Motif 1170 (n=56)

Position-wise Probabilities
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uniprot genes site source protein function
A6NJZ7 RIMBP3C Y1615 ochoa RIMS-binding protein 3C (RIM-BP3.C) (RIMS-binding protein 3.3) (RIM-BP3.3) Probable component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development. {ECO:0000250|UniProtKB:Q3V0F0}.
A6NKT7 RGPD3 Y794 ochoa RanBP2-like and GRIP domain-containing protein 3 None
A6NNM3 RIMBP3B Y1615 ochoa RIMS-binding protein 3B (RIM-BP3.B) (RIMS-binding protein 3.2) (RIM-BP3.2) Probable component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development. {ECO:0000250|UniProtKB:Q3V0F0}.
O15264 MAPK13 Y182 ochoa|psp Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}.
O43353 RIPK2 S178 ochoa 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}.
O43781 DYRK3 Y369 ochoa Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC 2.7.12.1) (Regulatory erythroid kinase) (REDK) Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:29634919, PubMed:9748265). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}.
O60674 JAK2 Y1008 psp Tyrosine-protein kinase JAK2 (EC 2.7.10.2) (Janus kinase 2) (JAK-2) Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin receptor (MPL/TPOR); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:15690087, PubMed:7615558, PubMed:9657743, PubMed:15899890). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:15690087, PubMed:9618263). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980). Up-regulates the potassium voltage-gated channel activity of KCNA3 (PubMed:25644777). {ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:15690087, ECO:0000269|PubMed:19783980, ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:21368206, ECO:0000269|PubMed:21423214, ECO:0000269|PubMed:25644777, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:9618263, ECO:0000269|PubMed:9657743}.
P05771 PRKCB T498 ochoa Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13) Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P68404, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:25982116, ECO:0000269|PubMed:36040231}.
P06493 CDK1 Y160 ochoa Cyclin-dependent kinase 1 (CDK1) (EC 2.7.11.22) (EC 2.7.11.23) (Cell division control protein 2 homolog) (Cell division protein kinase 1) (p34 protein kinase) Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30139873, PubMed:30704899). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LBR, MKI67, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RBBP8/CtIP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19202191, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25012651, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30704899, PubMed:32351706, PubMed:34741373). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:18480403, PubMed:20360007, PubMed:2188730, PubMed:2344612, PubMed:30139873). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007). Phosphorylates KRT5 during prometaphase and metaphase (By similarity). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown (PubMed:2188730, PubMed:2344612, PubMed:37788673). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706). Phosphorylates SKA3 on multiple sites during mitosis which promotes SKA3 binding to the NDC80 complex and anchoring of the SKA complex to kinetochores, to enable stable attachment of mitotic spindle microtubules to kinetochores (PubMed:28479321, PubMed:31804178, PubMed:32491969). {ECO:0000250|UniProtKB:P11440, ECO:0000250|UniProtKB:P39951, ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:25012651, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:28479321, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:30723163, ECO:0000269|PubMed:31804178, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32491969, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:37788673}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. {ECO:0000269|PubMed:21516087}.
P08581 MET S1236 ochoa 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}.
P0DJD0 RGPD1 Y784 ochoa RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) None
P0DJD1 RGPD2 Y792 ochoa RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) None
P17252 PRKCA T495 ochoa Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13) Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250|UniProtKB:P20444, ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826, ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403, ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361, ECO:0000269|PubMed:21806543, ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}.
P21127 CDK11B Y594 ochoa Cyclin-dependent kinase 11B (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 1) (CLK-1) (Cell division protein kinase 11B) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L1) (p58 CLK-1) Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:18216018, ECO:0000269|PubMed:2217177}.
P23396 RPS3 Y107 ochoa Small ribosomal subunit protein uS3 (40S ribosomal protein S3) (EC 4.2.99.18) Component of the small ribosomal subunit (PubMed:23636399, PubMed:8706699). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:8706699). Has endonuclease activity and plays a role in repair of damaged DNA (PubMed:7775413). Cleaves phosphodiester bonds of DNAs containing altered bases with broad specificity and cleaves supercoiled DNA more efficiently than relaxed DNA (PubMed:15707971). Displays high binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG), a common DNA lesion caused by reactive oxygen species (ROS) (PubMed:14706345). Has also been shown to bind with similar affinity to intact and damaged DNA (PubMed:18610840). Stimulates the N-glycosylase activity of the base excision protein OGG1 (PubMed:15518571). Enhances the uracil excision activity of UNG1 (PubMed:18973764). Also stimulates the cleavage of the phosphodiester backbone by APEX1 (PubMed:18973764). When located in the mitochondrion, reduces cellular ROS levels and mitochondrial DNA damage (PubMed:23911537). Has also been shown to negatively regulate DNA repair in cells exposed to hydrogen peroxide (PubMed:17049931). Plays a role in regulating transcription as part of the NF-kappa-B p65-p50 complex where it binds to the RELA/p65 subunit, enhances binding of the complex to DNA and promotes transcription of target genes (PubMed:18045535). Represses its own translation by binding to its cognate mRNA (PubMed:20217897). Binds to and protects TP53/p53 from MDM2-mediated ubiquitination (PubMed:19656744). Involved in spindle formation and chromosome movement during mitosis by regulating microtubule polymerization (PubMed:23131551). Involved in induction of apoptosis through its role in activation of CASP8 (PubMed:14988002). Induces neuronal apoptosis by interacting with the E2F1 transcription factor and acting synergistically with it to up-regulate pro-apoptotic proteins BCL2L11/BIM and HRK/Dp5 (PubMed:20605787). Interacts with TRADD following exposure to UV radiation and induces apoptosis by caspase-dependent JNK activation (PubMed:22510408). {ECO:0000269|PubMed:14706345, ECO:0000269|PubMed:14988002, ECO:0000269|PubMed:15518571, ECO:0000269|PubMed:15707971, ECO:0000269|PubMed:17049931, ECO:0000269|PubMed:18045535, ECO:0000269|PubMed:18610840, ECO:0000269|PubMed:18973764, ECO:0000269|PubMed:19656744, ECO:0000269|PubMed:20217897, ECO:0000269|PubMed:20605787, ECO:0000269|PubMed:22510408, ECO:0000269|PubMed:23131551, ECO:0000269|PubMed:23636399, ECO:0000269|PubMed:23911537, ECO:0000269|PubMed:7775413, ECO:0000269|PubMed:8706699}.
P23443 RPS6KB1 T250 ochoa Ribosomal protein S6 kinase beta-1 (S6K-beta-1) (S6K1) (EC 2.7.11.1) (70 kDa ribosomal protein S6 kinase 1) (P70S6K1) (p70-S6K 1) (Ribosomal protein S6 kinase I) (Serine/threonine-protein kinase 14A) (p70 ribosomal S6 kinase alpha) (p70 S6 kinase alpha) (p70 S6K-alpha) (p70 S6KA) Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:22017876, PubMed:23429703, PubMed:28178239). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating MAPKAP1/SIN1, MTOR and RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling (PubMed:15899889, PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (By similarity). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex (PubMed:17936702). The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function (PubMed:17936702). Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1 (PubMed:18952604). In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (PubMed:17052453). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239). {ECO:0000250|UniProtKB:P67999, ECO:0000250|UniProtKB:Q8BSK8, ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500, ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:15899889, ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147, ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745, ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:28178239}.
P23458 JAK1 Y1035 psp Tyrosine-protein kinase JAK1 (EC 2.7.10.2) (Janus kinase 1) (JAK-1) Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552). {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:12133952, ECO:0000269|PubMed:16239216, ECO:0000269|PubMed:28111307, ECO:0000269|PubMed:32750333, ECO:0000269|PubMed:7615558, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:8232552}.
P24941 CDK2 Y159 ochoa Cyclin-dependent kinase 2 (EC 2.7.11.22) (Cell division protein kinase 2) (p33 protein kinase) Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:29203878, ECO:0000303|PubMed:19238148, ECO:0000303|PubMed:19561645}.
P27361 MAPK3 T198 ochoa|psp Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}.
P28482 MAPK1 T181 ochoa|psp Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}.
P29317 EPHA2 T771 ochoa Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}.
P29597 TYK2 Y1055 psp Non-receptor tyrosine-protein kinase TYK2 (EC 2.7.10.2) Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862). {ECO:0000269|PubMed:10542297, ECO:0000269|PubMed:10995743, ECO:0000269|PubMed:25762719, ECO:0000269|PubMed:29162862, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7638186, ECO:0000269|PubMed:7657660, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:8232552}.
P41743 PRKCI T410 ochoa Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota) Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5, ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349, ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363, ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373, ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810, ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}.
P42680 TEC S521 ochoa 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}.
P43403 ZAP70 Y493 ochoa|psp Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase) Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Also contributes to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:38614099, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.
P43405 SYK Y526 psp Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) (p72-Syk) Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity). {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:34634301, ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.
P49792 RANBP2 Y793 ochoa E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.
P50613 CDK7 Y169 ochoa Cyclin-dependent kinase 7 (EC 2.7.11.22) (EC 2.7.11.23) (39 kDa protein kinase) (p39 Mo15) (CDK-activating kinase 1) (Cell division protein kinase 7) (Serine/threonine-protein kinase 1) (TFIIH basal transcription factor complex kinase subunit) Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription (PubMed:9852112, PubMed:19136461, PubMed:26257281, PubMed:28768201). Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201). Initiates transcription by RNA polymerase II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, PubMed:28768201). CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the CTD of POLR2A, allowing its escape from the promoter and elongation of the transcripts (PubMed:9852112). Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130, ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173, ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:28768201, ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}.
P52333 JAK3 Y981 psp Tyrosine-protein kinase JAK3 (EC 2.7.10.2) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK) Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:20440074, ECO:0000269|PubMed:7662955, ECO:0000269|PubMed:8022485}.
P53778 MAPK12 Y185 ochoa Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}.
Q04759 PRKCQ T536 ochoa Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta) Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation (PubMed:21964608). Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (PubMed:23509302). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11342610, ECO:0000269|PubMed:14988727, ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:16252004, ECO:0000269|PubMed:16356855, ECO:0000269|PubMed:16709830, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:21964608, ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:8657160}.
Q06187 BTK S553 ochoa 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}.
Q07912 TNK2 Y284 ochoa|psp Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Tyrosine kinase non-receptor protein 2) Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). {ECO:0000269|PubMed:10652228, ECO:0000269|PubMed:11278436, ECO:0000269|PubMed:16247015, ECO:0000269|PubMed:16257963, ECO:0000269|PubMed:16472662, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:18262180, ECO:0000269|PubMed:18435854, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:20110370, ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20383201}.
Q08881 ITK S514 ochoa 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}.
Q13470 TNK1 Y277 psp Non-receptor tyrosine-protein kinase TNK1 (EC 2.7.10.2) (CD38 negative kinase 1) Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction. {ECO:0000269|PubMed:10873601, ECO:0000269|PubMed:18974114}.
