Motif 1116 (n=54)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| 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}. |
| P0DPH7 | TUBA3C | Y357 | ochoa | Tubulin alpha-3C chain (EC 3.6.5.-) (Alpha-tubulin 2) (Alpha-tubulin 3C) (Tubulin alpha-2 chain) [Cleaved into: Detyrosinated tubulin alpha-3C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH8 | TUBA3D | Y357 | ochoa | Tubulin alpha-3D chain (EC 3.6.5.-) (Alpha-tubulin 3D) [Cleaved into: Detyrosinated tubulin alpha-3D chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P51812 | RPS6KA3 | Y529 | psp | Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) | Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}. |
| 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}. |
| P60709 | ACTB | Y169 | ochoa | Actin, cytoplasmic 1 (EC 3.6.4.-) (Beta-actin) [Cleaved into: Actin, cytoplasmic 1, N-terminally processed] | Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:25255767, PubMed:29581253). Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). Plays a role in the assembly of the gamma-tubulin ring complex (gTuRC), which regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments (PubMed:39321809, PubMed:38609661). Part of the ACTR1A/ACTB filament around which the dynactin complex is built (By similarity). The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). {ECO:0000250|UniProtKB:Q6QAQ1, ECO:0000269|PubMed:25255767, ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:38609661, ECO:0000269|PubMed:39321809}. |
| P62736 | ACTA2 | Y171 | ochoa | Actin, aortic smooth muscle (EC 3.6.4.-) (Alpha-actin-2) (Cell growth-inhibiting gene 46 protein) [Cleaved into: Actin, aortic smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P63261 | ACTG1 | Y169 | ochoa | Actin, cytoplasmic 2 (EC 3.6.4.-) (Gamma-actin) [Cleaved into: Actin, cytoplasmic 2, N-terminally processed] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. May play a role in the repair of noise-induced stereocilia gaps thereby maintains hearing sensitivity following loud noise damage (By similarity). {ECO:0000250|UniProtKB:P63260, ECO:0000305|PubMed:29581253}. |
| P63267 | ACTG2 | Y170 | ochoa | Actin, gamma-enteric smooth muscle (EC 3.6.4.-) (Alpha-actin-3) (Gamma-2-actin) (Smooth muscle gamma-actin) [Cleaved into: Actin, gamma-enteric smooth muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68032 | ACTC1 | Y171 | ochoa | Actin, alpha cardiac muscle 1 (EC 3.6.4.-) (Alpha-cardiac actin) [Cleaved into: Actin, alpha cardiac muscle 1, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68133 | ACTA1 | Y171 | ochoa | Actin, alpha skeletal muscle (EC 3.6.4.-) (Alpha-actin-1) [Cleaved into: Actin, alpha skeletal muscle, intermediate form] | Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. |
| P68363 | TUBA1B | Y357 | ochoa | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P68366 | TUBA4A | Y357 | ochoa | Tubulin alpha-4A chain (EC 3.6.5.-) (Alpha-tubulin 1) (Testis-specific alpha-tubulin) (Tubulin H2-alpha) (Tubulin alpha-1 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| 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}. |
| Q6PEY2 | TUBA3E | Y357 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q71U36 | TUBA1A | Y357 | ochoa | Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 3) (Tubulin B-alpha-1) (Tubulin alpha-3 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9BQE3 | TUBA1C | Y357 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9NY65 | TUBA8 | Y357 | ochoa | Tubulin alpha-8 chain (EC 3.6.5.-) (Alpha-tubulin 8) (Tubulin alpha chain-like 2) [Cleaved into: Dephenylalaninated tubulin alpha-8 chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| 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}. |
| P27348 | YWHAQ | Y118 | Sugiyama | 14-3-3 protein theta (14-3-3 protein T-cell) (14-3-3 protein tau) (Protein HS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| P31946 | YWHAB | Y120 | Sugiyama | 14-3-3 protein beta/alpha (Protein 1054) (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein beta/alpha, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13. {ECO:0000269|PubMed:17717073, ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:21224381}. |
| P31947 | SFN | Y120 | Sugiyama | 14-3-3 protein sigma (Epithelial cell marker protein 1) (Stratifin) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Binding generally results in the modulation of the activity of the binding partner (PubMed:15731107, PubMed:22634725, PubMed:28202711, PubMed:37797010). Promotes cytosolic retention of GBP1 GTPase by binding to phosphorylated GBP1, thereby inhibiting the innate immune response (PubMed:37797010). Also acts as a TP53/p53-regulated inhibitor of G2/M progression (PubMed:9659898). When bound to KRT17, regulates protein synthesis and epithelial cell growth by stimulating Akt/mTOR pathway (By similarity). Acts to maintain desmosome cell junction adhesion in epithelial cells via interacting with and sequestering PKP3 to the cytoplasm, thereby restricting its translocation to existing desmosome structures and therefore maintaining desmosome protein homeostasis (PubMed:24124604). Also acts to facilitate PKP3 exchange at desmosome plaques, thereby maintaining keratinocyte intercellular adhesion (PubMed:29678907). May also regulate MDM2 autoubiquitination and degradation and thereby activate p53/TP53 (PubMed:18382127). {ECO:0000250|UniProtKB:O70456, ECO:0000269|PubMed:15731107, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:22634725, ECO:0000269|PubMed:24124604, ECO:0000269|PubMed:28202711, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:37797010, ECO:0000269|PubMed:9659898}. |
| P61981 | YWHAG | Y123 | Sugiyama | 14-3-3 protein gamma (Protein kinase C inhibitor protein 1) (KCIP-1) [Cleaved into: 14-3-3 protein gamma, N-terminally processed] | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:15696159, PubMed:16511572, PubMed:36732624). Binding generally results in the modulation of the activity of the binding partner (PubMed:16511572). Promotes inactivation of WDR24 component of the GATOR2 complex by binding to phosphorylated WDR24 (PubMed:36732624). Participates in the positive regulation of NMDA glutamate receptor activity by promoting the L-glutamate secretion through interaction with BEST1 (PubMed:29121962). Reduces keratinocyte intercellular adhesion, via interacting with PKP1 and sequestering it in the cytoplasm, thereby reducing its incorporation into desmosomes (PubMed:29678907). Plays a role in mitochondrial protein catabolic process (also named MALM) that promotes the degradation of damaged proteins inside mitochondria (PubMed:22532927). {ECO:0000269|PubMed:15696159, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:22532927, ECO:0000269|PubMed:29121962, ECO:0000269|PubMed:29678907, ECO:0000269|PubMed:36732624}. |
| P63104 | YWHAZ | Y118 | Sugiyama | 14-3-3 protein zeta/delta (Protein kinase C inhibitor protein 1) (KCIP-1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:14578935, PubMed:15071501, PubMed:15644438, PubMed:16376338, PubMed:16959763, PubMed:31024343, PubMed:9360956). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35662396). Binding generally results in the modulation of the activity of the binding partner (PubMed:35662396). Promotes cytosolic retention and inactivation of TFEB transcription factor by binding to phosphorylated TFEB (PubMed:35662396). Induces ARHGEF7 activity on RAC1 as well as lamellipodia and membrane ruffle formation (PubMed:16959763). In neurons, regulates spine maturation through the modulation of ARHGEF7 activity (By similarity). {ECO:0000250|UniProtKB:O55043, ECO:0000269|PubMed:14578935, ECO:0000269|PubMed:15071501, ECO:0000269|PubMed:15644438, ECO:0000269|PubMed:16376338, ECO:0000269|PubMed:16959763, ECO:0000269|PubMed:31024343, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9360956}. |
| Q04917 | YWHAH | Y123 | Sugiyama | 14-3-3 protein eta (Protein AS1) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negatively regulates the kinase activity of PDPK1. {ECO:0000269|PubMed:12177059}. |
| 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}. |
