Motif 990 (n=76)

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O00141 SGK1 S255 ochoa 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}.
O14733 MAP2K7 T275 psp Dual specificity mitogen-activated protein kinase kinase 7 (MAP kinase kinase 7) (MAPKK 7) (EC 2.7.12.2) (JNK-activating kinase 2) (MAPK/ERK kinase 7) (MEK 7) (Stress-activated protein kinase kinase 4) (SAPK kinase 4) (SAPKK-4) (SAPKK4) (c-Jun N-terminal kinase kinase 2) (JNK kinase 2) (JNKK 2) Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074). {ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:9312068, ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, ECO:0000269|Ref.5}.
O14965 AURKA T287 psp Aurora kinase A (EC 2.7.11.1) (Aurora 2) (Aurora/IPL1-related kinase 1) (ARK-1) (Aurora-related kinase 1) (Breast tumor-amplified kinase) (Ipl1- and aurora-related kinase 1) (Serine/threonine-protein kinase 15) (Serine/threonine-protein kinase 6) (Serine/threonine-protein kinase Ayk1) (Serine/threonine-protein kinase aurora-A) Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (PubMed:11039908, PubMed:12390251, PubMed:17125279, PubMed:17360485, PubMed:18615013, PubMed:26246606). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:14523000, PubMed:26246606). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (PubMed:27335426). Required for initial activation of CDK1 at centrosomes (PubMed:13678582, PubMed:15128871). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (PubMed:11551964, PubMed:14702041, PubMed:15128871, PubMed:15147269, PubMed:15987997, PubMed:17604723, PubMed:18056443, PubMed:18615013). Phosphorylates MCRS1 which is required for MCRS1-mediated kinetochore fiber assembly and mitotic progression (PubMed:27192185). Regulates KIF2A tubulin depolymerase activity (PubMed:19351716). Important for microtubule formation and/or stabilization (PubMed:18056443). Required for normal axon formation (PubMed:19812038). Plays a role in microtubule remodeling during neurite extension (PubMed:19668197). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (PubMed:14702041). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (PubMed:11551964). Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (PubMed:17604723, PubMed:20643351). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (PubMed:28218735). {ECO:0000250|UniProtKB:A0A8I3S724, ECO:0000269|PubMed:11039908, ECO:0000269|PubMed:11551964, ECO:0000269|PubMed:12390251, ECO:0000269|PubMed:13678582, ECO:0000269|PubMed:14523000, ECO:0000269|PubMed:14702041, ECO:0000269|PubMed:15128871, ECO:0000269|PubMed:15147269, ECO:0000269|PubMed:15987997, ECO:0000269|PubMed:17125279, ECO:0000269|PubMed:17360485, ECO:0000269|PubMed:17604723, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:18615013, ECO:0000269|PubMed:19351716, ECO:0000269|PubMed:19668197, ECO:0000269|PubMed:19812038, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:26246606, ECO:0000269|PubMed:27192185, ECO:0000269|PubMed:27335426, ECO:0000269|PubMed:28218735}.
O15264 MAPK13 T180 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}.
O43318 MAP3K7 T187 psp Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1) Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}.
O75914 PAK3 S435 ochoa Serine/threonine-protein kinase PAK 3 (EC 2.7.11.1) (Beta-PAK) (Oligophrenin-3) (p21-activated kinase 3) (PAK-3) Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as a downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). {ECO:0000250|UniProtKB:Q61036, ECO:0000269|PubMed:21177870}.
O76039 CDKL5 T169 psp Cyclin-dependent kinase-like 5 (EC 2.7.11.22) (Serine/threonine-protein kinase 9) Mediates phosphorylation of MECP2 (PubMed:15917271, PubMed:16935860). May regulate ciliogenesis (PubMed:29420175). {ECO:0000269|PubMed:15917271, ECO:0000269|PubMed:16935860, ECO:0000269|PubMed:29420175}.
P06493 CDK1 T161 ochoa|psp 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}.
P11802 CDK4 T172 psp Cyclin-dependent kinase 4 (EC 2.7.11.22) (Cell division protein kinase 4) (PSK-J3) Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:9003781}.
P19525 EIF2AK2 T446 psp Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}.
P20794 MAK T157 psp Serine/threonine-protein kinase MAK (EC 2.7.11.1) (Male germ cell-associated kinase) Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors (By similarity). Phosphorylates FZR1 in a cell cycle-dependent manner. Plays a role in the transcriptional coactivation of AR. Could play an important function in spermatogenesis. May play a role in chromosomal stability in prostate cancer cells. {ECO:0000250, ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:21986944}.
P21127 CDK11B T595 ochoa|psp 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}.
P24941 CDK2 T160 ochoa|psp 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 T202 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 T185 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}.
P37173 TGFBR2 S416 psp TGF-beta receptor type-2 (TGFR-2) (EC 2.7.11.30) (TGF-beta type II receptor) (Transforming growth factor-beta receptor type II) (TGF-beta receptor type II) (TbetaR-II) Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. {ECO:0000269|PubMed:7774578}.; FUNCTION: [Isoform 1]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 2]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 3]: Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1. {ECO:0000269|PubMed:34568316}.
P41743 PRKCI S411 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}.
P45983 MAPK8 T183 ochoa|psp Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1) Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:28943315, ECO:0000269|PubMed:34048572}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms.
P45984 MAPK9 T183 ochoa|psp Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2) Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:10376527). In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (PubMed:15805466). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (PubMed:17525747, PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:19290929). Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels (PubMed:19290929). Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (PubMed:20595622). When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (PubMed:19675674). Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:10376527, ECO:0000269|PubMed:15805466, ECO:0000269|PubMed:17525747, ECO:0000269|PubMed:19675674, ECO:0000269|PubMed:20595622, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:34048572, ECO:0000303|PubMed:19290929}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it.
P45985 MAP2K4 T261 psp Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK) Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}.
P46734 MAP2K3 T222 psp Dual specificity mitogen-activated protein kinase kinase 3 (MAP kinase kinase 3) (MAPKK 3) (EC 2.7.12.2) (MAPK/ERK kinase 3) (MEK 3) (Stress-activated protein kinase kinase 2) (SAPK kinase 2) (SAPKK-2) (SAPKK2) Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. {ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8622669}.
P49137 MAPKAPK2 T221 ochoa MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}.
P49759 CLK1 S337 ochoa Dual specificity protein kinase CLK1 (EC 2.7.12.1) (CDC-like kinase 1) Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1 (PubMed:10480872, PubMed:19168442). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (PubMed:19168442). {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442}.
P50613 CDK7 T170 ochoa|psp 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}.
P50750 CDK9 T186 ochoa|psp Cyclin-dependent kinase 9 (EC 2.7.11.22) (EC 2.7.11.23) (C-2K) (Cell division cycle 2-like protein kinase 4) (Cell division protein kinase 9) (Serine/threonine-protein kinase PITALRE) (Tat-associated kinase complex catalytic subunit) Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:16427012, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:16427012, PubMed:20081228, PubMed:20980437, PubMed:21127351, PubMed:9857195). Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166). Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:10912001, PubMed:11112772, PubMed:9857195). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245). {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011, ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:9857195}.
P51812 RPS6KA3 Y226 ochoa Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2) Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835, ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.
P52564 MAP2K6 T211 psp Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3) Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. {ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11727828, ECO:0000269|PubMed:15550393, ECO:0000269|PubMed:20869211, ECO:0000269|PubMed:8622669, ECO:0000269|PubMed:8626699, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9218798}.
P53778 MAPK12 T183 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}.
P53779 MAPK10 T221 ochoa|psp Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (MAP kinase p49 3F12) (Stress-activated protein kinase 1b) (SAPK1b) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3) Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000269|PubMed:11718727, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692}.
Q00526 CDK3 T160 ochoa Cyclin-dependent kinase 3 (EC 2.7.11.22) (Cell division protein kinase 3) Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner. {ECO:0000269|PubMed:15084261, ECO:0000269|PubMed:18794154, ECO:0000269|PubMed:8846921}.
Q00534 CDK6 T177 psp Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}.
Q00535 CDK5 S159 psp Cyclin-dependent kinase 5 (EC 2.7.11.1) (Cell division protein kinase 5) (Cyclin-dependent-like kinase 5) (Serine/threonine-protein kinase PSSALRE) (Tau protein kinase II catalytic subunit) (TPKII catalytic subunit) Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Negatively regulates the CACNA1B/CAV2.2 -mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in postmitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Also phosphorylates exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-BMAL1 heterodimer in association with altered stability and subcellular distribution. {ECO:0000250|UniProtKB:Q03114, ECO:0000269|PubMed:12393264, ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15992363, ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17121855, ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17611284, ECO:0000269|PubMed:17671990, ECO:0000269|PubMed:18042622, ECO:0000269|PubMed:19081376, ECO:0000269|PubMed:19693690, ECO:0000269|PubMed:20061803, ECO:0000269|PubMed:20213743, ECO:0000269|PubMed:20826806, ECO:0000269|PubMed:21209322, ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:21442427, ECO:0000269|PubMed:21465480, ECO:0000269|PubMed:21499257, ECO:0000269|PubMed:24235147, ECO:0000269|PubMed:9822744}.
Q05513 PRKCZ S409 ochoa Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta) Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Phosphorylates VAMP2 in vitro (PubMed:17313651). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:36040231, ECO:0000269|PubMed:9447975}.; FUNCTION: [Isoform 2]: Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance. {ECO:0000250|UniProtKB:Q02956}.
Q05655 PRKCD S506 ochoa Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)] Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250|UniProtKB:P28867, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692, ECO:0000303|PubMed:21810427}.
Q13153 PAK1 S422 ochoa Serine/threonine-protein kinase PAK 1 (EC 2.7.11.1) (Alpha-PAK) (p21-activated kinase 1) (PAK-1) (p65-PAK) Protein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes (PubMed:10551809, PubMed:11896197, PubMed:12876277, PubMed:14585966, PubMed:15611088, PubMed:17726028, PubMed:17989089, PubMed:30290153, PubMed:17420447). Can directly phosphorylate BAD and protects cells against apoptosis (By similarity). Activated by interaction with CDC42 and RAC1 (PubMed:8805275, PubMed:9528787). Functions as a GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway (PubMed:8805275, PubMed:9528787). Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases (By similarity). Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes (PubMed:9032240, PubMed:9395435). Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton (PubMed:15831477). Plays a role in the regulation of insulin secretion in response to elevated glucose levels (PubMed:22669945). Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ) (By similarity). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2 (PubMed:12624090). Phosphorylates MYL9/MLC2 (By similarity). Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2 (PubMed:11733498). Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus (PubMed:15833848). In podocytes, promotes NR3C2 nuclear localization (By similarity). Required for atypical chemokine receptor ACKR2-induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation (By similarity). Plays a role in RUFY3-mediated facilitating gastric cancer cells migration and invasion (PubMed:25766321). In response to DNA damage, phosphorylates MORC2 which activates its ATPase activity and facilitates chromatin remodeling (PubMed:23260667). In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in F-actin stabilization (By similarity). In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity). Along with GIT1, positively regulates microtubule nucleation during interphase (PubMed:27012601). Phosphorylates FXR1, promoting its localization to stress granules and activity (PubMed:20417602). Phosphorylates ILK on 'Thr-173' and 'Ser-246', promoting nuclear export of ILK (PubMed:17420447). {ECO:0000250|UniProtKB:O88643, ECO:0000250|UniProtKB:P35465, ECO:0000269|PubMed:10551809, ECO:0000269|PubMed:11733498, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12624090, ECO:0000269|PubMed:12876277, ECO:0000269|PubMed:14585966, ECO:0000269|PubMed:15611088, ECO:0000269|PubMed:15831477, ECO:0000269|PubMed:15833848, ECO:0000269|PubMed:17420447, ECO:0000269|PubMed:17726028, ECO:0000269|PubMed:17989089, ECO:0000269|PubMed:20417602, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:23260667, ECO:0000269|PubMed:23633677, ECO:0000269|PubMed:25766321, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:30290153, ECO:0000269|PubMed:8805275, ECO:0000269|PubMed:9032240, ECO:0000269|PubMed:9395435, ECO:0000269|PubMed:9528787}.