Q13627 DYRK1A Y321 ochoa|psp Dual specificity tyrosine-phosphorylation-regulated kinase 1A (EC 2.7.11.23) (EC 2.7.12.1) (Dual specificity YAK1-related kinase) (HP86) (Protein kinase minibrain homolog) (MNBH) (hMNB) Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3 (PubMed:23665168). Plays an important role in double-strand breaks (DSBs) repair following DNA damage (PubMed:31024071). Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR) (PubMed:30773093). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:25620562, PubMed:29849146). May play a role in a signaling pathway regulating nuclear functions of cell proliferation (PubMed:14500717). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (By similarity). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (By similarity). This in turn inhibits p53/TP53 activity and apoptosis (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By similarity). {ECO:0000250|UniProtKB:Q61214, ECO:0000250|UniProtKB:Q63470, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:20981014, ECO:0000269|PubMed:21127067, ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:25620562, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30773093, ECO:0000269|PubMed:31024071, ECO:0000269|PubMed:8769099}.
Q14315 FLNC T1464 ochoa Filamin-C (FLN-C) (FLNc) (ABP-280-like protein) (ABP-L) (Actin-binding-like protein) (Filamin-2) (Gamma-filamin) Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity). {ECO:0000250|UniProtKB:Q8VHX6, ECO:0000269|PubMed:34405687}.
Q15759 MAPK11 Y182 ochoa|psp Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}.
Q16512 PKN1 T772 ochoa Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N) PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594, ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664, ECO:0000269|PubMed:9175763}.
Q16513 PKN2 T814 ochoa|psp Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2) PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936, ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804, ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}.
Q16539 MAPK14 Y182 ochoa|psp Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}.
Q6P5Z2 PKN3 T716 ochoa Serine/threonine-protein kinase N3 (EC 2.7.11.13) (Protein kinase PKN-beta) (Protein-kinase C-related kinase 3) Contributes to invasiveness in malignant prostate cancer. {ECO:0000269|PubMed:15282551}.
Q7Z3J3 RGPD4 Y794 ochoa RanBP2-like and GRIP domain-containing protein 4 None
Q86Z02 HIPK1 T351 ochoa Homeodomain-interacting protein kinase 1 (EC 2.7.11.1) (Nuclear body-associated kinase 2) Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:24559171). {ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:24559171}.
Q92630 DYRK2 Y382 ochoa Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC 2.7.12.1) Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}.
Q9H2X6 HIPK2 T360 ochoa|psp Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}.
Q9H422 HIPK3 T358 ochoa Homeodomain-interacting protein kinase 3 (EC 2.7.11.1) (Androgen receptor-interacting nuclear protein kinase) (ANPK) (Fas-interacting serine/threonine-protein kinase) (FIST) (Homolog of protein kinase YAK1) Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}.
Q9NR20 DYRK4 Y264 ochoa|psp Dual specificity tyrosine-phosphorylation-regulated kinase 4 (EC 2.7.12.1) Possible non-essential role in spermiogenesis. {ECO:0000250}.
Q9UFD9 RIMBP3 Y1615 ochoa RIMS-binding protein 3A (RIM-BP3.A) (RIMS-binding protein 3.1) (RIM-BP3.1) Probable component of the manchette, a microtubule-based structure which plays a key role in sperm head morphogenesis during late stages of sperm development. {ECO:0000250|UniProtKB:Q3V0F0}.
Q9UQ88 CDK11A Y582 ochoa Cyclin-dependent kinase 11A (EC 2.7.11.22) (Cell division cycle 2-like protein kinase 2) (Cell division protein kinase 11A) (Galactosyltransferase-associated protein kinase p58/GTA) (PITSLRE serine/threonine-protein kinase CDC2L2) Appears to play multiple roles in cell cycle progression, cytokinesis and apoptosis. The p110 isoforms have been suggested to be involved in pre-mRNA splicing, potentially by phosphorylating the splicing protein SFRS7. The p58 isoform may act as a negative regulator of normal cell cycle progression. {ECO:0000269|PubMed:12501247, ECO:0000269|PubMed:12624090}.
Q9Y463 DYRK1B Y273 ochoa|psp Dual specificity tyrosine-phosphorylation-regulated kinase 1B (EC 2.7.12.1) (Minibrain-related kinase) (Mirk protein kinase) Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenance (PubMed:33469661). During DNA damage, mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2 (PubMed:32611815). Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase catalytic subunit 1 (G6PC1). {ECO:0000269|PubMed:10910078, ECO:0000269|PubMed:11980910, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:24827035, ECO:0000269|PubMed:33469661}.
O00141 SGK1 T254 Sugiyama Serine/threonine-protein kinase Sgk1 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 1) Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269|PubMed:11154281, ECO:0000269|PubMed:11410590, ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:12397388, ECO:0000269|PubMed:12590200, ECO:0000269|PubMed:12634932, ECO:0000269|PubMed:12650886, ECO:0000269|PubMed:12761204, ECO:0000269|PubMed:12911626, ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:14706641, ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15044175, ECO:0000269|PubMed:15234985, ECO:0000269|PubMed:15319523, ECO:0000269|PubMed:15496163, ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:15737648, ECO:0000269|PubMed:15845389, ECO:0000269|PubMed:15888551, ECO:0000269|PubMed:16036218, ECO:0000269|PubMed:16443776, ECO:0000269|PubMed:16982696, ECO:0000269|PubMed:17382906, ECO:0000269|PubMed:18005662, ECO:0000269|PubMed:18304449, ECO:0000269|PubMed:18753299, ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19756449, ECO:0000269|PubMed:20511718, ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:21865597}.
O75369 FLNB S1442 Sugiyama Filamin-B (FLN-B) (ABP-278) (ABP-280 homolog) (Actin-binding-like protein) (Beta-filamin) (Filamin homolog 1) (Fh1) (Filamin-3) (Thyroid autoantigen) (Truncated actin-binding protein) (Truncated ABP) Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
P42681 TXK S422 Sugiyama Tyrosine-protein kinase TXK (EC 2.7.10.2) (Protein-tyrosine kinase 4) (Resting lymphocyte kinase) Non-receptor tyrosine kinase that plays a redundant role with ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation leads to the recruitment of TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Also contributes to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskeleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with PARP1 and EEF1A1 (PubMed:11859127, PubMed:17177976). Within the complex, phosphorylates both PARP1 and EEF1A1 (PubMed:17177976). Also phosphorylates key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr-201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor. {ECO:0000269|PubMed:10523612, ECO:0000269|PubMed:11564877, ECO:0000269|PubMed:11859127, ECO:0000269|PubMed:17177976, ECO:0000269|PubMed:9813138}.
P51813 BMX S568 Sugiyama 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}.
Q04912 MST1R S1240 Sugiyama 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}.
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reactome_id name p -log10_p
R-HSA-110056 MAPK3 (ERK1) activation 3.691456e-09 8.433
R-HSA-112409 RAF-independent MAPK1/3 activation 3.016309e-09 8.521
R-HSA-187687 Signalling to ERKs 3.278280e-08 7.484
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 6.354185e-08 7.197
R-HSA-9732724 IFNG signaling activates MAPKs 1.244858e-07 6.905
R-HSA-112411 MAPK1 (ERK2) activation 2.564735e-07 6.591
R-HSA-450341 Activation of the AP-1 family of transcription factors 2.564735e-07 6.591
R-HSA-212436 Generic Transcription Pathway 3.583992e-07 6.446
R-HSA-1640170 Cell Cycle 3.792472e-07 6.421
R-HSA-162582 Signal Transduction 7.380836e-07 6.132
R-HSA-168638 NOD1/2 Signaling Pathway 1.049957e-06 5.979
R-HSA-5684996 MAPK1/MAPK3 signaling 1.000525e-06 6.000
R-HSA-5633007 Regulation of TP53 Activity 1.022843e-06 5.990
R-HSA-69278 Cell Cycle, Mitotic 1.139516e-06 5.943
R-HSA-171007 p38MAPK events 1.575897e-06 5.802
R-HSA-73857 RNA Polymerase II Transcription 1.555149e-06 5.808
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling 2.749049e-06 5.561
R-HSA-187037 Signaling by NTRK1 (TRKA) 2.902446e-06 5.537
R-HSA-198753 ERK/MAPK targets 5.402669e-06 5.267
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 5.161686e-06 5.287
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 3.676188e-06 5.435