| Q15746 | MYLK | Y1575 | GPS6|PSP | Myosin light chain kinase, smooth muscle (MLCK) (smMLCK) (EC 2.7.11.18) (Kinase-related protein) (KRP) (Telokin) [Cleaved into: Myosin light chain kinase, smooth muscle, deglutamylated form] | Calcium/calmodulin-dependent myosin light chain kinase implicated in smooth muscle contraction via phosphorylation of myosin light chains (MLC). Also regulates actin-myosin interaction through a non-kinase activity. Phosphorylates PTK2B/PYK2 and myosin light-chains. Involved in the inflammatory response (e.g. apoptosis, vascular permeability, leukocyte diapedesis), cell motility and morphology, airway hyperreactivity and other activities relevant to asthma. Required for tonic airway smooth muscle contraction that is necessary for physiological and asthmatic airway resistance. Necessary for gastrointestinal motility. Implicated in the regulation of endothelial as well as vascular permeability, probably via the regulation of cytoskeletal rearrangements. In the nervous system it has been shown to control the growth initiation of astrocytic processes in culture and to participate in transmitter release at synapses formed between cultured sympathetic ganglion cells. Critical participant in signaling sequences that result in fibroblast apoptosis. Plays a role in the regulation of epithelial cell survival. Required for epithelial wound healing, especially during actomyosin ring contraction during purse-string wound closure. Mediates RhoA-dependent membrane blebbing. Triggers TRPC5 channel activity in a calcium-dependent signaling, by inducing its subcellular localization at the plasma membrane. Promotes cell migration (including tumor cells) and tumor metastasis. PTK2B/PYK2 activation by phosphorylation mediates ITGB2 activation and is thus essential to trigger neutrophil transmigration during acute lung injury (ALI). May regulate optic nerve head astrocyte migration. Probably involved in mitotic cytoskeletal regulation. Regulates tight junction probably by modulating ZO-1 exchange in the perijunctional actomyosin ring. Mediates burn-induced microvascular barrier injury; triggers endothelial contraction in the development of microvascular hyperpermeability by phosphorylating MLC. Essential for intestinal barrier dysfunction. Mediates Giardia spp.-mediated reduced epithelial barrier function during giardiasis intestinal infection via reorganization of cytoskeletal F-actin and tight junctional ZO-1. Necessary for hypotonicity-induced Ca(2+) entry and subsequent activation of volume-sensitive organic osmolyte/anion channels (VSOAC) in cervical cancer cells. Responsible for high proliferative ability of breast cancer cells through anti-apoptosis. {ECO:0000269|PubMed:11113114, ECO:0000269|PubMed:11976941, ECO:0000269|PubMed:15020676, ECO:0000269|PubMed:15825080, ECO:0000269|PubMed:16284075, ECO:0000269|PubMed:16723733, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18710790, ECO:0000269|PubMed:19826488, ECO:0000269|PubMed:20139351, ECO:0000269|PubMed:20181817, ECO:0000269|PubMed:20375339, ECO:0000269|PubMed:20453870}. |
| 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}. |
| P62258 | YWHAE | Y121 | Sugiyama | 14-3-3 protein epsilon (14-3-3E) | Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways (PubMed:21189250). Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif (PubMed:35343654). Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326). Plays a positive role in the antiviral signaling pathway upstream of TBK1 via interaction with RIGI (PubMed:37555661). Mechanistically, directs RIGI redistribution from the cytosol to mitochondrial associated membranes where it mediates MAVS-dependent innate immune signaling during viral infection (PubMed:22607805). Plays a role in proliferation inhibition and cell cycle arrest by exporting HNRNPC from the nucleus to the cytoplasm to be degraded by ubiquitination (PubMed:37599448). {ECO:0000250|UniProtKB:P62261, ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:21189250, ECO:0000269|PubMed:22607805, ECO:0000269|PubMed:35343654, ECO:0000269|PubMed:37555661, ECO:0000269|PubMed:37599448}. |
| 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}. |
| Q13164 | MAPK7 | Y172 | Sugiyama | Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) | Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}. |
| Q13233 | MAP3K1 | Y1359 | Sugiyama | Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1) (EC 2.3.2.27) | Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). {ECO:0000269|PubMed:17761173, ECO:0000269|PubMed:9808624}. |
| 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}. |
| Q96PF2 | TSSK2 | Y126 | Sugiyama | Testis-specific serine/threonine-protein kinase 2 (TSK-2) (TSK2) (TSSK-2) (Testis-specific kinase 2) (EC 2.7.11.1) (DiGeorge syndrome protein G) (DGS-G) (Serine/threonine-protein kinase 22B) | Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates TSKS at 'Ser-288' and SPAG16. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body. {ECO:0000269|PubMed:15044604, ECO:0000269|PubMed:18533145, ECO:0000269|PubMed:20729278}. |
| 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}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 1.110223e-16 | 15.955 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 1.110223e-16 | 15.955 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 1.110223e-16 | 15.955 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 1.110223e-16 | 15.955 |
| R-HSA-162582 | Signal Transduction | 1.110223e-16 | 15.955 |
| R-HSA-422475 | Axon guidance | 3.330669e-16 | 15.477 |
| R-HSA-9675108 | Nervous system development | 1.221245e-15 | 14.913 |
| R-HSA-5683057 | MAPK family signaling cascades | 1.332268e-15 | 14.875 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 6.217249e-15 | 14.206 |
| R-HSA-437239 | Recycling pathway of L1 | 6.217249e-15 | 14.206 |
| R-HSA-438064 | Post NMDA receptor activation events | 8.348877e-14 | 13.078 |
| R-HSA-373760 | L1CAM interactions | 1.177947e-13 | 12.929 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 1.399991e-13 | 12.854 |
| R-HSA-190828 | Gap junction trafficking | 1.653122e-13 | 12.782 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 3.224088e-13 | 12.492 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 3.573808e-13 | 12.447 |
| R-HSA-157858 | Gap junction trafficking and regulation | 4.057865e-13 | 12.392 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 4.581890e-13 | 12.339 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 5.524470e-13 | 12.258 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 8.857359e-13 | 12.053 |
| R-HSA-1266738 | Developmental Biology | 2.220557e-12 | 11.654 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 3.733680e-12 | 11.428 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 4.339973e-12 | 11.363 |
| R-HSA-2682334 | EPH-Ephrin signaling | 4.619971e-12 | 11.335 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 5.072609e-12 | 11.295 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 5.675127e-12 | 11.246 |
| R-HSA-111447 | Activation of BAD and translocation to mitochondria | 9.379497e-12 | 11.028 |
| R-HSA-9755779 | SARS-CoV-2 targets host intracellular signalling and regulatory pathways | 9.379497e-12 | 11.028 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 9.714007e-12 | 11.013 |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways | 9.379497e-12 | 11.028 |
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 1.000222e-11 | 11.000 |
| R-HSA-1226099 | Signaling by FGFR in disease | 1.395606e-11 | 10.855 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 2.938660e-11 | 10.532 |
| R-HSA-190861 | Gap junction assembly | 4.349621e-11 | 10.362 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 6.998424e-11 | 10.155 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 7.055767e-11 | 10.151 |
| R-HSA-9646399 | Aggrephagy | 1.266497e-10 | 9.897 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 1.753626e-10 | 9.756 |
| R-HSA-1643685 | Disease | 2.223969e-10 | 9.653 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 4.314302e-10 | 9.365 |
| R-HSA-114452 | Activation of BH3-only proteins | 7.686716e-10 | 9.114 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 1.238571e-09 | 8.907 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 1.506661e-09 | 8.822 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 1.943728e-09 | 8.711 |