Q13164 MAPK7 T219 ochoa|psp Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}.
Q13177 PAK2 S401 ochoa Serine/threonine-protein kinase PAK 2 (EC 2.7.11.1) (Gamma-PAK) (PAK65) (S6/H4 kinase) (p21-activated kinase 2) (PAK-2) (p58) [Cleaved into: PAK-2p27 (p27); PAK-2p34 (p34) (C-t-PAK2)] Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation (PubMed:12853446, PubMed:16617111, PubMed:19273597, PubMed:19923322, PubMed:33693784, PubMed:7744004, PubMed:9171063). Acts as a downstream effector of the small GTPases CDC42 and RAC1 (PubMed:7744004). Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues (PubMed:7744004). Full-length PAK2 stimulates cell survival and cell growth (PubMed:7744004). Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration (PubMed:21317288). Phosphorylates JUN and plays an important role in EGF-induced cell proliferation (PubMed:21177766). Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP (PubMed:21724829). Phosphorylates CASP7, thereby preventing its activity (PubMed:21555521, PubMed:27889207). Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis (PubMed:19273597, PubMed:19923322). On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway (PubMed:12853446, PubMed:16617111, PubMed:9171063). Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (PubMed:15234964). {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19273597, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:33693784, ECO:0000269|PubMed:7744004, ECO:0000269|PubMed:9171063}.
Q13523 PRP4K T847 ochoa Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}.
Q13627 DYRK1A Y319 ochoa 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}.
Q14012 CAMK1 S176 ochoa Calcium/calmodulin-dependent protein kinase type 1 (EC 2.7.11.17) (CaM kinase I) (CaM-KI) (CaM kinase I alpha) (CaMKI-alpha) Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}.
Q15131 CDK10 T196 ochoa Cyclin-dependent kinase 10 (EC 2.7.11.22) (Cell division protein kinase 10) (Serine/threonine-protein kinase PISSLRE) Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells) (PubMed:24218572). Involved in the regulation of actin cytoskeleton organization through the phosphorylation of actin dynamics regulators such as PKN2. Is a negative regulator of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling (PubMed:27104747). {ECO:0000269|PubMed:24218572, ECO:0000269|PubMed:27104747}.
Q15418 RPS6KA1 Y220 ochoa Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1) Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269|PubMed:10679322, ECO:0000269|PubMed:11684016, ECO:0000269|PubMed:12213813, ECO:0000269|PubMed:15117958, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362, ECO:0000269|PubMed:16763566, ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121, ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:35772404, ECO:0000269|PubMed:9430688, ECO:0000303|PubMed:18508509, ECO:0000303|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269|PubMed:30842327}.
Q15759 MAPK11 T180 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 S773 ochoa|psp 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 S815 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 T180 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 S717 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}.
Q86Z02 HIPK1 S350 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}.
Q8IU85 CAMK1D S179 ochoa Calcium/calmodulin-dependent protein kinase type 1D (EC 2.7.11.17) (CaM kinase I delta) (CaM kinase ID) (CaM-KI delta) (CaMKI delta) (CaMKID) (CaMKI-like protein kinase) (CKLiK) Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta. {ECO:0000269|PubMed:11050006, ECO:0000269|PubMed:15840691, ECO:0000269|PubMed:16324104, ECO:0000269|PubMed:17056143}.
Q8N165 PDIK1L S216 psp Serine/threonine-protein kinase PDIK1L (EC 2.7.11.1) (PDLIM1-interacting kinase 1-like) None
Q8TD08 MAPK15 T175 psp Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}.
Q8TDR2 STK35 S413 ochoa|psp Serine/threonine-protein kinase 35 (EC 2.7.11.1) (CLP-36-interacting kinase 1) (CLIK-1) (PDLIM1-interacting kinase 1) (Serine/threonine-protein kinase 35 L1) None
Q9H2X6 HIPK2 S359 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 S357 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}.
Q9HAZ1 CLK4 S335 ochoa Dual specificity protein kinase CLK4 (EC 2.7.12.1) (CDC-like kinase 4) Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:11170754, ECO:0000269|PubMed:19168442}.
Q9NRP7 STK36 T158 ochoa Serine/threonine-protein kinase 36 (EC 2.7.11.1) (Fused homolog) Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur (PubMed:10806483). Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia. {ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:28543983}.
Q9NWZ3 IRAK4 S346 psp Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64) Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}.
Q9NZJ5 EIF2AK3 T982 psp Eukaryotic translation initiation factor 2-alpha kinase 3 (EC 2.7.11.1) (PRKR-like endoplasmic reticulum kinase) (Pancreatic eIF2-alpha kinase) (HsPEK) (Protein tyrosine kinase EIF2AK3) (EC 2.7.10.2) Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR) (PubMed:10026192, PubMed:10677345, PubMed:11907036, PubMed:12086964, PubMed:25925385, PubMed:31023583). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognizes and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation (PubMed:10677345, PubMed:27917829, PubMed:31023583). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:10026192, PubMed:10677345, PubMed:31023583, PubMed:33384352). The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes (PubMed:31023583). In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites (PubMed:39116259). In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity). {ECO:0000250|UniProtKB:Q9Z2B5, ECO:0000269|PubMed:10026192, ECO:0000269|PubMed:10677345, ECO:0000269|PubMed:11907036, ECO:0000269|PubMed:12086964, ECO:0000269|PubMed:25925385, ECO:0000269|PubMed:27917829, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:33384352, ECO:0000269|PubMed:39116259}.
Q9P2K8 EIF2AK4 T899 psp eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}.
Q9UBE8 NLK T298 ochoa Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1) Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}.
Q9UK32 RPS6KA6 Y231 ochoa Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4) Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092, ECO:0000269|PubMed:15632195}.
Q9UPZ9 CILK1 T157 ochoa|psp Serine/threonine-protein kinase ICK (EC 2.7.11.1) (Ciliogenesis associated kinase 1) (Intestinal cell kinase) (hICK) (Laryngeal cancer kinase 2) (LCK2) (MAK-related kinase) (MRK) Required for ciliogenesis (PubMed:24797473). Phosphorylates KIF3A (By similarity). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (By similarity). May play a key role in the development of multiple organ systems and particularly in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity (By similarity). {ECO:0000250|UniProtKB:Q62726, ECO:0000250|UniProtKB:Q9JKV2, ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502}.
Q9UQ07 MOK T159 psp MAPK/MAK/MRK overlapping kinase (EC 2.7.11.22) (MOK protein kinase) (Renal tumor antigen 1) (RAGE-1) Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner. {ECO:0000250|UniProtKB:Q9WVS4}.
Q9UQ88 CDK11A T583 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}.
Q9Y2H1 STK38L Y281 ochoa Serine/threonine-protein kinase 38-like (EC 2.7.11.1) (NDR2 protein kinase) (Nuclear Dbf2-related kinase 2) Involved in the regulation of structural processes in differentiating and mature neuronal cells. {ECO:0000250, ECO:0000269|PubMed:15037617, ECO:0000269|PubMed:15067004}.
Q9Y463 DYRK1B Y271 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}.
O00444 PLK4 Y169 Sugiyama Serine/threonine-protein kinase PLK4 (EC 2.7.11.21) (Polo-like kinase 4) (PLK-4) (Serine/threonine-protein kinase 18) (Serine/threonine-protein kinase Sak) Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). {ECO:0000269|PubMed:16244668, ECO:0000269|PubMed:16326102, ECO:0000269|PubMed:17681131, ECO:0000269|PubMed:18239451, ECO:0000269|PubMed:19164942, ECO:0000269|PubMed:21725316, ECO:0000269|PubMed:22020124, ECO:0000269|PubMed:27796307, ECO:0000269|PubMed:30804208}.
P61163 ACTR1A T248 Sugiyama Alpha-centractin (Centractin) (ARP1) (Actin-RPV) (Centrosome-associated actin homolog) Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules. {ECO:0000250|UniProtKB:F2Z5G5}.
Q59H18 TNNI3K T622 Sugiyama Serine/threonine-protein kinase TNNI3K (EC 2.7.11.1) (Cardiac ankyrin repeat kinase) (Cardiac troponin I-interacting kinase) (TNNI3-interacting kinase) May play a role in cardiac physiology. {ECO:0000303|PubMed:12721663}.
Q86V86 PIM3 T202 Sugiyama Serine/threonine-protein kinase pim-3 (EC 2.7.11.1) Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth. {ECO:0000269|PubMed:15540201, ECO:0000269|PubMed:16818649, ECO:0000269|PubMed:17270021, ECO:0000269|PubMed:17876606, ECO:0000269|PubMed:18593906}.
P31152 MAPK4 S186 ochoa|psp Mitogen-activated protein kinase 4 (MAP kinase 4) (MAPK 4) (EC 2.7.11.24) (Extracellular signal-regulated kinase 4) (ERK-4) (MAP kinase isoform p63) (p63-MAPK) Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle (By similarity). {ECO:0000250}.
P55211 CASP9 T107 ochoa Caspase-9 (CASP-9) (EC 3.4.22.62) (Apoptotic protease Mch-6) (Apoptotic protease-activating factor 3) (APAF-3) (ICE-like apoptotic protease 6) (ICE-LAP6) [Cleaved into: Caspase-9 subunit p35; Caspase-9 subunit p10] Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates effector caspases caspase-3 (CASP3) or caspase-7 (CASP7). Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758105, PubMed:36758106). {ECO:0000269|PubMed:15657060, ECO:0000269|PubMed:16352606, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:27889207, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120}.; FUNCTION: [Isoform 2]: Lacks activity is an dominant-negative inhibitor of caspase-9. {ECO:0000269|PubMed:10070954}.