R-HSA-5683057 MAPK family signaling cascades 3.763410e-06 5.424
R-HSA-167044 Signalling to RAS 5.402669e-06 5.267
R-HSA-74160 Gene expression (Transcription) 4.934923e-06 5.307
R-HSA-9705462 Inactivation of CSF3 (G-CSF) signaling 6.262831e-06 5.203
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 6.262831e-06 5.203
R-HSA-166520 Signaling by NTRKs 7.630011e-06 5.117
R-HSA-8854691 Interleukin-20 family signaling 8.281508e-06 5.082
R-HSA-450294 MAP kinase activation 1.292171e-05 4.889
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 1.310554e-05 4.883
R-HSA-9700206 Signaling by ALK in cancer 1.310554e-05 4.883
R-HSA-8878171 Transcriptional regulation by RUNX1 1.082104e-05 4.966
R-HSA-9674555 Signaling by CSF3 (G-CSF) 1.723447e-05 4.764
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 1.723447e-05 4.764
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 1.582834e-05 4.801
R-HSA-4420097 VEGFA-VEGFR2 Pathway 2.056755e-05 4.687
R-HSA-68875 Mitotic Prophase 2.541031e-05 4.595
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 2.437494e-05 4.613
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 2.437494e-05 4.613
R-HSA-448424 Interleukin-17 signaling 2.315498e-05 4.635
R-HSA-1538133 G0 and Early G1 2.371733e-05 4.625
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 2.610686e-05 4.583
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 2.648828e-05 4.577
R-HSA-9020956 Interleukin-27 signaling 2.648828e-05 4.577
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 2.758732e-05 4.559
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 2.758732e-05 4.559
R-HSA-194138 Signaling by VEGF 3.239177e-05 4.490
R-HSA-9020558 Interleukin-2 signaling 3.298190e-05 4.482
R-HSA-8984722 Interleukin-35 Signalling 4.893141e-05 4.310
R-HSA-451927 Interleukin-2 family signaling 5.391963e-05 4.268
R-HSA-6788467 IL-6-type cytokine receptor ligand interactions 5.851174e-05 4.233
R-HSA-1059683 Interleukin-6 signaling 5.851174e-05 4.233
R-HSA-5673001 RAF/MAP kinase cascade 5.421107e-05 4.266
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 5.851174e-05 4.233
R-HSA-9730414 MITF-M-regulated melanocyte development 6.535568e-05 4.185
R-HSA-8986944 Transcriptional Regulation by MECP2 7.458546e-05 4.127
R-HSA-453279 Mitotic G1 phase and G1/S transition 7.724736e-05 4.112
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 8.252133e-05 4.083
R-HSA-9679191 Potential therapeutics for SARS 8.807865e-05 4.055
R-HSA-449147 Signaling by Interleukins 9.159165e-05 4.038
R-HSA-975871 MyD88 cascade initiated on plasma membrane 1.114046e-04 3.953
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 1.114046e-04 3.953
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 1.114046e-04 3.953
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 1.055703e-04 3.976
R-HSA-4419969 Depolymerization of the Nuclear Lamina 1.422640e-04 3.847
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 1.546155e-04 3.811
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 1.611443e-04 3.793
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 1.737555e-04 3.760
R-HSA-975155 MyD88 dependent cascade initiated on endosome 1.805215e-04 3.743
R-HSA-2980766 Nuclear Envelope Breakdown 1.861604e-04 3.730
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 1.874869e-04 3.727
R-HSA-166166 MyD88-independent TLR4 cascade 1.874869e-04 3.727
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 2.273441e-04 3.643
R-HSA-1280215 Cytokine Signaling in Immune system 1.964600e-04 3.707
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 2.096195e-04 3.679
R-HSA-3700989 Transcriptional Regulation by TP53 2.290433e-04 3.640
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 2.336909e-04 3.631
R-HSA-2871809 FCERI mediated Ca+2 mobilization 2.421647e-04 3.616
R-HSA-76002 Platelet activation, signaling and aggregation 2.710633e-04 3.567
R-HSA-912526 Interleukin receptor SHC signaling 2.799808e-04 3.553
R-HSA-982772 Growth hormone receptor signaling 2.799808e-04 3.553
R-HSA-168898 Toll-like Receptor Cascades 2.920181e-04 3.535
R-HSA-6783589 Interleukin-6 family signaling 3.090076e-04 3.510
R-HSA-9652169 Signaling by MAP2K mutants 3.203285e-04 3.494
R-HSA-913531 Interferon Signaling 3.358572e-04 3.474
R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun... 3.358585e-04 3.474
R-HSA-525793 Myogenesis 3.727335e-04 3.429
R-HSA-1169408 ISG15 antiviral mechanism 4.671602e-04 3.331
R-HSA-5674499 Negative feedback regulation of MAPK pathway 5.663290e-04 3.247
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 6.604652e-04 3.180
R-HSA-9842640 Signaling by LTK in cancer 7.147798e-04 3.146
R-HSA-6804757 Regulation of TP53 Degradation 8.744929e-04 3.058
R-HSA-9856651 MITF-M-dependent gene expression 7.980141e-04 3.098
R-HSA-9679506 SARS-CoV Infections 7.794996e-04 3.108
R-HSA-114516 Disinhibition of SNARE formation 8.800068e-04 3.056
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 8.859325e-04 3.053
R-HSA-6806003 Regulation of TP53 Expression and Degradation 1.060835e-03 2.974
R-HSA-8985947 Interleukin-9 signaling 1.061868e-03 2.974
R-HSA-9020933 Interleukin-23 signaling 1.061868e-03 2.974
R-HSA-8939246 RUNX1 regulates transcription of genes involved in differentiation of myeloid ce... 1.061868e-03 2.974
R-HSA-444257 RSK activation 1.061868e-03 2.974
R-HSA-9020958 Interleukin-21 signaling 1.260223e-03 2.900
R-HSA-9656223 Signaling by RAF1 mutants 1.270539e-03 2.896
R-HSA-5675221 Negative regulation of MAPK pathway 1.270539e-03 2.896
R-HSA-1433557 Signaling by SCF-KIT 1.423841e-03 2.847
R-HSA-2559580 Oxidative Stress Induced Senescence 1.458013e-03 2.836
R-HSA-74749 Signal attenuation 1.474930e-03 2.831
R-HSA-9627069 Regulation of the apoptosome activity 1.474930e-03 2.831
R-HSA-111458 Formation of apoptosome 1.474930e-03 2.831
R-HSA-202670 ERKs are inactivated 1.952846e-03 2.709
R-HSA-9649948 Signaling downstream of RAS mutants 1.674792e-03 2.776
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 1.674792e-03 2.776
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 1.674792e-03 2.776
R-HSA-6802949 Signaling by RAS mutants 1.674792e-03 2.776
R-HSA-453274 Mitotic G2-G2/M phases 1.994074e-03 2.700
R-HSA-69275 G2/M Transition 1.912078e-03 2.718
R-HSA-9635465 Suppression of apoptosis 1.705850e-03 2.768
R-HSA-202403 TCR signaling 1.924860e-03 2.716
R-HSA-2559583 Cellular Senescence 1.680910e-03 2.774
R-HSA-69231 Cyclin D associated events in G1 1.504655e-03 2.823
R-HSA-69236 G1 Phase 1.504655e-03 2.823
R-HSA-111461 Cytochrome c-mediated apoptotic response 1.952846e-03 2.709
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 2.064767e-03 2.685
R-HSA-8983432 Interleukin-15 signaling 2.215779e-03 2.654
R-HSA-877312 Regulation of IFNG signaling 2.215779e-03 2.654
R-HSA-879415 Advanced glycosylation endproduct receptor signaling 2.215779e-03 2.654
R-HSA-209543 p75NTR recruits signalling complexes 2.215779e-03 2.654
R-HSA-168256 Immune System 2.365175e-03 2.626
R-HSA-170968 Frs2-mediated activation 2.494513e-03 2.603
R-HSA-418597 G alpha (z) signalling events 2.587613e-03 2.587
R-HSA-5578768 Physiological factors 2.788911e-03 2.555
R-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression 2.788911e-03 2.555
R-HSA-193639 p75NTR signals via NF-kB 3.098838e-03 2.509
R-HSA-1502540 Signaling by Activin 3.098838e-03 2.509
R-HSA-1295596 Spry regulation of FGF signaling 3.098838e-03 2.509
R-HSA-69206 G1/S Transition 3.151589e-03 2.501
R-HSA-169893 Prolonged ERK activation events 3.424161e-03 2.465
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... 3.424161e-03 2.465
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 3.424161e-03 2.465
R-HSA-5099900 WNT5A-dependent internalization of FZD4 3.424161e-03 2.465
R-HSA-69615 G1/S DNA Damage Checkpoints 3.614833e-03 2.442
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 3.905196e-03 2.408
R-HSA-9705683 SARS-CoV-2-host interactions 4.303933e-03 2.366
R-HSA-168249 Innate Immune System 4.468171e-03 2.350
R-HSA-416993 Trafficking of GluR2-containing AMPA receptors 4.491169e-03 2.348
R-HSA-111471 Apoptotic factor-mediated response 4.491169e-03 2.348
R-HSA-9664417 Leishmania phagocytosis 4.721734e-03 2.326
R-HSA-9664422 FCGR3A-mediated phagocytosis 4.721734e-03 2.326
R-HSA-9664407 Parasite infection 4.721734e-03 2.326
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 4.827801e-03 2.316
R-HSA-449836 Other interleukin signaling 4.876746e-03 2.312
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 5.031707e-03 2.298
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 5.044726e-03 2.297
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 5.206944e-03 2.283
R-HSA-445144 Signal transduction by L1 5.277060e-03 2.278