| R-HSA-983189 | Kinesins | 2.236839e-09 | 8.650 |
| R-HSA-391251 | Protein folding | 2.538754e-09 | 8.595 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 2.798301e-09 | 8.553 |
| R-HSA-74751 | Insulin receptor signalling cascade | 3.477898e-09 | 8.459 |
| R-HSA-199991 | Membrane Trafficking | 4.043659e-09 | 8.393 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 5.275443e-09 | 8.278 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 7.105372e-09 | 8.148 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 9.145416e-09 | 8.039 |
| R-HSA-9614399 | Regulation of localization of FOXO transcription factors | 1.130972e-08 | 7.947 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 1.625141e-08 | 7.789 |
| R-HSA-9833482 | PKR-mediated signaling | 1.625141e-08 | 7.789 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.954621e-08 | 7.709 |
| R-HSA-109704 | PI3K Cascade | 1.984889e-08 | 7.702 |
| R-HSA-9663891 | Selective autophagy | 3.417140e-08 | 7.466 |
| R-HSA-9913351 | Formation of the dystrophin-glycoprotein complex (DGC) | 3.822555e-08 | 7.418 |
| R-HSA-112399 | IRS-mediated signalling | 4.286293e-08 | 7.368 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 3.860734e-08 | 7.413 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 4.918448e-08 | 7.308 |
| R-HSA-74752 | Signaling by Insulin receptor | 5.007909e-08 | 7.300 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 5.504831e-08 | 7.259 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 6.408343e-08 | 7.193 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 7.199318e-08 | 7.143 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 7.199318e-08 | 7.143 |
| R-HSA-69275 | G2/M Transition | 8.173142e-08 | 7.088 |
| R-HSA-2428924 | IGF1R signaling cascade | 8.530314e-08 | 7.069 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 8.935239e-08 | 7.049 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 9.198186e-08 | 7.036 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 9.357851e-08 | 7.029 |
| R-HSA-5617833 | Cilium Assembly | 9.759278e-08 | 7.011 |
| R-HSA-5653656 | Vesicle-mediated transport | 1.048118e-07 | 6.980 |
| R-HSA-68877 | Mitotic Prometaphase | 1.112094e-07 | 6.954 |
| R-HSA-9824446 | Viral Infection Pathways | 1.322683e-07 | 6.879 |
| R-HSA-112315 | Transmission across Chemical Synapses | 1.369758e-07 | 6.863 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 1.610760e-07 | 6.793 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 1.821078e-07 | 6.740 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 2.037609e-07 | 6.691 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 2.118872e-07 | 6.674 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 2.211838e-07 | 6.655 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 2.427109e-07 | 6.615 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 4.135614e-07 | 6.383 |
| R-HSA-5620924 | Intraflagellar transport | 4.263967e-07 | 6.370 |
| R-HSA-2132295 | MHC class II antigen presentation | 4.615096e-07 | 6.336 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 5.222015e-07 | 6.282 |
| R-HSA-1640170 | Cell Cycle | 5.250306e-07 | 6.280 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 8.194351e-07 | 6.086 |
| R-HSA-9764561 | Regulation of CDH1 Function | 1.006463e-06 | 5.997 |
| R-HSA-190236 | Signaling by FGFR | 1.342590e-06 | 5.872 |
| R-HSA-9609690 | HCMV Early Events | 1.330453e-06 | 5.876 |
| R-HSA-1632852 | Macroautophagy | 1.328645e-06 | 5.877 |
| R-HSA-5663205 | Infectious disease | 1.763710e-06 | 5.754 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 1.827831e-06 | 5.738 |
| R-HSA-9692914 | SARS-CoV-1-host interactions | 2.257600e-06 | 5.646 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 2.307101e-06 | 5.637 |
| R-HSA-9612973 | Autophagy | 2.697224e-06 | 5.569 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 2.853346e-06 | 5.545 |
| R-HSA-2467813 | Separation of Sister Chromatids | 3.743517e-06 | 5.427 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 3.834774e-06 | 5.416 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 4.065037e-06 | 5.391 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 4.226148e-06 | 5.374 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 5.186885e-06 | 5.285 |
| R-HSA-112316 | Neuronal System | 5.425299e-06 | 5.266 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 8.269767e-06 | 5.083 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 8.269767e-06 | 5.083 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 8.269767e-06 | 5.083 |
| R-HSA-6802949 | Signaling by RAS mutants | 8.269767e-06 | 5.083 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 6.900834e-06 | 5.161 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 7.527377e-06 | 5.123 |
| R-HSA-69481 | G2/M Checkpoints | 7.502547e-06 | 5.125 |
| R-HSA-9609646 | HCMV Infection | 8.303404e-06 | 5.081 |
| R-HSA-5654221 | Phospholipase C-mediated cascade; FGFR2 | 8.361511e-06 | 5.078 |
| R-HSA-190241 | FGFR2 ligand binding and activation | 9.745023e-06 | 5.011 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 1.420278e-05 | 4.848 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 1.515324e-05 | 4.819 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 1.701513e-05 | 4.769 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 1.932692e-05 | 4.714 |
| R-HSA-5610787 | Hedgehog 'off' state | 2.083447e-05 | 4.681 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 2.205444e-05 | 4.657 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 2.275869e-05 | 4.643 |
| R-HSA-68882 | Mitotic Anaphase | 2.414155e-05 | 4.617 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 2.463221e-05 | 4.608 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 2.487307e-05 | 4.604 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 2.517697e-05 | 4.599 |
| R-HSA-9679506 | SARS-CoV Infections | 2.742299e-05 | 4.562 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 2.765219e-05 | 4.558 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 3.093516e-05 | 4.510 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 3.093516e-05 | 4.510 |
| R-HSA-68886 | M Phase | 3.206310e-05 | 4.494 |
| R-HSA-913531 | Interferon Signaling | 3.273704e-05 | 4.485 |
| R-HSA-109581 | Apoptosis | 3.394433e-05 | 4.469 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 3.422672e-05 | 4.466 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 3.449505e-05 | 4.462 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 3.449505e-05 | 4.462 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 3.449505e-05 | 4.462 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 3.469260e-05 | 4.460 |
| R-HSA-9020558 | Interleukin-2 signaling | 5.135091e-05 | 4.289 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 5.695315e-05 | 4.244 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 5.031436e-05 | 4.298 |
| R-HSA-9678108 | SARS-CoV-1 Infection | 5.425179e-05 | 4.266 |
| R-HSA-1236394 | Signaling by ERBB4 | 5.992310e-05 | 4.222 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 6.248088e-05 | 4.204 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 7.469586e-05 | 4.127 |
| R-HSA-2033514 | FGFR3 mutant receptor activation | 9.096036e-05 | 4.041 |
| R-HSA-1839130 | Signaling by activated point mutants of FGFR3 | 9.096036e-05 | 4.041 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 9.615734e-05 | 4.017 |
| R-HSA-451927 | Interleukin-2 family signaling | 9.615734e-05 | 4.017 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.077704e-04 | 3.968 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.127491e-04 | 3.948 |
| R-HSA-5358351 | Signaling by Hedgehog | 1.299865e-04 | 3.886 |
| R-HSA-5357801 | Programmed Cell Death | 1.354668e-04 | 3.868 |
| R-HSA-69278 | Cell Cycle, Mitotic | 1.549944e-04 | 3.810 |
| R-HSA-109582 | Hemostasis | 1.637729e-04 | 3.786 |
| R-HSA-1250347 | SHC1 events in ERBB4 signaling | 1.690270e-04 | 3.772 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 1.936489e-04 | 3.713 |
| R-HSA-3928664 | Ephrin signaling | 2.204854e-04 | 3.657 |
| R-HSA-2033519 | Activated point mutants of FGFR2 | 2.204854e-04 | 3.657 |