Q14004 CDK13 T871 ochoa Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}.
Q14694 USP10 Y77 ochoa Ubiquitin carboxyl-terminal hydrolase 10 (EC 3.4.19.12) (Deubiquitinating enzyme 10) (Ubiquitin thioesterase 10) (Ubiquitin-specific-processing protease 10) Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): USP10 acts by removing monoubiquitination of RPS2/us5 and RPS3/us3, promoting 40S ribosomal subunit recycling (PubMed:34469731). Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling (PubMed:19398555). Involved in a TANK-dependent negative feedback response to attenuate NF-kappa-B activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). Plays a negative role in the RLR signaling pathway upon RNA virus infection by blocking the RIGI-mediated MAVS activation. Mechanistically, removes the unanchored 'Lys-63'-linked polyubiquitin chains of MAVS to inhibit its aggregation, essential for its activation (PubMed:37582970). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:31981475, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:34348161, ECO:0000269|PubMed:34469731, ECO:0000269|PubMed:37582970}.
Q16659 MAPK6 S189 ochoa|psp Mitogen-activated protein kinase 6 (MAP kinase 6) (MAPK 6) (EC 2.7.11.24) (Extracellular signal-regulated kinase 3) (ERK-3) (MAP kinase isoform p97) (p97-MAPK) Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity). {ECO:0000250}.
Q9NYV4 CDK12 T893 ochoa Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}.
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reactome_id name p -log10_p
R-HSA-450282 MAPK targets/ Nuclear events mediated by MAP kinases 1.110223e-16 15.955
R-HSA-450294 MAP kinase activation 1.110223e-16 15.955
R-HSA-448424 Interleukin-17 signaling 1.110223e-16 15.955
R-HSA-975155 MyD88 dependent cascade initiated on endosome 1.110223e-16 15.955
R-HSA-975871 MyD88 cascade initiated on plasma membrane 1.110223e-16 15.955
R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade 1.110223e-16 15.955
R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade 1.110223e-16 15.955
R-HSA-166058 MyD88:MAL(TIRAP) cascade initiated on plasma membrane 1.110223e-16 15.955
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade 1.110223e-16 15.955
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade 1.110223e-16 15.955
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade 1.110223e-16 15.955
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade 1.110223e-16 15.955
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation 1.110223e-16 15.955
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade 1.110223e-16 15.955
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade 1.110223e-16 15.955
R-HSA-937061 TRIF (TICAM1)-mediated TLR4 signaling 1.110223e-16 15.955
R-HSA-166166 MyD88-independent TLR4 cascade 1.110223e-16 15.955
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade 1.110223e-16 15.955
R-HSA-2559583 Cellular Senescence 1.110223e-16 15.955
R-HSA-168898 Toll-like Receptor Cascades 2.886580e-15 14.540
R-HSA-2559580 Oxidative Stress Induced Senescence 3.330669e-15 14.477
R-HSA-450341 Activation of the AP-1 family of transcription factors 8.335554e-13 12.079
R-HSA-187037 Signaling by NTRK1 (TRKA) 3.032985e-11 10.518
R-HSA-198725 Nuclear Events (kinase and transcription factor activation) 3.258760e-11 10.487
R-HSA-198753 ERK/MAPK targets 1.755498e-10 9.756
R-HSA-166520 Signaling by NTRKs 1.639989e-10 9.785
R-HSA-449147 Signaling by Interleukins 2.190801e-09 8.659
R-HSA-4420097 VEGFA-VEGFR2 Pathway 3.111435e-09 8.507
R-HSA-1280215 Cytokine Signaling in Immune system 3.899580e-09 8.409
R-HSA-168638 NOD1/2 Signaling Pathway 3.981659e-09 8.400
R-HSA-187687 Signalling to ERKs 4.692328e-09 8.329
R-HSA-444257 RSK activation 5.885711e-09 8.230
R-HSA-194138 Signaling by VEGF 6.714086e-09 8.173
R-HSA-2262752 Cellular responses to stress 7.429165e-09 8.129
R-HSA-450321 JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... 9.178972e-09 8.037
R-HSA-450302 activated TAK1 mediates p38 MAPK activation 1.146093e-08 7.941
R-HSA-8953897 Cellular responses to stimuli 1.315016e-08 7.881
R-HSA-2871796 FCERI mediated MAPK activation 3.474607e-08 7.459
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP) 4.496698e-08 7.347
R-HSA-168249 Innate Immune System 4.837742e-08 7.315
R-HSA-5687128 MAPK6/MAPK4 signaling 5.767573e-08 7.239
R-HSA-5633007 Regulation of TP53 Activity 6.253172e-08 7.204
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases 6.583218e-08 7.182
R-HSA-171007 p38MAPK events 8.740107e-08 7.058
R-HSA-168643 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... 1.786391e-07 6.748
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK 2.750301e-07 6.561
R-HSA-167044 Signalling to RAS 4.068383e-07 6.391
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling 4.676500e-07 6.330
R-HSA-3700989 Transcriptional Regulation by TP53 4.710830e-07 6.327
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation 1.122732e-06 5.950
R-HSA-162582 Signal Transduction 2.177764e-06 5.662
R-HSA-1640170 Cell Cycle 2.334479e-06 5.632
R-HSA-442742 CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling 2.920076e-06 5.535
R-HSA-69278 Cell Cycle, Mitotic 4.234366e-06 5.373
R-HSA-5683057 MAPK family signaling cascades 6.125524e-06 5.213
R-HSA-5210891 Uptake and function of anthrax toxins 7.752677e-06 5.111
R-HSA-199920 CREB phosphorylation 1.912526e-05 4.718
R-HSA-438064 Post NMDA receptor activation events 1.708473e-05 4.767
R-HSA-69275 G2/M Transition 1.949000e-05 4.710
R-HSA-168256 Immune System 2.075481e-05 4.683
R-HSA-453274 Mitotic G2-G2/M phases 2.087683e-05 4.680
R-HSA-525793 Myogenesis 3.327241e-05 4.478
R-HSA-453279 Mitotic G1 phase and G1/S transition 3.775277e-05 4.423
R-HSA-442755 Activation of NMDA receptors and postsynaptic events 4.216767e-05 4.375
R-HSA-9627069 Regulation of the apoptosome activity 5.672419e-05 4.246
R-HSA-111458 Formation of apoptosome 5.672419e-05 4.246
R-HSA-2151209 Activation of PPARGC1A (PGC-1alpha) by phosphorylation 5.672419e-05 4.246
R-HSA-1538133 G0 and Early G1 6.451553e-05 4.190
R-HSA-202670 ERKs are inactivated 8.644575e-05 4.063
R-HSA-111461 Cytochrome c-mediated apoptotic response 8.644575e-05 4.063
R-HSA-428540 Activation of RAC1 8.644575e-05 4.063
R-HSA-9768919 NPAS4 regulates expression of target genes 8.633588e-05 4.064
R-HSA-373760 L1CAM interactions 9.072451e-05 4.042
R-HSA-380270 Recruitment of mitotic centrosome proteins and complexes 9.409432e-05 4.026
R-HSA-2559585 Oncogene Induced Senescence 9.467360e-05 4.024
R-HSA-380287 Centrosome maturation 1.053845e-04 3.977
R-HSA-9661069 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) 1.248388e-04 3.904
R-HSA-9659787 Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects 1.248388e-04 3.904
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization 1.248388e-04 3.904
R-HSA-389359 CD28 dependent Vav1 pathway 1.248388e-04 3.904
R-HSA-9632693 Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects 1.344565e-04 3.871
R-HSA-9630750 Evasion of Oncogene Induced Senescence Due to p16INK4A Defects 1.344565e-04 3.871
R-HSA-9630794 Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... 1.344565e-04 3.871
R-HSA-9632700 Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... 1.344565e-04 3.871
R-HSA-399954 Sema3A PAK dependent Axon repulsion 1.729014e-04 3.762
R-HSA-69236 G1 Phase 2.133128e-04 3.671
R-HSA-69231 Cyclin D associated events in G1 2.133128e-04 3.671
R-HSA-9675132 Diseases of cellular response to stress 2.381755e-04 3.623
R-HSA-9630747 Diseases of Cellular Senescence 2.381755e-04 3.623
R-HSA-437239 Recycling pathway of L1 2.636274e-04 3.579
R-HSA-111471 Apoptotic factor-mediated response 3.018528e-04 3.520
R-HSA-3928664 Ephrin signaling 3.018528e-04 3.520
R-HSA-212436 Generic Transcription Pathway 3.151365e-04 3.502
R-HSA-170834 Signaling by TGF-beta Receptor Complex 3.529055e-04 3.452
R-HSA-9634815 Transcriptional Regulation by NPAS4 3.656315e-04 3.437
R-HSA-5339562 Uptake and actions of bacterial toxins 3.656315e-04 3.437
R-HSA-445144 Signal transduction by L1 3.845662e-04 3.415
R-HSA-109606 Intrinsic Pathway for Apoptosis 4.654597e-04 3.332
R-HSA-109581 Apoptosis 5.133848e-04 3.290
