331 -0.058 1 0.177
CAMK1ACAMK1A 0.331 -0.009 -3 0.119
EEF2KEEF2K 0.331 -0.034 3 0.459
P70S6KBP70S6KB 0.331 -0.037 -3 0.189
RIPK1RIPK1 0.330 -0.010 1 0.196
MAPKAPK5MAPKAPK5 0.330 -0.011 -3 0.196
SGK1SGK1 0.330 -0.017 -3 0.116
MLK3MLK3 0.330 -0.021 2 0.275
DLKDLK 0.330 -0.087 1 0.173
DCAMKL2DCAMKL2 0.329 -0.008 -3 0.199
PAK2PAK2 0.329 -0.025 -2 0.171
P90RSKP90RSK 0.329 -0.036 -3 0.208
AURAAURA 0.329 -0.017 -2 0.087
ALK4ALK4 0.328 -0.065 -2 0.181
DAPK3DAPK3 0.328 -0.033 -3 0.195
TTKTTK 0.328 -0.042 -2 0.163
RIPK3RIPK3 0.328 -0.011 3 0.305
PLK1PLK1 0.328 -0.048 -2 0.163
CAMK2ACAMK2A 0.328 -0.030 2 0.396
TLK2TLK2 0.328 -0.033 1 0.200
CAMK1GCAMK1G 0.327 -0.022 -3 0.168
MLK1MLK1 0.327 -0.076 2 0.321
TLK1TLK1 0.327 -0.033 -2 0.217
TTBK2TTBK2 0.327 -0.025 2 0.302
RSK2RSK2 0.327 -0.044 -3 0.184
STLK3STLK3 0.327 -0.052 1 0.202
MEK1MEK1 0.326 -0.106 2 0.388
PLK4PLK4 0.326 0.006 2 0.196
TGFBR2TGFBR2 0.326 -0.062 -2 0.158
ERK7ERK7 0.326 -0.007 2 0.166
PLK3PLK3 0.325 -0.044 2 0.344
PKCHPKCH 0.325 -0.027 2 0.238
ZAKZAK 0.325 -0.073 1 0.186
TGFBR1TGFBR1 0.325 -0.060 -2 0.183
CAMK2GCAMK2G 0.325 -0.073 2 0.384
PKCEPKCE 0.325 -0.005 2 0.250
VRK1VRK1 0.325 -0.073 2 0.321
PKG1PKG1 0.324 -0.010 -2 0.094
MSK2MSK2 0.324 -0.045 -3 0.175
OSR1OSR1 0.324 -0.069 2 0.350
IRE2IRE2 0.324 -0.042 2 0.243
MSK1MSK1 0.324 -0.033 -3 0.182
CAMK2BCAMK2B 0.323 -0.042 2 0.412
STK33STK33 0.323 0.004 2 0.218
CDK2CDK2 0.322 -0.030 1 0.153
ATMATM 0.322 -0.047 1 0.141
GCN2GCN2 0.322 -0.104 2 0.336
MEKK3MEKK3 0.322 -0.079 1 0.226
SMMLCKSMMLCK 0.322 -0.062 -3 0.200
RSK4RSK4 0.321 -0.046 -3 0.166
PKN1PKN1 0.321 -0.032 -3 0.170
CAMK4CAMK4 0.320 -0.083 -3 0.196
GRK5GRK5 0.319 -0.127 -3 0.224
SNRKSNRK 0.318 -0.054 2 0.220
MYLK4MYLK4 0.318 -0.058 -2 0.204
JNK1JNK1 0.318 -0.032 1 0.141
GRK6GRK6 0.317 -0.098 1 0.165
DAPK1DAPK1 0.317 -0.053 -3 0.186
GRK7GRK7 0.316 -0.066 1 0.152
P70S6KP70S6K 0.315 -0.052 -3 0.150
GSK3AGSK3A 0.315 -0.010 4 0.126
MLK4MLK4 0.314 -0.088 2 0.249
PASKPASK 0.314 -0.097 -3 0.218
BMPR1ABMPR1A 0.313 -0.088 1 0.102
GRK1GRK1 0.312 -0.074 -2 0.147
ACVR2AACVR2A 0.310 -0.124 -2 0.158
ACVR2BACVR2B 0.309 -0.126 -2 0.175
CK2A2CK2A2 0.309 -0.026 1 0.098
DRAK1DRAK1 0.308 -0.112 1 0.121
TTBK1TTBK1 0.307 -0.055 2 0.239
CK1ECK1E 0.305 -0.061 -3 0.086
KISKIS 0.305 -0.063 1 0.167
GSK3BGSK3B 0.305 -0.038 4 0.124
PLK2PLK2 0.304 -0.062 -3 0.180
RIPK2RIPK2 0.303 -0.099 1 0.207
GRK4GRK4 0.303 -0.160 -2 0.175
CK2A1CK2A1 0.303 -0.038 1 0.085
GRK2GRK2 0.302 -0.117 -2 0.146
ALPHAK3ALPHAK3 0.301 -0.125 -1 0.384
CK1G1CK1G1 0.299 -0.045 -3 0.073
CK1DCK1D 0.298 -0.073 -3 0.069
CK1A2CK1A2 0.293 -0.075 -3 0.062
GRK3GRK3 0.287 -0.126 -2 0.119
YANK3YANK3 0.283 -0.056 2 0.138
CK1G3CK1G3 0.276 -0.065 -3 0.020
YANK2YANK2 0.273 -0.066 2 0.145
CK1ACK1A 0.266 -0.092 -3 0.038
CK1G2CK1G2 0.238 -0.112 -3 0.047