Motif 1122 (n=57)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| O43353 | RIPK2 | S176 | ochoa|psp | Receptor-interacting serine/threonine-protein kinase 2 (EC 2.7.11.1) (CARD-containing interleukin-1 beta-converting enzyme-associated kinase) (CARD-containing IL-1 beta ICE-kinase) (RIP-like-interacting CLARP kinase) (Receptor-interacting protein 2) (RIP-2) (Tyrosine-protein kinase RIPK2) (EC 2.7.10.2) | Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:14638696, PubMed:17054981, PubMed:21123652, PubMed:28656966, PubMed:9575181, PubMed:9642260). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17054981, PubMed:17562858, PubMed:21123652, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:28545134, PubMed:29452636, PubMed:30026309, PubMed:30279485, PubMed:30478312). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:17562858, PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation (PubMed:14638696). Plays a role in the inactivation of RHOA in response to NGFR signaling (PubMed:26646181). {ECO:0000269|PubMed:14638696, ECO:0000269|PubMed:17054981, ECO:0000269|PubMed:17562858, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:21123652, ECO:0000269|PubMed:21887730, ECO:0000269|PubMed:22607974, ECO:0000269|PubMed:26646181, ECO:0000269|PubMed:28545134, ECO:0000269|PubMed:28656966, ECO:0000269|PubMed:29452636, ECO:0000269|PubMed:30026309, ECO:0000269|PubMed:30279485, ECO:0000269|PubMed:30478312, ECO:0000269|PubMed:9575181, ECO:0000269|PubMed:9642260}. |
| P00519 | ABL1 | Y393 | ochoa|psp | Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150) | Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9 (PubMed:22810897). Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (PubMed:28428613). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 also acts as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Regulates T-cell differentiation in a TBX21-dependent manner (By similarity). Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (By similarity). {ECO:0000250|UniProtKB:P00520, ECO:0000269|PubMed:10391250, ECO:0000269|PubMed:11971963, ECO:0000269|PubMed:12379650, ECO:0000269|PubMed:12531427, ECO:0000269|PubMed:12672821, ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:15556646, ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16424036, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:16943190, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:17623672, ECO:0000269|PubMed:18328268, ECO:0000269|PubMed:18945674, ECO:0000269|PubMed:19891780, ECO:0000269|PubMed:20357770, ECO:0000269|PubMed:20417104, ECO:0000269|PubMed:22810897, ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:9037071, ECO:0000269|PubMed:9144171, ECO:0000269|PubMed:9461559}. |
| P04626 | ERBB2 | T875 | ochoa | Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Metastatic lymph node gene 19 protein) (MLN 19) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (Tyrosine kinase-type cell surface receptor HER2) (p185erbB2) (CD antigen CD340) | Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization. {ECO:0000305}.; FUNCTION: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. {ECO:0000269|PubMed:10358079, ECO:0000269|PubMed:15380516, ECO:0000269|PubMed:21555369}. |
| P04629 | NTRK1 | Y680 | ochoa|psp | High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (TRK1-transforming tyrosine kinase protein) (Tropomyosin-related kinase A) (Tyrosine kinase receptor) (Tyrosine kinase receptor A) (Trk-A) (gp140trk) (p140-TrkA) | Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand (PubMed:1281417, PubMed:15488758, PubMed:17196528, PubMed:1849459, PubMed:1850821, PubMed:22649032, PubMed:27445338, PubMed:8325889). Can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival (By similarity). Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:1281417). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors. {ECO:0000250|UniProtKB:P35739, ECO:0000250|UniProtKB:Q3UFB7, ECO:0000269|PubMed:11244088, ECO:0000269|PubMed:1281417, ECO:0000269|PubMed:15488758, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:1849459, ECO:0000269|PubMed:1850821, ECO:0000269|PubMed:22649032, ECO:0000269|PubMed:27445338, ECO:0000269|PubMed:27676246, ECO:0000269|PubMed:8155326, ECO:0000269|PubMed:8325889}.; FUNCTION: [Isoform TrkA-III]: Resistant to NGF, it constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed. {ECO:0000269|PubMed:15488758}. |
| P06213 | INSR | Y1189 | ochoa|psp | Insulin receptor (IR) (EC 2.7.10.1) (CD antigen CD220) [Cleaved into: Insulin receptor subunit alpha; Insulin receptor subunit beta] | Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosine residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. In adipocytes, inhibits lipolysis (By similarity). {ECO:0000250|UniProtKB:P15208, ECO:0000269|PubMed:12138094, ECO:0000269|PubMed:16314505, ECO:0000269|PubMed:16831875, ECO:0000269|PubMed:8257688, ECO:0000269|PubMed:8276809, ECO:0000269|PubMed:8452530, ECO:0000269|PubMed:9428692}. |
| P06239 | LCK | Y394 | ochoa|psp | Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK) | Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-cell antigen receptor (TCR)-linked signal transduction pathways. Constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, thereby recruiting the associated LCK protein to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the cytoplasmic tails of the TCR-gamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. Once stimulated, the TCR recruits the tyrosine kinase ZAP70, that becomes phosphorylated and activated by LCK. Following this, a large number of signaling molecules are recruited, ultimately leading to lymphokine production. LCK also contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, which leads to hyperphosphorylation and activation of LCK. Also plays a role in the IL2 receptor-linked signaling pathway that controls the T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR. Phosphorylates other substrates including RUNX3, PTK2B/PYK2, the microtubule-associated protein MAPT, RHOH or TYROBP. Interacts with FYB2 (PubMed:27335501). {ECO:0000269|PubMed:16339550, ECO:0000269|PubMed:16709819, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20851766, ECO:0000269|PubMed:21269457, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:27335501, ECO:0000269|PubMed:38614099}. |
| P06241 | FYN | Y420 | ochoa|psp | Tyrosine-protein kinase Fyn (EC 2.7.10.2) (Proto-oncogene Syn) (Proto-oncogene c-Fyn) (Src-like kinase) (SLK) (p59-Fyn) | Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance (PubMed:11536198, PubMed:15489916, PubMed:15557120, PubMed:16387660, PubMed:20100835, PubMed:7568038, PubMed:7822789). Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain (PubMed:15489916). Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions (PubMed:15489916). Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin) (PubMed:17194753). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT (PubMed:14707117, PubMed:15536091). Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage (PubMed:16841086). Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6 (PubMed:14761972, PubMed:18258597, PubMed:19179337). Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein (PubMed:11162638, PubMed:12788081, PubMed:19652227). Involved in reelin signaling by mediating phosphorylation of DAB1 following reelin (RELN)-binding to its receptor (By similarity). Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation (PubMed:22080863). Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation (PubMed:20028775). Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts (PubMed:18056706). CSK maintains LCK and FYN in an inactive form (By similarity). Promotes CD28-induced phosphorylation of VAV1 (PubMed:11005864). In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (By similarity). Can also promote CD244-mediated NK cell activation (PubMed:15713798). {ECO:0000250|UniProtKB:P39688, ECO:0000269|PubMed:11005864, ECO:0000269|PubMed:11162638, ECO:0000269|PubMed:11536198, ECO:0000269|PubMed:12788081, ECO:0000269|PubMed:14707117, ECO:0000269|PubMed:14761972, ECO:0000269|PubMed:15536091, ECO:0000269|PubMed:15557120, ECO:0000269|PubMed:15713798, ECO:0000269|PubMed:16387660, ECO:0000269|PubMed:16841086, ECO:0000269|PubMed:17194753, ECO:0000269|PubMed:18056706, ECO:0000269|PubMed:18258597, ECO:0000269|PubMed:19179337, ECO:0000269|PubMed:19652227, ECO:0000269|PubMed:20028775, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:22080863, ECO:0000269|PubMed:7568038, ECO:0000269|PubMed:7822789, ECO:0000303|PubMed:15489916}. |
| P07332 | FES | Y713 | ochoa|psp | Tyrosine-protein kinase Fes/Fps (EC 2.7.10.2) (Feline sarcoma/Fujinami avian sarcoma oncogene homolog) (Proto-oncogene c-Fes) (Proto-oncogene c-Fps) (p93c-fes) | Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28. {ECO:0000269|PubMed:11509660, ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:15485904, ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:17595334, ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:19001085, ECO:0000269|PubMed:19051325, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:2656706, ECO:0000269|PubMed:8955135}. |
| P07947 | YES1 | Y426 | ochoa|psp | Tyrosine-protein kinase Yes (EC 2.7.10.2) (Proto-oncogene c-Yes) (p61-Yes) | Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGFR, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. Catalyzes phosphorylation of organic cation transporter OCT2 which induces its transport activity (PubMed:26979622). {ECO:0000269|PubMed:11901164, ECO:0000269|PubMed:18479465, ECO:0000269|PubMed:19276087, ECO:0000269|PubMed:21566460, ECO:0000269|PubMed:21713032, ECO:0000269|PubMed:26979622}. |
| P07948 | LYN | Y397 | ochoa|psp | Tyrosine-protein kinase Lyn (EC 2.7.10.2) (Lck/Yes-related novel protein tyrosine kinase) (V-yes-1 Yamaguchi sarcoma viral related oncogene homolog) (p53Lyn) (p56Lyn) | Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration (PubMed:36932076). Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-107'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (By similarity). Phosphorylates CLNK (By similarity). Phosphorylates BCAR1/CAS and NEDD9/HEF1 (PubMed:9020138). {ECO:0000250|UniProtKB:P25911, ECO:0000269|PubMed:10574931, ECO:0000269|PubMed:10748115, ECO:0000269|PubMed:10891478, ECO:0000269|PubMed:11435302, ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:11825908, ECO:0000269|PubMed:14726379, ECO:0000269|PubMed:15795233, ECO:0000269|PubMed:16467205, ECO:0000269|PubMed:17640867, ECO:0000269|PubMed:17977829, ECO:0000269|PubMed:18056483, ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18235045, ECO:0000269|PubMed:18577747, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19290919, ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:36122175, ECO:0000269|PubMed:36932076, ECO:0000269|PubMed:7687428, ECO:0000269|PubMed:9020138}. |
| P08069 | IGF1R | Y1165 | ochoa|psp | Insulin-like growth factor 1 receptor (EC 2.7.10.1) (Insulin-like growth factor I receptor) (IGF-I receptor) (CD antigen CD221) [Cleaved into: Insulin-like growth factor 1 receptor alpha chain; Insulin-like growth factor 1 receptor beta chain] | Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.; FUNCTION: When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin. |
| P08581 | MET | Y1234 | ochoa|psp | Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}. |