R-HSA-9754119 Drug-mediated inhibition of CDK4/CDK6 activity 5.320562e-04 3.274
R-HSA-9652169 Signaling by MAP2K mutants 5.320562e-04 3.274
R-HSA-112409 RAF-independent MAPK1/3 activation 5.338719e-04 3.273
R-HSA-9725370 Signaling by ALK fusions and activated point mutants 5.466308e-04 3.262
R-HSA-9700206 Signaling by ALK in cancer 5.466308e-04 3.262
R-HSA-5621575 CD209 (DC-SIGN) signaling 6.514334e-04 3.186
R-HSA-373755 Semaphorin interactions 6.846547e-04 3.165
R-HSA-8854518 AURKA Activation by TPX2 7.978399e-04 3.098
R-HSA-5674499 Negative feedback regulation of MAPK pathway 9.391076e-04 3.027
R-HSA-8849470 PTK6 Regulates Cell Cycle 9.391076e-04 3.027
R-HSA-73857 RNA Polymerase II Transcription 9.497056e-04 3.022
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements 1.062814e-03 2.974
R-HSA-9687139 Aberrant regulation of mitotic cell cycle due to RB1 defects 1.099140e-03 2.959
R-HSA-69206 G1/S Transition 1.125553e-03 2.949
R-HSA-422475 Axon guidance 1.161227e-03 2.935
R-HSA-9842640 Signaling by LTK in cancer 1.184299e-03 2.927
R-HSA-9675126 Diseases of mitotic cell cycle 1.282466e-03 2.892
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition 1.380907e-03 2.860
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes 1.384231e-03 2.859
R-HSA-9732724 IFNG signaling activates MAPKs 1.456862e-03 2.837
R-HSA-5357801 Programmed Cell Death 1.608438e-03 2.794
R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition 1.768043e-03 2.753
R-HSA-6804757 Regulation of TP53 Degradation 1.821719e-03 2.740
R-HSA-913531 Interferon Signaling 1.825879e-03 2.739
R-HSA-9675108 Nervous system development 1.852972e-03 2.732
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission 1.874815e-03 2.727
R-HSA-9730414 MITF-M-regulated melanocyte development 1.915445e-03 2.718
R-HSA-2173796 SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription 1.944068e-03 2.711
R-HSA-9634635 Estrogen-stimulated signaling through PRKCZ 2.082890e-03 2.681
R-HSA-6806003 Regulation of TP53 Expression and Degradation 2.203855e-03 2.657
R-HSA-202433 Generation of second messenger molecules 2.341432e-03 2.631
R-HSA-110056 MAPK3 (ERK1) activation 2.435758e-03 2.613
R-HSA-74749 Signal attenuation 2.435758e-03 2.613
R-HSA-5218920 VEGFR2 mediated vascular permeability 2.484224e-03 2.605
R-HSA-446652 Interleukin-1 family signaling 2.612494e-03 2.583
R-HSA-5675221 Negative regulation of MAPK pathway 2.632296e-03 2.580
R-HSA-9635465 Suppression of apoptosis 2.814802e-03 2.551
R-HSA-9006936 Signaling by TGFB family members 3.177074e-03 2.498
R-HSA-9020702 Interleukin-1 signaling 3.573049e-03 2.447
R-HSA-879415 Advanced glycosylation endproduct receptor signaling 3.650248e-03 2.438
R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) 5.092491e-03 2.293
R-HSA-170968 Frs2-mediated activation 4.106071e-03 2.387
R-HSA-5578768 Physiological factors 4.586914e-03 2.338
R-HSA-5621481 C-type lectin receptors (CLRs) 4.182081e-03 2.379
R-HSA-2032785 YAP1- and WWTR1 (TAZ)-stimulated gene expression 4.586914e-03 2.338
R-HSA-1502540 Signaling by Activin 5.092491e-03 2.293
R-HSA-1295596 Spry regulation of FGF signaling 5.092491e-03 2.293
R-HSA-416476 G alpha (q) signalling events 5.029096e-03 2.299
R-HSA-74160 Gene expression (Transcription) 5.485021e-03 2.261
R-HSA-202403 TCR signaling 4.825688e-03 2.316
R-HSA-389356 Co-stimulation by CD28 3.821885e-03 2.418
R-HSA-2173793 Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer 5.527467e-03 2.257
R-HSA-169893 Prolonged ERK activation events 5.622524e-03 2.250
R-HSA-1362300 Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL... 5.622524e-03 2.250
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA 5.622524e-03 2.250
R-HSA-6791312 TP53 Regulates Transcription of Cell Cycle Genes 5.767827e-03 2.239
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest 6.176731e-03 2.209
R-HSA-8878166 Transcriptional regulation by RUNX2 6.511883e-03 2.186
R-HSA-380284 Loss of proteins required for interphase microtubule organization from the centr... 7.341274e-03 2.134
R-HSA-380259 Loss of Nlp from mitotic centrosomes 7.341274e-03 2.134
R-HSA-69615 G1/S DNA Damage Checkpoints 7.341274e-03 2.134
R-HSA-1181150 Signaling by NODAL 8.629824e-03 2.064
R-HSA-69202 Cyclin E associated events during G1/S transition 9.469144e-03 2.024
R-HSA-453276 Regulation of mitotic cell cycle 9.799410e-03 2.009
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins 9.799410e-03 2.009
R-HSA-9856649 Transcriptional and post-translational regulation of MITF-M expression and activ... 9.799410e-03 2.009
R-HSA-9825892 Regulation of MITF-M-dependent genes involved in cell cycle and proliferation 9.994343e-03 2.000
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry 1.013633e-02 1.994
R-HSA-4086398 Ca2+ pathway 1.047993e-02 1.980
R-HSA-211728 Regulation of PAK-2p34 activity by PS-GAP/RHG10 1.099365e-02 1.959
R-HSA-9630791 Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 1.099365e-02 1.959
R-HSA-9632697 Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... 1.099365e-02 1.959
R-HSA-3642279 TGFBR2 MSI Frameshift Mutants in Cancer 1.099365e-02 1.959
R-HSA-169131 Inhibition of PKR 1.099365e-02 1.959
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling 1.144801e-02 1.941
R-HSA-982772 Growth hormone receptor signaling 1.144801e-02 1.941
R-HSA-1852241 Organelle biogenesis and maintenance 1.161004e-02 1.935
R-HSA-112315 Transmission across Chemical Synapses 1.208035e-02 1.918
R-HSA-5218921 VEGFR2 mediated cell proliferation 1.298875e-02 1.886
R-HSA-9833482 PKR-mediated signaling 1.307409e-02 1.884
R-HSA-9006925 Intracellular signaling by second messengers 1.537597e-02 1.813
R-HSA-5654732 Negative regulation of FGFR3 signaling 1.545866e-02 1.811
R-HSA-8940973 RUNX2 regulates osteoblast differentiation 1.545866e-02 1.811
R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes 1.550313e-02 1.810
R-HSA-73887 Death Receptor Signaling 1.550313e-02 1.810
R-HSA-5654733 Negative regulation of FGFR4 signaling 1.632330e-02 1.787
R-HSA-176034 Interactions of Tat with host cellular proteins 1.644558e-02 1.784
R-HSA-380320 Recruitment of NuMA to mitotic centrosomes 1.690276e-02 1.772
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs) 1.720820e-02 1.764
R-HSA-5620912 Anchoring of the basal body to the plasma membrane 1.782987e-02 1.749
R-HSA-8986944 Transcriptional Regulation by MECP2 1.830388e-02 1.737
R-HSA-2173795 Downregulation of SMAD2/3:SMAD4 transcriptional activity 1.903780e-02 1.720
R-HSA-2682334 EPH-Ephrin signaling 1.927287e-02 1.715
R-HSA-5654726 Negative regulation of FGFR1 signaling 1.998202e-02 1.699
R-HSA-1266738 Developmental Biology 2.115076e-02 1.675
R-HSA-211736 Stimulation of the cell death response by PAK-2p34 2.186778e-02 1.660
R-HSA-8854521 Interaction between PHLDA1 and AURKA 2.186778e-02 1.660
R-HSA-198765 Signalling to ERK5 2.186778e-02 1.660
R-HSA-3642278 Loss of Function of TGFBR2 in Cancer 2.186778e-02 1.660
R-HSA-3645790 TGFBR2 Kinase Domain Mutants in Cancer 2.186778e-02 1.660
R-HSA-3656535 TGFBR1 LBD Mutants in Cancer 2.186778e-02 1.660
R-HSA-5654727 Negative regulation of FGFR2 signaling 2.192809e-02 1.659
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis 2.254396e-02 1.647
R-HSA-76002 Platelet activation, signaling and aggregation 2.383754e-02 1.623
R-HSA-69205 G1/S-Specific Transcription 2.394946e-02 1.621
R-HSA-8941326 RUNX2 regulates bone development 2.394946e-02 1.621
R-HSA-5603037 IRAK4 deficiency (TLR5) 2.726043e-02 1.564
R-HSA-3656532 TGFBR1 KD Mutants in Cancer 3.262369e-02 1.486
R-HSA-69200 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 ... 3.262369e-02 1.486
R-HSA-3656534 Loss of Function of TGFBR1 in Cancer 3.795770e-02 1.421
R-HSA-68911 G2 Phase 3.795770e-02 1.421
R-HSA-3304356 SMAD2/3 Phosphorylation Motif Mutants in Cancer 3.795770e-02 1.421
R-HSA-111459 Activation of caspases through apoptosome-mediated cleavage 4.326262e-02 1.364
R-HSA-9652817 Signaling by MAPK mutants 4.326262e-02 1.364
R-HSA-69478 G2/M DNA replication checkpoint 4.853863e-02 1.314
R-HSA-113507 E2F-enabled inhibition of pre-replication complex formation 4.853863e-02 1.314
R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat 2.711864e-02 1.567