R-HSA-1181150 Signaling by NODAL 5.277060e-03 2.278
R-HSA-380287 Centrosome maturation 5.568367e-03 2.254
R-HSA-9020591 Interleukin-12 signaling 5.754593e-03 2.240
R-HSA-912694 Regulation of IFNA/IFNB signaling 6.565128e-03 2.183
R-HSA-9734091 Drug-mediated inhibition of MET activation 8.533743e-03 2.069
R-HSA-6802957 Oncogenic MAPK signaling 7.599490e-03 2.119
R-HSA-877300 Interferon gamma signaling 7.157898e-03 2.145
R-HSA-1266695 Interleukin-7 signaling 7.981214e-03 2.098
R-HSA-447115 Interleukin-12 family signaling 8.283358e-03 2.082
R-HSA-5218921 VEGFR2 mediated cell proliferation 7.981214e-03 2.098
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 9.617807e-03 2.017
R-HSA-68886 M Phase 7.674536e-03 2.115
R-HSA-416476 G alpha (q) signalling events 7.536193e-03 2.123
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 6.950373e-03 2.158
R-HSA-69620 Cell Cycle Checkpoints 6.906905e-03 2.161
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 7.023101e-03 2.153
R-HSA-5654732 Negative regulation of FGFR3 signaling 9.521935e-03 2.021
R-HSA-5654733 Negative regulation of FGFR4 signaling 1.006263e-02 1.997
R-HSA-9658195 Leishmania infection 9.535226e-03 2.021
R-HSA-9824443 Parasitic Infection Pathways 9.535226e-03 2.021
R-HSA-9022699 MECP2 regulates neuronal receptors and channels 8.481105e-03 2.072
R-HSA-109582 Hemostasis 7.304983e-03 2.136
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 9.521935e-03 2.021
R-HSA-109581 Apoptosis 7.583086e-03 2.120
R-HSA-2424491 DAP12 signaling 1.061668e-02 1.974
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs) 1.061668e-02 1.974
R-HSA-422475 Axon guidance 1.066319e-02 1.972
R-HSA-399719 Trafficking of AMPA receptors 1.118397e-02 1.951
R-HSA-9833109 Evasion by RSV of host interferon responses 1.118397e-02 1.951
R-HSA-111465 Apoptotic cleavage of cellular proteins 1.176438e-02 1.929
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 1.176438e-02 1.929
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticity 1.235778e-02 1.908
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 1.235778e-02 1.908
R-HSA-5654726 Negative regulation of FGFR1 signaling 1.235778e-02 1.908
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 1.283289e-02 1.892
R-HSA-5663205 Infectious disease 1.286346e-02 1.891
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling 1.297842e-02 1.887
R-HSA-5654727 Negative regulation of FGFR2 signaling 1.358310e-02 1.867
R-HSA-9768919 NPAS4 regulates expression of target genes 1.358310e-02 1.867
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 1.421479e-02 1.847
R-HSA-2559585 Oncogene Induced Senescence 1.421479e-02 1.847
R-HSA-9675108 Nervous system development 1.467771e-02 1.833
R-HSA-69205 G1/S-Specific Transcription 1.485901e-02 1.828
R-HSA-8941326 RUNX2 regulates bone development 1.485901e-02 1.828
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 1.551564e-02 1.809
R-HSA-5689896 Ovarian tumor domain proteases 1.551564e-02 1.809
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 1.551564e-02 1.809
R-HSA-5357801 Programmed Cell Death 1.605473e-02 1.794
R-HSA-2871796 FCERI mediated MAPK activation 1.640434e-02 1.785
R-HSA-202433 Generation of second messenger molecules 1.755886e-02 1.756
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 1.775117e-02 1.751
R-HSA-1592230 Mitochondrial biogenesis 1.893921e-02 1.723
R-HSA-5674135 MAP2K and MAPK activation 1.898100e-02 1.722
R-HSA-9006925 Intracellular signaling by second messengers 1.967643e-02 1.706
R-HSA-8878166 Transcriptional regulation by RUNX2 1.970117e-02 1.706
R-HSA-111996 Ca-dependent events 1.970972e-02 1.705
R-HSA-9637690 Response of Mtb to phagocytosis 2.045007e-02 1.689
R-HSA-5654743 Signaling by FGFR4 2.045007e-02 1.689
R-HSA-3371556 Cellular response to heat stress 2.047993e-02 1.689
R-HSA-9694516 SARS-CoV-2 Infection 2.116806e-02 1.674
R-HSA-8875513 MET interacts with TNS proteins 2.119996e-02 1.674
R-HSA-8865999 MET activates PTPN11 2.119996e-02 1.674
R-HSA-8875791 MET activates STAT3 2.119996e-02 1.674
R-HSA-2172127 DAP12 interactions 2.120194e-02 1.674
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 2.127551e-02 1.672
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 2.196521e-02 1.658
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 2.196521e-02 1.658
R-HSA-5654741 Signaling by FGFR3 2.196521e-02 1.658
R-HSA-2514859 Inactivation, recovery and regulation of the phototransduction cascade 2.273978e-02 1.643
R-HSA-75153 Apoptotic execution phase 2.273978e-02 1.643
R-HSA-9824446 Viral Infection Pathways 2.404303e-02 1.619
R-HSA-199418 Negative regulation of the PI3K/AKT network 2.462613e-02 1.609
R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... 2.538649e-02 1.595
R-HSA-9706374 FLT3 signaling through SRC family kinases 2.538649e-02 1.595
R-HSA-2514856 The phototransduction cascade 2.677838e-02 1.572
R-HSA-9634815 Transcriptional Regulation by NPAS4 2.761850e-02 1.559
R-HSA-68911 G2 Phase 2.955537e-02 1.529
R-HSA-5654736 Signaling by FGFR1 3.108358e-02 1.507
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 3.108358e-02 1.507
R-HSA-109606 Intrinsic Pathway for Apoptosis 3.108358e-02 1.507
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 3.197549e-02 1.495
R-HSA-8849470 PTK6 Regulates Cell Cycle 3.370668e-02 1.472
R-HSA-9652817 Signaling by MAPK mutants 3.370668e-02 1.472
R-HSA-8852405 Signaling by MST1 3.370668e-02 1.472
R-HSA-176417 Phosphorylation of Emi1 3.370668e-02 1.472
R-HSA-8943724 Regulation of PTEN gene transcription 3.471112e-02 1.460
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 3.471112e-02 1.460
R-HSA-112043 PLC beta mediated events 3.564263e-02 1.448
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 3.658381e-02 1.437
R-HSA-375165 NCAM signaling for neurite out-growth 3.658381e-02 1.437
R-HSA-9027283 Erythropoietin activates STAT5 3.784048e-02 1.422
R-HSA-69478 G2/M DNA replication checkpoint 3.784048e-02 1.422
R-HSA-113507 E2F-enabled inhibition of pre-replication complex formation 3.784048e-02 1.422
R-HSA-6806942 MET Receptor Activation 3.784048e-02 1.422
R-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7 3.784048e-02 1.422
R-HSA-1266738 Developmental Biology 3.789435e-02 1.421
R-HSA-8851907 MET activates PI3K/AKT signaling 4.195686e-02 1.377
R-HSA-8875656 MET receptor recycling 4.605588e-02 1.337
R-HSA-8875555 MET activates RAP1 and RAC1 5.420213e-02 1.266
R-HSA-9027277 Erythropoietin activates Phospholipase C gamma (PLCG) 5.420213e-02 1.266
R-HSA-416550 Sema4D mediated inhibition of cell attachment and migration 6.227982e-02 1.206
R-HSA-8851805 MET activates RAS signaling 6.629313e-02 1.179
R-HSA-9027276 Erythropoietin activates Phosphoinositide-3-kinase (PI3K) 6.629313e-02 1.179
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 7.028951e-02 1.153
R-HSA-1170546 Prolactin receptor signaling 7.426904e-02 1.129
R-HSA-383280 Nuclear Receptor transcription pathway 5.287885e-02 1.277
R-HSA-2586552 Signaling by Leptin 5.420213e-02 1.266
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 4.650572e-02 1.332
R-HSA-69202 Cyclin E associated events during G1/S transition 4.444939e-02 1.352
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 7.028951e-02 1.153
R-HSA-73864 RNA Polymerase I Transcription 5.287885e-02 1.277
R-HSA-6783783 Interleukin-10 signaling 5.287885e-02 1.277
R-HSA-9010642 ROBO receptors bind AKAP5 4.605588e-02 1.337
R-HSA-73854 RNA Polymerase I Promoter Clearance 5.072116e-02 1.295
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messenge... 7.245781e-02 1.140
R-HSA-111995 phospho-PLA2 pathway 4.605588e-02 1.337
R-HSA-2179392 EGFR Transactivation by Gastrin 5.420213e-02 1.266
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 4.547320e-02 1.342
R-HSA-453276 Regulation of mitotic cell cycle 4.547320e-02 1.342
R-HSA-2465910 MASTL Facilitates Mitotic Progression 5.013761e-02 1.300
R-HSA-2514853 Condensation of Prometaphase Chromosomes 6.227982e-02 1.206
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 4.014000e-02 1.396
R-HSA-202424 Downstream TCR signaling 6.766238e-02 1.170
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 7.028951e-02 1.153
R-HSA-9634635 Estrogen-stimulated signaling through PRKCZ 5.013761e-02 1.300
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 5.013761e-02 1.300
R-HSA-1433559 Regulation of KIT signaling 7.426904e-02 1.129
R-HSA-9662834 CD163 mediating an anti-inflammatory response 5.824951e-02 1.235
R-HSA-1852241 Organelle biogenesis and maintenance 5.836354e-02 1.234
R-HSA-9842663 Signaling by LTK 6.629313e-02 1.179
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 4.547320e-02 1.342