| P08631 | HCK | Y411 | ochoa|psp | Tyrosine-protein kinase HCK (EC 2.7.10.2) (Hematopoietic cell kinase) (Hemopoietic cell kinase) (p59-HCK/p60-HCK) (p59Hck) (p61Hck) | Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790, ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024, ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982, ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996, ECO:0000269|PubMed:9407116}. |
| P09769 | FGR | Y412 | ochoa|psp | Tyrosine-protein kinase Fgr (EC 2.7.10.2) (Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog) (Proto-oncogene c-Fgr) (p55-Fgr) (p58-Fgr) (p58c-Fgr) | Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as a negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as a positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production (By similarity). {ECO:0000250|UniProtKB:P14234, ECO:0000269|PubMed:10739672, ECO:0000269|PubMed:17164290, ECO:0000269|PubMed:1737799, ECO:0000269|PubMed:7519620}. |
| P11362 | FGFR1 | Y653 | ochoa|psp | Fibroblast growth factor receptor 1 (FGFR-1) (EC 2.7.10.1) (Basic fibroblast growth factor receptor 1) (BFGFR) (bFGF-R-1) (Fms-like tyrosine kinase 2) (FLT-2) (N-sam) (Proto-oncogene c-Fgr) (CD antigen CD331) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation. {ECO:0000250|UniProtKB:P16092, ECO:0000269|PubMed:10830168, ECO:0000269|PubMed:11353842, ECO:0000269|PubMed:12181353, ECO:0000269|PubMed:1379697, ECO:0000269|PubMed:1379698, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:19224897, ECO:0000269|PubMed:19261810, ECO:0000269|PubMed:19665973, ECO:0000269|PubMed:20133753, ECO:0000269|PubMed:20139426, ECO:0000269|PubMed:21765395, ECO:0000269|PubMed:8622701, ECO:0000269|PubMed:8663044}. |
| P12931 | SRC | Y419 | ochoa|psp | Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src) | Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors (PubMed:34234773). Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (PubMed:21411625). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Phosphorylates PKP3 at 'Tyr-195' in response to reactive oxygen species, which may cause the release of PKP3 from desmosome cell junctions into the cytoplasm (PubMed:25501895). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (By similarity). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1 (PubMed:11389730). Plays a role in EGF-mediated calcium-activated chloride channel activation (PubMed:18586953). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:7853507). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14585963, PubMed:8755529). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation (PubMed:16186108). Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731' (PubMed:20100835, PubMed:21309750). Enhances RIGI-elicited antiviral signaling (PubMed:19419966). Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376' (PubMed:14585963). Phosphorylates BCAR1 at 'Tyr-128' (PubMed:22710723). Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity (PubMed:20525694). Phosphorylates synaptic vesicle protein synaptophysin (SYP) (By similarity). Involved in anchorage-independent cell growth (PubMed:19307596). Required for podosome formation (By similarity). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). Phosphorylates caspase CASP8 at 'Tyr-380' which negatively regulates CASP8 processing and activation, down-regulating CASP8 proapoptotic function (PubMed:16619028). {ECO:0000250|UniProtKB:P05480, ECO:0000250|UniProtKB:Q9WUD9, ECO:0000269|PubMed:11389730, ECO:0000269|PubMed:12615910, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:16619028, ECO:0000269|PubMed:18586953, ECO:0000269|PubMed:19307596, ECO:0000269|PubMed:19419966, ECO:0000269|PubMed:20100835, ECO:0000269|PubMed:20525694, ECO:0000269|PubMed:21309750, ECO:0000269|PubMed:21411625, ECO:0000269|PubMed:22710723, ECO:0000269|PubMed:25501895, ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:34234773, ECO:0000269|PubMed:35927303, ECO:0000269|PubMed:7853507, ECO:0000269|PubMed:8755529, ECO:0000269|PubMed:8759729, ECO:0000305|PubMed:11964124, ECO:0000305|PubMed:8672527, ECO:0000305|PubMed:9442882}.; FUNCTION: [Isoform 1]: Non-receptor protein tyrosine kinase which phosphorylates synaptophysin with high affinity. {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 2]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in L1CAM-mediated neurite elongation, possibly by acting downstream of L1CAM to drive cytoskeletal rearrangements involved in neurite outgrowth (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}.; FUNCTION: [Isoform 3]: Non-receptor protein tyrosine kinase which shows higher basal kinase activity than isoform 1, possibly due to weakened intramolecular interactions which enhance autophosphorylation of Tyr-419 and subsequent activation (By similarity). The SH3 domain shows reduced affinity with the linker sequence between the SH2 and kinase domains which may account for the increased basal activity (By similarity). Displays altered substrate specificity compared to isoform 1, showing weak affinity for synaptophysin and for peptide substrates containing class I or class II SH3 domain-binding motifs (By similarity). Plays a role in neurite elongation (By similarity). {ECO:0000250|UniProtKB:Q9WUD9}. |
| P16591 | FER | Y714 | ochoa|psp | Tyrosine-protein kinase Fer (EC 2.7.10.2) (Feline encephalitis virus-related kinase FER) (Fujinami poultry sarcoma/Feline sarcoma-related protein Fer) (Proto-oncogene c-Fer) (Tyrosine kinase 3) (p94-Fer) | Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus. {ECO:0000269|PubMed:12972546, ECO:0000269|PubMed:14517306, ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:19339212, ECO:0000269|PubMed:19738202, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21518868, ECO:0000269|PubMed:22223638, ECO:0000269|PubMed:7623846, ECO:0000269|PubMed:9722593}. |
| P21802 | FGFR2 | Y656 | psp | Fibroblast growth factor receptor 2 (FGFR-2) (EC 2.7.10.1) (K-sam) (KGFR) (Keratinocyte growth factor receptor) (CD antigen CD332) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1. {ECO:0000269|PubMed:12529371, ECO:0000269|PubMed:15190072, ECO:0000269|PubMed:15629145, ECO:0000269|PubMed:16384934, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18374639, ECO:0000269|PubMed:19103595, ECO:0000269|PubMed:19387476, ECO:0000269|PubMed:19410646, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:8663044}. |
| P22455 | FGFR4 | Y642 | ochoa|psp | 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}. |
| P22607 | FGFR3 | Y647 | psp | Fibroblast growth factor receptor 3 (FGFR-3) (EC 2.7.10.1) (CD antigen CD333) | Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Required for normal development of the inner ear. Phosphorylates PLCG1, CBL and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Plays a role in the regulation of vitamin D metabolism. Mutations that lead to constitutive kinase activation or impair normal FGFR3 maturation, internalization and degradation lead to aberrant signaling. Over-expressed or constitutively activated FGFR3 promotes activation of PTPN11/SHP2, STAT1, STAT5A and STAT5B. Secreted isoform 3 retains its capacity to bind FGF1 and FGF2 and hence may interfere with FGF signaling. {ECO:0000269|PubMed:10611230, ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:11703096, ECO:0000269|PubMed:14534538, ECO:0000269|PubMed:16410555, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17145761, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17509076, ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:19286672, ECO:0000269|PubMed:8663044}. |
| P29323 | EPHB2 | S776 | ochoa | 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}. |
| P29323 | EPHB2 | Y780 | ochoa | 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}. |
| P30530 | AXL | Y702 | ochoa|psp | Tyrosine-protein kinase receptor UFO (EC 2.7.10.1) (AXL oncogene) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. {ECO:0000269|PubMed:10403904, ECO:0000269|PubMed:11484958, ECO:0000269|PubMed:12364394, ECO:0000269|PubMed:12490074, ECO:0000269|PubMed:15507525, ECO:0000269|PubMed:15733062, ECO:0000269|PubMed:1656220, ECO:0000269|PubMed:18840707}.; FUNCTION: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:21501828, ECO:0000269|PubMed:22156524, ECO:0000269|PubMed:25277499}.; FUNCTION: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope. {ECO:0000269|PubMed:22673088}.; FUNCTION: (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes (PubMed:28076778, PubMed:29379210, PubMed:31311882). Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection (PubMed:28076778). Interferon signaling inhibition occurs via an SOCS1-dependent mechanism (PubMed:29379210). {ECO:0000269|PubMed:28076778, ECO:0000269|PubMed:29379210, ECO:0000269|PubMed:31311882}. |
| P33981 | TTK | T676 | psp | Dual specificity protein kinase TTK (EC 2.7.12.1) (Phosphotyrosine picked threonine-protein kinase) (PYT) | Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments (PubMed:18243099, PubMed:28441529, PubMed:29162720). Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint (PubMed:18243099, PubMed:29162720). Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore (PubMed:18243099). Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments (PubMed:28441529). Phosphorylates KNL1, KNTC1 and autophosphorylates (PubMed:28441529). Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment (PubMed:30785839). {ECO:0000269|PubMed:18243099, ECO:0000269|PubMed:28441529, ECO:0000269|PubMed:29162720, ECO:0000269|PubMed:30785839}. |
| P42680 | TEC | Y519 | ochoa|psp | 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 | Y420 | psp | 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}. |
| P42684 | ABL2 | Y439 | ochoa|psp | Tyrosine-protein kinase ABL2 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 2) (Abelson tyrosine-protein kinase 2) (Abelson-related gene protein) (Tyrosine-protein kinase ARG) | Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (By similarity). {ECO:0000250|UniProtKB:Q4JIM5, ECO:0000269|PubMed:15735735, ECO:0000269|PubMed:15886098, ECO:0000269|PubMed:16678104, ECO:0000269|PubMed:17306540, ECO:0000269|PubMed:18945674}. |
| P51451 | BLK | Y389 | ochoa|psp | Tyrosine-protein kinase Blk (EC 2.7.10.2) (B lymphocyte kinase) (p55-Blk) | Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling (By similarity). B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors (By similarity). Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation (By similarity). Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor (By similarity). Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207' (By similarity). Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C (PubMed:8756631). With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation (By similarity). Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation (By similarity). In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose (PubMed:19667185). Phosphorylates CGAS, promoting retention of CGAS in the cytosol (PubMed:30356214). {ECO:0000250|UniProtKB:P16277, ECO:0000269|PubMed:19667185, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:8756631}. |
| P51617 | IRAK1 | S370 | ochoa | Interleukin-1 receptor-associated kinase 1 (IRAK-1) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}. |