R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript 2.821070e-02 1.550
R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat 2.821070e-02 1.550
R-HSA-5674135 MAP2K and MAPK activation 3.044696e-02 1.516
R-HSA-112382 Formation of RNA Pol II elongation complex 4.391740e-02 1.357
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 3.392843e-02 1.469
R-HSA-75955 RNA Polymerase II Transcription Elongation 4.523441e-02 1.345
R-HSA-3304351 Signaling by TGF-beta Receptor Complex in Cancer 4.853863e-02 1.314
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants 2.498780e-02 1.602
R-HSA-167169 HIV Transcription Elongation 2.821070e-02 1.550
R-HSA-9656223 Signaling by RAF1 mutants 3.044696e-02 1.516
R-HSA-9649948 Signaling downstream of RAS mutants 3.633163e-02 1.440
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF 3.633163e-02 1.440
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants 3.633163e-02 1.440
R-HSA-139910 Activation of BMF and translocation to mitochondria 2.726043e-02 1.564
R-HSA-111446 Activation of BIM and translocation to mitochondria 2.726043e-02 1.564
R-HSA-3304349 Loss of Function of SMAD2/3 in Cancer 4.326262e-02 1.364
R-HSA-176417 Phosphorylation of Emi1 4.326262e-02 1.364
R-HSA-6802949 Signaling by RAS mutants 3.633163e-02 1.440
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling 4.075092e-02 1.390
R-HSA-912446 Meiotic recombination 4.261512e-02 1.370
R-HSA-111464 SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes 3.795770e-02 1.421
R-HSA-199418 Negative regulation of the PI3K/AKT network 4.684161e-02 1.329
R-HSA-68875 Mitotic Prophase 3.857807e-02 1.414
R-HSA-9931529 Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK 3.795770e-02 1.421
R-HSA-111463 SMAC (DIABLO) binds to IAPs 3.795770e-02 1.421
R-HSA-2980767 Activation of NIMA Kinases NEK9, NEK6, NEK7 4.853863e-02 1.314
R-HSA-9009391 Extra-nuclear estrogen signaling 2.453800e-02 1.610
R-HSA-9007892 Interleukin-38 signaling 3.262369e-02 1.486
R-HSA-111469 SMAC, XIAP-regulated apoptotic response 4.326262e-02 1.364
R-HSA-164944 Nef and signal transduction 4.853863e-02 1.314
R-HSA-3371453 Regulation of HSF1-mediated heat shock response 2.510306e-02 1.600
R-HSA-111996 Ca-dependent events 3.159072e-02 1.500
R-HSA-9725371 Nuclear events stimulated by ALK signaling in cancer 3.879863e-02 1.411
R-HSA-69613 p53-Independent G1/S DNA Damage Checkpoint 3.512195e-02 1.454
R-HSA-69601 Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A 3.512195e-02 1.454
R-HSA-75153 Apoptotic execution phase 3.633163e-02 1.440
R-HSA-5663202 Diseases of signal transduction by growth factor receptors and second messengers 2.918402e-02 1.535
R-HSA-9031628 NGF-stimulated transcription 3.879863e-02 1.411
R-HSA-1257604 PIP3 activates AKT signaling 3.080115e-02 1.511
R-HSA-3371556 Cellular response to heat stress 3.929556e-02 1.406
R-HSA-111885 Opioid Signalling 2.625420e-02 1.581
R-HSA-9637690 Response of Mtb to phagocytosis 3.275129e-02 1.485
R-HSA-445355 Smooth Muscle Contraction 4.523441e-02 1.345
R-HSA-5654743 Signaling by FGFR4 3.275129e-02 1.485
R-HSA-5654741 Signaling by FGFR3 3.512195e-02 1.454
R-HSA-397014 Muscle contraction 4.012919e-02 1.397
R-HSA-1592230 Mitochondrial biogenesis 3.646653e-02 1.438
R-HSA-9824439 Bacterial Infection Pathways 2.665458e-02 1.574
R-HSA-5654736 Signaling by FGFR1 4.927183e-02 1.307
R-HSA-75893 TNF signaling 4.927183e-02 1.307
R-HSA-3858494 Beta-catenin independent WNT signaling 5.335601e-02 1.273
R-HSA-9839389 TGFBR3 regulates TGF-beta signaling 5.378586e-02 1.269
R-HSA-9032845 Activated NTRK2 signals through CDK5 5.378586e-02 1.269
R-HSA-112316 Neuronal System 5.409656e-02 1.267
R-HSA-8939211 ESR-mediated signaling 5.458555e-02 1.263
R-HSA-8943724 Regulation of PTEN gene transcription 5.484940e-02 1.261
R-HSA-9764725 Negative Regulation of CDH1 Gene Transcription 5.484940e-02 1.261
R-HSA-112043 PLC beta mediated events 5.627723e-02 1.250
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation 5.763795e-02 1.239
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase 5.771807e-02 1.239
R-HSA-9616222 Transcriptional regulation of granulopoiesis 5.771807e-02 1.239
R-HSA-375165 NCAM signaling for neurite out-growth 5.771807e-02 1.239
R-HSA-111995 phospho-PLA2 pathway 5.900448e-02 1.229
R-HSA-8848021 Signaling by PTK6 5.917174e-02 1.228
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases 5.917174e-02 1.228
R-HSA-1643685 Disease 6.031223e-02 1.220
R-HSA-74751 Insulin receptor signalling cascade 6.063804e-02 1.217
R-HSA-6802952 Signaling by BRAF and RAF1 fusions 6.211680e-02 1.207
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulati... 6.211680e-02 1.207
R-HSA-112411 MAPK1 (ERK2) activation 6.419464e-02 1.193
R-HSA-9700645 ALK mutants bind TKIs 6.419464e-02 1.193
R-HSA-9619229 Activation of RAC1 downstream of NMDARs 6.419464e-02 1.193
R-HSA-937042 IRAK2 mediated activation of TAK1 complex 6.419464e-02 1.193
R-HSA-418889 Caspase activation via Dependence Receptors in the absence of ligand 6.419464e-02 1.193
R-HSA-2465910 MASTL Facilitates Mitotic Progression 6.419464e-02 1.193
R-HSA-450520 HuR (ELAVL1) binds and stabilizes mRNA 6.419464e-02 1.193
R-HSA-69242 S Phase 6.481726e-02 1.188
R-HSA-112040 G-protein mediated events 6.511100e-02 1.186
R-HSA-5688426 Deubiquitination 6.652830e-02 1.177
R-HSA-167172 Transcription of the HIV genome 6.662608e-02 1.176
R-HSA-9856651 MITF-M-dependent gene expression 6.667395e-02 1.176
R-HSA-388841 Regulation of T cell activation by CD28 family 6.722886e-02 1.172
R-HSA-9755511 KEAP1-NFE2L2 pathway 6.761143e-02 1.170
R-HSA-69620 Cell Cycle Checkpoints 6.864156e-02 1.163
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex 6.935649e-02 1.159
R-HSA-9764560 Regulation of CDH1 Gene Transcription 6.969135e-02 1.157
R-HSA-388396 GPCR downstream signalling 7.299184e-02 1.137
R-HSA-68886 M Phase 7.299538e-02 1.137
R-HSA-9645460 Alpha-protein kinase 1 signaling pathway 7.449018e-02 1.128
R-HSA-9662834 CD163 mediating an anti-inflammatory response 7.449018e-02 1.128
R-HSA-877300 Interferon gamma signaling 7.532691e-02 1.123
R-HSA-674695 RNA Polymerase II Pre-transcription Events 7.595750e-02 1.119
R-HSA-1169408 ISG15 antiviral mechanism 7.755131e-02 1.110
R-HSA-73854 RNA Polymerase I Promoter Clearance 7.915571e-02 1.102
R-HSA-9020591 Interleukin-12 signaling 7.915571e-02 1.102
R-HSA-2514853 Condensation of Prometaphase Chromosomes 7.959588e-02 1.099
R-HSA-73864 RNA Polymerase I Transcription 8.239560e-02 1.084
R-HSA-9931530 Phosphorylation and nuclear translocation of the CRY:PER:kinase complex 8.467372e-02 1.072
R-HSA-198323 AKT phosphorylates targets in the cytosol 8.467372e-02 1.072
R-HSA-209543 p75NTR recruits signalling complexes 8.467372e-02 1.072
R-HSA-5654738 Signaling by FGFR2 8.567590e-02 1.067
R-HSA-9824443 Parasitic Infection Pathways 8.597883e-02 1.066
R-HSA-9658195 Leishmania infection 8.597883e-02 1.066
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex 8.972386e-02 1.047
R-HSA-6811555 PI5P Regulates TP53 Acetylation 8.972386e-02 1.047
R-HSA-6802957 Oncogenic MAPK signaling 9.404524e-02 1.027
R-HSA-1500620 Meiosis 9.404524e-02 1.027
R-HSA-399956 CRMPs in Sema3A signaling 9.474645e-02 1.023
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation 9.474645e-02 1.023
R-HSA-205043 NRIF signals cell death from the nucleus 9.474645e-02 1.023
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation 9.474645e-02 1.023
R-HSA-6807505 RNA polymerase II transcribes snRNA genes 9.745721e-02 1.011
R-HSA-5684996 MAPK1/MAPK3 signaling 9.833371e-02 1.007
R-HSA-447115 Interleukin-12 family signaling 9.917637e-02 1.004
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex 9.974164e-02 1.001
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA 9.974164e-02 1.001
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA 9.974164e-02 1.001
R-HSA-193639 p75NTR signals via NF-kB 9.974164e-02 1.001
R-HSA-176412 Phosphorylation of the APC/C 1.047096e-01 0.980
R-HSA-9664420 Killing mechanisms 1.047096e-01 0.980
R-HSA-9673324 WNT5:FZD7-mediated leishmania damping 1.047096e-01 0.980
R-HSA-6804116 TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest 1.047096e-01 0.980