R-HSA-74751 Insulin receptor signalling cascade 3.849475e-02 1.415
R-HSA-112040 G-protein mediated events 4.143118e-02 1.383
R-HSA-1257604 PIP3 activates AKT signaling 4.648666e-02 1.333
R-HSA-74752 Signaling by Insulin receptor 7.124872e-02 1.147
R-HSA-2262752 Cellular responses to stress 7.586508e-02 1.120
R-HSA-8953897 Cellular responses to stimuli 6.053735e-02 1.218
R-HSA-5654738 Signaling by FGFR2 5.506890e-02 1.259
R-HSA-4086400 PCP/CE pathway 5.287885e-02 1.277
R-HSA-9764560 Regulation of CDH1 Gene Transcription 4.444939e-02 1.352
R-HSA-438064 Post NMDA receptor activation events 6.413913e-02 1.193
R-HSA-446728 Cell junction organization 3.926805e-02 1.406
R-HSA-1500931 Cell-Cell communication 5.636288e-02 1.249
R-HSA-112315 Transmission across Chemical Synapses 5.988896e-02 1.223
R-HSA-9027284 Erythropoietin activates RAS 7.823177e-02 1.107
R-HSA-8875360 InlB-mediated entry of Listeria monocytogenes into host cell 7.823177e-02 1.107
R-HSA-8964315 G beta:gamma signalling through BTK 7.823177e-02 1.107
R-HSA-446353 Cell-extracellular matrix interactions 7.823177e-02 1.107
R-HSA-170834 Signaling by TGF-beta Receptor Complex 7.860216e-02 1.105
R-HSA-190236 Signaling by FGFR 7.985027e-02 1.098
R-HSA-193704 p75 NTR receptor-mediated signalling 8.110461e-02 1.091
R-HSA-176412 Phosphorylation of the APC/C 8.217779e-02 1.085
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest 8.217779e-02 1.085
R-HSA-9009391 Extra-nuclear estrogen signaling 8.363172e-02 1.078
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 8.490434e-02 1.071
R-HSA-1280218 Adaptive Immune System 8.547430e-02 1.068
R-HSA-399997 Acetylcholine regulates insulin secretion 8.610716e-02 1.065
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 8.610716e-02 1.065
R-HSA-111885 Opioid Signalling 8.746733e-02 1.058
R-HSA-9833110 RSV-host interactions 8.875757e-02 1.052
R-HSA-1643685 Disease 9.263952e-02 1.033
R-HSA-432142 Platelet sensitization by LDL 9.391623e-02 1.027
R-HSA-174048 APC/C:Cdc20 mediated degradation of Cyclin B 9.779606e-02 1.010
R-HSA-912631 Regulation of signaling by CBL 9.779606e-02 1.010
R-HSA-113510 E2F mediated regulation of DNA replication 9.779606e-02 1.010
R-HSA-6807004 Negative regulation of MET activity 1.016595e-01 0.993
R-HSA-5602498 MyD88 deficiency (TLR2/4) 1.055067e-01 0.977
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 1.055067e-01 0.977
R-HSA-9931295 PD-L1(CD274) glycosylation and translocation to plasma membrane 1.055067e-01 0.977
R-HSA-909733 Interferon alpha/beta signaling 1.060265e-01 0.975
R-HSA-373760 L1CAM interactions 1.073907e-01 0.969
R-HSA-5603041 IRAK4 deficiency (TLR2/4) 1.093376e-01 0.961
R-HSA-8876384 Listeria monocytogenes entry into host cells 1.093376e-01 0.961
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 1.093376e-01 0.961
R-HSA-421270 Cell-cell junction organization 1.106967e-01 0.956
R-HSA-166208 mTORC1-mediated signalling 1.131524e-01 0.946
R-HSA-9670439 Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT m... 1.131524e-01 0.946
R-HSA-9669938 Signaling by KIT in disease 1.131524e-01 0.946
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 1.142819e-01 0.942
R-HSA-9635486 Infection with Mycobacterium tuberculosis 1.142819e-01 0.942
R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE 1.169510e-01 0.932
R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection 1.169510e-01 0.932
R-HSA-3000170 Syndecan interactions 1.169510e-01 0.932
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse 1.207336e-01 0.918
R-HSA-418592 ADP signalling through P2Y purinoceptor 1 1.207336e-01 0.918
R-HSA-69481 G2/M Checkpoints 1.241153e-01 0.906
R-HSA-400685 Sema4D in semaphorin signaling 1.245003e-01 0.905
R-HSA-420029 Tight junction interactions 1.245003e-01 0.905
R-HSA-388396 GPCR downstream signalling 1.251029e-01 0.903
R-HSA-8874081 MET activates PTK2 signaling 1.282510e-01 0.892
R-HSA-5576891 Cardiac conduction 1.312616e-01 0.882
R-HSA-3928663 EPHA-mediated growth cone collapse 1.319859e-01 0.879
R-HSA-73863 RNA Polymerase I Transcription Termination 1.319859e-01 0.879
R-HSA-73728 RNA Polymerase I Promoter Opening 1.319859e-01 0.879
R-HSA-76005 Response to elevated platelet cytosolic Ca2+ 1.341467e-01 0.872
R-HSA-113418 Formation of the Early Elongation Complex 1.357050e-01 0.867
R-HSA-171319 Telomere Extension By Telomerase 1.357050e-01 0.867
R-HSA-167158 Formation of the HIV-1 Early Elongation Complex 1.357050e-01 0.867
R-HSA-9006335 Signaling by Erythropoietin 1.394084e-01 0.856
R-HSA-72086 mRNA Capping 1.394084e-01 0.856
R-HSA-3858494 Beta-catenin independent WNT signaling 1.399601e-01 0.854
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 1.414221e-01 0.849
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... 1.430962e-01 0.844
R-HSA-68962 Activation of the pre-replicative complex 1.430962e-01 0.844
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 1.430962e-01 0.844
R-HSA-1250196 SHC1 events in ERBB2 signaling 1.430962e-01 0.844
R-HSA-6807070 PTEN Regulation 1.443561e-01 0.841
R-HSA-1855196 IP3 and IP4 transport between cytosol and nucleus 1.467684e-01 0.833
R-HSA-1855229 IP6 and IP7 transport between cytosol and nucleus 1.467684e-01 0.833
R-HSA-162599 Late Phase of HIV Life Cycle 1.502628e-01 0.823
R-HSA-9675126 Diseases of mitotic cell cycle 1.504251e-01 0.823
R-HSA-1855170 IPs transport between nucleus and cytosol 1.540664e-01 0.812
R-HSA-159227 Transport of the SLBP independent Mature mRNA 1.540664e-01 0.812
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 1.540664e-01 0.812
R-HSA-176187 Activation of ATR in response to replication stress 1.540664e-01 0.812
R-HSA-397795 G-protein beta:gamma signalling 1.540664e-01 0.812
R-HSA-354192 Integrin signaling 1.540664e-01 0.812
R-HSA-9022692 Regulation of MECP2 expression and activity 1.540664e-01 0.812
R-HSA-159230 Transport of the SLBP Dependant Mature mRNA 1.576923e-01 0.802
R-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein 1.576923e-01 0.802
R-HSA-114508 Effects of PIP2 hydrolysis 1.576923e-01 0.802
R-HSA-2187338 Visual phototransduction 1.577140e-01 0.802
R-HSA-112316 Neuronal System 1.578062e-01 0.802
R-HSA-69242 S Phase 1.592128e-01 0.798
R-HSA-8953854 Metabolism of RNA 1.601191e-01 0.796
R-HSA-9735869 SARS-CoV-1 modulates host translation machinery 1.613028e-01 0.792
R-HSA-180746 Nuclear import of Rev protein 1.613028e-01 0.792
R-HSA-392518 Signal amplification 1.613028e-01 0.792
R-HSA-5673000 RAF activation 1.613028e-01 0.792
R-HSA-73887 Death Receptor Signaling 1.682611e-01 0.774
R-HSA-114604 GPVI-mediated activation cascade 1.684783e-01 0.773
R-HSA-111933 Calmodulin induced events 1.684783e-01 0.773
R-HSA-111997 CaM pathway 1.684783e-01 0.773
R-HSA-8853659 RET signaling 1.684783e-01 0.773
R-HSA-168273 Influenza Viral RNA Transcription and Replication 1.697780e-01 0.770
R-HSA-180910 Vpr-mediated nuclear import of PICs 1.720432e-01 0.764
R-HSA-162587 HIV Life Cycle 1.728188e-01 0.762
R-HSA-372790 Signaling by GPCR 1.737233e-01 0.760
R-HSA-8875878 MET promotes cell motility 1.755932e-01 0.755
R-HSA-165054 Rev-mediated nuclear export of HIV RNA 1.755932e-01 0.755
R-HSA-9006936 Signaling by TGFB family members 1.773972e-01 0.751
R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript 1.791281e-01 0.747
R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat 1.791281e-01 0.747
R-HSA-168276 NS1 Mediated Effects on Host Pathways 1.791281e-01 0.747
R-HSA-201556 Signaling by ALK 1.791281e-01 0.747
R-HSA-9648002 RAS processing 1.791281e-01 0.747
R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts 1.826481e-01 0.738
R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat 1.826481e-01 0.738
R-HSA-177243 Interactions of Rev with host cellular proteins 1.826481e-01 0.738
R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript 1.826481e-01 0.738
R-HSA-176033 Interactions of Vpr with host cellular proteins 1.826481e-01 0.738
R-HSA-5602358 Diseases associated with the TLR signaling cascade 1.826481e-01 0.738
R-HSA-5260271 Diseases of Immune System 1.826481e-01 0.738
R-HSA-167169 HIV Transcription Elongation 1.826481e-01 0.738
R-HSA-5696395 Formation of Incision Complex in GG-NER 1.826481e-01 0.738
R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening 1.826481e-01 0.738
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 1.861532e-01 0.730
R-HSA-168271 Transport of Ribonucleoproteins into the Host Nucleus 1.861532e-01 0.730
R-HSA-9607240 FLT3 Signaling 1.861532e-01 0.730
R-HSA-167162 RNA Polymerase II HIV Promoter Escape 1.896435e-01 0.722
R-HSA-167161 HIV Transcription Initiation 1.896435e-01 0.722
R-HSA-75953 RNA Polymerase II Transcription Initiation 1.896435e-01 0.722