| R-HSA-1280218 | Adaptive Immune System | 2.230772e-04 | 3.652 |
| R-HSA-9614085 | FOXO-mediated transcription | 2.336564e-04 | 3.631 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 2.496201e-04 | 3.603 |
| R-HSA-2023837 | Signaling by FGFR2 amplification mutants | 2.997834e-04 | 3.523 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 3.516313e-04 | 3.454 |
| R-HSA-1227986 | Signaling by ERBB2 | 3.894128e-04 | 3.410 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 4.062602e-04 | 3.391 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 4.062602e-04 | 3.391 |
| R-HSA-912526 | Interleukin receptor SHC signaling | 4.326055e-04 | 3.364 |
| R-HSA-8854691 | Interleukin-20 family signaling | 4.326055e-04 | 3.364 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 4.576429e-04 | 3.339 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 4.576429e-04 | 3.339 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 4.576429e-04 | 3.339 |
| R-HSA-8848021 | Signaling by PTK6 | 4.576429e-04 | 3.339 |
| R-HSA-69620 | Cell Cycle Checkpoints | 4.829699e-04 | 3.316 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 5.083504e-04 | 3.294 |
| R-HSA-9620244 | Long-term potentiation | 5.246699e-04 | 3.280 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 5.339994e-04 | 3.272 |
| R-HSA-212436 | Generic Transcription Pathway | 6.045862e-04 | 3.219 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 6.284158e-04 | 3.202 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 7.132144e-04 | 3.147 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 7.321035e-04 | 3.135 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 7.444147e-04 | 3.128 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 7.467501e-04 | 3.127 |
| R-HSA-380287 | Centrosome maturation | 8.171434e-04 | 3.088 |
| R-HSA-5654738 | Signaling by FGFR2 | 1.013437e-03 | 2.994 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 1.179979e-03 | 2.928 |
| R-HSA-196025 | Formation of annular gap junctions | 1.423189e-03 | 2.847 |
| R-HSA-8985947 | Interleukin-9 signaling | 1.423189e-03 | 2.847 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 1.192683e-03 | 2.923 |
| R-HSA-9679191 | Potential therapeutics for SARS | 1.553425e-03 | 2.809 |
| R-HSA-418990 | Adherens junctions interactions | 1.231375e-03 | 2.910 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 1.557976e-03 | 2.807 |
| R-HSA-201556 | Signaling by ALK | 1.625124e-03 | 2.789 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 1.635401e-03 | 2.786 |
| R-HSA-73857 | RNA Polymerase II Transcription | 1.640338e-03 | 2.785 |
| R-HSA-9020958 | Interleukin-21 signaling | 1.688274e-03 | 2.773 |
| R-HSA-190873 | Gap junction degradation | 1.688274e-03 | 2.773 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 1.688274e-03 | 2.773 |
| R-HSA-1474244 | Extracellular matrix organization | 1.852226e-03 | 2.732 |
| R-HSA-9020956 | Interleukin-27 signaling | 1.975018e-03 | 2.704 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 1.975018e-03 | 2.704 |
| R-HSA-190377 | FGFR2b ligand binding and activation | 2.283205e-03 | 2.641 |
| R-HSA-421270 | Cell-cell junction organization | 2.359641e-03 | 2.627 |
| R-HSA-1250342 | PI3K events in ERBB4 signaling | 2.612620e-03 | 2.583 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 2.893556e-03 | 2.539 |
| R-HSA-8983432 | Interleukin-15 signaling | 2.963050e-03 | 2.528 |
| R-HSA-8984722 | Interleukin-35 Signalling | 2.963050e-03 | 2.528 |
| R-HSA-877312 | Regulation of IFNG signaling | 2.963050e-03 | 2.528 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 3.109875e-03 | 2.507 |
| R-HSA-190375 | FGFR2c ligand binding and activation | 3.334286e-03 | 2.477 |
| R-HSA-6788467 | IL-6-type cytokine receptor ligand interactions | 3.334286e-03 | 2.477 |
| R-HSA-1059683 | Interleukin-6 signaling | 3.334286e-03 | 2.477 |
| R-HSA-74160 | Gene expression (Transcription) | 3.530982e-03 | 2.452 |
| R-HSA-445355 | Smooth Muscle Contraction | 3.593231e-03 | 2.445 |
| R-HSA-5654227 | Phospholipase C-mediated cascade; FGFR3 | 3.726116e-03 | 2.429 |
| R-HSA-446728 | Cell junction organization | 3.755470e-03 | 2.425 |
| R-HSA-168256 | Immune System | 3.781112e-03 | 2.422 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 4.016356e-03 | 2.396 |
| R-HSA-190239 | FGFR3 ligand binding and activation | 4.138334e-03 | 2.383 |
| R-HSA-446353 | Cell-extracellular matrix interactions | 4.138334e-03 | 2.383 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 4.471169e-03 | 2.350 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 4.471169e-03 | 2.350 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 4.834241e-03 | 2.316 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 4.834241e-03 | 2.316 |
| R-HSA-9700649 | Drug resistance of ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717264 | ASP-3026-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717316 | alectinib-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717329 | lorlatinib-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717301 | NVP-TAE684-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717323 | ceritinib-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717326 | crizotinib-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-9717319 | brigatinib-resistant ALK mutants | 4.955852e-03 | 2.305 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 5.023105e-03 | 2.299 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 5.023105e-03 | 2.299 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 5.089973e-03 | 2.293 |
| R-HSA-2028269 | Signaling by Hippo | 5.495250e-03 | 2.260 |
| R-HSA-180292 | GAB1 signalosome | 5.986965e-03 | 2.223 |
| R-HSA-397014 | Muscle contraction | 6.106705e-03 | 2.214 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 6.498050e-03 | 2.187 |
| R-HSA-392517 | Rap1 signalling | 6.498050e-03 | 2.187 |
| R-HSA-1500931 | Cell-Cell communication | 6.656586e-03 | 2.177 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 7.577531e-03 | 2.120 |
| R-HSA-198753 | ERK/MAPK targets | 7.577531e-03 | 2.120 |
| R-HSA-9013695 | NOTCH4 Intracellular Domain Regulates Transcription | 7.577531e-03 | 2.120 |
| R-HSA-9734091 | Drug-mediated inhibition of MET activation | 9.887448e-03 | 2.005 |
| R-HSA-1839128 | FGFR4 mutant receptor activation | 1.479491e-02 | 1.830 |
| R-HSA-8853334 | Signaling by FGFR3 fusions in cancer | 1.479491e-02 | 1.830 |
| R-HSA-8853333 | Signaling by FGFR2 fusions | 1.479491e-02 | 1.830 |
| R-HSA-2033515 | t(4;14) translocations of FGFR3 | 1.479491e-02 | 1.830 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 8.145534e-03 | 2.089 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 1.334242e-02 | 1.875 |
| R-HSA-6783589 | Interleukin-6 family signaling | 9.960260e-03 | 2.002 |
| R-HSA-2424491 | DAP12 signaling | 1.407082e-02 | 1.852 |
| R-HSA-9664417 | Leishmania phagocytosis | 7.942034e-03 | 2.100 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 7.942034e-03 | 2.100 |
| R-HSA-9664407 | Parasite infection | 7.942034e-03 | 2.100 |
| R-HSA-445095 | Interaction between L1 and Ankyrins | 1.193704e-02 | 1.923 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 8.116194e-03 | 2.091 |
| R-HSA-1266695 | Interleukin-7 signaling | 1.060143e-02 | 1.975 |
| R-HSA-449147 | Signaling by Interleukins | 1.497173e-02 | 1.825 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 1.334242e-02 | 1.875 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 1.263111e-02 | 1.899 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 9.600460e-03 | 2.018 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 8.732119e-03 | 2.059 |
| R-HSA-9013694 | Signaling by NOTCH4 | 8.103886e-03 | 2.091 |
| R-HSA-9830364 | Formation of the nephric duct | 1.060143e-02 | 1.975 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 8.145534e-03 | 2.089 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.126042e-02 | 1.948 |
| R-HSA-2262752 | Cellular responses to stress | 1.362342e-02 | 1.866 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 1.587730e-02 | 1.799 |
| R-HSA-354192 | Integrin signaling | 1.635662e-02 | 1.786 |
| R-HSA-390522 | Striated Muscle Contraction | 1.715150e-02 | 1.766 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.730960e-02 | 1.762 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.730960e-02 | 1.762 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.730960e-02 | 1.762 |