| P51813 | BMX | Y566 | psp | Cytoplasmic tyrosine-protein kinase BMX (EC 2.7.10.2) (Bone marrow tyrosine kinase gene in chromosome X protein) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38) | Non-receptor tyrosine kinase that plays central but diverse modulatory roles in various signaling processes involved in the regulation of actin reorganization, cell migration, cell proliferation and survival, cell adhesion, and apoptosis. Participates in signal transduction stimulated by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen receptors and integrins. Induces tyrosine phosphorylation of BCAR1 in response to integrin regulation. Activation of BMX by integrins is mediated by PTK2/FAK1, a key mediator of integrin signaling events leading to the regulation of actin cytoskeleton and cell motility. Plays a critical role in TNF-induced angiogenesis, and implicated in the signaling of TEK and FLT1 receptors, 2 important receptor families essential for angiogenesis. Required for the phosphorylation and activation of STAT3, a transcription factor involved in cell differentiation. Also involved in interleukin-6 (IL6) induced differentiation. Also plays a role in programming adaptive cytoprotection against extracellular stress in different cell systems, salivary epithelial cells, brain endothelial cells, and dermal fibroblasts. May be involved in regulation of endocytosis through its interaction with an endosomal protein RUFY1. May also play a role in the growth and differentiation of hematopoietic cells; as well as in signal transduction in endocardial and arterial endothelial cells. {ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:12370298, ECO:0000269|PubMed:12832404, ECO:0000269|PubMed:15788485, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:9520419}. |
| P54753 | EPHB3 | Y792 | ochoa | 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 | S770 | ochoa | 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}. |
| P54760 | EPHB4 | Y774 | ochoa|psp | 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}. |
| P54762 | EPHB1 | S774 | ochoa | Ephrin type-B receptor 1 (EC 2.7.10.1) (ELK) (EPH tyrosine kinase 2) (EPH-like kinase 6) (EK6) (hEK6) (Neuronally-expressed EPH-related tyrosine kinase) (NET) (Tyrosine-protein kinase receptor EPH-2) | Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Cognate/functional ephrin ligands for this receptor include EFNB1, EFNB2 and EFNB3. During nervous system development, regulates retinal axon guidance redirecting ipsilaterally ventrotemporal retinal ganglion cells axons at the optic chiasm midline. This probably requires repulsive interaction with EFNB2. In the adult nervous system together with EFNB3, regulates chemotaxis, proliferation and polarity of the hippocampus neural progenitors. In addition to its role in axon guidance also plays an important redundant role with other ephrin-B receptors in development and maturation of dendritic spines and synapse formation. May also regulate angiogenesis. More generally, may play a role in targeted cell migration and adhesion. Upon activation by EFNB1 and probably other ephrin-B ligands activates the MAPK/ERK and the JNK signaling cascades to regulate cell migration and adhesion respectively. Involved in the maintenance of the pool of satellite cells (muscle stem cells) by promoting their self-renewal and reducing their activation and differentiation (By similarity). {ECO:0000250|UniProtKB:Q8CBF3, ECO:0000269|PubMed:12223469, ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:18034775, ECO:0000269|PubMed:9430661, ECO:0000269|PubMed:9499402}. |
| Q04912 | MST1R | Y1238 | ochoa|psp | Macrophage-stimulating protein receptor (MSP receptor) (EC 2.7.10.1) (CDw136) (Protein-tyrosine kinase 8) (p185-Ron) (CD antigen CD136) [Cleaved into: Macrophage-stimulating protein receptor alpha chain; Macrophage-stimulating protein receptor beta chain] | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Also plays a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}. |
| Q05397 | PTK2 | Y576 | ochoa|psp | Focal adhesion kinase 1 (FADK 1) (EC 2.7.10.2) (Focal adhesion kinase-related nonkinase) (FRNK) (Protein phosphatase 1 regulatory subunit 71) (PPP1R71) (Protein-tyrosine kinase 2) (p125FAK) (pp125FAK) | Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698, ECO:0000269|PubMed:9360983}.; FUNCTION: [Isoform 6]: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:20109444}. |
| Q05655 | PRKCD | S503 | ochoa|psp | Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] | Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}. |
| Q06187 | BTK | Y551 | ochoa|psp | 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}. |
| Q08345 | DDR1 | Y796 | ochoa|psp | Epithelial discoidin domain-containing receptor 1 (Epithelial discoidin domain receptor 1) (EC 2.7.10.1) (CD167 antigen-like family member A) (Cell adhesion kinase) (Discoidin receptor tyrosine kinase) (HGK2) (Mammary carcinoma kinase 10) (MCK-10) (Protein-tyrosine kinase 3A) (Protein-tyrosine kinase RTK-6) (TRK E) (Tyrosine kinase DDR) (Tyrosine-protein kinase CAK) (CD antigen CD167a) | Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing. Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing. Also plays a role in tumor cell invasion. Phosphorylates PTPN11. {ECO:0000250, ECO:0000269|PubMed:12065315, ECO:0000269|PubMed:16234985, ECO:0000269|PubMed:16337946, ECO:0000269|PubMed:19401332, ECO:0000269|PubMed:20093046, ECO:0000269|PubMed:20432435, ECO:0000269|PubMed:20884741, ECO:0000269|PubMed:21044884, ECO:0000269|PubMed:9659899}. |
| Q08881 | ITK | Y512 | ochoa|psp | Tyrosine-protein kinase ITK/TSK (EC 2.7.10.2) (Interleukin-2-inducible T-cell kinase) (IL-2-inducible T-cell kinase) (Kinase EMT) (T-cell-specific kinase) (Tyrosine-protein kinase Lyk) | Tyrosine kinase that plays an essential role 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 lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and 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. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation (PubMed:12186560, PubMed:12682224, PubMed:21725281). Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (By similarity). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity). {ECO:0000250|UniProtKB:Q03526, ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}. |
| Q12866 | MERTK | Y753 | psp | Tyrosine-protein kinase Mer (EC 2.7.10.1) (Proto-oncogene c-Mer) (Receptor tyrosine kinase MerTK) | Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment (PubMed:32640697). Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. {ECO:0000269|PubMed:17005688, ECO:0000269|PubMed:32640697}. |
| Q13882 | PTK6 | Y342 | ochoa|psp | Protein-tyrosine kinase 6 (EC 2.7.10.2) (Breast tumor kinase) (Tyrosine-protein kinase BRK) | Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Phosphorylates the GTPase-activating protein ARAP1 following EGF stimulation which enhances EGFR signaling by delaying EGFR down-regulation (PubMed:20554524). Also associates with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage-independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways. {ECO:0000269|PubMed:20554524}.; FUNCTION: [Isoform 2]: Inhibits PTK6 phosphorylation and PTK6 association with other tyrosine-phosphorylated proteins. |
| Q14004 | CDK13 | S867 | ochoa | Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) | Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}. |
| Q14289 | PTK2B | Y579 | ochoa|psp | Protein-tyrosine kinase 2-beta (EC 2.7.10.2) (Calcium-dependent tyrosine kinase) (CADTK) (Calcium-regulated non-receptor proline-rich tyrosine kinase) (Cell adhesion kinase beta) (CAK-beta) (CAKB) (Focal adhesion kinase 2) (FADK 2) (Proline-rich tyrosine kinase 2) (Related adhesion focal tyrosine kinase) (RAFTK) | Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T-cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}. |
| Q16288 | NTRK3 | Y709 | psp | NT-3 growth factor receptor (EC 2.7.10.1) (GP145-TrkC) (Trk-C) (Neurotrophic tyrosine kinase receptor type 3) (TrkC tyrosine kinase) | Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation. {ECO:0000269|PubMed:25196463}. |
| Q16620 | NTRK2 | Y706 | psp | BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (GP145-TrkB) (Trk-B) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Tropomyosin-related kinase B) | Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity (By similarity). Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2 (PubMed:15494731, PubMed:7574684). Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:15494731). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia. {ECO:0000250|UniProtKB:P15209, ECO:0000269|PubMed:15494731, ECO:0000269|PubMed:7574684}. |
| Q16832 | DDR2 | Y740 | psp | Discoidin domain-containing receptor 2 (Discoidin domain receptor 2) (EC 2.7.10.1) (CD167 antigen-like family member B) (Discoidin domain-containing receptor tyrosine kinase 2) (Neurotrophic tyrosine kinase, receptor-related 3) (Receptor protein-tyrosine kinase TKT) (Tyrosine-protein kinase TYRO10) (CD antigen CD167b) | Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as a cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing. {ECO:0000269|PubMed:16186104, ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:17665456, ECO:0000269|PubMed:18201965, ECO:0000269|PubMed:20004161, ECO:0000269|PubMed:20564243, ECO:0000269|PubMed:20734453, ECO:0000269|PubMed:30449416, ECO:0000269|PubMed:9659899}. |
| Q8TDX7 | NEK7 | T191 | ochoa | Serine/threonine-protein kinase Nek7 (EC 2.7.11.34) (Never in mitosis A-related kinase 7) (NimA-related protein kinase 7) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132, PubMed:19941817, PubMed:31409757). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596, PubMed:19941817, PubMed:26522158, PubMed:31409757). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). Phosphorylates RPS6KB1 (By similarity). Acts as an essential activator of the NLRP3 inflammasome assembly independently of its kinase activity (PubMed:26642356, PubMed:36442502, PubMed:39173637). Acts by unlocking NLRP3 following NLRP3 tranlocation into the microtubule organizing center (MTOC), relieving NLRP3 autoinhibition and promoting formation of the NLRP3:PYCARD complex, and activation of CASP1 (PubMed:26642356, PubMed:31189953, PubMed:36442502, PubMed:39173637). Serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division: interaction with NEK9 prevents interaction with NLRP3 and activation of the inflammasome during mitosis (PubMed:26642356, PubMed:31189953). {ECO:0000250|UniProtKB:D3ZBE5, ECO:0000269|PubMed:17101132, ECO:0000269|PubMed:17586473, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:19941817, ECO:0000269|PubMed:26522158, ECO:0000269|PubMed:26642356, ECO:0000269|PubMed:31189953, ECO:0000269|PubMed:31409757, ECO:0000269|PubMed:36442502, ECO:0000269|PubMed:39173637}. |
| Q9H3Y6 | SRMS | Y380 | psp | Tyrosine-protein kinase Srms (EC 2.7.10.2) | Non-receptor tyrosine-protein kinase which phosphorylates DOK1 on tyrosine residues (PubMed:23822091). Also phosphorylates KHDRBS1/SAM68 and VIM on tyrosine residues (PubMed:29496907). Phosphorylation of KHDRBS1 is EGF-dependent (PubMed:29496907). Phosphorylates OTUB1, promoting deubiquitination of RPTOR (PubMed:35927303). {ECO:0000269|PubMed:23822091, ECO:0000269|PubMed:29496907, ECO:0000269|PubMed:35927303}. |