R-HSA-8964616 G beta:gamma signalling through CDC42 1.096504e-01 0.960
R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling 1.096504e-01 0.960
R-HSA-74752 Signaling by Insulin receptor 1.096666e-01 0.960
R-HSA-5617833 Cilium Assembly 1.097629e-01 0.960
R-HSA-372790 Signaling by GPCR 1.124796e-01 0.949
R-HSA-68877 Mitotic Prometaphase 1.132608e-01 0.946
R-HSA-9909505 Modulation of host responses by IFN-stimulated genes 1.145643e-01 0.941
R-HSA-5607764 CLEC7A (Dectin-1) signaling 1.186227e-01 0.926
R-HSA-4419969 Depolymerization of the Nuclear Lamina 1.194513e-01 0.923
R-HSA-432142 Platelet sensitization by LDL 1.194513e-01 0.923
R-HSA-190236 Signaling by FGFR 1.222555e-01 0.913
R-HSA-193704 p75 NTR receptor-mediated signalling 1.240822e-01 0.906
R-HSA-174048 APC/C:Cdc20 mediated degradation of Cyclin B 1.243117e-01 0.905
R-HSA-113510 E2F mediated regulation of DNA replication 1.243117e-01 0.905
R-HSA-376176 Signaling by ROBO receptors 1.252220e-01 0.902
R-HSA-5603041 IRAK4 deficiency (TLR2/4) 1.387342e-01 0.858
R-HSA-9617324 Negative regulation of NMDA receptor-mediated neuronal transmission 1.387342e-01 0.858
R-HSA-2995383 Initiation of Nuclear Envelope (NE) Reformation 1.387342e-01 0.858
R-HSA-2173788 Downregulation of TGF-beta receptor signaling 1.434893e-01 0.843
R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection 1.482185e-01 0.829
R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE 1.482185e-01 0.829
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer 1.482185e-01 0.829
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis 1.482185e-01 0.829
R-HSA-5663205 Infectious disease 1.482226e-01 0.829
R-HSA-8863678 Neurodegenerative Diseases 1.529218e-01 0.816
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's dis... 1.529218e-01 0.816
R-HSA-418592 ADP signalling through P2Y purinoceptor 1 1.529218e-01 0.816
R-HSA-8878171 Transcriptional regulation by RUNX1 1.556505e-01 0.808
R-HSA-162906 HIV Infection 1.569661e-01 0.804
R-HSA-109582 Hemostasis 1.574118e-01 0.803
R-HSA-420029 Tight junction interactions 1.575994e-01 0.802
R-HSA-73894 DNA Repair 1.593477e-01 0.798
R-HSA-909733 Interferon alpha/beta signaling 1.599198e-01 0.796
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway 1.622516e-01 0.790
R-HSA-8934593 Regulation of RUNX1 Expression and Activity 1.622516e-01 0.790
R-HSA-9006931 Signaling by Nuclear Receptors 1.624999e-01 0.789
R-HSA-167243 Tat-mediated HIV elongation arrest and recovery 1.668783e-01 0.778
R-HSA-167238 Pausing and recovery of Tat-mediated HIV elongation 1.668783e-01 0.778
R-HSA-73863 RNA Polymerase I Transcription Termination 1.668783e-01 0.778
R-HSA-9734009 Defective Intrinsic Pathway for Apoptosis 1.668783e-01 0.778
R-HSA-73728 RNA Polymerase I Promoter Opening 1.668783e-01 0.778
R-HSA-5357956 TNFR1-induced NF-kappa-B signaling pathway 1.668783e-01 0.778
R-HSA-9006115 Signaling by NTRK2 (TRKB) 1.668783e-01 0.778
R-HSA-167287 HIV elongation arrest and recovery 1.714797e-01 0.766
R-HSA-167290 Pausing and recovery of HIV elongation 1.714797e-01 0.766
R-HSA-113418 Formation of the Early Elongation Complex 1.714797e-01 0.766
R-HSA-171319 Telomere Extension By Telomerase 1.714797e-01 0.766
R-HSA-167158 Formation of the HIV-1 Early Elongation Complex 1.714797e-01 0.766
R-HSA-9635486 Infection with Mycobacterium tuberculosis 1.716082e-01 0.765
R-HSA-72086 mRNA Capping 1.760560e-01 0.754
R-HSA-5656169 Termination of translesion DNA synthesis 1.760560e-01 0.754
R-HSA-180024 DARPP-32 events 1.760560e-01 0.754
R-HSA-162909 Host Interactions of HIV factors 1.775056e-01 0.751
R-HSA-68962 Activation of the pre-replicative complex 1.806073e-01 0.743
R-HSA-1250196 SHC1 events in ERBB2 signaling 1.806073e-01 0.743
R-HSA-114452 Activation of BH3-only proteins 1.806073e-01 0.743
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation 1.851338e-01 0.733
R-HSA-9833109 Evasion by RSV of host interferon responses 1.851338e-01 0.733
R-HSA-69481 G2/M Checkpoints 1.854179e-01 0.732
R-HSA-421270 Cell-cell junction organization 1.895186e-01 0.722
R-HSA-111465 Apoptotic cleavage of cellular proteins 1.896355e-01 0.722
R-HSA-1474165 Reproduction 1.933808e-01 0.714
R-HSA-397795 G-protein beta:gamma signalling 1.941127e-01 0.712
R-HSA-8939243 RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... 1.941127e-01 0.712
R-HSA-176187 Activation of ATR in response to replication stress 1.941127e-01 0.712
R-HSA-6804758 Regulation of TP53 Activity through Acetylation 1.941127e-01 0.712
R-HSA-9022692 Regulation of MECP2 expression and activity 1.941127e-01 0.712
R-HSA-5576891 Cardiac conduction 1.953787e-01 0.709
R-HSA-114508 Effects of PIP2 hydrolysis 1.985654e-01 0.702
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D 2.029937e-01 0.693
R-HSA-392518 Signal amplification 2.029937e-01 0.693
R-HSA-169911 Regulation of Apoptosis 2.073979e-01 0.683
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis 2.073979e-01 0.683
R-HSA-3301854 Nuclear Pore Complex (NPC) Disassembly 2.073979e-01 0.683
R-HSA-381042 PERK regulates gene expression 2.073979e-01 0.683
R-HSA-111933 Calmodulin induced events 2.117780e-01 0.674
R-HSA-111997 CaM pathway 2.117780e-01 0.674
R-HSA-114604 GPVI-mediated activation cascade 2.117780e-01 0.674
R-HSA-8853659 RET signaling 2.117780e-01 0.674
R-HSA-6807070 PTEN Regulation 2.134710e-01 0.671
R-HSA-9711123 Cellular response to chemical stress 2.135495e-01 0.671
R-HSA-9664422 FCGR3A-mediated phagocytosis 2.154920e-01 0.667
R-HSA-9664417 Leishmania phagocytosis 2.154920e-01 0.667
R-HSA-9664407 Parasite infection 2.154920e-01 0.667
R-HSA-5689896 Ovarian tumor domain proteases 2.161341e-01 0.665
R-HSA-162599 Late Phase of HIV Life Cycle 2.215658e-01 0.654
R-HSA-168276 NS1 Mediated Effects on Host Pathways 2.247752e-01 0.648
R-HSA-446728 Cell junction organization 2.279870e-01 0.642
R-HSA-5696395 Formation of Incision Complex in GG-NER 2.290603e-01 0.640
R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening 2.290603e-01 0.640
R-HSA-5260271 Diseases of Immune System 2.290603e-01 0.640
R-HSA-5602358 Diseases associated with the TLR signaling cascade 2.290603e-01 0.640
R-HSA-5625886 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene... 2.333220e-01 0.632
R-HSA-9929491 SPOP-mediated proteasomal degradation of PD-L1(CD274) 2.333220e-01 0.632
R-HSA-110313 Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templa... 2.333220e-01 0.632
R-HSA-167162 RNA Polymerase II HIV Promoter Escape 2.375604e-01 0.624
R-HSA-167161 HIV Transcription Initiation 2.375604e-01 0.624
R-HSA-75953 RNA Polymerase II Transcription Initiation 2.375604e-01 0.624
R-HSA-73762 RNA Polymerase I Transcription Initiation 2.417756e-01 0.617
R-HSA-5693532 DNA Double-Strand Break Repair 2.439446e-01 0.613
R-HSA-5673001 RAF/MAP kinase cascade 2.440805e-01 0.612
R-HSA-73776 RNA Polymerase II Promoter Escape 2.459678e-01 0.609
R-HSA-2173789 TGF-beta receptor signaling activates SMADs 2.459678e-01 0.609
R-HSA-3214858 RMTs methylate histone arginines 2.501371e-01 0.602
R-HSA-3928662 EPHB-mediated forward signaling 2.501371e-01 0.602
R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX) 2.501371e-01 0.602
R-HSA-162587 HIV Life Cycle 2.521111e-01 0.598
R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance 2.542836e-01 0.595
R-HSA-1489509 DAG and IP3 signaling 2.542836e-01 0.595
R-HSA-9824585 Regulation of MITF-M-dependent genes involved in pigmentation 2.542836e-01 0.595
R-HSA-195721 Signaling by WNT 2.573859e-01 0.589
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex 2.584074e-01 0.588
R-HSA-2299718 Condensation of Prophase Chromosomes 2.584074e-01 0.588
R-HSA-9839373 Signaling by TGFBR3 2.584074e-01 0.588
R-HSA-5357905 Regulation of TNFR1 signaling 2.584074e-01 0.588
R-HSA-445989 TAK1-dependent IKK and NF-kappa-B activation 2.625087e-01 0.581
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint 2.706440e-01 0.568
R-HSA-69563 p53-Dependent G1 DNA Damage Response 2.706440e-01 0.568
R-HSA-73893 DNA Damage Bypass 2.706440e-01 0.568
R-HSA-6798695 Neutrophil degranulation 2.719270e-01 0.566
R-HSA-1169091 Activation of NF-kappaB in B cells 2.786906e-01 0.555
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A 2.826810e-01 0.549