| R-HSA-5673000 | RAF activation | 1.796255e-02 | 1.746 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 1.796255e-02 | 1.746 |
| R-HSA-8853659 | RET signaling | 1.963249e-02 | 1.707 |
| R-HSA-198765 | Signalling to ERK5 | 1.967835e-02 | 1.706 |
| R-HSA-168898 | Toll-like Receptor Cascades | 2.090447e-02 | 1.680 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 2.222380e-02 | 1.653 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 2.270448e-02 | 1.644 |
| R-HSA-9607240 | FLT3 Signaling | 2.407826e-02 | 1.618 |
| R-HSA-8875513 | MET interacts with TNS proteins | 2.453788e-02 | 1.610 |
| R-HSA-8865999 | MET activates PTPN11 | 2.453788e-02 | 1.610 |
| R-HSA-8875791 | MET activates STAT3 | 2.453788e-02 | 1.610 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 2.468381e-02 | 1.608 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 2.622774e-02 | 1.581 |
| R-HSA-1433557 | Signaling by SCF-KIT | 2.692476e-02 | 1.570 |
| R-HSA-2172127 | DAP12 interactions | 2.790244e-02 | 1.554 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 2.790244e-02 | 1.554 |
| R-HSA-5654741 | Signaling by FGFR3 | 2.889427e-02 | 1.539 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 2.889427e-02 | 1.539 |
| R-HSA-9824272 | Somitogenesis | 2.889427e-02 | 1.539 |
| R-HSA-8953897 | Cellular responses to stimuli | 2.915868e-02 | 1.535 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 2.937362e-02 | 1.532 |
| R-HSA-1307965 | betaKlotho-mediated ligand binding | 2.937362e-02 | 1.532 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 2.937362e-02 | 1.532 |
| R-HSA-205025 | NADE modulates death signalling | 2.937362e-02 | 1.532 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 2.937362e-02 | 1.532 |
| R-HSA-74713 | IRS activation | 3.418569e-02 | 1.466 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 3.470799e-02 | 1.460 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 3.622004e-02 | 1.441 |
| R-HSA-5638303 | Inhibition of Signaling by Overexpressed EGFR | 3.897420e-02 | 1.409 |
| R-HSA-5638302 | Signaling by Overexpressed Wild-Type EGFR in Cancer | 3.897420e-02 | 1.409 |
| R-HSA-8852405 | Signaling by MST1 | 3.897420e-02 | 1.409 |
| R-HSA-177929 | Signaling by EGFR | 4.069345e-02 | 1.390 |
| R-HSA-9662361 | Sensory processing of sound by outer hair cells of the cochlea | 4.069345e-02 | 1.390 |
| R-HSA-157118 | Signaling by NOTCH | 4.089739e-02 | 1.388 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 4.184294e-02 | 1.378 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 4.373926e-02 | 1.359 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 4.373926e-02 | 1.359 |
| R-HSA-6806942 | MET Receptor Activation | 4.373926e-02 | 1.359 |
| R-HSA-199920 | CREB phosphorylation | 4.373926e-02 | 1.359 |
| R-HSA-8856828 | Clathrin-mediated endocytosis | 4.653201e-02 | 1.332 |
| R-HSA-450294 | MAP kinase activation | 4.656102e-02 | 1.332 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 4.656102e-02 | 1.332 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 4.848099e-02 | 1.314 |
| R-HSA-190371 | FGFR3b ligand binding and activation | 4.848099e-02 | 1.314 |
| R-HSA-9726840 | SHOC2 M1731 mutant abolishes MRAS complex function | 4.848099e-02 | 1.314 |
| R-HSA-166520 | Signaling by NTRKs | 5.012773e-02 | 1.300 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 5.160312e-02 | 1.287 |
| R-HSA-9734767 | Developmental Cell Lineages | 5.279072e-02 | 1.277 |
| R-HSA-444257 | RSK activation | 5.319950e-02 | 1.274 |
| R-HSA-212718 | EGFR interacts with phospholipase C-gamma | 5.319950e-02 | 1.274 |
| R-HSA-8875656 | MET receptor recycling | 5.319950e-02 | 1.274 |
| R-HSA-9660537 | Signaling by MRAS-complex mutants | 5.319950e-02 | 1.274 |
| R-HSA-9726842 | Gain-of-function MRAS complexes activate RAF signaling | 5.319950e-02 | 1.274 |
| R-HSA-9020933 | Interleukin-23 signaling | 5.319950e-02 | 1.274 |
| R-HSA-416476 | G alpha (q) signalling events | 5.334651e-02 | 1.273 |
| R-HSA-9830369 | Kidney development | 5.398287e-02 | 1.268 |
| R-HSA-9662360 | Sensory processing of sound by inner hair cells of the cochlea | 5.525828e-02 | 1.258 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 5.525828e-02 | 1.258 |
| R-HSA-448424 | Interleukin-17 signaling | 5.784082e-02 | 1.238 |
| R-HSA-9700645 | ALK mutants bind TKIs | 5.789490e-02 | 1.237 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 5.789490e-02 | 1.237 |
| R-HSA-170984 | ARMS-mediated activation | 5.789490e-02 | 1.237 |
| R-HSA-9013700 | NOTCH4 Activation and Transmission of Signal to the Nucleus | 5.789490e-02 | 1.237 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 5.908059e-02 | 1.229 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 6.046478e-02 | 1.218 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 6.046478e-02 | 1.218 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 6.256731e-02 | 1.204 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 6.256731e-02 | 1.204 |
| R-HSA-390450 | Folding of actin by CCT/TriC | 6.256731e-02 | 1.204 |
| R-HSA-2586552 | Signaling by Leptin | 6.256731e-02 | 1.204 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 6.256731e-02 | 1.204 |
| R-HSA-428359 | Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RN... | 6.256731e-02 | 1.204 |
| R-HSA-74749 | Signal attenuation | 6.256731e-02 | 1.204 |
| R-HSA-9658195 | Leishmania infection | 6.328386e-02 | 1.199 |
| R-HSA-9824443 | Parasitic Infection Pathways | 6.328386e-02 | 1.199 |
| R-HSA-9020591 | Interleukin-12 signaling | 6.583275e-02 | 1.182 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 6.857472e-02 | 1.164 |
| R-HSA-9659379 | Sensory processing of sound | 6.995976e-02 | 1.155 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 7.184358e-02 | 1.144 |
| R-HSA-202670 | ERKs are inactivated | 7.184358e-02 | 1.144 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 7.416962e-02 | 1.130 |
| R-HSA-8851805 | MET activates RAS signaling | 7.644766e-02 | 1.117 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 7.644766e-02 | 1.117 |
| R-HSA-179812 | GRB2 events in EGFR signaling | 7.644766e-02 | 1.117 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 7.990600e-02 | 1.097 |
| R-HSA-190322 | FGFR4 ligand binding and activation | 8.102919e-02 | 1.091 |
| R-HSA-9933947 | Formation of the non-canonical BAF (ncBAF) complex | 8.102919e-02 | 1.091 |
| R-HSA-170968 | Frs2-mediated activation | 8.102919e-02 | 1.091 |
| R-HSA-447115 | Interleukin-12 family signaling | 8.282486e-02 | 1.082 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 8.558828e-02 | 1.068 |
| R-HSA-1170546 | Prolactin receptor signaling | 8.558828e-02 | 1.068 |
| R-HSA-190372 | FGFR3c ligand binding and activation | 8.558828e-02 | 1.068 |
| R-HSA-9933937 | Formation of the canonical BAF (cBAF) complex | 8.558828e-02 | 1.068 |
| R-HSA-9933939 | Formation of the polybromo-BAF (pBAF) complex | 8.558828e-02 | 1.068 |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | 8.817154e-02 | 1.055 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 8.875931e-02 | 1.052 |
| R-HSA-9027284 | Erythropoietin activates RAS | 9.012503e-02 | 1.045 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 9.012503e-02 | 1.045 |
| R-HSA-180336 | SHC1 events in EGFR signaling | 9.012503e-02 | 1.045 |
| R-HSA-5654228 | Phospholipase C-mediated cascade; FGFR4 | 9.012503e-02 | 1.045 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 9.012503e-02 | 1.045 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 9.012503e-02 | 1.045 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 9.012503e-02 | 1.045 |
| R-HSA-9933946 | Formation of the embryonic stem cell BAF (esBAF) complex | 9.012503e-02 | 1.045 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 9.329124e-02 | 1.030 |
| R-HSA-169893 | Prolonged ERK activation events | 9.463955e-02 | 1.024 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 9.463955e-02 | 1.024 |
| R-HSA-9706369 | Negative regulation of FLT3 | 9.463955e-02 | 1.024 |
| R-HSA-389948 | Co-inhibition by PD-1 | 9.592523e-02 | 1.018 |