R-HSA-165159 MTOR signalling 1.931190e-01 0.714
R-HSA-73762 RNA Polymerase I Transcription Initiation 1.931190e-01 0.714
R-HSA-73776 RNA Polymerase II Promoter Escape 1.965799e-01 0.706
R-HSA-9664433 Leishmania parasite growth and survival 1.990005e-01 0.701
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 1.990005e-01 0.701
R-HSA-9764265 Regulation of CDH1 Expression and Function 1.990005e-01 0.701
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 1.990005e-01 0.701
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 2.000261e-01 0.699
R-HSA-3214858 RMTs methylate histone arginines 2.000261e-01 0.699
R-HSA-373752 Netrin-1 signaling 2.000261e-01 0.699
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 2.021142e-01 0.694
R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance 2.034577e-01 0.692
R-HSA-168333 NEP/NS2 Interacts with the Cellular Export Machinery 2.034577e-01 0.692
R-HSA-76009 Platelet Aggregation (Plug Formation) 2.034577e-01 0.692
R-HSA-1489509 DAG and IP3 signaling 2.034577e-01 0.692
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 2.034577e-01 0.692
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 2.068749e-01 0.684
R-HSA-72695 Formation of the ternary complex, and subsequently, the 43S complex 2.068749e-01 0.684
R-HSA-2299718 Condensation of Prophase Chromosomes 2.068749e-01 0.684
R-HSA-168274 Export of Viral Ribonucleoproteins from Nucleus 2.068749e-01 0.684
R-HSA-168255 Influenza Infection 2.083589e-01 0.681
R-HSA-3928665 EPH-ephrin mediated repulsion of cells 2.102776e-01 0.677
R-HSA-437239 Recycling pathway of L1 2.102776e-01 0.677
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 2.102776e-01 0.677
R-HSA-9031628 NGF-stimulated transcription 2.136659e-01 0.670
R-HSA-69563 p53-Dependent G1 DNA Damage Response 2.170399e-01 0.663
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 2.170399e-01 0.663
R-HSA-1169091 Activation of NF-kappaB in B cells 2.237451e-01 0.650
R-HSA-912446 Meiotic recombination 2.237451e-01 0.650
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 2.270764e-01 0.644
R-HSA-73772 RNA Polymerase I Promoter Escape 2.270764e-01 0.644
R-HSA-112382 Formation of RNA Pol II elongation complex 2.270764e-01 0.644
R-HSA-68949 Orc1 removal from chromatin 2.270764e-01 0.644
R-HSA-68877 Mitotic Prometaphase 2.303645e-01 0.638
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 2.303937e-01 0.638
R-HSA-75955 RNA Polymerase II Transcription Elongation 2.303937e-01 0.638
R-HSA-72649 Translation initiation complex formation 2.336969e-01 0.631
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 2.336969e-01 0.631
R-HSA-9754678 SARS-CoV-2 modulates host translation machinery 2.336969e-01 0.631
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 2.351036e-01 0.629
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 2.369862e-01 0.625
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER 2.402615e-01 0.619
R-HSA-72702 Ribosomal scanning and start codon recognition 2.402615e-01 0.619
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 2.402615e-01 0.619
R-HSA-5621480 Dectin-2 family 2.435230e-01 0.613
R-HSA-376176 Signaling by ROBO receptors 2.461838e-01 0.609
R-HSA-6782135 Dual incision in TC-NER 2.467707e-01 0.608
R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and sub... 2.467707e-01 0.608
R-HSA-191859 snRNP Assembly 2.500047e-01 0.602
R-HSA-194441 Metabolism of non-coding RNA 2.500047e-01 0.602
R-HSA-180786 Extension of Telomeres 2.500047e-01 0.602
R-HSA-1227986 Signaling by ERBB2 2.532249e-01 0.596
R-HSA-168325 Viral Messenger RNA Synthesis 2.564315e-01 0.591
R-HSA-9824439 Bacterial Infection Pathways 2.581410e-01 0.588
R-HSA-6784531 tRNA processing in the nucleus 2.596246e-01 0.586
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 2.596246e-01 0.586
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 2.596246e-01 0.586
R-HSA-9616222 Transcriptional regulation of granulopoiesis 2.596246e-01 0.586
R-HSA-1660499 Synthesis of PIPs at the plasma membrane 2.596246e-01 0.586
R-HSA-397014 Muscle contraction 2.620485e-01 0.582
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 2.628042e-01 0.580
R-HSA-380259 Loss of Nlp from mitotic centrosomes 2.628042e-01 0.580
R-HSA-373755 Semaphorin interactions 2.628042e-01 0.580
R-HSA-8848021 Signaling by PTK6 2.628042e-01 0.580
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 2.628042e-01 0.580
R-HSA-68882 Mitotic Anaphase 2.684001e-01 0.571
R-HSA-2555396 Mitotic Metaphase and Anaphase 2.699881e-01 0.569
R-HSA-418990 Adherens junctions interactions 2.715761e-01 0.566
R-HSA-8854518 AURKA Activation by TPX2 2.722623e-01 0.565
R-HSA-167172 Transcription of the HIV genome 2.785012e-01 0.555
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 2.846873e-01 0.546
R-HSA-162906 HIV Infection 2.858634e-01 0.544
R-HSA-427413 NoRC negatively regulates rRNA expression 2.877608e-01 0.541
R-HSA-5578749 Transcriptional regulation by small RNAs 2.908212e-01 0.536
R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript 2.938687e-01 0.532
R-HSA-69052 Switching of origins to a post-replicative state 2.938687e-01 0.532
R-HSA-4086398 Ca2+ pathway 2.938687e-01 0.532
R-HSA-674695 RNA Polymerase II Pre-transcription Events 2.969032e-01 0.527
R-HSA-69473 G2/M DNA damage checkpoint 2.969032e-01 0.527
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) 2.999250e-01 0.523
R-HSA-3000171 Non-integrin membrane-ECM interactions 2.999250e-01 0.523
R-HSA-8939211 ESR-mediated signaling 3.017108e-01 0.520
R-HSA-416482 G alpha (12/13) signalling events 3.089135e-01 0.510
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 3.089135e-01 0.510
R-HSA-9925561 Developmental Lineage of Pancreatic Acinar Cells 3.118843e-01 0.506
R-HSA-6806834 Signaling by MET 3.148426e-01 0.502
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 3.148426e-01 0.502
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 3.148426e-01 0.502
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 3.148426e-01 0.502
R-HSA-9833482 PKR-mediated signaling 3.148426e-01 0.502
R-HSA-5693607 Processing of DNA double-strand break ends 3.177883e-01 0.498
R-HSA-72202 Transport of Mature Transcript to Cytoplasm 3.207215e-01 0.494
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 3.265508e-01 0.486
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 3.265508e-01 0.486
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 3.265508e-01 0.486
R-HSA-1500620 Meiosis 3.294469e-01 0.482
R-HSA-5687128 MAPK6/MAPK4 signaling 3.294469e-01 0.482
R-HSA-5688426 Deubiquitination 3.300864e-01 0.481
R-HSA-141424 Amplification of signal from the kinetochores 3.323307e-01 0.478
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... 3.323307e-01 0.478
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 3.323307e-01 0.478
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 3.352023e-01 0.475
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 3.409090e-01 0.467
R-HSA-156902 Peptide chain elongation 3.409090e-01 0.467
R-HSA-1236974 ER-Phagosome pathway 3.437443e-01 0.464
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 3.465675e-01 0.460
R-HSA-9954714 PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA 3.493787e-01 0.457
R-HSA-1912408 Pre-NOTCH Transcription and Translation 3.493787e-01 0.457
R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) 3.521781e-01 0.453
R-HSA-156842 Eukaryotic Translation Elongation 3.549655e-01 0.450
R-HSA-2682334 EPH-Ephrin signaling 3.549655e-01 0.450
R-HSA-2029481 FCGR activation 3.577412e-01 0.446
R-HSA-2219530 Constitutive Signaling by Aberrant PI3K in Cancer 3.605050e-01 0.443
R-HSA-9954716 ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ri... 3.632572e-01 0.440
R-HSA-72689 Formation of a pool of free 40S subunits 3.659976e-01 0.437
R-HSA-72764 Eukaryotic Translation Termination 3.659976e-01 0.437
R-HSA-2730905 Role of LAT2/NTAL/LAB on calcium mobilization 3.687265e-01 0.433
R-HSA-5607764 CLEC7A (Dectin-1) signaling 3.687265e-01 0.433
R-HSA-157579 Telomere Maintenance 3.714437e-01 0.430
R-HSA-422356 Regulation of insulin secretion 3.741495e-01 0.427
R-HSA-69618 Mitotic Spindle Checkpoint 3.795266e-01 0.421
R-HSA-70171 Glycolysis 3.795266e-01 0.421
R-HSA-2408557 Selenocysteine synthesis 3.821980e-01 0.418
R-HSA-9020702 Interleukin-1 signaling 3.821980e-01 0.418
R-HSA-1483255 PI Metabolism 3.848581e-01 0.415
R-HSA-192823 Viral mRNA Translation 3.875070e-01 0.412
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 3.901445e-01 0.409
R-HSA-9860931 Response of endothelial cells to shear stress 3.901445e-01 0.409
R-HSA-5696398 Nucleotide Excision Repair 3.953862e-01 0.403
R-HSA-195721 Signaling by WNT 3.964470e-01 0.402