| Q9HC98 | NEK6 | T202 | ochoa|psp | Serine/threonine-protein kinase Nek6 (EC 2.7.11.34) (Never in mitosis A-related kinase 6) (NimA-related protein kinase 6) (Protein kinase SID6-1512) | Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:11516946, PubMed:14563848). Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis (PubMed:19414596). Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3 (PubMed:12054534, PubMed:20873783). Phosphorylates KIF11 to promote mitotic spindle formation (PubMed:19001501). Involved in G2/M phase cell cycle arrest induced by DNA damage (PubMed:18728393). Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (PubMed:21099361). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757). {ECO:0000269|PubMed:11516946, ECO:0000269|PubMed:12054534, ECO:0000269|PubMed:14563848, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19001501, ECO:0000269|PubMed:19414596, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:21099361, ECO:0000269|PubMed:31409757}. |
| Q9NYV4 | CDK12 | S889 | ochoa | Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) | Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| Q9UM73 | ALK | Y1282 | psp | ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246) | Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}. |
| O15146 | MUSK | Y755 | 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}. |
| P07949 | RET | S904 | Sugiyama | 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}. |
| P14616 | INSRR | Y1145 | Sugiyama | Insulin receptor-related protein (IRR) (EC 2.7.10.1) (IR-related receptor) [Cleaved into: Insulin receptor-related protein alpha chain; Insulin receptor-related protein beta chain] | Receptor with tyrosine-protein kinase activity. Functions as a pH sensing receptor which is activated by increased extracellular pH. Activates an intracellular signaling pathway that involves IRS1 and AKT1/PKB. {ECO:0000269|PubMed:21641549}. |
| P51955 | NEK2 | S171 | SIGNOR|EPSD|PSP|Sugiyama | Serine/threonine-protein kinase Nek2 (EC 2.7.11.1) (HSPK 21) (Never in mitosis A-related kinase 2) (NimA-related protein kinase 2) (NimA-like protein kinase 1) | Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143). Involved in the regulation of centrosome disjunction (PubMed:26220856). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835). {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344, ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308, ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858, ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856, ECO:0000269|PubMed:30404835}.; FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}.; FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells. {ECO:0000269|PubMed:15161910}. |
| Q9UBE8 | NLK | S294 | Sugiyama | Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1) | Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 1.110223e-16 | 15.955 |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer | 1.110223e-16 | 15.955 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1.110223e-16 | 15.955 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 1.110223e-16 | 15.955 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 1.110223e-16 | 15.955 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 3.330669e-16 | 15.477 |
| R-HSA-1226099 | Signaling by FGFR in disease | 6.661338e-16 | 15.176 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 2.886580e-15 | 14.540 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 3.330669e-15 | 14.477 |
| R-HSA-162582 | Signal Transduction | 2.756684e-13 | 12.560 |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | 4.317324e-12 | 11.365 |
| R-HSA-2428924 | IGF1R signaling cascade | 6.525225e-12 | 11.185 |
| R-HSA-74751 | Insulin receptor signalling cascade | 6.525225e-12 | 11.185 |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | 7.459033e-12 | 11.127 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 1.130263e-11 | 10.947 |
| R-HSA-109704 | PI3K Cascade | 2.944911e-11 | 10.531 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 7.477574e-11 | 10.126 |
| R-HSA-112399 | IRS-mediated signalling | 7.974199e-11 | 10.098 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 1.016993e-10 | 9.993 |
| R-HSA-74752 | Signaling by Insulin receptor | 1.873881e-10 | 9.727 |
| R-HSA-190236 | Signaling by FGFR | 3.534085e-10 | 9.452 |
| R-HSA-1433557 | Signaling by SCF-KIT | 3.563025e-10 | 9.448 |
| R-HSA-3928665 | EPH-ephrin mediated repulsion of cells | 6.410181e-10 | 9.193 |
| R-HSA-422475 | Axon guidance | 6.872549e-10 | 9.163 |
| R-HSA-5683057 | MAPK family signaling cascades | 7.794021e-10 | 9.108 |
| R-HSA-9675108 | Nervous system development | 1.853516e-09 | 8.732 |
| R-HSA-3928664 | Ephrin signaling | 3.136974e-09 | 8.503 |
| R-HSA-2682334 | EPH-Ephrin signaling | 3.939489e-09 | 8.405 |
| R-HSA-210990 | PECAM1 interactions | 1.448189e-08 | 7.839 |
| R-HSA-1433559 | Regulation of KIT signaling | 5.005562e-08 | 7.301 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 7.528684e-08 | 7.123 |
| R-HSA-1839126 | FGFR2 mutant receptor activation | 1.232912e-07 | 6.909 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 1.516549e-07 | 6.819 |
| R-HSA-9664407 | Parasite infection | 1.516549e-07 | 6.819 |
| R-HSA-9664417 | Leishmania phagocytosis | 1.516549e-07 | 6.819 |
| R-HSA-8851708 | Signaling by FGFR2 IIIa TM | 2.058297e-07 | 6.686 |
| R-HSA-389513 | Co-inhibition by CTLA4 | 2.514080e-07 | 6.600 |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... | 4.376752e-07 | 6.359 |
| R-HSA-9669938 | Signaling by KIT in disease | 4.376752e-07 | 6.359 |
| R-HSA-5655253 | Signaling by FGFR2 in disease | 6.977334e-07 | 6.156 |
| R-HSA-1227986 | Signaling by ERBB2 | 1.738535e-06 | 5.760 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 2.794163e-06 | 5.554 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 2.794163e-06 | 5.554 |
| R-HSA-1643685 | Disease | 2.737610e-06 | 5.563 |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | 4.818688e-06 | 5.317 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 7.265260e-06 | 5.139 |
| R-HSA-912631 | Regulation of signaling by CBL | 8.655547e-06 | 5.063 |
| R-HSA-5654221 | Phospholipase C-mediated cascade; FGFR2 | 1.015052e-05 | 4.994 |
| R-HSA-190241 | FGFR2 ligand binding and activation | 1.182771e-05 | 4.927 |
| R-HSA-389356 | Co-stimulation by CD28 | 1.249470e-05 | 4.903 |
| R-HSA-164944 | Nef and signal transduction | 1.608033e-05 | 4.794 |
| R-HSA-2029481 | FCGR activation | 1.816512e-05 | 4.741 |
| R-HSA-187015 | Activation of TRKA receptors | 2.197516e-05 | 4.658 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 | 2.343433e-05 | 4.630 |
| R-HSA-9032500 | Activated NTRK2 signals through FYN | 2.913904e-05 | 4.536 |
| R-HSA-5654699 | SHC-mediated cascade:FGFR2 | 2.985536e-05 | 4.525 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 2.985536e-05 | 4.525 |
| R-HSA-166520 | Signaling by NTRKs | 2.800136e-05 | 4.553 |
| R-HSA-9658195 | Leishmania infection | 2.898155e-05 | 4.538 |
| R-HSA-9824443 | Parasitic Infection Pathways | 2.898155e-05 | 4.538 |
| R-HSA-5654700 | FRS-mediated FGFR2 signaling | 3.350911e-05 | 4.475 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 6.296150e-05 | 4.201 |
| R-HSA-5654696 | Downstream signaling of activated FGFR2 | 7.559575e-05 | 4.122 |
| R-HSA-209543 | p75NTR recruits signalling complexes | 8.800099e-05 | 4.056 |
| R-HSA-5654738 | Signaling by FGFR2 | 1.051143e-04 | 3.978 |
| R-HSA-194138 | Signaling by VEGF | 9.830431e-05 | 4.007 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 1.021705e-04 | 3.991 |
| R-HSA-2033514 | FGFR3 mutant receptor activation | 1.051578e-04 | 3.978 |
| R-HSA-1839130 | Signaling by activated point mutants of FGFR3 | 1.051578e-04 | 3.978 |
| R-HSA-391160 | Signal regulatory protein family interactions | 1.243597e-04 | 3.905 |
| R-HSA-9607240 | FLT3 Signaling | 1.259400e-04 | 3.900 |
| R-HSA-193639 | p75NTR signals via NF-kB | 1.457105e-04 | 3.837 |
| R-HSA-418885 | DCC mediated attractive signaling | 1.457105e-04 | 3.837 |
| R-HSA-69236 | G1 Phase | 1.707453e-04 | 3.768 |
| R-HSA-69231 | Cyclin D associated events in G1 | 1.707453e-04 | 3.768 |
| R-HSA-2033519 | Activated point mutants of FGFR2 | 2.546173e-04 | 3.594 |
| R-HSA-1839120 | Signaling by FGFR1 amplification mutants | 3.304373e-04 | 3.481 |
| R-HSA-2023837 | Signaling by FGFR2 amplification mutants | 3.304373e-04 | 3.481 |
| R-HSA-187042 | TRKA activation by NGF | 3.304373e-04 | 3.481 |
| R-HSA-1266738 | Developmental Biology | 3.758271e-04 | 3.425 |
| R-HSA-212436 | Generic Transcription Pathway | 4.029536e-04 | 3.395 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 5.505726e-04 | 3.259 |
| R-HSA-8848021 | Signaling by PTK6 | 5.505726e-04 | 3.259 |
| R-HSA-373755 | Semaphorin interactions | 5.505726e-04 | 3.259 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 5.222576e-04 | 3.282 |
| R-HSA-164952 | The role of Nef in HIV-1 replication and disease pathogenesis | 4.990228e-04 | 3.302 |
| R-HSA-168249 | Innate Immune System | 5.394600e-04 | 3.268 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 5.277985e-04 | 3.278 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 5.277985e-04 | 3.278 |
| R-HSA-2871809 | FCERI mediated Ca+2 mobilization | 6.025015e-04 | 3.220 |
| R-HSA-8849472 | PTK6 Down-Regulation | 6.432845e-04 | 3.192 |
| R-HSA-9032759 | NTRK2 activates RAC1 | 6.432845e-04 | 3.192 |
| R-HSA-8939245 | RUNX1 regulates transcription of genes involved in BCR signaling | 6.432845e-04 | 3.192 |
| R-HSA-8874081 | MET activates PTK2 signaling | 6.629671e-04 | 3.179 |
| R-HSA-9006115 | Signaling by NTRK2 (TRKB) | 7.243633e-04 | 3.140 |
| R-HSA-5655332 | Signaling by FGFR3 in disease | 7.243633e-04 | 3.140 |
| R-HSA-187024 | NGF-independant TRKA activation | 8.373690e-04 | 3.077 |
| R-HSA-2424491 | DAP12 signaling | 9.299121e-04 | 3.032 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 7.892676e-04 | 3.103 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 8.980253e-04 | 3.047 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 7.892676e-04 | 3.103 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 1.056215e-03 | 2.976 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.085509e-03 | 2.964 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 1.114684e-03 | 2.953 |
| R-HSA-73857 | RNA Polymerase II Transcription | 1.157266e-03 | 2.937 |
| R-HSA-354192 | Integrin signaling | 1.169098e-03 | 2.932 |
| R-HSA-1839124 | FGFR1 mutant receptor activation | 1.169098e-03 | 2.932 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 1.169098e-03 | 2.932 |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K | 1.299566e-03 | 2.886 |
| R-HSA-428890 | Role of ABL in ROBO-SLIT signaling | 1.299566e-03 | 2.886 |
| R-HSA-8849473 | PTK6 Expression | 1.299566e-03 | 2.886 |
| R-HSA-187687 | Signalling to ERKs | 1.443880e-03 | 2.840 |
| R-HSA-114604 | GPVI-mediated activation cascade | 1.543706e-03 | 2.811 |
| R-HSA-8941326 | RUNX2 regulates bone development | 1.543706e-03 | 2.811 |
| R-HSA-8875878 | MET promotes cell motility | 1.756103e-03 | 2.755 |
| R-HSA-201556 | Signaling by ALK | 1.868801e-03 | 2.728 |
| R-HSA-5655302 | Signaling by FGFR1 in disease | 2.233630e-03 | 2.651 |
| R-HSA-983695 | Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... | 2.150215e-03 | 2.668 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 1.869845e-03 | 2.728 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 1.933065e-03 | 2.714 |
| R-HSA-202733 | Cell surface interactions at the vascular wall | 2.323691e-03 | 2.634 |
| R-HSA-190377 | FGFR2b ligand binding and activation | 2.512950e-03 | 2.600 |
| R-HSA-9020558 | Interleukin-2 signaling | 2.512950e-03 | 2.600 |
| R-HSA-2172127 | DAP12 interactions | 2.639791e-03 | 2.578 |
| R-HSA-373752 | Netrin-1 signaling | 2.639791e-03 | 2.578 |