| R-HSA-5637812 | Signaling by EGFRvIII in Cancer | 1.036023e-01 | 0.985 |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII | 1.036023e-01 | 0.985 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 1.080508e-01 | 0.966 |
| R-HSA-912631 | Regulation of signaling by CBL | 1.124775e-01 | 0.949 |
| R-HSA-449836 | Other interleukin signaling | 1.124775e-01 | 0.949 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.152697e-01 | 0.938 |
| R-HSA-6807004 | Negative regulation of MET activity | 1.168825e-01 | 0.932 |
| R-HSA-9934037 | Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) | 1.168825e-01 | 0.932 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 1.168825e-01 | 0.932 |
| R-HSA-445144 | Signal transduction by L1 | 1.168825e-01 | 0.932 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 1.212658e-01 | 0.916 |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 1.212658e-01 | 0.916 |
| R-HSA-5637815 | Signaling by Ligand-Responsive EGFR Variants in Cancer | 1.212658e-01 | 0.916 |
| R-HSA-9931295 | PD-L1(CD274) glycosylation and translocation to plasma membrane | 1.212658e-01 | 0.916 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 1.234148e-01 | 0.909 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 1.234148e-01 | 0.909 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 1.256277e-01 | 0.901 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 1.256277e-01 | 0.901 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 1.256277e-01 | 0.901 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 1.267116e-01 | 0.897 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 1.299683e-01 | 0.886 |
| R-HSA-912694 | Regulation of IFNA/IFNB signaling | 1.299683e-01 | 0.886 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 1.299683e-01 | 0.886 |
| R-HSA-166208 | mTORC1-mediated signalling | 1.299683e-01 | 0.886 |
| R-HSA-9669938 | Signaling by KIT in disease | 1.299683e-01 | 0.886 |
| R-HSA-9013507 | NOTCH3 Activation and Transmission of Signal to the Nucleus | 1.299683e-01 | 0.886 |
| R-HSA-982772 | Growth hormone receptor signaling | 1.342875e-01 | 0.872 |
| R-HSA-9830674 | Formation of the ureteric bud | 1.342875e-01 | 0.872 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.342875e-01 | 0.872 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 1.350441e-01 | 0.870 |
| R-HSA-8939211 | ESR-mediated signaling | 1.362397e-01 | 0.866 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 1.385856e-01 | 0.858 |
| R-HSA-9836573 | Mitochondrial RNA degradation | 1.385856e-01 | 0.858 |
| R-HSA-8863678 | Neurodegenerative Diseases | 1.385856e-01 | 0.858 |
| R-HSA-8862803 | Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... | 1.385856e-01 | 0.858 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 1.428626e-01 | 0.845 |
| R-HSA-9932444 | ATP-dependent chromatin remodelers | 1.428626e-01 | 0.845 |
| R-HSA-9932451 | SWI/SNF chromatin remodelers | 1.428626e-01 | 0.845 |
| R-HSA-8874081 | MET activates PTK2 signaling | 1.471186e-01 | 0.832 |
| R-HSA-1643713 | Signaling by EGFR in Cancer | 1.471186e-01 | 0.832 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 1.513537e-01 | 0.820 |
| R-HSA-9734009 | Defective Intrinsic Pathway for Apoptosis | 1.513537e-01 | 0.820 |
| R-HSA-194138 | Signaling by VEGF | 1.537847e-01 | 0.813 |
| R-HSA-77387 | Insulin receptor recycling | 1.555681e-01 | 0.808 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 1.582692e-01 | 0.801 |
| R-HSA-9006335 | Signaling by Erythropoietin | 1.597618e-01 | 0.797 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 1.597618e-01 | 0.797 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 1.639350e-01 | 0.785 |
| R-HSA-182971 | EGFR downregulation | 1.680876e-01 | 0.774 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 1.680876e-01 | 0.774 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 1.680876e-01 | 0.774 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 1.763320e-01 | 0.754 |
| R-HSA-397795 | G-protein beta:gamma signalling | 1.763320e-01 | 0.754 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 1.765335e-01 | 0.753 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 1.783058e-01 | 0.749 |
| R-HSA-5696394 | DNA Damage Recognition in GG-NER | 1.804238e-01 | 0.744 |
| R-HSA-187687 | Signalling to ERKs | 1.885474e-01 | 0.725 |
| R-HSA-114604 | GPVI-mediated activation cascade | 1.925794e-01 | 0.715 |
| R-HSA-3371511 | HSF1 activation | 1.925794e-01 | 0.715 |
| R-HSA-3769402 | Deactivation of the beta-catenin transactivating complex | 1.965915e-01 | 0.706 |
| R-HSA-8875878 | MET promotes cell motility | 2.005840e-01 | 0.698 |
| R-HSA-9758941 | Gastrulation | 2.015803e-01 | 0.696 |
| R-HSA-5260271 | Diseases of Immune System | 2.085102e-01 | 0.681 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 2.085102e-01 | 0.681 |
| R-HSA-9604323 | Negative regulation of NOTCH4 signaling | 2.085102e-01 | 0.681 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 2.124442e-01 | 0.673 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 2.163588e-01 | 0.665 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 2.178977e-01 | 0.662 |
| R-HSA-877300 | Interferon gamma signaling | 2.197187e-01 | 0.658 |
| R-HSA-165159 | MTOR signalling | 2.202542e-01 | 0.657 |
| R-HSA-5654743 | Signaling by FGFR4 | 2.241306e-01 | 0.649 |
| R-HSA-168249 | Innate Immune System | 2.263148e-01 | 0.645 |
| R-HSA-69231 | Cyclin D associated events in G1 | 2.279878e-01 | 0.642 |
| R-HSA-69236 | G1 Phase | 2.279878e-01 | 0.642 |
| R-HSA-3214858 | RMTs methylate histone arginines | 2.279878e-01 | 0.642 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 2.318262e-01 | 0.635 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 2.453308e-01 | 0.610 |
| R-HSA-2559583 | Cellular Senescence | 2.600296e-01 | 0.585 |
| R-HSA-5250924 | B-WICH complex positively regulates rRNA expression | 2.618621e-01 | 0.582 |
| R-HSA-9012852 | Signaling by NOTCH3 | 2.691880e-01 | 0.570 |
| R-HSA-5621480 | Dectin-2 family | 2.764421e-01 | 0.558 |
| R-HSA-9845323 | Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) | 2.871901e-01 | 0.542 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 2.966907e-01 | 0.528 |
| R-HSA-373755 | Semaphorin interactions | 2.977805e-01 | 0.526 |
| R-HSA-5250913 | Positive epigenetic regulation of rRNA expression | 3.252678e-01 | 0.488 |
| R-HSA-3000178 | ECM proteoglycans | 3.252678e-01 | 0.488 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 3.319719e-01 | 0.479 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 3.386102e-01 | 0.470 |
| R-HSA-5689603 | UCH proteinases | 3.419049e-01 | 0.466 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 3.459689e-01 | 0.461 |
| R-HSA-6783783 | Interleukin-10 signaling | 3.484457e-01 | 0.458 |
| R-HSA-416482 | G alpha (12/13) signalling events | 3.484457e-01 | 0.458 |
| R-HSA-6806834 | Signaling by MET | 3.549223e-01 | 0.450 |
| R-HSA-3247509 | Chromatin modifying enzymes | 3.603529e-01 | 0.443 |
| R-HSA-5696399 | Global Genome Nucleotide Excision Repair (GG-NER) | 3.676855e-01 | 0.435 |
| R-HSA-8876198 | RAB GEFs exchange GTP for GDP on RABs | 3.739732e-01 | 0.427 |
| R-HSA-9645723 | Diseases of programmed cell death | 3.832892e-01 | 0.416 |
| R-HSA-1236974 | ER-Phagosome pathway | 3.863640e-01 | 0.413 |
| R-HSA-4839726 | Chromatin organization | 3.870087e-01 | 0.412 |
| R-HSA-2029481 | FCGR activation | 4.015124e-01 | 0.396 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 4.074678e-01 | 0.390 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 4.133647e-01 | 0.384 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 4.133647e-01 | 0.384 |
| R-HSA-3214847 | HATs acetylate histones | 4.221015e-01 | 0.375 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 4.221015e-01 | 0.375 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 4.278546e-01 | 0.369 |
| R-HSA-9842860 | Regulation of endogenous retroelements | 4.307099e-01 | 0.366 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 4.307099e-01 | 0.366 |
| R-HSA-8856825 | Cargo recognition for clathrin-mediated endocytosis | 4.363783e-01 | 0.360 |
| R-HSA-9833110 | RSV-host interactions | 4.391915e-01 | 0.357 |
| R-HSA-5696398 | Nucleotide Excision Repair | 4.419909e-01 | 0.355 |
| R-HSA-9700206 | Signaling by ALK in cancer | 4.475484e-01 | 0.349 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 4.475484e-01 | 0.349 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 4.503066e-01 | 0.346 |