R-HSA-73772 RNA Polymerase I Promoter Escape 2.826810e-01 0.549
R-HSA-68949 Orc1 removal from chromatin 2.826810e-01 0.549
R-HSA-1500931 Cell-Cell communication 2.842795e-01 0.546
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... 2.866495e-01 0.543
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of th... 2.866495e-01 0.543
R-HSA-5689880 Ub-specific processing proteases 2.868612e-01 0.542
R-HSA-9764274 Regulation of Expression and Function of Type I Classical Cadherins 2.868612e-01 0.542
R-HSA-9764265 Regulation of CDH1 Expression and Function 2.868612e-01 0.542
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6 2.905962e-01 0.537
R-HSA-983231 Factors involved in megakaryocyte development and platelet production 2.909449e-01 0.536
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins 2.945214e-01 0.531
R-HSA-6811436 COPI-independent Golgi-to-ER retrograde traffic 2.945214e-01 0.531
R-HSA-418597 G alpha (z) signalling events 2.945214e-01 0.531
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER 2.984252e-01 0.525
R-HSA-193648 NRAGE signals death through JNK 2.984252e-01 0.525
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins 2.984252e-01 0.525
R-HSA-2980766 Nuclear Envelope Breakdown 3.023075e-01 0.520
R-HSA-6782135 Dual incision in TC-NER 3.061686e-01 0.514
R-HSA-180786 Extension of Telomeres 3.100086e-01 0.509
R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... 3.100086e-01 0.509
R-HSA-1227986 Signaling by ERBB2 3.138276e-01 0.503
R-HSA-2559586 DNA Damage/Telomere Stress Induced Senescence 3.214029e-01 0.493
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint 3.214029e-01 0.493
R-HSA-9759476 Regulation of Homotypic Cell-Cell Adhesion 3.335906e-01 0.477
R-HSA-8953854 Metabolism of RNA 3.356202e-01 0.474
R-HSA-5693606 DNA Double Strand Break Response 3.399815e-01 0.469
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... 3.436364e-01 0.464
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) 3.508862e-01 0.455
R-HSA-427413 NoRC negatively regulates rRNA expression 3.544814e-01 0.450
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE 3.616128e-01 0.442
R-HSA-69052 Switching of origins to a post-replicative state 3.616128e-01 0.442
R-HSA-69473 G2/M DNA damage checkpoint 3.651492e-01 0.438
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) 3.686663e-01 0.433
R-HSA-5689603 UCH proteinases 3.721641e-01 0.429
R-HSA-418990 Adherens junctions interactions 3.794523e-01 0.421
R-HSA-9925561 Developmental Lineage of Pancreatic Acinar Cells 3.825429e-01 0.417
R-HSA-9856530 High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... 3.859647e-01 0.413
R-HSA-5250941 Negative epigenetic regulation of rRNA expression 3.859647e-01 0.413
R-HSA-2995410 Nuclear Envelope (NE) Reassembly 3.859647e-01 0.413
R-HSA-5693607 Processing of DNA double-strand break ends 3.893677e-01 0.410
R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) 3.994652e-01 0.399
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs 3.994652e-01 0.399
R-HSA-9909615 Regulation of PD-L1(CD274) Post-translational modification 4.061050e-01 0.391
R-HSA-9645723 Diseases of programmed cell death 4.159289e-01 0.381
R-HSA-202424 Downstream TCR signaling 4.223886e-01 0.374
R-HSA-418594 G alpha (i) signalling events 4.225458e-01 0.374
R-HSA-1912408 Pre-NOTCH Transcription and Translation 4.255920e-01 0.371
R-HSA-6807878 COPI-mediated anterograde transport 4.475288e-01 0.349
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation 4.475288e-01 0.349
R-HSA-157579 Telomere Maintenance 4.505943e-01 0.346
R-HSA-9633012 Response of EIF2AK4 (GCN2) to amino acid deficiency 4.715866e-01 0.326
R-HSA-9860931 Response of endothelial cells to shear stress 4.715866e-01 0.326
R-HSA-9833110 RSV-host interactions 4.745200e-01 0.324
R-HSA-5696398 Nucleotide Excision Repair 4.774373e-01 0.321
R-HSA-418346 Platelet homeostasis 4.803386e-01 0.318
R-HSA-69239 Synthesis of DNA 4.832240e-01 0.316
R-HSA-2672351 Stimuli-sensing channels 4.860935e-01 0.313
R-HSA-69002 DNA Replication Pre-Initiation 4.889473e-01 0.311
R-HSA-1912422 Pre-NOTCH Expression and Processing 5.002066e-01 0.301
R-HSA-9855142 Cellular responses to mechanical stimuli 5.029829e-01 0.298
R-HSA-5693567 HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA) 5.029829e-01 0.298
R-HSA-2029485 Role of phospholipids in phagocytosis 5.112205e-01 0.291
R-HSA-2219528 PI3K/AKT Signaling in Cancer 5.193232e-01 0.285
R-HSA-5693538 Homology Directed Repair 5.193232e-01 0.285
R-HSA-2500257 Resolution of Sister Chromatid Cohesion 5.272930e-01 0.278
R-HSA-73886 Chromosome Maintenance 5.272930e-01 0.278
R-HSA-2132295 MHC class II antigen presentation 5.325334e-01 0.274
R-HSA-9841922 MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesi... 5.402866e-01 0.267
R-HSA-9851695 Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes 5.402866e-01 0.267
R-HSA-9818564 Epigenetic regulation of gene expression by MLL3 and MLL4 complexes 5.402866e-01 0.267
R-HSA-1280218 Adaptive Immune System 5.427124e-01 0.265
R-HSA-9843745 Adipogenesis 5.578864e-01 0.253
R-HSA-8856688 Golgi-to-ER retrograde transport 5.603456e-01 0.252
R-HSA-9909396 Circadian clock 5.603456e-01 0.252
R-HSA-212165 Epigenetic regulation of gene expression 5.677836e-01 0.246
R-HSA-9018519 Estrogen-dependent gene expression 5.724405e-01 0.242
R-HSA-9820952 Respiratory Syncytial Virus Infection Pathway 5.748196e-01 0.240
R-HSA-381119 Unfolded Protein Response (UPR) 5.795388e-01 0.237
R-HSA-9705671 SARS-CoV-2 activates/modulates innate and adaptive immune responses 5.888223e-01 0.230
R-HSA-2871837 FCERI mediated NF-kB activation 5.933878e-01 0.227
R-HSA-199977 ER to Golgi Anterograde Transport 6.001421e-01 0.222
R-HSA-9820448 Developmental Cell Lineages of the Exocrine Pancreas 6.111537e-01 0.214
R-HSA-2142753 Arachidonate metabolism 6.111537e-01 0.214
R-HSA-69306 DNA Replication 6.133198e-01 0.212
R-HSA-9917777 Epigenetic regulation by WDR5-containing histone modifying complexes 6.154739e-01 0.211
R-HSA-9711097 Cellular response to starvation 6.239725e-01 0.205
R-HSA-983705 Signaling by the B Cell Receptor (BCR) 6.239725e-01 0.205
R-HSA-9909648 Regulation of PD-L1(CD274) expression 6.542199e-01 0.184
R-HSA-9664433 Leishmania parasite growth and survival 6.561486e-01 0.183
R-HSA-9662851 Anti-inflammatory response favouring Leishmania parasite infection 6.561486e-01 0.183
R-HSA-168255 Influenza Infection 6.674995e-01 0.176
R-HSA-983712 Ion channel transport 6.855998e-01 0.164
R-HSA-72163 mRNA Splicing - Major Pathway 6.942811e-01 0.158
R-HSA-6811442 Intra-Golgi and retrograde Golgi-to-ER traffic 7.043863e-01 0.152
R-HSA-389948 Co-inhibition by PD-1 7.043863e-01 0.152
R-HSA-948021 Transport to the Golgi and subsequent modification 7.076807e-01 0.150
R-HSA-72172 mRNA Splicing 7.125544e-01 0.147
R-HSA-597592 Post-translational protein modification 7.222729e-01 0.141
R-HSA-68882 Mitotic Anaphase 7.312586e-01 0.136
R-HSA-2555396 Mitotic Metaphase and Anaphase 7.327618e-01 0.135
R-HSA-9705683 SARS-CoV-2-host interactions 7.487585e-01 0.126
R-HSA-3247509 Chromatin modifying enzymes 7.570810e-01 0.121
R-HSA-157118 Signaling by NOTCH 7.651308e-01 0.116
R-HSA-9824446 Viral Infection Pathways 7.687105e-01 0.114
R-HSA-4839726 Chromatin organization 7.767135e-01 0.110
R-HSA-9734767 Developmental Cell Lineages 7.936179e-01 0.100
R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA 8.113919e-01 0.091
R-HSA-9694516 SARS-CoV-2 Infection 8.729486e-01 0.059
R-HSA-8978868 Fatty acid metabolism 9.090574e-01 0.041
R-HSA-446203 Asparagine N-linked glycosylation 9.164855e-01 0.038
R-HSA-9679506 SARS-CoV Infections 9.609080e-01 0.017
R-HSA-392499 Metabolism of proteins 9.679160e-01 0.014
R-HSA-199991 Membrane Trafficking 9.770976e-01 0.010
R-HSA-5653656 Vesicle-mediated transport 9.909407e-01 0.004
R-HSA-382551 Transport of small molecules 9.967130e-01 0.001
R-HSA-556833 Metabolism of lipids 9.998427e-01 0.000
R-HSA-1430728 Metabolism 1.000000e+00 0.000
Download
kinase JSD_mean pearson_surrounding kinase_max_IC_position max_position_JSD
DAPK2DAPK2 0.739 0.176 -3 0.877
SKMLCKSKMLCK 0.736 0.179 -2 0.849
DAPK3DAPK3 0.735 0.174 -3 0.837
CAMLCKCAMLCK 0.732 0.118 -2 0.845
DAPK1DAPK1 0.732 0.179 -3 0.818