| R-HSA-76009 | Platelet Aggregation (Plug Formation) | 2.784624e-03 | 2.555 |
| R-HSA-5654741 | Signaling by FGFR3 | 2.784624e-03 | 2.555 |
| R-HSA-1839122 | Signaling by activated point mutants of FGFR1 | 2.875041e-03 | 2.541 |
| R-HSA-75153 | Apoptotic execution phase | 2.934271e-03 | 2.532 |
| R-HSA-109582 | Hemostasis | 3.097717e-03 | 2.509 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 3.297485e-03 | 2.482 |
| R-HSA-190375 | FGFR2c ligand binding and activation | 3.667994e-03 | 2.436 |
| R-HSA-389359 | CD28 dependent Vav1 pathway | 3.667994e-03 | 2.436 |
| R-HSA-75892 | Platelet Adhesion to exposed collagen | 3.667994e-03 | 2.436 |
| R-HSA-9700649 | Drug resistance of ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717301 | NVP-TAE684-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717326 | crizotinib-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717264 | ASP-3026-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717323 | ceritinib-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717329 | lorlatinib-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717316 | alectinib-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-9717319 | brigatinib-resistant ALK mutants | 5.202999e-03 | 2.284 |
| R-HSA-399956 | CRMPs in Sema3A signaling | 4.098371e-03 | 2.387 |
| R-HSA-5654227 | Phospholipase C-mediated cascade; FGFR3 | 4.098371e-03 | 2.387 |
| R-HSA-8847993 | ERBB2 Activates PTK6 Signaling | 4.098371e-03 | 2.387 |
| R-HSA-354194 | GRB2:SOS provides linkage to MAPK signaling for Integrins | 5.025728e-03 | 2.299 |
| R-HSA-399955 | SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion | 5.025728e-03 | 2.299 |
| R-HSA-5654736 | Signaling by FGFR1 | 4.706278e-03 | 2.327 |
| R-HSA-190239 | FGFR3 ligand binding and activation | 4.551028e-03 | 2.342 |
| R-HSA-169893 | Prolonged ERK activation events | 5.025728e-03 | 2.299 |
| R-HSA-399954 | Sema3A PAK dependent Axon repulsion | 4.551028e-03 | 2.342 |
| R-HSA-8866910 | TFAP2 (AP-2) family regulates transcription of growth factors and their receptor... | 5.522233e-03 | 2.258 |
| R-HSA-5654219 | Phospholipase C-mediated cascade: FGFR1 | 6.040311e-03 | 2.219 |
| R-HSA-372708 | p130Cas linkage to MAPK signaling for integrins | 6.040311e-03 | 2.219 |
| R-HSA-74160 | Gene expression (Transcription) | 6.207877e-03 | 2.207 |
| R-HSA-449147 | Signaling by Interleukins | 6.573837e-03 | 2.182 |
| R-HSA-190242 | FGFR1 ligand binding and activation | 6.579727e-03 | 2.182 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 6.831235e-03 | 2.166 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 | 7.140253e-03 | 2.146 |
| R-HSA-9734091 | Drug-mediated inhibition of MET activation | 1.037925e-02 | 1.984 |
| R-HSA-5654704 | SHC-mediated cascade:FGFR3 | 8.323717e-03 | 2.080 |
| R-HSA-9034015 | Signaling by NTRK3 (TRKC) | 8.946203e-03 | 2.048 |
| R-HSA-5654706 | FRS-mediated FGFR3 signaling | 8.946203e-03 | 2.048 |
| R-HSA-9938206 | Developmental Lineage of Mammary Stem Cells | 9.588893e-03 | 2.018 |
| R-HSA-5654688 | SHC-mediated cascade:FGFR1 | 1.093400e-02 | 1.961 |
| R-HSA-5654693 | FRS-mediated FGFR1 signaling | 1.163597e-02 | 1.934 |
| R-HSA-6806834 | Signaling by MET | 1.119175e-02 | 1.951 |
| R-HSA-5654689 | PI-3K cascade:FGFR1 | 9.588893e-03 | 2.018 |
| R-HSA-8876384 | Listeria monocytogenes entry into host cells | 8.946203e-03 | 2.048 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 1.163597e-02 | 1.934 |
| R-HSA-9705462 | Inactivation of CSF3 (G-CSF) signaling | 8.946203e-03 | 2.048 |
| R-HSA-167044 | Signalling to RAS | 8.323717e-03 | 2.080 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 1.163597e-02 | 1.934 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 8.323717e-03 | 2.080 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 8.946203e-03 | 2.048 |
| R-HSA-9830364 | Formation of the nephric duct | 1.163597e-02 | 1.934 |
| R-HSA-9825892 | Regulation of MITF-M-dependent genes involved in cell cycle and proliferation | 8.946203e-03 | 2.048 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 1.093400e-02 | 1.961 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 1.128380e-02 | 1.948 |
| R-HSA-1500931 | Cell-Cell communication | 8.397027e-03 | 2.076 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 1.088921e-02 | 1.963 |
| R-HSA-9022699 | MECP2 regulates neuronal receptors and channels | 1.235728e-02 | 1.908 |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling | 1.309769e-02 | 1.883 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 1.378530e-02 | 1.861 |
| R-HSA-5654708 | Downstream signaling of activated FGFR3 | 1.463500e-02 | 1.835 |
| R-HSA-9674555 | Signaling by CSF3 (G-CSF) | 1.463500e-02 | 1.835 |
| R-HSA-9927432 | Developmental Lineage of Mammary Gland Myoepithelial Cells | 1.463500e-02 | 1.835 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 1.463500e-02 | 1.835 |
| R-HSA-5663205 | Infectious disease | 1.488602e-02 | 1.827 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 1.543148e-02 | 1.812 |
| R-HSA-1839128 | FGFR4 mutant receptor activation | 1.552888e-02 | 1.809 |
| R-HSA-9603505 | NTRK3 as a dependence receptor | 1.552888e-02 | 1.809 |
| R-HSA-2033515 | t(4;14) translocations of FGFR3 | 1.552888e-02 | 1.809 |
| R-HSA-8853333 | Signaling by FGFR2 fusions | 1.552888e-02 | 1.809 |
| R-HSA-8853334 | Signaling by FGFR3 fusions in cancer | 1.552888e-02 | 1.809 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 1.773351e-02 | 1.751 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 1.968374e-02 | 1.706 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 1.968374e-02 | 1.706 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 2.015353e-02 | 1.696 |
| R-HSA-5654687 | Downstream signaling of activated FGFR1 | 2.058675e-02 | 1.686 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 2.058675e-02 | 1.686 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 2.058675e-02 | 1.686 |
| R-HSA-9665230 | Drug resistance in ERBB2 KD mutants | 2.065203e-02 | 1.685 |
| R-HSA-9024909 | BDNF activates NTRK2 (TRKB) signaling | 2.065203e-02 | 1.685 |
| R-HSA-9025046 | NTF3 activates NTRK2 (TRKB) signaling | 2.065203e-02 | 1.685 |
| R-HSA-9026357 | NTF4 activates NTRK2 (TRKB) signaling | 2.065203e-02 | 1.685 |
| R-HSA-9652282 | Drug-mediated inhibition of ERBB2 signaling | 2.065203e-02 | 1.685 |
| R-HSA-9034013 | NTF3 activates NTRK3 signaling | 2.065203e-02 | 1.685 |
| R-HSA-9665246 | Resistance of ERBB2 KD mutants to neratinib | 2.065203e-02 | 1.685 |
| R-HSA-9665737 | Drug resistance in ERBB2 TMD/JMD mutants | 2.065203e-02 | 1.685 |
| R-HSA-9665245 | Resistance of ERBB2 KD mutants to tesevatinib | 2.065203e-02 | 1.685 |
| R-HSA-9665247 | Resistance of ERBB2 KD mutants to osimertinib | 2.065203e-02 | 1.685 |
| R-HSA-9665244 | Resistance of ERBB2 KD mutants to sapitinib | 2.065203e-02 | 1.685 |
| R-HSA-9665233 | Resistance of ERBB2 KD mutants to trastuzumab | 2.065203e-02 | 1.685 |
| R-HSA-9665251 | Resistance of ERBB2 KD mutants to lapatinib | 2.065203e-02 | 1.685 |
| R-HSA-9665249 | Resistance of ERBB2 KD mutants to afatinib | 2.065203e-02 | 1.685 |
| R-HSA-9665250 | Resistance of ERBB2 KD mutants to AEE788 | 2.065203e-02 | 1.685 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 2.111686e-02 | 1.675 |
| R-HSA-8853659 | RET signaling | 2.150681e-02 | 1.667 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 2.260865e-02 | 1.646 |
| R-HSA-167021 | PLC-gamma1 signalling | 2.574884e-02 | 1.589 |
| R-HSA-9034793 | Activated NTRK3 signals through PLCG1 | 2.574884e-02 | 1.589 |
| R-HSA-8853336 | Signaling by plasma membrane FGFR1 fusions | 2.574884e-02 | 1.589 |
| R-HSA-8875513 | MET interacts with TNS proteins | 2.574884e-02 | 1.589 |
| R-HSA-198745 | Signalling to STAT3 | 2.574884e-02 | 1.589 |
| R-HSA-8865999 | MET activates PTPN11 | 2.574884e-02 | 1.589 |
| R-HSA-9026527 | Activated NTRK2 signals through PLCG1 | 3.081944e-02 | 1.511 |
| R-HSA-1307965 | betaKlotho-mediated ligand binding | 3.081944e-02 | 1.511 |
| R-HSA-1251932 | PLCG1 events in ERBB2 signaling | 3.081944e-02 | 1.511 |
| R-HSA-1306955 | GRB7 events in ERBB2 signaling | 3.081944e-02 | 1.511 |
| R-HSA-74713 | IRS activation | 3.586396e-02 | 1.445 |
| R-HSA-190374 | FGFR1c and Klotho ligand binding and activation | 3.586396e-02 | 1.445 |
| R-HSA-187706 | Signalling to p38 via RIT and RIN | 4.088253e-02 | 1.388 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 4.088253e-02 | 1.388 |
| R-HSA-9027283 | Erythropoietin activates STAT5 | 4.587530e-02 | 1.338 |
| R-HSA-8849468 | PTK6 Regulates Proteins Involved in RNA Processing | 3.586396e-02 | 1.445 |
| R-HSA-191650 | Regulation of gap junction activity | 3.081944e-02 | 1.511 |
| R-HSA-8852405 | Signaling by MST1 | 4.088253e-02 | 1.388 |
| R-HSA-5654743 | Signaling by FGFR4 | 2.945771e-02 | 1.531 |
| R-HSA-9851151 | MDK and PTN in ALK signaling | 3.081944e-02 | 1.511 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 4.587530e-02 | 1.338 |
| R-HSA-9927418 | Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 2.840823e-02 | 1.547 |
| R-HSA-6806942 | MET Receptor Activation | 4.587530e-02 | 1.338 |
| R-HSA-8849474 | PTK6 Activates STAT3 | 3.586396e-02 | 1.445 |
| R-HSA-8875791 | MET activates STAT3 | 2.574884e-02 | 1.589 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 3.273742e-02 | 1.485 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 3.273742e-02 | 1.485 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 3.462076e-02 | 1.461 |
| R-HSA-202403 | TCR signaling | 2.630801e-02 | 1.580 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 3.462076e-02 | 1.461 |
| R-HSA-8866376 | Reelin signalling pathway | 3.586396e-02 | 1.445 |
| R-HSA-202433 | Generation of second messenger molecules | 2.535361e-02 | 1.596 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 4.567827e-02 | 1.340 |
| R-HSA-9758919 | Epithelial-Mesenchymal Transition (EMT) during gastrulation | 4.088253e-02 | 1.388 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 3.380709e-02 | 1.471 |
| R-HSA-168256 | Immune System | 2.729137e-02 | 1.564 |
| R-HSA-9766229 | Degradation of CDH1 | 3.607011e-02 | 1.443 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 2.855908e-02 | 1.544 |
| R-HSA-5621480 | Dectin-2 family | 4.567827e-02 | 1.340 |
| R-HSA-162909 | Host Interactions of HIV factors | 3.590701e-02 | 1.445 |
| R-HSA-69278 | Cell Cycle, Mitotic | 3.384128e-02 | 1.471 |
| R-HSA-9764561 | Regulation of CDH1 Function | 4.567827e-02 | 1.340 |
| R-HSA-1640170 | Cell Cycle | 3.652528e-02 | 1.437 |
| R-HSA-373760 | L1CAM interactions | 3.090956e-02 | 1.510 |
| R-HSA-451927 | Interleukin-2 family signaling | 2.535361e-02 | 1.596 |
| R-HSA-8864260 | Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors | 3.052252e-02 | 1.515 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 3.957107e-02 | 1.403 |
| R-HSA-177929 | Signaling by EGFR | 4.443040e-02 | 1.352 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 3.273742e-02 | 1.485 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 5.009817e-02 | 1.300 |
| R-HSA-450294 | MAP kinase activation | 5.079699e-02 | 1.294 |
| R-HSA-9032845 | Activated NTRK2 signals through CDK5 | 5.084237e-02 | 1.294 |
| R-HSA-8851907 | MET activates PI3K/AKT signaling | 5.084237e-02 | 1.294 |
| R-HSA-190371 | FGFR3b ligand binding and activation | 5.084237e-02 | 1.294 |
| R-HSA-418886 | Netrin mediated repulsion signals | 5.084237e-02 | 1.294 |
| R-HSA-167590 | Nef Mediated CD4 Down-regulation | 5.084237e-02 | 1.294 |