| R-HSA-202403 | TCR signaling | 4.557823e-01 | 0.341 |
| R-HSA-597592 | Post-translational protein modification | 4.582509e-01 | 0.339 |
| R-HSA-909733 | Interferon alpha/beta signaling | 4.745263e-01 | 0.324 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 4.745263e-01 | 0.324 |
| R-HSA-9007101 | Rab regulation of trafficking | 4.797637e-01 | 0.319 |
| R-HSA-3371556 | Cellular response to heat stress | 4.900842e-01 | 0.310 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 5.051870e-01 | 0.297 |
| R-HSA-114608 | Platelet degranulation | 5.076608e-01 | 0.294 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 5.246390e-01 | 0.280 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 5.501577e-01 | 0.260 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 5.590979e-01 | 0.253 |
| R-HSA-388396 | GPCR downstream signalling | 5.613814e-01 | 0.251 |
| R-HSA-73887 | Death Receptor Signaling | 5.764550e-01 | 0.239 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 6.130796e-01 | 0.212 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 6.169507e-01 | 0.210 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 6.169507e-01 | 0.210 |
| R-HSA-8953854 | Metabolism of RNA | 6.205193e-01 | 0.207 |
| R-HSA-201681 | TCF dependent signaling in response to WNT | 6.357399e-01 | 0.197 |
| R-HSA-372790 | Signaling by GPCR | 6.406224e-01 | 0.193 |
| R-HSA-5688426 | Deubiquitination | 7.479191e-01 | 0.126 |
| R-HSA-195721 | Signaling by WNT | 7.972208e-01 | 0.098 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 8.213703e-01 | 0.085 |
| R-HSA-73894 | DNA Repair | 8.519905e-01 | 0.070 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 8.690168e-01 | 0.061 |
| R-HSA-392499 | Metabolism of proteins | 8.703956e-01 | 0.060 |
| R-HSA-9824439 | Bacterial Infection Pathways | 8.736077e-01 | 0.059 |
| R-HSA-9709957 | Sensory Perception | 9.883904e-01 | 0.005 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
LIMK2_TYR |
0.578 | 0.095 | -3 | 0.398 |
TESK1_TYR |
0.572 | 0.031 | 3 | 0.603 |
NEK10_TYR |
0.572 | 0.087 | 1 | 0.370 |
PDHK3_TYR |
0.571 | 0.038 | 4 | 0.562 |
TNNI3K_TYR |
0.570 | 0.046 | 1 | 0.384 |
TYK2 |
0.568 | 0.062 | 1 | 0.436 |
RET |
0.567 | 0.051 | 1 | 0.416 |
MAP2K7_TYR |
0.565 | -0.019 | 2 | 0.557 |
PINK1_TYR |
0.564 | -0.090 | 1 | 0.327 |
ABL2 |
0.563 | 0.034 | -1 | 0.473 |
PKMYT1_TYR |
0.563 | -0.037 | 3 | 0.562 |
JAK2 |
0.562 | 0.041 | 1 | 0.429 |
LIMK1_TYR |
0.562 | -0.050 | 2 | 0.578 |
JAK1 |
0.561 | 0.074 | 1 | 0.437 |
ABL1 |
0.561 | 0.033 | -1 | 0.457 |
PDHK4_TYR |
0.560 | -0.055 | 2 | 0.559 |
MAP2K4_TYR |
0.559 | -0.109 | -1 | 0.577 |
TNK1 |
0.559 | 0.013 | 3 | 0.484 |
ROS1 |
0.558 | 0.010 | 3 | 0.451 |
MST1R |
0.556 | -0.022 | 3 | 0.515 |
MAP2K6_TYR |
0.556 | -0.119 | -1 | 0.589 |
BMPR2_TYR |
0.555 | -0.072 | -1 | 0.556 |
EPHA6 |
0.553 | -0.049 | -1 | 0.528 |
CSF1R |
0.552 | -0.023 | 3 | 0.501 |
PDHK1_TYR |
0.552 | -0.123 | -1 | 0.584 |
DDR1 |
0.549 | -0.091 | 4 | 0.516 |
JAK3 |
0.549 | -0.073 | 1 | 0.356 |
TYRO3 |
0.548 | -0.092 | 3 | 0.490 |
PDGFRA |
0.547 | -0.040 | 3 | 0.473 |
EPHB4 |
0.546 | -0.081 | -1 | 0.524 |
PDGFRB |
0.546 | -0.087 | 3 | 0.487 |
KDR |
0.546 | -0.056 | 3 | 0.461 |
FLT3 |
0.545 | -0.082 | 3 | 0.484 |
TNK2 |
0.544 | -0.068 | 3 | 0.435 |
WEE1_TYR |
0.544 | -0.057 | -1 | 0.497 |
INSRR |
0.542 | -0.074 | 3 | 0.449 |
FER |
0.541 | -0.119 | 1 | 0.375 |
ALK |
0.540 | -0.059 | 3 | 0.416 |
KIT |
0.540 | -0.087 | 3 | 0.486 |
AXL |
0.540 | -0.079 | 3 | 0.470 |
LTK |
0.539 | -0.068 | 3 | 0.441 |
MUSK |
0.538 | -0.044 | 1 | 0.315 |
FGR |
0.538 | -0.135 | 1 | 0.367 |
FGFR2 |
0.536 | -0.121 | 3 | 0.485 |
FGFR1 |
0.536 | -0.108 | 3 | 0.461 |
FRK |
0.536 | -0.070 | -1 | 0.471 |
FLT1 |
0.535 | -0.097 | -1 | 0.541 |
DDR2 |
0.535 | -0.066 | 3 | 0.416 |
EPHB3 |
0.534 | -0.103 | -1 | 0.512 |
LCK |
0.534 | -0.100 | -1 | 0.423 |
HCK |
0.534 | -0.124 | -1 | 0.422 |
TEK |
0.533 | -0.118 | 3 | 0.404 |
ERBB2 |
0.533 | -0.094 | 1 | 0.368 |
SRMS |
0.533 | -0.132 | 1 | 0.362 |
FLT4 |
0.533 | -0.100 | 3 | 0.443 |
PTK6 |
0.532 | -0.125 | -1 | 0.414 |
MERTK |
0.532 | -0.106 | 3 | 0.490 |
MET |
0.531 | -0.120 | 3 | 0.494 |
MATK |
0.531 | -0.085 | -1 | 0.468 |
ITK |
0.531 | -0.135 | -1 | 0.443 |
EPHA1 |
0.530 | -0.086 | 3 | 0.460 |
INSR |
0.530 | -0.111 | 3 | 0.427 |
EPHA4 |
0.530 | -0.118 | 2 | 0.446 |
YES1 |
0.530 | -0.156 | -1 | 0.447 |
CSK |
0.529 | -0.092 | 2 | 0.465 |
NTRK1 |
0.529 | -0.122 | -1 | 0.511 |
TEC |
0.529 | -0.117 | -1 | 0.380 |
BLK |
0.529 | -0.113 | -1 | 0.436 |
BTK |
0.529 | -0.149 | -1 | 0.419 |
EPHB1 |
0.528 | -0.157 | 1 | 0.386 |
TXK |
0.528 | -0.142 | 1 | 0.290 |
NTRK3 |
0.527 | -0.110 | -1 | 0.474 |
NTRK2 |
0.527 | -0.141 | 3 | 0.457 |
EGFR |
0.526 | -0.080 | 1 | 0.298 |
EPHB2 |
0.526 | -0.139 | -1 | 0.499 |
FGFR3 |
0.525 | -0.131 | 3 | 0.468 |
FGFR4 |
0.523 | -0.084 | -1 | 0.462 |
EPHA7 |
0.522 | -0.122 | 2 | 0.447 |
EPHA3 |
0.521 | -0.129 | 2 | 0.419 |
BMX |
0.520 | -0.141 | -1 | 0.356 |
PTK2B |
0.518 | -0.117 | -1 | 0.408 |
LYN |
0.517 | -0.147 | 3 | 0.396 |
EPHA5 |
0.516 | -0.126 | 2 | 0.426 |
SYK |
0.514 | -0.106 | -1 | 0.438 |
EPHA8 |
0.514 | -0.133 | -1 | 0.481 |
ZAP70 |
0.513 | -0.065 | -1 | 0.386 |
FYN |
0.511 | -0.161 | -1 | 0.377 |
IGF1R |
0.508 | -0.138 | 3 | 0.369 |
EPHA2 |
0.505 | -0.135 | -1 | 0.446 |
PTK2 |
0.505 | -0.126 | -1 | 0.427 |
ERBB4 |
0.503 | -0.115 | 1 | 0.297 |
SRC |
0.503 | -0.182 | -1 | 0.380 |
TNIK |
0.495 | 0.228 | 3 | 0.563 |
KHS1 |
0.495 | 0.286 | 1 | 0.532 |
KHS2 |
0.495 | 0.260 | 1 | 0.529 |
FES |
0.491 | -0.153 | -1 | 0.340 |
PRP4 |
0.489 | 0.367 | -3 | 0.720 |
PRKD1 |
0.489 | 0.146 | -3 | 0.378 |
PRKD2 |
0.489 | 0.120 | -3 | 0.375 |
MINK |
0.488 | 0.243 | 1 | 0.491 |
HGK |
0.488 | 0.200 | 3 | 0.547 |
DNAPK |
0.487 | 0.185 | 1 | 0.591 |
MST4 |
0.486 | 0.143 | 2 | 0.619 |
LKB1 |
0.486 | 0.188 | -3 | 0.427 |
MST1 |
0.485 | 0.200 | 1 | 0.481 |
GCK |
0.483 | 0.226 | 1 | 0.471 |
HPK1 |
0.483 | 0.225 | 1 | 0.503 |
CAMKK2 |
0.483 | 0.164 | -2 | 0.452 |
NEK1 |
0.483 | 0.159 | 1 | 0.407 |
MST3 |
0.481 | 0.144 | 2 | 0.582 |
LOK |
0.481 | 0.150 | -2 | 0.291 |
NEK4 |
0.480 | 0.196 | 1 | 0.471 |
NEK2 |
0.480 | 0.141 | 2 | 0.566 |
CAMKK1 |
0.480 | 0.143 | -2 | 0.470 |
MYO3B |
0.479 | 0.144 | 2 | 0.595 |
TBK1 |
0.479 | 0.258 | 1 | 0.482 |
PAK6 |
0.479 | 0.081 | -2 | 0.273 |
IKKE |
0.479 | 0.285 | 1 | 0.505 |
PKR |
0.478 | 0.108 | 1 | 0.381 |
RAF1 |
0.478 | 0.182 | 1 | 0.451 |
NEK5 |
0.478 | 0.126 | 1 | 0.412 |
PRKD3 |
0.477 | 0.054 | -3 | 0.351 |
NIK |
0.477 | 0.074 | -3 | 0.393 |
BUB1 |
0.477 | 0.090 | -5 | 0.472 |
AMPKA1 |
0.477 | 0.055 | -3 | 0.397 |
YSK1 |
0.477 | 0.115 | 2 | 0.567 |
TAO3 |
0.476 | 0.116 | 1 | 0.397 |
AMPKA2 |
0.476 | 0.048 | -3 | 0.386 |
TAO2 |
0.476 | 0.118 | 2 | 0.582 |
PKCD |
0.475 | 0.077 | 2 | 0.542 |
TAO1 |
0.475 | 0.142 | 1 | 0.409 |
TSSK2 |
0.475 | 0.069 | -5 | 0.539 |
MST2 |
0.474 | 0.138 | 1 | 0.466 |
TSSK1 |
0.474 | 0.068 | -3 | 0.414 |
CHAK2 |
0.474 | 0.089 | -1 | 0.659 |
CLK3 |
0.473 | 0.035 | 1 | 0.306 |
AURC |
0.473 | 0.047 | -2 | 0.171 |
ULK2 |
0.473 | 0.078 | 2 | 0.519 |
MEKK2 |
0.473 | 0.093 | 2 | 0.557 |
MTOR |
0.473 | 0.060 | 1 | 0.374 |
MYO3A |
0.473 | 0.129 | 1 | 0.444 |
MNK2 |
0.473 | 0.084 | -2 | 0.244 |
DSTYK |
0.472 | 0.055 | 2 | 0.596 |
MAPKAPK3 |
0.472 | 0.050 | -3 | 0.354 |
ERK5 |
0.471 | 0.060 | 1 | 0.378 |
NEK9 |
0.471 | 0.093 | 2 | 0.571 |
CDK16 |
0.471 | 0.052 | 1 | 0.161 |
CHAK1 |
0.471 | 0.088 | 2 | 0.544 |
PKN3 |
0.471 | 0.020 | -3 | 0.385 |
PKN2 |
0.471 | 0.044 | -3 | 0.401 |
NLK |
0.470 | 0.051 | 1 | 0.329 |
ATR |
0.470 | 0.043 | 1 | 0.453 |
NUAK2 |
0.470 | 0.008 | -3 | 0.381 |
IKKB |
0.470 | 0.084 | -2 | 0.370 |
CDKL1 |
0.470 | -0.008 | -3 | 0.332 |
EEF2K |
0.470 | 0.044 | 3 | 0.515 |
SRPK1 |
0.470 | 0.023 | -3 | 0.346 |
MEKK6 |
0.470 | 0.073 | 1 | 0.420 |
COT |
0.469 | 0.023 | 2 | 0.565 |
WNK1 |
0.469 | 0.046 | -2 | 0.311 |
NEK3 |
0.469 | 0.107 | 1 | 0.398 |
ROCK2 |
0.469 | 0.056 | -3 | 0.378 |
PKCA |
0.469 | 0.083 | 2 | 0.512 |
SSTK |
0.469 | 0.068 | 4 | 0.532 |
SLK |
0.469 | 0.093 | -2 | 0.230 |
TAK1 |
0.469 | 0.078 | 1 | 0.437 |
MEKK1 |
0.469 | 0.085 | 1 | 0.399 |
LRRK2 |
0.468 | 0.052 | 2 | 0.551 |
MAPKAPK2 |
0.468 | 0.033 | -3 | 0.323 |
PHKG2 |
0.468 | 0.079 | -3 | 0.390 |