R-HSA-418346 Platelet homeostasis 3.979903e-01 0.400
R-HSA-9692914 SARS-CoV-1-host interactions 3.979903e-01 0.400
R-HSA-1799339 SRP-dependent cotranslational protein targeting to membrane 4.005834e-01 0.397
R-HSA-69239 Synthesis of DNA 4.005834e-01 0.397
R-HSA-211000 Gene Silencing by RNA 4.005834e-01 0.397
R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit 4.031655e-01 0.395
R-HSA-156827 L13a-mediated translational silencing of Ceruloplasmin expression 4.031655e-01 0.395
R-HSA-1236975 Antigen processing-Cross presentation 4.031655e-01 0.395
R-HSA-2672351 Stimuli-sensing channels 4.031655e-01 0.395
R-HSA-9648025 EML4 and NUDC in mitotic spindle formation 4.057366e-01 0.392
R-HSA-69002 DNA Replication Pre-Initiation 4.057366e-01 0.392
R-HSA-927802 Nonsense-Mediated Decay (NMD) 4.133846e-01 0.384
R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) 4.133846e-01 0.384
R-HSA-1483249 Inositol phosphate metabolism 4.133846e-01 0.384
R-HSA-1912422 Pre-NOTCH Expression and Processing 4.159123e-01 0.381
R-HSA-9855142 Cellular responses to mechanical stimuli 4.184293e-01 0.378
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 4.184293e-01 0.378
R-HSA-2029485 Role of phospholipids in phagocytosis 4.259163e-01 0.371
R-HSA-72737 Cap-dependent Translation Initiation 4.283908e-01 0.368
R-HSA-72613 Eukaryotic Translation Initiation 4.283908e-01 0.368
R-HSA-70326 Glucose metabolism 4.308548e-01 0.366
R-HSA-2219528 PI3K/AKT Signaling in Cancer 4.333083e-01 0.363
R-HSA-5693538 Homology Directed Repair 4.333083e-01 0.363
R-HSA-73886 Chromosome Maintenance 4.406065e-01 0.356
R-HSA-162909 Host Interactions of HIV factors 4.478120e-01 0.349
R-HSA-9664323 FCGR3A-mediated IL10 synthesis 4.549260e-01 0.342
R-HSA-1474165 Reproduction 4.665826e-01 0.331
R-HSA-163685 Integration of energy metabolism 4.824900e-01 0.317
R-HSA-73894 DNA Repair 4.865491e-01 0.313
R-HSA-9948299 Ribosome-associated quality control 4.869485e-01 0.313
R-HSA-9006931 Signaling by Nuclear Receptors 4.907034e-01 0.309
R-HSA-2871837 FCERI mediated NF-kB activation 5.022571e-01 0.299
R-HSA-9755511 KEAP1-NFE2L2 pathway 5.171154e-01 0.286
R-HSA-9010553 Regulation of expression of SLITs and ROBOs 5.192020e-01 0.285
R-HSA-9820448 Developmental Cell Lineages of the Exocrine Pancreas 5.192020e-01 0.285
R-HSA-446652 Interleukin-1 family signaling 5.192020e-01 0.285
R-HSA-69306 DNA Replication 5.212797e-01 0.283
R-HSA-5693532 DNA Double-Strand Break Repair 5.212797e-01 0.283
R-HSA-9610379 HCMV Late Events 5.295025e-01 0.276
R-HSA-9711097 Cellular response to starvation 5.315363e-01 0.274
R-HSA-2467813 Separation of Sister Chromatids 5.435587e-01 0.265
R-HSA-2408522 Selenoamino acid metabolism 5.435587e-01 0.265
R-HSA-5619102 SLC transporter disorders 5.494554e-01 0.260
R-HSA-418594 G alpha (i) signalling events 5.504786e-01 0.259
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol 5.572009e-01 0.254
R-HSA-72306 tRNA processing 5.572009e-01 0.254
R-HSA-5621481 C-type lectin receptors (CLRs) 5.591167e-01 0.252
R-HSA-9909648 Regulation of PD-L1(CD274) expression 5.610244e-01 0.251
R-HSA-9678108 SARS-CoV-1 Infection 5.666986e-01 0.247
R-HSA-8868773 rRNA processing in the nucleus and cytosol 5.904629e-01 0.229
R-HSA-983712 Ion channel transport 5.922368e-01 0.228
R-HSA-5617833 Cilium Assembly 5.940031e-01 0.226
R-HSA-9609690 HCMV Early Events 6.044438e-01 0.219
R-HSA-6798695 Neutrophil degranulation 6.110517e-01 0.214
R-HSA-389948 Co-inhibition by PD-1 6.112567e-01 0.214
R-HSA-72312 rRNA processing 6.632239e-01 0.178
R-HSA-3247509 Chromatin modifying enzymes 6.661434e-01 0.176
R-HSA-157118 Signaling by NOTCH 6.747529e-01 0.171
R-HSA-5619115 Disorders of transmembrane transporters 6.845211e-01 0.165
R-HSA-4839726 Chromatin organization 6.872585e-01 0.163
R-HSA-9609646 HCMV Infection 6.886184e-01 0.162
R-HSA-388841 Regulation of T cell activation by CD28 family 6.966564e-01 0.157
R-HSA-9734767 Developmental Cell Lineages 7.057758e-01 0.151
R-HSA-9711123 Cellular response to chemical stress 7.121238e-01 0.147
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 7.256179e-01 0.139
R-HSA-1483257 Phospholipid metabolism 7.441400e-01 0.128
R-HSA-212165 Epigenetic regulation of gene expression 7.736346e-01 0.111
R-HSA-1474244 Extracellular matrix organization 7.814279e-01 0.107
R-HSA-983169 Class I MHC mediated antigen processing & presentation 8.267798e-01 0.083
R-HSA-72766 Translation 8.585299e-01 0.066
R-HSA-71387 Metabolism of carbohydrates and carbohydrate derivatives 8.738612e-01 0.059
R-HSA-597592 Post-translational protein modification 9.382652e-01 0.028
R-HSA-71291 Metabolism of amino acids and derivatives 9.388159e-01 0.027
R-HSA-9709957 Sensory Perception 9.749977e-01 0.011
R-HSA-392499 Metabolism of proteins 9.844106e-01 0.007
R-HSA-382551 Transport of small molecules 9.881198e-01 0.005
R-HSA-556833 Metabolism of lipids 9.988742e-01 0.000
R-HSA-1430728 Metabolism 9.999818e-01 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
BMPR2_TYRBMPR2_TYR 0.725 0.301 -1 0.753
GRK7GRK7 0.720 0.296 1 0.681
COTCOT 0.713 0.293 2 0.663
PDHK3_TYRPDHK3_TYR 0.713 0.103 4 0.757
TXKTXK 0.711 0.213 1 0.675
MAP2K6_TYRMAP2K6_TYR 0.710 0.137 -1 0.691
PDHK4_TYRPDHK4_TYR 0.710 0.116 2 0.683
PLK1PLK1 0.709 0.208 -2 0.778
FLT1FLT1 0.709 0.163 -1 0.685
PDHK1_TYRPDHK1_TYR 0.709 0.108 -1 0.694
PKMYT1_TYRPKMYT1_TYR 0.708 0.033 3 0.646
BMXBMX 0.708 0.202 -1 0.672
MAP2K7_TYRMAP2K7_TYR 0.708 0.022 2 0.688
KDRKDR 0.707 0.134 3 0.575
FYNFYN 0.707 0.211 -1 0.687
PINK1_TYRPINK1_TYR 0.707 0.011 1 0.700
MAP2K4_TYRMAP2K4_TYR 0.707 0.035 -1 0.676
ITKITK 0.706 0.153 -1 0.645
ALK4ALK4 0.706 0.145 -2 0.770
KITKIT 0.705 0.139 3 0.591
MEKK2MEKK2 0.705 0.153 2 0.683
MEKK3MEKK3 0.704 0.153 1 0.698
GRK1GRK1 0.704 0.246 -2 0.754
ACVR2BACVR2B 0.703 0.211 -2 0.797
BMPR1BBMPR1B 0.703 0.202 1 0.666
FLT3FLT3 0.703 0.114 3 0.591
YES1YES1 0.702 0.094 -1 0.614
FGFR2FGFR2 0.702 0.072 3 0.600
TESK1_TYRTESK1_TYR 0.702 -0.080 3 0.661
PRPKPRPK 0.702 0.118 -1 0.706
EPHA6EPHA6 0.702 0.079 -1 0.687
WEE1_TYRWEE1_TYR 0.702 0.091 -1 0.664
METMET 0.701 0.123 3 0.550
TGFBR1TGFBR1 0.701 0.142 -2 0.753
CSF1RCSF1R 0.701 0.074 3 0.580
ACVR2AACVR2A 0.701 0.195 -2 0.786
BMPR2BMPR2 0.701 0.085 -2 0.796
GRK2GRK2 0.701 0.214 -2 0.808
JAK3JAK3 0.701 0.057 1 0.675
SYKSYK 0.700 0.202 -1 0.697
EGFREGFR 0.700 0.134 1 0.685
DLKDLK 0.700 0.100 1 0.753
OSR1OSR1 0.700 0.160 2 0.673
MLK4MLK4 0.700 0.152 2 0.576
FGRFGR 0.700 0.055 1 0.688
MOSMOS 0.700 0.113 1 0.629
FGFR3FGFR3 0.699 0.092 3 0.577
GAKGAK 0.698 0.056 1 0.654
ZAP70ZAP70 0.698 0.201 -1 0.738
INSRRINSRR 0.698 0.067 3 0.555
FLT4FLT4 0.698 0.082 3 0.603
ERBB2ERBB2 0.698 0.086 1 0.708
BRAFBRAF 0.698 0.072 -4 0.640
RETRET 0.697 -0.028 1 0.681
SRMSSRMS 0.697 0.068 1 0.686
MST1RMST1R 0.697 -0.005 3 0.578
PDGFRBPDGFRB 0.696 0.019 3 0.595
TLK2TLK2 0.696 0.122 1 0.627
DSTYKDSTYK 0.696 0.164 2 0.645
LCKLCK 0.696 0.111 -1 0.685
ABL2ABL2 0.696 0.054 -1 0.667
LIMK2_TYRLIMK2_TYR 0.696 -0.073 -3 0.741
FERFER 0.696 0.052 1 0.661
ANKRD3ANKRD3 0.695 0.042 1 0.709
VRK2VRK2 0.695 -0.054 1 0.718
ZAKZAK 0.695 0.074 1 0.743
PTK2PTK2 0.695 0.150 -1 0.689
MERTKMERTK 0.695 0.049 3 0.568
GRK6GRK6 0.695 0.115 1 0.742
MLK1MLK1 0.695 0.079 2 0.628
EPHB4EPHB4 0.695 0.035 -1 0.624
GRK5GRK5 0.695 0.093 -3 0.710
SRCSRC 0.694 0.115 -1 0.644
MATKMATK 0.694 0.102 -1 0.663
PKRPKR 0.694 0.016 1 0.700
BMPR1ABMPR1A 0.694 0.173 1 0.650
TAO3TAO3 0.694 0.071 1 0.671
TYRO3TYRO3 0.694 -0.045 3 0.586
BLKBLK 0.694 0.111 -1 0.664
HCKHCK 0.693 0.051 -1 0.659
ULK2ULK2 0.693 0.087 2 0.669
NEK8NEK8 0.693 0.061 2 0.651
SKMLCKSKMLCK 0.693 0.062 -2 0.744
ROS1ROS1 0.693 -0.030 3 0.572
LIMK1_TYRLIMK1_TYR 0.693 -0.120 2 0.668
FGFR4FGFR4 0.692 0.106 -1 0.646
PASKPASK 0.692 0.079 -3 0.655
ALK2ALK2 0.692 0.092 -2 0.765
TYK2TYK2 0.692 -0.105 1 0.663
ERBB4ERBB4 0.692 0.132 1 0.681
GRK4GRK4 0.691 0.159 -2 0.824
EEF2KEEF2K 0.691 0.031 3 0.639
MST3MST3 0.691 0.020 2 0.630
FGFR1FGFR1 0.691 -0.001 3 0.566
MEK5MEK5 0.691 -0.035 2 0.694
MEK1MEK1 0.691 -0.032 2 0.720
CHAK2CHAK2 0.691 0.024 -1 0.638
CAMLCKCAMLCK 0.690 -0.012 -2 0.732
EPHB1EPHB1 0.690 0.036 1 0.679
TECTEC 0.690 0.035 -1 0.560
DDR1DDR1 0.690 -0.103 4 0.666
IKKAIKKA 0.690 0.226 -2 0.738
ABL1ABL1 0.690 0.002 -1 0.650
RIPK3RIPK3 0.690 0.052 3 0.625
VRK1VRK1 0.690 0.012 2 0.707
EPHB2EPHB2 0.690 0.055 -1 0.613
JAK2JAK2 0.689 -0.064 1 0.663
NIKNIK 0.689 -0.091 -3 0.720
RAF1RAF1 0.689 0.020 1 0.673
EPHA4EPHA4 0.689 0.015 2 0.599
GRK3GRK3 0.689 0.205 -2 0.798
MLK3MLK3 0.689 0.068 2 0.555
TEKTEK 0.688 -0.006 3 0.553
PTK6PTK6 0.688 -0.008 -1 0.597
NEK7NEK7 0.688 0.099 -3 0.677
CLK3CLK3 0.688 0.117 1 0.629
FRKFRK 0.688 0.042 -1 0.638
TTKTTK 0.688 0.112 -2 0.810
NTRK1NTRK1 0.688 0.018 -1 0.639
NTRK2NTRK2 0.687 0.011 3 0.578