| R-HSA-1280218 | Adaptive Immune System | 5.097757e-02 | 1.293 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 5.476506e-02 | 1.261 |
| R-HSA-190370 | FGFR1b ligand binding and activation | 5.578390e-02 | 1.253 |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K | 5.578390e-02 | 1.253 |
| R-HSA-8875656 | MET receptor recycling | 5.578390e-02 | 1.253 |
| R-HSA-8849469 | PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 | 5.578390e-02 | 1.253 |
| R-HSA-1253288 | Downregulation of ERBB4 signaling | 5.578390e-02 | 1.253 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 5.643429e-02 | 1.248 |
| R-HSA-9830369 | Kidney development | 5.883901e-02 | 1.230 |
| R-HSA-8936459 | RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... | 6.021979e-02 | 1.220 |
| R-HSA-170984 | ARMS-mediated activation | 6.070000e-02 | 1.217 |
| R-HSA-9700645 | ALK mutants bind TKIs | 6.070000e-02 | 1.217 |
| R-HSA-430116 | GP1b-IX-V activation signalling | 6.070000e-02 | 1.217 |
| R-HSA-428542 | Regulation of commissural axon pathfinding by SLIT and ROBO | 6.070000e-02 | 1.217 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 6.070000e-02 | 1.217 |
| R-HSA-73887 | Death Receptor Signaling | 6.142531e-02 | 1.212 |
| R-HSA-448424 | Interleukin-17 signaling | 6.301466e-02 | 1.201 |
| R-HSA-8875555 | MET activates RAP1 and RAC1 | 6.559082e-02 | 1.183 |
| R-HSA-9027277 | Erythropoietin activates Phospholipase C gamma (PLCG) | 6.559082e-02 | 1.183 |
| R-HSA-198203 | PI3K/AKT activation | 6.559082e-02 | 1.183 |
| R-HSA-8934903 | Receptor Mediated Mitophagy | 6.559082e-02 | 1.183 |
| R-HSA-74749 | Signal attenuation | 6.559082e-02 | 1.183 |
| R-HSA-9924644 | Developmental Lineages of the Mammary Gland | 6.585292e-02 | 1.181 |
| R-HSA-4086398 | Ca2+ pathway | 6.728796e-02 | 1.172 |
| R-HSA-109581 | Apoptosis | 6.839011e-02 | 1.165 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 7.018913e-02 | 1.154 |
| R-HSA-9034864 | Activated NTRK3 signals through RAS | 7.045646e-02 | 1.152 |
| R-HSA-8876493 | InlA-mediated entry of Listeria monocytogenes into host cells | 7.045646e-02 | 1.152 |
| R-HSA-383280 | Nuclear Receptor transcription pathway | 7.461644e-02 | 1.127 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 7.461644e-02 | 1.127 |
| R-HSA-416550 | Sema4D mediated inhibition of cell attachment and migration | 7.529708e-02 | 1.123 |
| R-HSA-9026519 | Activated NTRK2 signals through RAS | 7.529708e-02 | 1.123 |
| R-HSA-209560 | NF-kB is activated and signals survival | 7.529708e-02 | 1.123 |
| R-HSA-8851805 | MET activates RAS signaling | 8.011278e-02 | 1.096 |
| R-HSA-9634285 | Constitutive Signaling by Overexpressed ERBB2 | 8.011278e-02 | 1.096 |
| R-HSA-9028731 | Activated NTRK2 signals through FRS2 and FRS3 | 8.011278e-02 | 1.096 |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 8.011278e-02 | 1.096 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 8.011278e-02 | 1.096 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 8.011278e-02 | 1.096 |
| R-HSA-2428933 | SHC-related events triggered by IGF1R | 8.011278e-02 | 1.096 |
| R-HSA-1358803 | Downregulation of ERBB2:ERBB3 signaling | 8.011278e-02 | 1.096 |
| R-HSA-190322 | FGFR4 ligand binding and activation | 8.490370e-02 | 1.071 |
| R-HSA-190373 | FGFR1c ligand binding and activation | 8.490370e-02 | 1.071 |
| R-HSA-170968 | Frs2-mediated activation | 8.490370e-02 | 1.071 |
| R-HSA-5655291 | Signaling by FGFR4 in disease | 8.966996e-02 | 1.047 |
| R-HSA-177504 | Retrograde neurotrophin signalling | 8.966996e-02 | 1.047 |
| R-HSA-190372 | FGFR3c ligand binding and activation | 8.966996e-02 | 1.047 |
| R-HSA-8875360 | InlB-mediated entry of Listeria monocytogenes into host cell | 9.441169e-02 | 1.025 |
| R-HSA-9027284 | Erythropoietin activates RAS | 9.441169e-02 | 1.025 |
| R-HSA-8964315 | G beta:gamma signalling through BTK | 9.441169e-02 | 1.025 |
| R-HSA-5654228 | Phospholipase C-mediated cascade; FGFR4 | 9.441169e-02 | 1.025 |
| R-HSA-6785631 | ERBB2 Regulates Cell Motility | 9.441169e-02 | 1.025 |
| R-HSA-171007 | p38MAPK events | 9.441169e-02 | 1.025 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 9.441169e-02 | 1.025 |
| R-HSA-202424 | Downstream TCR signaling | 9.476360e-02 | 1.023 |
| R-HSA-168898 | Toll-like Receptor Cascades | 9.747024e-02 | 1.011 |
| R-HSA-388844 | Receptor-type tyrosine-protein phosphatases | 9.912902e-02 | 1.004 |
| R-HSA-9706369 | Negative regulation of FLT3 | 9.912902e-02 | 1.004 |
| R-HSA-68877 | Mitotic Prometaphase | 9.956448e-02 | 1.002 |
| R-HSA-1963640 | GRB2 events in ERBB2 signaling | 1.038221e-01 | 0.984 |
| R-HSA-975110 | TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling | 1.038221e-01 | 0.984 |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization | 1.078514e-01 | 0.967 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 1.078514e-01 | 0.967 |
| R-HSA-1963642 | PI3K events in ERBB2 signaling | 1.084909e-01 | 0.965 |
| R-HSA-164938 | Nef-mediates down modulation of cell surface receptors by recruiting them to cla... | 1.084909e-01 | 0.965 |
| R-HSA-376176 | Signaling by ROBO receptors | 1.103049e-01 | 0.957 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.111960e-01 | 0.954 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.111960e-01 | 0.954 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.111960e-01 | 0.954 |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants | 1.131358e-01 | 0.946 |
| R-HSA-432142 | Platelet sensitization by LDL | 1.131358e-01 | 0.946 |
| R-HSA-180292 | GAB1 signalosome | 1.131358e-01 | 0.946 |
| R-HSA-5357801 | Programmed Cell Death | 1.136119e-01 | 0.945 |
| R-HSA-9020702 | Interleukin-1 signaling | 1.162636e-01 | 0.935 |
| R-HSA-6807004 | Negative regulation of MET activity | 1.223539e-01 | 0.912 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 | 1.223539e-01 | 0.912 |
| R-HSA-373753 | Nephrin family interactions | 1.223539e-01 | 0.912 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 1.223539e-01 | 0.912 |
| R-HSA-445144 | Signal transduction by L1 | 1.223539e-01 | 0.912 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.248373e-01 | 0.904 |
| R-HSA-179409 | APC-Cdc20 mediated degradation of Nek2A | 1.269274e-01 | 0.896 |
| R-HSA-5602498 | MyD88 deficiency (TLR2/4) | 1.269274e-01 | 0.896 |
| R-HSA-9734779 | Developmental Cell Lineages of the Integumentary System | 1.300533e-01 | 0.886 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 1.300533e-01 | 0.886 |
| R-HSA-5654719 | SHC-mediated cascade:FGFR4 | 1.314773e-01 | 0.881 |
| R-HSA-5603041 | IRAK4 deficiency (TLR2/4) | 1.314773e-01 | 0.881 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 1.318033e-01 | 0.880 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 1.318033e-01 | 0.880 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 1.335588e-01 | 0.874 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 1.335588e-01 | 0.874 |
| R-HSA-5654712 | FRS-mediated FGFR4 signaling | 1.360038e-01 | 0.866 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 1.388572e-01 | 0.857 |
| R-HSA-162906 | HIV Infection | 1.389678e-01 | 0.857 |
| R-HSA-9830674 | Formation of the ureteric bud | 1.405070e-01 | 0.852 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 1.405070e-01 | 0.852 |
| R-HSA-982772 | Growth hormone receptor signaling | 1.405070e-01 | 0.852 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 1.442014e-01 | 0.841 |
| R-HSA-9665686 | Signaling by ERBB2 TMD/JMD mutants | 1.449869e-01 | 0.839 |
| R-HSA-202430 | Translocation of ZAP-70 to Immunological synapse | 1.449869e-01 | 0.839 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 1.449869e-01 | 0.839 |
| R-HSA-9620244 | Long-term potentiation | 1.494439e-01 | 0.826 |
| R-HSA-8939211 | ESR-mediated signaling | 1.510827e-01 | 0.821 |
| R-HSA-525793 | Myogenesis | 1.538778e-01 | 0.813 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 1.538778e-01 | 0.813 |
| R-HSA-68875 | Mitotic Prophase | 1.550167e-01 | 0.810 |
| R-HSA-202427 | Phosphorylation of CD3 and TCR zeta chains | 1.582889e-01 | 0.801 |
| R-HSA-77387 | Insulin receptor recycling | 1.626773e-01 | 0.789 |
| R-HSA-9638334 | Iron assimilation using enterobactin | 1.626773e-01 | 0.789 |
| R-HSA-9006335 | Signaling by Erythropoietin | 1.670431e-01 | 0.777 |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants | 1.670431e-01 | 0.777 |
| R-HSA-1227990 | Signaling by ERBB2 in Cancer | 1.713864e-01 | 0.766 |
| R-HSA-5654716 | Downstream signaling of activated FGFR4 | 1.713864e-01 | 0.766 |
| R-HSA-8863795 | Downregulation of ERBB2 signaling | 1.713864e-01 | 0.766 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 1.713864e-01 | 0.766 |
| R-HSA-9820960 | Respiratory syncytial virus (RSV) attachment and entry | 1.757073e-01 | 0.755 |
| R-HSA-186763 | Downstream signal transduction | 1.757073e-01 | 0.755 |
| R-HSA-397795 | G-protein beta:gamma signalling | 1.842824e-01 | 0.735 |
| R-HSA-5685938 | HDR through Single Strand Annealing (SSA) | 1.842824e-01 | 0.735 |
| R-HSA-114508 | Effects of PIP2 hydrolysis | 1.885369e-01 | 0.725 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 1.901789e-01 | 0.721 |
| R-HSA-5673000 | RAF activation | 1.927694e-01 | 0.715 |
| R-HSA-392518 | Signal amplification | 1.927694e-01 | 0.715 |
| R-HSA-5205647 | Mitophagy | 1.927694e-01 | 0.715 |
| R-HSA-111933 | Calmodulin induced events | 2.011691e-01 | 0.696 |
| R-HSA-111997 | CaM pathway | 2.011691e-01 | 0.696 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 2.034017e-01 | 0.692 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 2.053366e-01 | 0.688 |
| R-HSA-5689896 | Ovarian tumor domain proteases | 2.053366e-01 | 0.688 |
| R-HSA-9929356 | GSK3B-mediated proteasomal degradation of PD-L1(CD274) | 2.136070e-01 | 0.670 |
| R-HSA-8941858 | Regulation of RUNX3 expression and activity | 2.177103e-01 | 0.662 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 2.177103e-01 | 0.662 |
| R-HSA-5260271 | Diseases of Immune System | 2.177103e-01 | 0.662 |
| R-HSA-1251985 | Nuclear signaling by ERBB4 | 2.177103e-01 | 0.662 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 2.186383e-01 | 0.660 |
| R-HSA-446652 | Interleukin-1 family signaling | 2.224642e-01 | 0.653 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 2.258536e-01 | 0.646 |
| R-HSA-5674135 | MAP2K and MAPK activation | 2.258536e-01 | 0.646 |
| R-HSA-111996 | Ca-dependent events | 2.298937e-01 | 0.638 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 2.379116e-01 | 0.624 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 2.418896e-01 | 0.616 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 2.418896e-01 | 0.616 |
| R-HSA-1489509 | DAG and IP3 signaling | 2.418896e-01 | 0.616 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 2.458470e-01 | 0.609 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 2.458470e-01 | 0.609 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 2.458470e-01 | 0.609 |
| R-HSA-6802949 | Signaling by RAS mutants | 2.458470e-01 | 0.609 |
| R-HSA-437239 | Recycling pathway of L1 | 2.497840e-01 | 0.602 |
| R-HSA-9634597 | GPER1 signaling | 2.537007e-01 | 0.596 |
| R-HSA-157858 | Gap junction trafficking and regulation | 2.575972e-01 | 0.589 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 2.648113e-01 | 0.577 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 2.648113e-01 | 0.577 |
| R-HSA-179419 | APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... | 2.729833e-01 | 0.564 |