PINK1 |
0.468 | 0.063 | 1 | 0.291 |
BMPR2 |
0.468 | -0.003 | -2 | 0.384 |
AKT2 |
0.468 | 0.009 | -3 | 0.316 |
BRAF |
0.468 | 0.011 | -4 | 0.562 |
AKT1 |
0.467 | 0.020 | -3 | 0.339 |
YSK4 |
0.467 | 0.107 | 1 | 0.429 |
NEK6 |
0.467 | 0.032 | -2 | 0.338 |
BCKDK |
0.467 | 0.153 | -1 | 0.599 |
P38A |
0.467 | 0.018 | 1 | 0.276 |
CAMK1B |
0.467 | -0.025 | -3 | 0.363 |
MARK4 |
0.467 | 0.034 | 4 | 0.528 |
IRAK4 |
0.467 | 0.093 | 1 | 0.375 |
PRPK |
0.467 | -0.003 | -1 | 0.560 |
IKKA |
0.467 | 0.075 | -2 | 0.343 |
MLK2 |
0.467 | 0.053 | 2 | 0.588 |
CHK1 |
0.467 | 0.034 | -3 | 0.351 |
PIM3 |
0.466 | -0.008 | -3 | 0.382 |
CDKL5 |
0.466 | 0.001 | -3 | 0.324 |
PIM1 |
0.466 | 0.003 | -3 | 0.345 |
MRCKB |
0.466 | 0.040 | -3 | 0.353 |
PKACB |
0.466 | 0.018 | -2 | 0.163 |
PKCB |
0.466 | 0.047 | 2 | 0.531 |
ASK1 |
0.466 | 0.040 | 1 | 0.360 |
MNK1 |
0.465 | 0.059 | -2 | 0.246 |
IRE1 |
0.465 | 0.046 | 1 | 0.348 |
PDHK1 |
0.465 | 0.120 | 1 | 0.461 |
HIPK1 |
0.465 | 0.015 | 1 | 0.240 |
DCAMKL1 |
0.465 | 0.026 | -3 | 0.397 |
SBK |
0.465 | 0.028 | -3 | 0.261 |
HUNK |
0.465 | 0.015 | 2 | 0.501 |
MAP3K15 |
0.465 | 0.049 | 1 | 0.382 |
RSK2 |
0.465 | 0.001 | -3 | 0.336 |
P38B |
0.465 | 0.011 | 1 | 0.258 |
LATS1 |
0.465 | 0.041 | -3 | 0.370 |
CLK1 |
0.464 | 0.013 | -3 | 0.346 |
CDC7 |
0.464 | -0.012 | 1 | 0.298 |
DYRK2 |
0.464 | 0.028 | 1 | 0.249 |
NIM1 |
0.464 | 0.039 | 3 | 0.499 |
ROCK1 |
0.464 | 0.040 | -3 | 0.362 |
MLK3 |
0.464 | 0.052 | 2 | 0.536 |
QSK |
0.464 | 0.028 | 4 | 0.529 |
PDHK4 |
0.464 | 0.065 | 1 | 0.414 |
PHKG1 |
0.464 | 0.039 | -3 | 0.386 |
CLK4 |
0.463 | 0.004 | -3 | 0.345 |
RSK3 |
0.463 | -0.001 | -3 | 0.351 |
MELK |
0.463 | 0.011 | -3 | 0.379 |
SMG1 |
0.463 | 0.055 | 1 | 0.471 |
ZAK |
0.463 | 0.030 | 1 | 0.367 |
PAK1 |
0.463 | 0.005 | -2 | 0.257 |
NEK11 |
0.463 | 0.065 | 1 | 0.410 |
SRPK2 |
0.463 | 0.012 | -3 | 0.289 |
P90RSK |
0.462 | 0.001 | -3 | 0.347 |
ERK1 |
0.462 | 0.004 | 1 | 0.245 |
P70S6KB |
0.462 | -0.007 | -3 | 0.349 |
CAMLCK |
0.462 | -0.033 | -2 | 0.325 |
DMPK1 |
0.462 | 0.010 | -3 | 0.362 |
CDK18 |
0.462 | 0.027 | 1 | 0.179 |
SGK3 |
0.462 | 0.011 | -3 | 0.374 |
ICK |
0.462 | -0.026 | -3 | 0.346 |
MLK1 |
0.462 | 0.001 | 2 | 0.567 |
TLK2 |
0.462 | 0.055 | 1 | 0.454 |
PKCG |
0.462 | 0.057 | 2 | 0.508 |
NEK8 |
0.461 | -0.007 | 2 | 0.539 |
ULK1 |
0.461 | 0.011 | -3 | 0.300 |
PBK |
0.461 | -0.011 | 1 | 0.301 |
CAMK2D |
0.461 | 0.032 | -3 | 0.366 |
PIM2 |
0.461 | -0.006 | -3 | 0.326 |
HIPK4 |
0.461 | 0.019 | 1 | 0.299 |
DLK |
0.461 | -0.040 | 1 | 0.358 |
SKMLCK |
0.461 | 0.012 | -2 | 0.270 |
NDR1 |
0.461 | 0.003 | -3 | 0.378 |
MEK5 |
0.461 | -0.016 | 2 | 0.569 |
HIPK3 |
0.461 | 0.010 | 1 | 0.279 |
PKACG |
0.461 | 0.016 | -2 | 0.194 |
PKCH |
0.461 | 0.031 | 2 | 0.499 |
MRCKA |
0.461 | 0.039 | -3 | 0.340 |
PAK3 |
0.460 | 0.001 | -2 | 0.279 |
ERK2 |
0.460 | -0.006 | 1 | 0.251 |
DAPK2 |
0.460 | -0.052 | -3 | 0.372 |
QIK |
0.460 | 0.004 | -3 | 0.364 |
PERK |
0.460 | -0.016 | -2 | 0.395 |
WNK4 |
0.460 | 0.024 | -2 | 0.329 |
PRKX |
0.460 | 0.017 | -3 | 0.351 |
ALK2 |
0.460 | 0.019 | -2 | 0.422 |
AURB |
0.460 | 0.018 | -2 | 0.168 |
PDK1 |
0.460 | -0.008 | 1 | 0.365 |
MOK |
0.460 | -0.004 | 1 | 0.281 |
BMPR1B |
0.460 | -0.006 | 1 | 0.241 |
TGFBR2 |
0.460 | 0.018 | -2 | 0.355 |
LATS2 |
0.460 | 0.018 | -5 | 0.483 |
PKG2 |
0.460 | 0.016 | -2 | 0.171 |
PKCT |
0.460 | 0.037 | 2 | 0.509 |
SRPK3 |
0.459 | 0.000 | -3 | 0.320 |
ALK4 |
0.459 | -0.002 | -2 | 0.405 |
MOS |
0.459 | -0.054 | 1 | 0.301 |
MEKK3 |
0.459 | 0.012 | 1 | 0.393 |
PKCZ |
0.459 | 0.035 | 2 | 0.529 |
GAK |
0.459 | -0.052 | 1 | 0.301 |
NEK7 |
0.459 | -0.019 | -3 | 0.315 |
CDK5 |
0.459 | 0.006 | 1 | 0.222 |
JNK2 |
0.459 | -0.006 | 1 | 0.213 |
P38D |
0.459 | 0.016 | 1 | 0.196 |
P38G |
0.459 | 0.004 | 1 | 0.159 |
HIPK2 |
0.459 | 0.013 | 1 | 0.182 |
SIK |
0.459 | 0.005 | -3 | 0.343 |
VRK2 |
0.458 | -0.070 | 1 | 0.360 |
GRK7 |
0.458 | 0.011 | 1 | 0.311 |
AKT3 |
0.458 | 0.008 | -3 | 0.296 |
ATM |
0.458 | 0.042 | 1 | 0.457 |
OSR1 |
0.458 | 0.010 | 2 | 0.568 |
NUAK1 |
0.458 | -0.013 | -3 | 0.352 |
HRI |
0.458 | -0.017 | -2 | 0.370 |
PKCE |
0.458 | 0.043 | 2 | 0.502 |
PKCI |
0.458 | 0.037 | 2 | 0.508 |
MAK |
0.458 | -0.012 | -2 | 0.265 |
CHK2 |
0.457 | 0.011 | -3 | 0.306 |
TTK |
0.457 | 0.001 | -2 | 0.306 |
MEK1 |
0.457 | -0.065 | 2 | 0.588 |
DYRK1B |
0.457 | 0.005 | 1 | 0.203 |
CAMK1D |
0.457 | -0.002 | -3 | 0.318 |
CDK14 |
0.457 | 0.009 | 1 | 0.208 |
CRIK |
0.456 | 0.006 | -3 | 0.310 |
PKACA |
0.456 | 0.005 | -2 | 0.141 |
CLK2 |
0.456 | 0.007 | -3 | 0.362 |
TGFBR1 |
0.455 | 0.008 | -2 | 0.401 |
TLK1 |
0.455 | 0.001 | -2 | 0.332 |
CDK17 |
0.455 | 0.003 | 1 | 0.154 |
WNK3 |
0.455 | -0.008 | 1 | 0.425 |
ANKRD3 |
0.455 | -0.043 | 1 | 0.406 |
MARK3 |
0.455 | 0.009 | 4 | 0.493 |
CDK13 |
0.455 | 0.014 | 1 | 0.208 |
MARK1 |
0.455 | 0.011 | 4 | 0.515 |
CDK8 |
0.455 | -0.015 | 1 | 0.207 |
IRE2 |
0.454 | 0.010 | 2 | 0.489 |
RIPK3 |
0.454 | 0.010 | 3 | 0.423 |
SGK1 |
0.454 | -0.005 | -3 | 0.278 |
CDK9 |
0.454 | 0.014 | 1 | 0.219 |
CDK12 |
0.454 | 0.024 | 1 | 0.204 |
PAK5 |
0.454 | 0.022 | -2 | 0.199 |
NDR2 |
0.454 | -0.021 | -3 | 0.391 |
DCAMKL2 |
0.453 | -0.010 | -3 | 0.379 |
RSK4 |
0.453 | -0.008 | -3 | 0.332 |
CDK7 |
0.453 | -0.007 | 1 | 0.214 |
DYRK3 |
0.453 | 0.003 | 1 | 0.250 |
RIPK1 |
0.453 | -0.038 | 1 | 0.354 |
PKN1 |
0.453 | 0.003 | -3 | 0.323 |
CDK19 |
0.453 | -0.013 | 1 | 0.191 |
BIKE |
0.452 | -0.018 | 1 | 0.230 |
DAPK3 |
0.452 | -0.036 | -3 | 0.375 |
CDK4 |
0.452 | 0.001 | 1 | 0.200 |
PAK2 |
0.452 | -0.023 | -2 | 0.264 |
TTBK2 |
0.452 | -0.018 | 2 | 0.465 |
MPSK1 |
0.452 | -0.042 | 1 | 0.272 |
CDK10 |
0.452 | 0.007 | 1 | 0.190 |
GCN2 |
0.452 | -0.063 | 2 | 0.509 |
CAMK1A |
0.452 | -0.005 | -3 | 0.322 |
JNK3 |
0.451 | -0.029 | 1 | 0.220 |
AURA |
0.451 | 0.014 | -2 | 0.146 |
CDK1 |
0.451 | -0.018 | 1 | 0.184 |
MARK2 |
0.451 | 0.004 | 4 | 0.447 |
MEK2 |
0.451 | -0.032 | 2 | 0.574 |
PLK1 |
0.451 | -0.024 | -2 | 0.322 |
CDK6 |
0.451 | 0.004 | 1 | 0.197 |
GRK6 |
0.451 | -0.036 | 1 | 0.337 |
BRSK1 |
0.450 | -0.014 | -3 | 0.381 |
FAM20C |
0.450 | 0.084 | 2 | 0.514 |
GRK5 |
0.449 | -0.090 | -3 | 0.349 |
DYRK1A |
0.449 | -0.019 | 1 | 0.262 |
STLK3 |
0.449 | -0.015 | 1 | 0.392 |
CAMK2G |
0.449 | -0.066 | 2 | 0.501 |
IRAK1 |
0.449 | -0.000 | -1 | 0.514 |
CDK2 |
0.449 | -0.010 | 1 | 0.237 |
AAK1 |
0.449 | -0.008 | 1 | 0.186 |
CAMK2A |
0.449 | -0.002 | 2 | 0.496 |
CAMK2B |
0.449 | 0.004 | 2 | 0.494 |
SMMLCK |
0.448 | -0.057 | -3 | 0.354 |
BRSK2 |
0.448 | -0.021 | -3 | 0.379 |
MSK2 |
0.448 | -0.037 | -3 | 0.310 |
CAMK4 |
0.448 | -0.062 | -3 | 0.361 |
CDK3 |
0.447 | -0.002 | 1 | 0.159 |
GSK3A |
0.447 | 0.061 | 4 | 0.376 |
MLK4 |
0.447 | -0.034 | 2 | 0.502 |
ACVR2A |
0.447 | -0.051 | -2 | 0.368 |
GSK3B |
0.445 | 0.037 | 4 | 0.374 |
MYLK4 |
0.445 | -0.048 | -2 | 0.251 |
PAK4 |
0.445 | 0.012 | -2 | 0.191 |
MASTL |
0.445 | -0.113 | -2 | 0.318 |
MSK1 |
0.445 | -0.029 | -3 | 0.328 |
HASPIN |
0.445 | -0.007 | -1 | 0.530 |
MAPKAPK5 |
0.444 | -0.027 | -3 | 0.295 |
CAMK1G |
0.444 | -0.045 | -3 | 0.328 |
VRK1 |
0.443 | -0.106 | 2 | 0.517 |
PLK4 |
0.443 | 0.003 | 2 | 0.376 |
ERK7 |
0.443 | -0.015 | 2 | 0.311 |
P70S6K |
0.443 | -0.033 | -3 | 0.299 |
BMPR1A |
0.443 | -0.034 | 1 | 0.220 |
KIS |
0.443 | -0.014 | 1 | 0.246 |
ACVR2B |
0.442 | -0.072 | -2 | 0.369 |
PLK3 |
0.441 | -0.047 | 2 | 0.455 |
DYRK4 |
0.439 | -0.015 | 1 | 0.193 |
GRK1 |
0.439 | -0.053 | -2 | 0.293 |
DAPK1 |
0.439 | -0.061 | -3 | 0.366 |
PASK |
0.438 | -0.084 | -3 | 0.378 |
TTBK1 |
0.438 | -0.021 | 2 | 0.385 |
PKG1 |
0.437 | -0.015 | -2 | 0.165 |
DRAK1 |
0.436 | -0.097 | 1 | 0.273 |
ALPHAK3 |
0.435 | -0.099 | -1 | 0.502 |
SNRK |
0.434 | -0.082 | 2 | 0.400 |
STK33 |
0.434 | -0.042 | 2 | 0.362 |
GRK4 |
0.432 | -0.112 | -2 | 0.304 |
GRK2 |
0.432 | -0.098 | -2 | 0.283 |
RIPK2 |
0.431 | -0.070 | 1 | 0.370 |
JNK1 |
0.429 | -0.047 | 1 | 0.184 |
CK1G1 |
0.424 | -0.041 | -3 | 0.174 |
CK2A2 |
0.424 | -0.002 | 1 | 0.174 |
PLK2 |
0.422 | -0.056 | -3 | 0.261 |
CK1E |
0.421 | -0.094 | -3 | 0.157 |
CK2A1 |
0.420 | -0.001 | 1 | 0.166 |
GRK3 |
0.420 | -0.091 | -2 | 0.251 |
CK1D |
0.420 | -0.083 | -3 | 0.131 |
CK1A2 |
0.414 | -0.090 | -3 | 0.135 |
YANK3 |
0.401 | -0.070 | 2 | 0.203 |
CK1G3 |
0.397 | -0.055 | -3 | 0.092 |
YANK2 |
0.394 | -0.072 | 2 | 0.221 |
CK1A |
0.385 | -0.098 | -3 | 0.095 |
CK1G2 |
0.363 | -0.097 | -3 | 0.141 |