NEK6NEK6 0.687 0.143 -2 0.821
NTRK3NTRK3 0.687 0.073 -1 0.625
ULK1ULK1 0.687 0.084 -3 0.727
DRAK1DRAK1 0.687 0.094 1 0.701
EPHA8EPHA8 0.687 0.083 -1 0.652
NEK5NEK5 0.686 -0.034 1 0.672
BTKBTK 0.686 -0.038 -1 0.583
CAMK2GCAMK2G 0.686 -0.006 2 0.564
PLK4PLK4 0.686 0.057 2 0.649
CAMK1BCAMK1B 0.686 -0.058 -3 0.694
AXLAXL 0.685 -0.068 3 0.570
CSKCSK 0.685 0.029 2 0.614
TNK1TNK1 0.685 -0.049 3 0.573
DAPK2DAPK2 0.685 -0.067 -3 0.696
TAK1TAK1 0.685 -0.002 1 0.655
IKKBIKKB 0.685 0.143 -2 0.725
CAMKK1CAMKK1 0.685 -0.025 -2 0.643
ALPHAK3ALPHAK3 0.684 0.122 -1 0.694
MLK2MLK2 0.684 -0.031 2 0.668
INSRINSR 0.684 0.006 3 0.527
PLK3PLK3 0.684 0.072 2 0.607
TNK2TNK2 0.684 -0.090 3 0.536
EPHA7EPHA7 0.684 0.018 2 0.609
LYNLYN 0.684 0.049 3 0.564
NEK11NEK11 0.684 -0.060 1 0.689
IGF1RIGF1R 0.684 0.070 3 0.493
TGFBR2TGFBR2 0.684 0.060 -2 0.790
PERKPERK 0.683 0.004 -2 0.783
RIPK1RIPK1 0.683 -0.055 1 0.726
YSK4YSK4 0.683 -0.043 1 0.654
MAP3K15MAP3K15 0.683 -0.033 1 0.688
GCKGCK 0.683 -0.029 1 0.661
NEK10_TYRNEK10_TYR 0.683 -0.090 1 0.544
TTBK2TTBK2 0.682 0.002 2 0.589
PTK2BPTK2B 0.682 0.009 -1 0.585
TNIKTNIK 0.682 -0.022 3 0.623
PDGFRAPDGFRA 0.682 -0.100 3 0.591
PDK1PDK1 0.682 -0.049 1 0.646
STLK3STLK3 0.682 0.051 1 0.682
GSK3AGSK3A 0.682 0.118 4 0.515
MEKK1MEKK1 0.681 -0.051 1 0.701
EPHB3EPHB3 0.681 -0.041 -1 0.598
MUSKMUSK 0.681 0.036 1 0.647
MST2MST2 0.681 -0.025 1 0.653
PIM3PIM3 0.681 0.006 -3 0.651
MTORMTOR 0.681 -0.018 1 0.638
NEK9NEK9 0.681 -0.065 2 0.652
PKCDPKCD 0.681 0.013 2 0.584
NLKNLK 0.681 -0.082 1 0.630
ATRATR 0.680 -0.083 1 0.600
TAO2TAO2 0.680 -0.058 2 0.620
LTKLTK 0.680 -0.028 3 0.544
EPHA5EPHA5 0.680 0.024 2 0.607
MST1MST1 0.680 -0.036 1 0.659
MINKMINK 0.680 -0.066 1 0.659
LATS1LATS1 0.680 -0.012 -3 0.668
ALKALK 0.679 -0.040 3 0.514
HRIHRI 0.679 -0.032 -2 0.802
CAMKK2CAMKK2 0.679 -0.065 -2 0.642
GSK3BGSK3B 0.679 0.091 4 0.508
JAK1JAK1 0.679 -0.066 1 0.631
TBK1TBK1 0.679 -0.015 1 0.611
GCN2GCN2 0.679 0.041 2 0.668
PAK1PAK1 0.679 0.018 -2 0.652
EPHA2EPHA2 0.679 0.074 -1 0.655
ASK1ASK1 0.679 -0.009 1 0.689
MST4MST4 0.679 0.001 2 0.575
EPHA3EPHA3 0.678 -0.039 2 0.589
HASPINHASPIN 0.678 0.088 -1 0.614
WNK1WNK1 0.678 -0.054 -2 0.724
PLK2PLK2 0.677 0.105 -3 0.683
MASTLMASTL 0.677 -0.159 -2 0.698
CHAK1CHAK1 0.677 -0.039 2 0.671
PRP4PRP4 0.677 0.062 -3 0.680
LRRK2LRRK2 0.677 -0.123 2 0.654
CDKL1CDKL1 0.677 -0.061 -3 0.626
PKN2PKN2 0.676 -0.027 -3 0.673
MEKK6MEKK6 0.676 -0.091 1 0.662
HGKHGK 0.676 -0.071 3 0.645
IRE1IRE1 0.676 -0.001 1 0.684
HUNKHUNK 0.676 -0.055 2 0.732
TNNI3K_TYRTNNI3K_TYR 0.675 -0.070 1 0.701
FESFES 0.675 0.072 -1 0.641
P70S6KBP70S6KB 0.675 -0.009 -3 0.629
RSK4RSK4 0.675 0.052 -3 0.560
MYO3AMYO3A 0.675 -0.016 1 0.686
DDR2DDR2 0.674 -0.039 3 0.541
PDHK4PDHK4 0.674 -0.225 1 0.681
SMMLCKSMMLCK 0.674 -0.036 -3 0.648
RSK2RSK2 0.674 0.021 -3 0.592
HPK1HPK1 0.674 -0.077 1 0.645
DCAMKL1DCAMKL1 0.674 -0.040 -3 0.608
IKKEIKKE 0.674 -0.025 1 0.601
EPHA1EPHA1 0.674 -0.077 3 0.538
JNK3JNK3 0.674 -0.025 1 0.435
IRE2IRE2 0.674 0.010 2 0.629
IRAK4IRAK4 0.673 -0.045 1 0.690
NEK1NEK1 0.673 -0.129 1 0.684
PKN3PKN3 0.673 -0.063 -3 0.680
PKCHPKCH 0.673 -0.015 2 0.577
PKCAPKCA 0.673 0.000 2 0.542
YSK1YSK1 0.673 -0.073 2 0.608
CDC7CDC7 0.672 -0.057 1 0.606
NEK4NEK4 0.672 -0.119 1 0.654
TLK1TLK1 0.672 -0.038 -2 0.831
STK33STK33 0.672 -0.025 2 0.556
PDHK1PDHK1 0.672 -0.171 1 0.675
PKCGPKCG 0.671 -0.003 2 0.555
LKB1LKB1 0.671 -0.115 -3 0.694
MPSK1MPSK1 0.671 -0.051 1 0.616
ICKICK 0.671 -0.080 -3 0.655
TSSK2TSSK2 0.671 -0.058 -5 0.632
PAK2PAK2 0.671 -0.022 -2 0.644
PKACGPKACG 0.670 0.025 -2 0.684
NDR1NDR1 0.670 -0.023 -3 0.661
WNK4WNK4 0.670 -0.096 -2 0.707
PKCBPKCB 0.669 -0.015 2 0.543
AMPKA1AMPKA1 0.669 -0.081 -3 0.684
MEK2MEK2 0.669 -0.133 2 0.710
MYO3BMYO3B 0.669 -0.031 2 0.615
JNK2JNK2 0.669 -0.036 1 0.407
DAPK3DAPK3 0.669 -0.028 -3 0.615
CDK1CDK1 0.669 -0.008 1 0.448
PKCZPKCZ 0.669 -0.032 2 0.612
KHS2KHS2 0.668 -0.065 1 0.639
NEK2NEK2 0.668 -0.124 2 0.636
KHS1KHS1 0.668 -0.097 1 0.622
WNK3WNK3 0.668 -0.163 1 0.672
LOKLOK 0.667 -0.081 -2 0.683
SGK3SGK3 0.667 -0.007 -3 0.594
SLKSLK 0.667 -0.036 -2 0.692
DCAMKL2DCAMKL2 0.666 -0.062 -3 0.636
PAK3PAK3 0.666 -0.037 -2 0.637
AURAAURA 0.666 0.041 -2 0.568
AURBAURB 0.666 0.018 -2 0.593
DAPK1DAPK1 0.666 -0.014 -3 0.593
NIM1NIM1 0.665 -0.059 3 0.571
PIM1PIM1 0.665 -0.043 -3 0.604
PINK1PINK1 0.665 -0.061 1 0.647
P90RSKP90RSK 0.664 -0.034 -3 0.597
SRPK3SRPK3 0.664 0.006 -3 0.538
DMPK1DMPK1 0.664 -0.004 -3 0.591
ROCK2ROCK2 0.664 -0.015 -3 0.614
TSSK1TSSK1 0.664 -0.066 -3 0.703
NDR2NDR2 0.664 -0.009 -3 0.651
CLK2CLK2 0.664 0.068 -3 0.573
SRPK1SRPK1 0.664 0.001 -3 0.562
AKT2AKT2 0.663 -0.007 -3 0.514
MNK2MNK2 0.663 -0.004 -2 0.677
P38GP38G 0.663 -0.038 1 0.363
ATMATM 0.662 -0.042 1 0.522
MARK4MARK4 0.662 -0.100 4 0.652
MSK1MSK1 0.662 0.003 -3 0.570
CK2A2CK2A2 0.662 0.106 1 0.526
MYLK4MYLK4 0.661 -0.032 -2 0.669
JNK1JNK1 0.661 -0.023 1 0.411
AURCAURC 0.661 0.037 -2 0.598
NUAK2NUAK2 0.661 -0.106 -3 0.671
CDK2CDK2 0.661 -0.042 1 0.559
ERK5ERK5 0.661 -0.143 1 0.516
RSK3RSK3 0.660 -0.028 -3 0.594
PKACBPKACB 0.660 0.033 -2 0.621
PKG2PKG2 0.660 0.027 -2 0.628
CAMK2BCAMK2B 0.660 -0.035 2 0.532
CLK4CLK4 0.660 -0.022 -3 0.589
PKCTPKCT 0.659 -0.033 2 0.577
CAMK4CAMK4 0.659 -0.103 -3 0.655
CK2A1CK2A1 0.658 0.116 1 0.523
MNK1MNK1 0.658 -0.021 -2 0.699
IRAK1IRAK1 0.658 -0.147 -1 0.590
DYRK2DYRK2 0.658 -0.049 1 0.493
PRKXPRKX 0.657 0.073 -3 0.508
MRCKAMRCKA 0.657 -0.025 -3 0.589
PKCEPKCE 0.657 -0.015 2 0.550
TAO1TAO1 0.657 -0.078 1 0.622
TTBK1TTBK1 0.657 -0.069 2 0.524
CDK5CDK5 0.656 -0.056 1 0.460
PBKPBK 0.656 -0.097 1 0.522
MELKMELK 0.656 -0.100 -3 0.638
AMPKA2AMPKA2 0.655 -0.104 -3 0.651
P38BP38B 0.654 -0.069 1 0.391
MSK2MSK2 0.654 -0.047 -3 0.545
HIPK1HIPK1 0.654 -0.063 1 0.526
HIPK4HIPK4 0.654 -0.071 1 0.590
RIPK2RIPK2 0.654 -0.106 1 0.658
AKT1AKT1 0.654 -0.014 -3 0.533
CAMK1GCAMK1G 0.654 -0.061 -3 0.594
SRPK2SRPK2 0.653 0.002 -3 0.499
BIKEBIKE 0.652 -0.076 1 0.527
CDKL5CDKL5 0.652 -0.105 -3 0.620
QIKQIK 0.652 -0.130 -3 0.662
P38AP38A 0.652 -0.107 1 0.455
PIM2PIM2 0.652 -0.067 -3 0.579
ROCK1ROCK1 0.652 -0.031 -3 0.589
MRCKBMRCKB 0.652 -0.031 -3 0.572
CAMK2ACAMK2A 0.652 -0.053 2 0.535
SGK1SGK1 0.652 -0.010 -3 0.445
SNRKSNRK 0.652 -0.097 2 0.651
ERK2ERK2 0.651 -0.099 1 0.459
CAMK2DCAMK2D 0.651 -0.156 -3 0.675
PKCIPKCI 0.651 -0.065 2 0.575
PAK6PAK6 0.651 0.005 -2 0.565
CLK1CLK1 0.651 -0.032 -3 0.572
BCKDKBCKDK 0.650 -0.173 -1 0.562
LATS2LATS2 0.649 -0.092 -5 0.593
BUB1BUB1 0.649 -0.023 -5 0.591
CK1A2CK1A2 0.648 -0.021 -3 0.325
SSTKSSTK 0.648 -0.057 4 0.621
MARK3MARK3 0.648 -0.072 4 0.592
SMG1SMG1 0.648 -0.156 1 0.538
KISKIS 0.648 -0.002 1 0.464
PKACAPKACA 0.648 0.015 -2 0.583
MARK2MARK2 0.648 -0.091 4 0.574
MAPKAPK3MAPKAPK3 0.648 -0.133 -3 0.605
BRSK1BRSK1 0.648 -0.054 -3 0.615
DNAPKDNAPK 0.647 -0.128 1 0.434
CDK3CDK3 0.646 -0.039 1 0.374
QSKQSK 0.646 -0.094 4 0.641
FAM20CFAM20C 0.646 -0.020 2 0.360
YANK3YANK3 0.646 -0.033 2 0.317
PAK5PAK5 0.646 -0.006 -2 0.548
BRSK2BRSK2 0.646 -0.083 -3 0.647
CDK13CDK13 0.645 -0.086 1 0.424
CDK8CDK8 0.645 -0.086 1 0.474
CRIKCRIK 0.645 -0.047 -3 0.536
CK1ECK1E 0.645 -0.035 -3 0.373
NEK3NEK3 0.645 -0.174 1 0.638
DYRK1ADYRK1A 0.645 -0.088 1 0.520
DYRK1BDYRK1B 0.644 -0.056 1 0.459
P70S6KP70S6K 0.644 -0.067 -3 0.547
CDK17CDK17 0.644 -0.073 1 0.374
ERK1ERK1 0.644 -0.088 1 0.381
DYRK3DYRK3 0.644 -0.048 1 0.533
CDK14CDK14 0.644 -0.081 1 0.457
PHKG1PHKG1 0.644 -0.124 -3 0.644
MARK1MARK1 0.643 -0.114 4 0.609
CDK12CDK12 0.642 -0.083 1 0.407
CK1DCK1D 0.642 -0.044 -3 0.329
HIPK2HIPK2 0.642 -0.052 1 0.415
MAPKAPK2MAPKAPK2 0.641 -0.075 -3 0.562
PAK4PAK4 0.641 0.004 -2 0.544
CHK1CHK1 0.640 -0.208 -3 0.694
DYRK4DYRK4 0.640 -0.044 1 0.417
AKT3AKT3 0.640 -0.012 -3 0.449
CDK18CDK18 0.640 -0.074 1 0.400
PRKD3PRKD3 0.640 -0.107 -3 0.553
SIKSIK 0.640 -0.098 -3 0.585
P38DP38D 0.639 -0.061 1 0.303
PRKD2PRKD2 0.639 -0.091 -3 0.597
YANK2YANK2 0.638 -0.018 2 0.323
MAKMAK 0.638 -0.059 -2 0.577
CDK16CDK16 0.638 -0.062 1 0.381
CHK2CHK2 0.638 -0.088 -3 0.470
CDK10CDK10 0.637 -0.069 1 0.440
CDK6CDK6 0.637 -0.083 1 0.417
NUAK1NUAK1 0.637 -0.137 -3 0.630
HIPK3HIPK3 0.636 -0.122 1 0.498
CAMK1DCAMK1D 0.636 -0.102 -3 0.507
PRKD1PRKD1 0.636 -0.161 -3 0.635
MAPKAPK5MAPKAPK5 0.635 -0.132 -3 0.558
ERK7ERK7 0.635 -0.105 2 0.339
MOKMOK 0.633 -0.080 1 0.502
CDK7CDK7 0.633 -0.128 1 0.442
CDK9CDK9 0.631 -0.130 1 0.433
AAK1AAK1 0.631 -0.070 1 0.418
CDK19CDK19 0.631 -0.101 1 0.437
CDK4CDK4 0.629 -0.100 1 0.399
PHKG2PHKG2 0.628 -0.120 -3 0.639
PKN1PKN1 0.624 -0.116 -3 0.559
CK1G1CK1G1 0.624 -0.066 -3 0.367
CAMK1ACAMK1A 0.620 -0.109 -3 0.483
PKG1PKG1 0.620 -0.019 -2 0.559
CK1G2CK1G2 0.619 0.028 -3 0.295
CK1ACK1A 0.614 -0.014 -3 0.251
SBKSBK 0.609 -0.117 -3 0.416
CK1G3CK1G3 0.604 -0.065 -3 0.211