| R-HSA-1474244 | Extracellular matrix organization | 2.771688e-01 | 0.557 |
| R-HSA-418597 | G alpha (z) signalling events | 2.805577e-01 | 0.552 |
| R-HSA-176409 | APC/C:Cdc20 mediated degradation of mitotic proteins | 2.805577e-01 | 0.552 |
| R-HSA-176814 | Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins | 2.843156e-01 | 0.546 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 2.954734e-01 | 0.529 |
| R-HSA-112043 | PLC beta mediated events | 3.028163e-01 | 0.519 |
| R-HSA-9793380 | Formation of paraxial mesoderm | 3.028163e-01 | 0.519 |
| R-HSA-186797 | Signaling by PDGF | 3.064593e-01 | 0.514 |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane | 3.064593e-01 | 0.514 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 3.091404e-01 | 0.510 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 3.100835e-01 | 0.509 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 3.100835e-01 | 0.509 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 3.100835e-01 | 0.509 |
| R-HSA-5690714 | CD22 mediated BCR regulation | 3.136890e-01 | 0.504 |
| R-HSA-389948 | Co-inhibition by PD-1 | 3.168122e-01 | 0.499 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 3.172758e-01 | 0.499 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 3.208442e-01 | 0.494 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 3.227321e-01 | 0.491 |
| R-HSA-112040 | G-protein mediated events | 3.243941e-01 | 0.489 |
| R-HSA-5693606 | DNA Double Strand Break Response | 3.243941e-01 | 0.489 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 3.349342e-01 | 0.475 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 3.384114e-01 | 0.471 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 3.384114e-01 | 0.471 |
| R-HSA-3000178 | ECM proteoglycans | 3.384114e-01 | 0.471 |
| R-HSA-9638482 | Metal ion assimilation from the host | 3.384114e-01 | 0.471 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 3.418705e-01 | 0.466 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 3.418705e-01 | 0.466 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 3.435033e-01 | 0.464 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 3.453118e-01 | 0.462 |
| R-HSA-1236394 | Signaling by ERBB4 | 3.487353e-01 | 0.458 |
| R-HSA-68886 | M Phase | 3.513054e-01 | 0.454 |
| R-HSA-380287 | Centrosome maturation | 3.521412e-01 | 0.453 |
| R-HSA-418990 | Adherens junctions interactions | 3.529621e-01 | 0.452 |
| R-HSA-416482 | G alpha (12/13) signalling events | 3.622534e-01 | 0.441 |
| R-HSA-9824439 | Bacterial Infection Pathways | 3.627117e-01 | 0.440 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 3.689081e-01 | 0.433 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 3.717391e-01 | 0.430 |
| R-HSA-9707564 | Cytoprotection by HMOX1 | 3.787617e-01 | 0.422 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 3.820123e-01 | 0.418 |
| R-HSA-8939236 | RUNX1 regulates transcription of genes involved in differentiation of HSCs | 3.820123e-01 | 0.418 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 3.852461e-01 | 0.414 |
| R-HSA-6794362 | Protein-protein interactions at synapses | 3.852461e-01 | 0.414 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 3.884632e-01 | 0.411 |
| R-HSA-9824446 | Viral Infection Pathways | 3.916987e-01 | 0.407 |
| R-HSA-438064 | Post NMDA receptor activation events | 3.948476e-01 | 0.404 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 3.980150e-01 | 0.400 |
| R-HSA-9663891 | Selective autophagy | 3.980150e-01 | 0.400 |
| R-HSA-1236974 | ER-Phagosome pathway | 4.011661e-01 | 0.397 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 4.043008e-01 | 0.393 |
| R-HSA-421270 | Cell-cell junction organization | 4.140757e-01 | 0.383 |
| R-HSA-8878159 | Transcriptional regulation by RUNX3 | 4.317939e-01 | 0.365 |
| R-HSA-9734767 | Developmental Cell Lineages | 4.356161e-01 | 0.361 |
| R-HSA-416476 | G alpha (q) signalling events | 4.373925e-01 | 0.359 |
| R-HSA-9711123 | Cellular response to chemical stress | 4.444685e-01 | 0.352 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 4.465220e-01 | 0.350 |
| R-HSA-1483255 | PI Metabolism | 4.465220e-01 | 0.350 |
| R-HSA-111885 | Opioid Signalling | 4.523071e-01 | 0.345 |
| R-HSA-6798695 | Neutrophil degranulation | 4.564113e-01 | 0.341 |
| R-HSA-418346 | Platelet homeostasis | 4.608728e-01 | 0.336 |
| R-HSA-446728 | Cell junction organization | 4.619449e-01 | 0.335 |
| R-HSA-9700206 | Signaling by ALK in cancer | 4.636986e-01 | 0.334 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 4.636986e-01 | 0.334 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 4.665097e-01 | 0.331 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 4.776092e-01 | 0.321 |
| R-HSA-5693567 | HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) | 4.830731e-01 | 0.316 |
| R-HSA-2029485 | Role of phospholipids in phagocytosis | 4.911632e-01 | 0.309 |
| R-HSA-195721 | Signaling by WNT | 4.959329e-01 | 0.305 |
| R-HSA-5693538 | Homology Directed Repair | 4.991282e-01 | 0.302 |
| R-HSA-9851695 | Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes | 5.197708e-01 | 0.284 |
| R-HSA-9841922 | MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... | 5.197708e-01 | 0.284 |
| R-HSA-9818564 | Epigenetic regulation of gene expression by MLL3 and MLL4 complexes | 5.197708e-01 | 0.284 |
| R-HSA-69206 | G1/S Transition | 5.197708e-01 | 0.284 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 5.538921e-01 | 0.257 |
| R-HSA-1632852 | Macroautophagy | 5.631932e-01 | 0.249 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 5.723026e-01 | 0.242 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 5.762846e-01 | 0.239 |
| R-HSA-69242 | S Phase | 5.812243e-01 | 0.236 |
| R-HSA-9679506 | SARS-CoV Infections | 5.819498e-01 | 0.235 |
| R-HSA-9758941 | Gastrulation | 5.834258e-01 | 0.234 |
| R-HSA-9679191 | Potential therapeutics for SARS | 5.856159e-01 | 0.232 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 5.877946e-01 | 0.231 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 5.921181e-01 | 0.228 |
| R-HSA-9917777 | Epigenetic regulation by WDR5-containing histone modifying complexes | 5.942631e-01 | 0.226 |
| R-HSA-9612973 | Autophagy | 5.985195e-01 | 0.223 |
| R-HSA-877300 | Interferon gamma signaling | 6.048216e-01 | 0.218 |
| R-HSA-418555 | G alpha (s) signalling events | 6.310201e-01 | 0.200 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 6.329628e-01 | 0.199 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 6.387304e-01 | 0.195 |
| R-HSA-418594 | G alpha (i) signalling events | 6.572852e-01 | 0.182 |
| R-HSA-69275 | G2/M Transition | 6.591222e-01 | 0.181 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 6.627056e-01 | 0.179 |
| R-HSA-5617833 | Cilium Assembly | 6.662518e-01 | 0.176 |
| R-HSA-9640148 | Infection with Enterobacteria | 6.884208e-01 | 0.162 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 7.044779e-01 | 0.152 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 7.245608e-01 | 0.140 |
| R-HSA-112316 | Neuronal System | 7.277221e-01 | 0.138 |
| R-HSA-8953897 | Cellular responses to stimuli | 7.359930e-01 | 0.133 |
| R-HSA-5688426 | Deubiquitination | 7.647027e-01 | 0.117 |
| R-HSA-69620 | Cell Cycle Checkpoints | 7.684196e-01 | 0.114 |
| R-HSA-388396 | GPCR downstream signalling | 7.900099e-01 | 0.102 |
| R-HSA-1483257 | Phospholipid metabolism | 8.097576e-01 | 0.092 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 8.334691e-01 | 0.079 |
| R-HSA-212165 | Epigenetic regulation of gene expression | 8.361104e-01 | 0.078 |
| R-HSA-112315 | Transmission across Chemical Synapses | 8.361104e-01 | 0.078 |
| R-HSA-372790 | Signaling by GPCR | 8.429196e-01 | 0.074 |
| R-HSA-73894 | DNA Repair | 8.654746e-01 | 0.063 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 8.816750e-01 | 0.055 |
| R-HSA-913531 | Interferon Signaling | 8.816750e-01 | 0.055 |
| R-HSA-199991 | Membrane Trafficking | 9.716846e-01 | 0.012 |
| R-HSA-2262752 | Cellular responses to stress | 9.749435e-01 | 0.011 |
| R-HSA-5653656 | Vesicle-mediated transport | 9.882005e-01 | 0.005 |
| R-HSA-8953854 | Metabolism of RNA | 9.898300e-01 | 0.004 |
| R-HSA-556833 | Metabolism of lipids | 9.997427e-01 | 0.000 |
| R-HSA-597592 | Post-translational protein modification | 9.999044e-01 | 0.000 |
| R-HSA-392499 | Metabolism of proteins | 9.999989e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 1.000000e+00 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
SYK |
0.701 | 0.370 | -1 | 0.704 |
PTK2 |
0.698 | 0.297 | -1 | 0.706 |
EGFR |
0.689 | 0.347 | 1 | 0.754 |
ERBB4 |
0.684 | 0.332 | 1 | 0.822 |
BMPR2_TYR |
0.683 | 0.289 | -1 | 0.624 |
FYN |
0.681 | 0.248 | -1 | 0.585 |
TXK |
0.680 | 0.207 | 1 | 0.692 |
FLT1 |
0.678 | 0.273 | -1 | 0.696 |
FRK |
0.678 | 0.270 | -1 | 0.603 |
ZAP70 |
0.677 | 0.263 | -1 | 0.561 |
EPHA8 |
0.676 | 0.232 | -1 | 0.630 |
BLK |
0.676 | 0.163 | -1 | 0.611 |
EPHB2 |
0.672 | 0.187 | -1 | 0.628 |
FGR |
0.672 | 0.177 | 1 | 0.641 |
ERBB2 |
0.672 | 0.250 | 1 | 0.721 |
EPHB4 |
0.671 | 0.148 | -1 | 0.606 |
EPHA6 |
0.671 | 0.157 | -1 | 0.651 |
BMX |
0.671 | 0.102 | -1 | 0.461 |
LCK |
0.670 | 0.156 | -1 | 0.584 |
PDHK1_TYR |
0.670 | 0.181 | -1 | 0.620 |
MET |
0.670 | 0.191 | 3 | 0.627 |
EPHB1 |
0.670 | 0.156 | 1 | 0.665 |
SRC |
0.669 | 0.185 | -1 | 0.554 |
ITK |
0.669 | 0.119 | -1 | 0.502 |
EPHA2 |
0.668 | 0.209 | -1 | 0.645 |
EPHA4 |
0.668 | 0.129 | 2 | 0.430 |
INSRR |
0.667 | 0.134 | 3 | 0.646 |
MAP2K6_TYR |
0.667 | 0.150 | -1 | 0.570 |
EPHA5 |
0.666 | 0.172 | 2 | 0.391 |
HCK |
0.666 | 0.111 | -1 | 0.564 |
YES1 |
0.665 | 0.113 | -1 | 0.519 |
MATK |
0.665 | 0.114 | -1 | 0.490 |
FER |
0.665 | 0.117 | 1 | 0.684 |
MUSK |
0.665 | 0.239 | 1 | 0.736 |
EPHB3 |
0.663 | 0.110 | -1 | 0.596 |
KIT |
0.663 | 0.116 | 3 | 0.652 |
ABL2 |
0.663 | 0.077 | -1 | 0.528 |
JAK3 |
0.663 | 0.121 | 1 | 0.558 |
PDHK3_TYR |
0.663 | 0.060 | 4 | 0.794 |
SRMS |
0.663 | 0.106 | 1 | 0.706 |
PINK1_TYR |
0.662 | 0.065 | 1 | 0.612 |
FGFR4 |
0.662 | 0.157 | -1 | 0.579 |
MAP2K4_TYR |
0.661 | 0.059 | -1 | 0.546 |
EPHA7 |
0.660 | 0.094 | 2 | 0.436 |
PDHK4_TYR |
0.660 | 0.051 | 2 | 0.501 |
TEC |
0.659 | 0.048 | -1 | 0.424 |
CSK |
0.658 | 0.108 | 2 | 0.440 |
FLT3 |
0.658 | 0.096 | 3 | 0.693 |
CSF1R |
0.657 | 0.057 | 3 | 0.651 |
LYN |
0.657 | 0.089 | 3 | 0.592 |
KDR |
0.657 | 0.105 | 3 | 0.619 |
ABL1 |
0.657 | 0.037 | -1 | 0.507 |
IGF1R |
0.656 | 0.101 | 3 | 0.576 |
NTRK3 |
0.656 | 0.091 | -1 | 0.511 |
FLT4 |
0.655 | 0.109 | 3 | 0.601 |
MST1R |
0.655 | 0.037 | 3 | 0.660 |
FGFR2 |
0.655 | 0.093 | 3 | 0.646 |
FGFR3 |
0.654 | 0.120 | 3 | 0.621 |
EPHA3 |
0.654 | 0.067 | 2 | 0.399 |
NTRK1 |
0.653 | 0.080 | -1 | 0.540 |
ROS1 |
0.651 | -0.024 | 3 | 0.693 |
BTK |
0.651 | -0.002 | -1 | 0.416 |
BMPR1B |
0.651 | 0.266 | 1 | 0.705 |
TYK2 |
0.651 | -0.032 | 1 | 0.526 |
RET |
0.650 | -0.036 | 1 | 0.551 |
ACVR2B |
0.650 | 0.320 | -2 | 0.753 |
INSR |
0.650 | 0.041 | 3 | 0.626 |
TESK1_TYR |
0.649 | -0.130 | 3 | 0.717 |
PDGFRB |
0.649 | -0.006 | 3 | 0.683 |
MAP2K7_TYR |
0.649 | -0.196 | 2 | 0.509 |
ACVR2A |
0.649 | 0.319 | -2 | 0.755 |
PTK2B |
0.648 | 0.046 | -1 | 0.441 |
WEE1_TYR |
0.648 | 0.015 | -1 | 0.368 |
JAK2 |
0.647 | -0.044 | 1 | 0.506 |
GRK7 |
0.647 | 0.315 | 1 | 0.774 |
PKMYT1_TYR |
0.647 | -0.155 | 3 | 0.683 |
MERTK |
0.646 | -0.001 | 3 | 0.595 |
TYRO3 |
0.646 | -0.083 | 3 | 0.698 |
NTRK2 |
0.646 | 0.020 | 3 | 0.608 |
ALK |
0.645 | -0.017 | 3 | 0.631 |
DSTYK |
0.645 | 0.322 | 2 | 0.611 |
FGFR1 |
0.645 | 0.036 | 3 | 0.626 |
BMPR1A |
0.643 | 0.232 | 1 | 0.681 |
PDGFRA |
0.643 | -0.026 | 3 | 0.685 |
TGFBR1 |
0.643 | 0.253 | -2 | 0.708 |
JAK1 |
0.642 | -0.032 | 1 | 0.464 |
TEK |
0.641 | -0.022 | 3 | 0.652 |
FES |
0.640 | 0.052 | -1 | 0.426 |
ALK2 |
0.639 | 0.216 | -2 | 0.717 |
ALK4 |
0.639 | 0.230 | -2 | 0.718 |
LTK |
0.638 | -0.057 | 3 | 0.614 |
DDR1 |
0.637 | -0.154 | 4 | 0.716 |
LIMK1_TYR |
0.637 | -0.188 | 2 | 0.540 |
COT |
0.637 | 0.195 | 2 | 0.546 |
TNNI3K_TYR |
0.636 | -0.023 | 1 | 0.489 |
MOS |
0.636 | 0.188 | 1 | 0.631 |
EPHA1 |
0.635 | -0.048 | 3 | 0.623 |
PTK6 |
0.635 | -0.098 | -1 | 0.396 |
GRK6 |
0.635 | 0.229 | 1 | 0.745 |
AXL |
0.633 | -0.113 | 3 | 0.620 |
PLK1 |
0.632 | 0.212 | -2 | 0.783 |
GRK2 |
0.631 | 0.152 | -2 | 0.561 |
LIMK2_TYR |
0.630 | -0.228 | -3 | 0.563 |
TNK2 |
0.629 | -0.149 | 3 | 0.607 |
GRK3 |
0.627 | 0.159 | -2 | 0.542 |
EEF2K |
0.627 | 0.204 | 3 | 0.794 |
BMPR2 |
0.626 | 0.149 | -2 | 0.720 |
PLK2 |
0.625 | 0.169 | -3 | 0.703 |
MLK1 |
0.625 | 0.102 | 2 | 0.603 |
DDR2 |
0.625 | -0.101 | 3 | 0.637 |
MLK4 |
0.625 | 0.139 | 2 | 0.552 |
GRK5 |
0.624 | 0.126 | -3 | 0.629 |
TLK1 |
0.623 | 0.190 | -2 | 0.755 |
NEK6 |
0.622 | 0.139 | -2 | 0.776 |
CLK3 |
0.622 | 0.106 | 1 | 0.549 |
DLK |
0.621 | 0.069 | 1 | 0.633 |
GRK4 |
0.621 | 0.129 | -2 | 0.696 |
ALPHAK3 |
0.619 | 0.164 | -1 | 0.540 |
CK2A2 |
0.619 | 0.163 | 1 | 0.651 |
TGFBR2 |
0.619 | 0.114 | -2 | 0.777 |
PLK3 |
0.619 | 0.128 | 2 | 0.410 |
NEK7 |
0.618 | 0.066 | -3 | 0.574 |
MLK3 |
0.618 | 0.102 | 2 | 0.617 |
PRPK |
0.618 | -0.063 | -1 | 0.494 |
GCN2 |
0.618 | 0.071 | 2 | 0.507 |
MST2 |
0.617 | 0.143 | 1 | 0.535 |
NEK10_TYR |
0.617 | -0.197 | 1 | 0.393 |
CAMK2G |
0.616 | 0.006 | 2 | 0.433 |
ANKRD3 |
0.615 | 0.025 | 1 | 0.553 |
HRI |
0.615 | 0.115 | -2 | 0.743 |
YSK4 |
0.615 | 0.070 | 1 | 0.509 |
PASK |
0.614 | 0.091 | -3 | 0.554 |
TTBK2 |
0.614 | 0.033 | 2 | 0.503 |
TTK |
0.614 | 0.190 | -2 | 0.808 |
CDK1 |
0.614 | 0.059 | 1 | 0.423 |
GRK1 |
0.614 | 0.108 | -2 | 0.601 |
MEKK3 |
0.614 | 0.039 | 1 | 0.550 |
DRAK1 |
0.613 | 0.085 | 1 | 0.689 |
CDC7 |
0.613 | 0.007 | 1 | 0.641 |
PKN3 |
0.612 | 0.016 | -3 | 0.523 |
ATM |
0.612 | 0.030 | 1 | 0.499 |
CAMK1B |
0.612 | -0.039 | -3 | 0.547 |
NUAK2 |
0.612 | 0.049 | -3 | 0.514 |
KIS |
0.611 | 0.068 | 1 | 0.375 |
MEK1 |
0.611 | -0.025 | 2 | 0.513 |
CHAK2 |
0.611 | 0.002 | -1 | 0.425 |
NIK |
0.609 | -0.080 | -3 | 0.572 |
CK2A1 |
0.609 | 0.139 | 1 | 0.654 |
PKR |
0.609 | -0.015 | 1 | 0.540 |
FAM20C |
0.609 | 0.035 | 2 | 0.262 |
PKN2 |
0.609 | 0.017 | -3 | 0.506 |
TNK1 |
0.608 | -0.256 | 3 | 0.653 |
ATR |
0.608 | -0.062 | 1 | 0.543 |
CDK2 |
0.608 | 0.086 | 1 | 0.558 |
MEKK2 |
0.608 | 0.021 | 2 | 0.533 |
PERK |
0.608 | 0.076 | -2 | 0.740 |
CK1E |
0.607 | 0.069 | -3 | 0.470 |
GAK |
0.607 | -0.005 | 1 | 0.536 |
NEK9 |
0.607 | -0.045 | 2 | 0.587 |
MTOR |
0.606 | -0.068 | 1 | 0.541 |
CDKL1 |
0.606 | -0.039 | -3 | 0.509 |
CK1D |
0.606 | 0.075 | -3 | 0.431 |
CK1A2 |
0.605 | 0.070 | -3 | 0.424 |
ZAK |
0.604 | -0.025 | 1 | 0.537 |
RAF1 |
0.604 | -0.120 | 1 | 0.562 |
PDHK4 |
0.604 | -0.166 | 1 | 0.580 |
MST1 |
0.604 | 0.057 | 1 | 0.515 |
OSR1 |
0.603 | 0.086 | 2 | 0.538 |
DAPK2 |
0.603 | -0.095 | -3 | 0.551 |
NEK8 |
0.602 | 0.003 | 2 | 0.582 |
TSSK2 |
0.602 | -0.011 | -5 | 0.736 |
SRPK3 |
0.601 | 0.048 | -3 | 0.462 |
MST3 |
0.601 | -0.001 | 2 | 0.668 |
LATS1 |
0.601 | 0.016 | -3 | 0.588 |
CAMK2B |
0.601 | 0.021 | 2 | 0.378 |
VRK2 |
0.601 | -0.224 | 1 | 0.578 |
TAO3 |
0.601 | -0.000 | 1 | 0.528 |
CAMLCK |
0.601 | -0.097 | -2 | 0.602 |
TLK2 |
0.600 | 0.011 | 1 | 0.535 |
GCK |
0.600 | 0.007 | 1 | 0.534 |
NLK |
0.600 | -0.110 | 1 | 0.521 |
MEKK1 |
0.599 | -0.047 | 1 | 0.501 |
ERK7 |
0.599 | 0.099 | 2 | 0.574 |
MST4 |
0.599 | -0.021 | 2 | 0.618 |
GSK3A |
0.598 | 0.082 | 4 | 0.570 |
PIM3 |
0.598 | -0.057 | -3 | 0.548 |
VRK1 |
0.598 | -0.074 | 2 | 0.514 |
ULK2 |
0.598 | -0.120 | 2 | 0.489 |
MAPKAPK2 |
0.598 | 0.045 | -3 | 0.427 |
HUNK |
0.598 | -0.102 | 2 | 0.517 |
TAK1 |
0.598 | -0.045 | 1 | 0.533 |
MEK5 |
0.597 | -0.145 | 2 | 0.526 |
CDK5 |
0.596 | 0.011 | 1 | 0.403 |
ERK5 |
0.596 | -0.078 | 1 | 0.506 |
GSK3B |
0.596 | 0.059 | 4 | 0.558 |
TNIK |
0.596 | 0.018 | 3 | 0.790 |
CAMK2A |
0.595 | -0.002 | 2 | 0.450 |
NEK5 |
0.594 | -0.115 | 1 | 0.513 |
IKKB |
0.594 | -0.101 | -2 | 0.509 |
MLK2 |
0.594 | -0.132 | 2 | 0.573 |
ULK1 |
0.593 | -0.099 | -3 | 0.573 |
IKKE |
0.593 | -0.106 | 1 | 0.449 |
CDK3 |
0.593 | 0.052 | 1 | 0.350 |
CDKL5 |
0.593 | -0.045 | -3 | 0.492 |
CHAK1 |
0.592 | -0.091 | 2 | 0.572 |
WNK1 |
0.592 | -0.119 | -2 | 0.621 |
RIPK3 |
0.592 | -0.162 | 3 | 0.606 |
TAO2 |
0.592 | -0.057 | 2 | 0.607 |
MINK |
0.592 | -0.039 | 1 | 0.478 |
JNK3 |
0.592 | -0.035 | 1 | 0.391 |
SRPK1 |
0.592 | -0.002 | -3 | 0.465 |
BRAF |
0.592 | -0.090 | -4 | 0.671 |
PKCH |
0.592 | -0.024 | 2 | 0.584 |
PKCD |
0.592 | -0.039 | 2 | 0.592 |
PDHK1 |
0.591 | -0.210 | 1 | 0.536 |
PINK1 |
0.591 | -0.061 | 1 | 0.494 |
IRE2 |
0.591 | -0.040 | 2 | 0.502 |
TBK1 |
0.591 | -0.142 | 1 | 0.455 |
CLK2 |
0.590 | 0.037 | -3 | 0.469 |
NEK11 |
0.590 | -0.135 | 1 | 0.519 |
CHK1 |
0.590 | -0.019 | -3 | 0.526 |
P38G |
0.590 | -0.025 | 1 | 0.328 |
RSK2 |
0.590 | -0.035 | -3 | 0.462 |
PKCB |
0.590 | -0.008 | 2 | 0.625 |
PRP4 |
0.589 | -0.042 | -3 | 0.548 |
PIM1 |
0.589 | -0.061 | -3 | 0.487 |
PKCG |
0.589 | -0.019 | 2 | 0.621 |
LRRK2 |
0.588 | -0.100 | 2 | 0.581 |
TTBK1 |
0.588 | -0.055 | 2 | 0.432 |
HGK |
0.588 | -0.041 | 3 | 0.801 |
NEK2 |
0.588 | -0.104 | 2 | 0.614 |
IRE1 |
0.588 | -0.093 | 1 | 0.499 |
MAPKAPK3 |
0.587 | -0.065 | -3 | 0.449 |
MASTL |
0.587 | -0.254 | -2 | 0.607 |
HPK1 |
0.586 | -0.058 | 1 | 0.506 |
CAMKK1 |
0.586 | -0.142 | -2 | 0.498 |
MYO3A |
0.586 | 0.005 | 1 | 0.480 |
CAMK4 |
0.585 | -0.119 | -3 | 0.493 |
SMMLCK |
0.585 | -0.085 | -3 | 0.495 |
P70S6KB |
0.585 | -0.082 | -3 | 0.483 |
ICK |
0.585 | -0.112 | -3 | 0.529 |
KHS2 |
0.585 | -0.011 | 1 | 0.488 |
SKMLCK |
0.585 | -0.150 | -2 | 0.624 |
CAMK1G |
0.584 | -0.060 | -3 | 0.442 |
CK1G2 |
0.584 | 0.100 | -3 | 0.439 |
SRPK2 |
0.584 | 0.001 | -3 | 0.408 |
AMPKA1 |
0.584 | -0.127 | -3 | 0.520 |
IKKA |
0.584 | -0.068 | -2 | 0.529 |
RIPK1 |
0.584 | -0.237 | 1 | 0.540 |
P38A |
0.583 | -0.066 | 1 | 0.402 |
NUAK1 |
0.583 | -0.030 | -3 | 0.481 |
CK1A |
0.583 | 0.085 | -3 | 0.389 |
PKCA |
0.583 | -0.031 | 2 | 0.612 |
P38B |
0.582 | -0.052 | 1 | 0.383 |
RSK3 |
0.582 | -0.067 | -3 | 0.471 |
JNK2 |
0.582 | -0.056 | 1 | 0.347 |
CAMK2D |
0.581 | -0.133 | -3 | 0.500 |
CDK13 |
0.581 | -0.052 | 1 | 0.362 |
MYLK4 |
0.581 | -0.074 | -2 | 0.514 |
JNK1 |
0.581 | -0.020 | 1 | 0.398 |
NEK1 |
0.581 | -0.162 | 1 | 0.492 |
DAPK1 |
0.581 | -0.046 | -3 | 0.472 |
CLK1 |
0.580 | -0.040 | -3 | 0.427 |
CK1G1 |
0.580 | 0.013 | -3 | 0.522 |
P90RSK |
0.580 | -0.081 | -3 | 0.484 |
CDK8 |
0.580 | -0.069 | 1 | 0.376 |
PDK1 |
0.580 | -0.142 | 1 | 0.495 |
KHS1 |
0.580 | -0.070 | 1 | 0.466 |
YSK1 |
0.579 | -0.072 | 2 | 0.613 |
MAP3K15 |
0.579 | -0.167 | 1 | 0.496 |
CLK4 |
0.579 | -0.060 | -3 | 0.471 |
TSSK1 |
0.578 | -0.100 | -3 | 0.532 |
DNAPK |
0.578 | -0.095 | 1 | 0.389 |
MYO3B |
0.578 | -0.032 | 2 | 0.626 |
AURA |
0.578 | -0.044 | -2 | 0.417 |
MAPKAPK5 |
0.577 | -0.077 | -3 | 0.425 |
ERK1 |
0.577 | -0.063 | 1 | 0.341 |
PKCZ |
0.577 | -0.095 | 2 | 0.602 |
WNK3 |
0.577 | -0.288 | 1 | 0.518 |
SMG1 |
0.576 | -0.126 | 1 | 0.484 |
DAPK3 |
0.576 | -0.084 | -3 | 0.487 |
AMPKA2 |
0.576 | -0.111 | -3 | 0.487 |
NDR2 |
0.576 | -0.123 | -3 | 0.544 |
YANK3 |
0.576 | -0.008 | 2 | 0.239 |
NEK4 |
0.576 | -0.191 | 1 | 0.459 |
PKCE |
0.576 | -0.014 | 2 | 0.631 |
DCAMKL2 |
0.576 | -0.109 | -3 | 0.475 |
RSK4 |
0.576 | -0.054 | -3 | 0.454 |
ERK2 |
0.575 | -0.092 | 1 | 0.397 |
HASPIN |
0.575 | -0.031 | -1 | 0.277 |
MSK2 |
0.575 | -0.083 | -3 | 0.456 |
BCKDK |
0.575 | -0.195 | -1 | 0.435 |
PHKG1 |
0.575 | -0.093 | -3 | 0.500 |
NDR1 |
0.574 | -0.151 | -3 | 0.528 |
PLK4 |
0.574 | -0.113 | 2 | 0.309 |
CDK12 |
0.574 | -0.061 | 1 | 0.342 |
MEK2 |
0.574 | -0.196 | 2 | 0.483 |
P38D |
0.574 | -0.046 | 1 | 0.259 |
CDK17 |
0.573 | -0.057 | 1 | 0.343 |
WNK4 |
0.573 | -0.193 | -2 | 0.629 |
DCAMKL1 |
0.572 | -0.130 | -3 | 0.459 |
MARK4 |
0.572 | -0.179 | 4 | 0.686 |
PRKD1 |
0.572 | -0.110 | -3 | 0.480 |
CHK2 |
0.572 | -0.051 | -3 | 0.330 |
MEKK6 |
0.572 | -0.223 | 1 | 0.503 |
BIKE |
0.571 | -0.059 | 1 | 0.405 |
STLK3 |
0.571 | -0.102 | 1 | 0.498 |
MSK1 |
0.571 | -0.068 | -3 | 0.455 |
CAMKK2 |
0.571 | -0.219 | -2 | 0.475 |
PRKD3 |
0.571 | -0.084 | -3 | 0.414 |
HIPK4 |
0.570 | -0.116 | 1 | 0.493 |
CDK19 |
0.570 | -0.077 | 1 | 0.339 |
PRKD2 |
0.570 | -0.091 | -3 | 0.425 |
MNK2 |
0.570 | -0.120 | -2 | 0.540 |
CDK18 |
0.569 | -0.064 | 1 | 0.345 |
DYRK2 |
0.569 | -0.099 | 1 | 0.447 |
IRAK4 |
0.569 | -0.209 | 1 | 0.473 |
MNK1 |
0.569 | -0.114 | -2 | 0.554 |
SLK |
0.569 | -0.090 | -2 | 0.490 |
AKT2 |
0.568 | -0.077 | -3 | 0.389 |
CDK16 |
0.568 | -0.049 | 1 | 0.354 |
MPSK1 |
0.567 | -0.156 | 1 | 0.446 |
HIPK1 |
0.567 | -0.100 | 1 | 0.441 |
ASK1 |
0.567 | -0.198 | 1 | 0.499 |
PKACG |
0.566 | -0.138 | -2 | 0.502 |
LOK |
0.566 | -0.134 | -2 | 0.518 |
PIM2 |
0.566 | -0.098 | -3 | 0.435 |
STK33 |
0.565 | -0.142 | 2 | 0.396 |
PKN1 |
0.565 | -0.043 | -3 | 0.397 |
PAK1 |
0.565 | -0.154 | -2 | 0.512 |
BUB1 |
0.565 | -0.054 | -5 | 0.672 |
PKCI |
0.564 | -0.075 | 2 | 0.606 |
SGK3 |
0.564 | -0.120 | -3 | 0.443 |
CAMK1D |
0.564 | -0.092 | -3 | 0.388 |
MELK |
0.564 | -0.176 | -3 | 0.465 |
LKB1 |
0.564 | -0.266 | -3 | 0.542 |
PHKG2 |
0.564 | -0.086 | -3 | 0.449 |
CDK7 |
0.563 | -0.112 | 1 | 0.378 |
CDK6 |
0.563 | -0.044 | 1 | 0.323 |
CDK10 |
0.563 | -0.051 | 1 | 0.359 |
CDK9 |
0.563 | -0.098 | 1 | 0.360 |
PKCT |
0.562 | -0.099 | 2 | 0.572 |
LATS2 |
0.561 | -0.151 | -5 | 0.412 |
YANK2 |
0.561 | -0.012 | 2 | 0.252 |
QIK |
0.560 | -0.215 | -3 | 0.495 |
HIPK2 |
0.560 | -0.083 | 1 | 0.358 |
CDK14 |
0.560 | -0.094 | 1 | 0.378 |
AURC |
0.560 | -0.100 | -2 | 0.432 |
AURB |
0.560 | -0.112 | -2 | 0.425 |
CK1G3 |
0.559 | 0.021 | -3 | 0.361 |
AAK1 |
0.559 | -0.033 | 1 | 0.301 |
TAO1 |
0.559 | -0.108 | 1 | 0.427 |
RIPK2 |
0.559 | -0.218 | 1 | 0.460 |
IRAK1 |
0.558 | -0.278 | -1 | 0.360 |
DYRK4 |
0.557 | -0.080 | 1 | 0.377 |
PAK2 |
0.557 | -0.196 | -2 | 0.497 |
PKG2 |
0.557 | -0.121 | -2 | 0.439 |
SNRK |
0.557 | -0.226 | 2 | 0.362 |
PAK3 |
0.557 | -0.211 | -2 | 0.499 |
DYRK1A |
0.556 | -0.117 | 1 | 0.424 |
PRKX |
0.556 | -0.060 | -3 | 0.389 |
P70S6K |
0.556 | -0.112 | -3 | 0.404 |
SIK |
0.556 | -0.145 | -3 | 0.445 |
PKACB |
0.556 | -0.095 | -2 | 0.450 |
NIM1 |
0.555 | -0.252 | 3 | 0.616 |
DMPK1 |
0.555 | -0.105 | -3 | 0.429 |
CAMK1A |
0.555 | -0.078 | -3 | 0.345 |
PAK6 |
0.555 | -0.067 | -2 | 0.420 |
HIPK3 |
0.554 | -0.139 | 1 | 0.397 |
MARK3 |
0.554 | -0.142 | 4 | 0.615 |
MRCKA |
0.552 | -0.120 | -3 | 0.448 |
QSK |
0.552 | -0.169 | 4 | 0.641 |
CDK4 |
0.552 | -0.077 | 1 | 0.342 |
MARK2 |
0.552 | -0.167 | 4 | 0.573 |
DYRK3 |
0.551 | -0.112 | 1 | 0.443 |
BRSK1 |
0.551 | -0.156 | -3 | 0.474 |
AKT1 |
0.550 | -0.106 | -3 | 0.392 |
MARK1 |
0.550 | -0.175 | 4 | 0.635 |
SSTK |
0.550 | -0.170 | 4 | 0.638 |
ROCK2 |
0.549 | -0.155 | -3 | 0.475 |
NEK3 |
0.548 | -0.230 | 1 | 0.417 |
DYRK1B |
0.548 | -0.119 | 1 | 0.396 |
SGK1 |
0.547 | -0.091 | -3 | 0.340 |
MRCKB |
0.547 | -0.130 | -3 | 0.419 |
PBK |
0.545 | -0.198 | 1 | 0.418 |
PKACA |
0.545 | -0.098 | -2 | 0.395 |
MOK |
0.544 | -0.107 | 1 | 0.459 |
MAK |
0.544 | -0.090 | -2 | 0.526 |
ROCK1 |
0.542 | -0.138 | -3 | 0.438 |
BRSK2 |
0.541 | -0.218 | -3 | 0.481 |
SBK |
0.540 | -0.078 | -3 | 0.286 |
CRIK |
0.539 | -0.119 | -3 | 0.392 |
AKT3 |
0.535 | -0.098 | -3 | 0.340 |
PAK5 |
0.532 | -0.135 | -2 | 0.369 |
PAK4 |
0.530 | -0.113 | -2 | 0.384 |
PKG1 |
0.511 | -0.156 | -2 | 0.349 |