NLKNLK 0.730 0.112 1 0.725
CAMK1BCAMK1B 0.730 0.149 -3 0.880
MOSMOS 0.729 0.073 1 0.784
ALK4ALK4 0.725 0.081 -2 0.712
VRK2VRK2 0.725 -0.022 1 0.692
BMPR1BBMPR1B 0.725 0.153 1 0.810
PRPKPRPK 0.724 0.019 -1 0.733
BMPR2BMPR2 0.723 -0.040 -2 0.777
NIKNIK 0.723 0.005 -3 0.883
ICKICK 0.722 0.107 -3 0.860
PKRPKR 0.721 -0.023 1 0.662
P38AP38A 0.721 0.120 1 0.647
PRP4PRP4 0.721 0.101 -3 0.761
GAKGAK 0.720 0.023 1 0.738
SMMLCKSMMLCK 0.720 0.105 -3 0.841
TGFBR1TGFBR1 0.720 0.092 -2 0.678
MEK1MEK1 0.720 -0.032 2 0.693
CDKL1CDKL1 0.720 0.071 -3 0.833
P38BP38B 0.719 0.121 1 0.594
PAK1PAK1 0.718 0.171 -2 0.824
DRAK1DRAK1 0.718 0.135 1 0.716
ACVR2BACVR2B 0.718 0.099 -2 0.677
JNK2JNK2 0.718 0.108 1 0.604
BMPR1ABMPR1A 0.718 0.138 1 0.788
COTCOT 0.718 0.099 2 0.754
ERK5ERK5 0.717 0.059 1 0.672
CAMK2GCAMK2G 0.717 0.080 2 0.821
ATRATR 0.717 -0.005 1 0.667
RIPK3RIPK3 0.716 0.023 3 0.435
ANKRD3ANKRD3 0.716 -0.057 1 0.648
BRAFBRAF 0.715 -0.023 -4 0.714
MYLK4MYLK4 0.715 0.123 -2 0.806
HIPK1HIPK1 0.715 0.119 1 0.670
CDC7CDC7 0.714 0.069 1 0.793
PAK2PAK2 0.714 0.114 -2 0.811
JNK3JNK3 0.714 0.085 1 0.628
PASKPASK 0.713 0.048 -3 0.855
ALK2ALK2 0.713 0.045 -2 0.682
GRK6GRK6 0.713 0.019 1 0.730
ACVR2AACVR2A 0.712 0.068 -2 0.655
DYRK2DYRK2 0.712 0.106 1 0.659
CDK5CDK5 0.712 0.081 1 0.688
RAF1RAF1 0.712 -0.062 1 0.644
DYRK1ADYRK1A 0.712 0.118 1 0.672
PIM3PIM3 0.711 0.080 -3 0.860
LATS1LATS1 0.711 0.035 -3 0.869
P38DP38D 0.711 0.121 1 0.566
VRK1VRK1 0.711 -0.051 2 0.728
P38GP38G 0.710 0.104 1 0.571
PAK3PAK3 0.710 0.128 -2 0.830
MLK2MLK2 0.710 -0.035 2 0.632
PIM1PIM1 0.710 0.080 -3 0.821
ERK2ERK2 0.710 0.071 1 0.629
TSSK2TSSK2 0.710 0.037 -5 0.700
RIPK1RIPK1 0.710 -0.010 1 0.620
CDK14CDK14 0.710 0.107 1 0.644
MPSK1MPSK1 0.709 0.023 1 0.675
PDK1PDK1 0.709 -0.016 1 0.578
DLKDLK 0.709 -0.105 1 0.658
DMPK1DMPK1 0.709 0.119 -3 0.804
HIPK3HIPK3 0.709 0.118 1 0.630
PLK1PLK1 0.709 0.014 -2 0.690
TAK1TAK1 0.709 -0.041 1 0.641
HIPK4HIPK4 0.709 0.090 1 0.714
MEK5MEK5 0.708 -0.143 2 0.665
ALPHAK3ALPHAK3 0.708 0.051 -1 0.687
ROCK2ROCK2 0.708 0.090 -3 0.813
JNK1JNK1 0.708 0.086 1 0.618
DCAMKL2DCAMKL2 0.708 0.141 -3 0.846
TAO2TAO2 0.708 -0.072 2 0.684
CDK18CDK18 0.707 0.129 1 0.619
TTKTTK 0.707 0.015 -2 0.688
NEK5NEK5 0.707 -0.067 1 0.625
WNK4WNK4 0.707 -0.027 -2 0.837
P70S6KBP70S6KB 0.707 0.072 -3 0.831
WNK3WNK3 0.707 -0.021 1 0.598
MASTLMASTL 0.707 -0.086 -2 0.771
CLK3CLK3 0.707 0.065 1 0.765
TAO3TAO3 0.707 -0.051 1 0.597
LRRK2LRRK2 0.707 -0.093 2 0.707
CDK17CDK17 0.707 0.113 1 0.585
TLK2TLK2 0.707 -0.009 1 0.616
CDK7CDK7 0.707 0.101 1 0.664
GRK5GRK5 0.707 -0.054 -3 0.828
CDKL5CDKL5 0.707 0.071 -3 0.824
MEKK2MEKK2 0.706 -0.097 2 0.650
DCAMKL1DCAMKL1 0.706 0.088 -3 0.829
CHAK2CHAK2 0.706 -0.036 -1 0.712
MAKMAK 0.706 0.141 -2 0.748
DYRK1BDYRK1B 0.706 0.104 1 0.651
WNK1WNK1 0.705 -0.010 -2 0.841
IRAK4IRAK4 0.705 -0.015 1 0.592
PBKPBK 0.705 0.032 1 0.645
GRK2GRK2 0.704 0.056 -2 0.604
CDK8CDK8 0.704 0.105 1 0.640
ERK1ERK1 0.704 0.088 1 0.585
MLK3MLK3 0.704 -0.009 2 0.589
MLK1MLK1 0.704 -0.077 2 0.634
DYRK3DYRK3 0.704 0.114 1 0.659
CLK4CLK4 0.703 0.098 -3 0.815
HIPK2HIPK2 0.703 0.120 1 0.614
PINK1PINK1 0.703 -0.020 1 0.737
NEK8NEK8 0.702 -0.104 2 0.674
MST3MST3 0.702 -0.060 2 0.626
MLK4MLK4 0.702 -0.018 2 0.569
TSSK1TSSK1 0.702 0.027 -3 0.887
PDHK4PDHK4 0.702 -0.169 1 0.659
ATMATM 0.702 0.005 1 0.618
PKCDPKCD 0.702 0.030 2 0.644
PIM2PIM2 0.702 0.060 -3 0.790
MAP3K15MAP3K15 0.702 -0.052 1 0.529
LKB1LKB1 0.702 -0.064 -3 0.813
DYRK4DYRK4 0.702 0.111 1 0.619
GSK3BGSK3B 0.701 -0.031 4 0.234
MEKK6MEKK6 0.701 -0.066 1 0.579
STK33STK33 0.701 0.130 2 0.775
TTBK2TTBK2 0.701 0.099 2 0.777
PLK3PLK3 0.700 0.044 2 0.814
CDK2CDK2 0.700 0.040 1 0.703
AMPKA1AMPKA1 0.700 -0.018 -3 0.867
BIKEBIKE 0.700 0.035 1 0.643
PKN3PKN3 0.700 -0.001 -3 0.857
PKACGPKACG 0.700 0.099 -2 0.804
GRK1GRK1 0.700 0.035 -2 0.691
GSK3AGSK3A 0.699 -0.011 4 0.236
IRE1IRE1 0.699 -0.051 1 0.618
NEK11NEK11 0.699 -0.108 1 0.583
TNIKTNIK 0.699 -0.090 3 0.398
NEK1NEK1 0.699 -0.086 1 0.582
MINKMINK 0.699 -0.099 1 0.560
MELKMELK 0.699 0.041 -3 0.832
CAMKK1CAMKK1 0.699 -0.118 -2 0.700
MEKK1MEKK1 0.699 -0.143 1 0.588
MRCKBMRCKB 0.699 0.089 -3 0.778
NEK9NEK9 0.699 -0.087 2 0.658
HPK1HPK1 0.699 -0.059 1 0.590
MEK2MEK2 0.699 -0.089 2 0.658
TGFBR2TGFBR2 0.698 -0.005 -2 0.674
MEKK3MEKK3 0.698 -0.125 1 0.601
AURBAURB 0.698 0.090 -2 0.716
MARK4MARK4 0.698 -0.048 4 0.457
YSK4YSK4 0.698 -0.108 1 0.554
SSTKSSTK 0.698 0.036 4 0.442
CDK1CDK1 0.698 0.057 1 0.661
PKN2PKN2 0.698 0.019 -3 0.845
CDK13CDK13 0.698 0.064 1 0.635
SGK3SGK3 0.697 0.081 -3 0.786
CDK3CDK3 0.697 0.074 1 0.607
CDK16CDK16 0.697 0.090 1 0.602
PLK4PLK4 0.697 0.044 2 0.655
AKT2AKT2 0.697 0.090 -3 0.745
CDK12CDK12 0.697 0.074 1 0.607
NDR1NDR1 0.697 0.053 -3 0.854
GCKGCK 0.697 -0.104 1 0.621
TBK1TBK1 0.697 -0.056 1 0.485
MARK2MARK2 0.697 -0.009 4 0.418
GRK7GRK7 0.697 -0.016 1 0.669
MST2MST2 0.697 -0.083 1 0.601
RSK2RSK2 0.697 0.081 -3 0.817
IRE2IRE2 0.697 -0.064 2 0.634
SMG1SMG1 0.696 0.001 1 0.607
MOKMOK 0.696 0.093 1 0.673
YANK3YANK3 0.696 0.197 2 0.709
HGKHGK 0.696 -0.107 3 0.404
BUB1BUB1 0.696 0.038 -5 0.689
PKG2PKG2 0.695 0.105 -2 0.751
ULK2ULK2 0.695 -0.064 2 0.680
NEK4NEK4 0.695 -0.122 1 0.558
ROCK1ROCK1 0.695 0.069 -3 0.790
CDK6CDK6 0.695 0.052 1 0.618
LOKLOK 0.695 -0.055 -2 0.790
ZAKZAK 0.695 -0.122 1 0.555
NUAK2NUAK2 0.695 -0.016 -3 0.861
CAMKK2CAMKK2 0.694 -0.138 -2 0.717
NIM1NIM1 0.694 -0.028 3 0.417
AURAAURA 0.694 0.097 -2 0.665
MYO3AMYO3A 0.694 -0.057 1 0.569
CAMK2DCAMK2D 0.694 0.031 -3 0.852
DSTYKDSTYK 0.694 -0.057 2 0.708
CDK4CDK4 0.693 0.056 1 0.602
HUNKHUNK 0.693 -0.095 2 0.718
PERKPERK 0.693 -0.143 -2 0.720
CAMK2BCAMK2B 0.693 0.054 2 0.775
CAMK1DCAMK1D 0.693 0.078 -3 0.746
CAMK1GCAMK1G 0.693 0.074 -3 0.810
IRAK1IRAK1 0.693 -0.097 -1 0.721
CHAK1CHAK1 0.692 -0.102 2 0.648
SRPK1SRPK1 0.692 0.048 -3 0.797
NEK7NEK7 0.692 -0.091 -3 0.793
EEF2KEEF2K 0.692 -0.124 3 0.380
PKCZPKCZ 0.692 -0.024 2 0.624
MRCKAMRCKA 0.692 0.053 -3 0.794
TLK1TLK1 0.691 -0.089 -2 0.700
CAMK4CAMK4 0.691 0.003 -3 0.842
NEK2NEK2 0.691 -0.088 2 0.634
PDHK1PDHK1 0.691 -0.195 1 0.607
PLK2PLK2 0.691 0.091 -3 0.786
MYO3BMYO3B 0.691 -0.067 2 0.631
CLK1CLK1 0.691 0.089 -3 0.796
CDK19CDK19 0.691 0.092 1 0.612
AURCAURC 0.691 0.102 -2 0.716
OSR1OSR1 0.691 -0.076 2 0.610
HASPINHASPIN 0.690 -0.003 -1 0.635
QIKQIK 0.690 -0.048 -3 0.836
HRIHRI 0.690 -0.171 -2 0.748
GRK4GRK4 0.690 -0.046 -2 0.697
KHS1KHS1 0.690 -0.094 1 0.543
IKKEIKKE 0.690 -0.081 1 0.480
KHS2KHS2 0.690 -0.081 1 0.579
CHK1CHK1 0.690 -0.029 -3 0.839
PRKD3PRKD3 0.690 0.057 -3 0.793
P90RSKP90RSK 0.690 0.039 -3 0.821
MST1MST1 0.690 -0.133 1 0.564
RSK3RSK3 0.689 0.069 -3 0.814
CAMK2ACAMK2A 0.689 0.055 2 0.756
MTORMTOR 0.689 -0.121 1 0.601
ERK7ERK7 0.689 -0.003 2 0.396
AMPKA2AMPKA2 0.689 -0.026 -3 0.842
MST4MST4 0.688 -0.064 2 0.622
MARK1MARK1 0.688 -0.027 4 0.419
ASK1ASK1 0.688 -0.105 1 0.521
CDK9CDK9 0.688 0.044 1 0.627
YSK1YSK1 0.688 -0.108 2 0.613
MARK3MARK3 0.688 -0.018 4 0.415
IKKBIKKB 0.688 -0.067 -2 0.692
MSK1MSK1 0.687 0.071 -3 0.780
PKCBPKCB 0.687 0.001 2 0.563
NDR2NDR2 0.687 0.046 -3 0.857
SGK1SGK1 0.687 0.082 -3 0.667
GRK3GRK3 0.687 0.049 -2 0.556
CDK10CDK10 0.687 0.068 1 0.643
SRPK3SRPK3 0.686 0.010 -3 0.772
FAM20CFAM20C 0.686 0.063 2 0.592
MAPKAPK3MAPKAPK3 0.686 0.018 -3 0.808
PKACBPKACB 0.685 0.097 -2 0.745
PKCHPKCH 0.685 -0.029 2 0.579
MSK2MSK2 0.685 0.050 -3 0.782
PKCGPKCG 0.685 -0.002 2 0.621
AKT1AKT1 0.685 0.070 -3 0.753
QSKQSK 0.685 -0.029 4 0.431
CLK2CLK2 0.685 0.087 -3 0.808
MNK2MNK2 0.684 0.048 -2 0.819
CK2A2CK2A2 0.684 0.029 1 0.750
PRKD2PRKD2 0.684 0.063 -3 0.816
RSK4RSK4 0.684 0.074 -3 0.789
IKKAIKKA 0.684 -0.020 -2 0.658
SNRKSNRK 0.683 -0.020 2 0.675
PKCAPKCA 0.683 -0.017 2 0.570
AAK1AAK1 0.683 0.043 1 0.567
CRIKCRIK 0.683 0.050 -3 0.749
PRKD1PRKD1 0.683 0.019 -3 0.849
YANK2YANK2 0.683 0.168 2 0.717
NEK6NEK6 0.682 -0.099 -2 0.746
TTBK1TTBK1 0.682 0.117 2 0.802
SLKSLK 0.682 -0.095 -2 0.723
GCN2GCN2 0.682 -0.112 2 0.651
BRSK1BRSK1 0.681 0.025 -3 0.829
LATS2LATS2 0.681 0.021 -5 0.753
PKCEPKCE 0.680 0.013 2 0.585
ULK1ULK1 0.680 -0.095 -3 0.796
NEK3NEK3 0.680 -0.078 1 0.508
TAO1TAO1 0.680 -0.107 1 0.483
P70S6KP70S6K 0.680 0.039 -3 0.749
MNK1MNK1 0.680 0.024 -2 0.822
PKCIPKCI 0.680 -0.015 2 0.589
CK2A1CK2A1 0.680 0.028 1 0.736
SIKSIK 0.680 -0.010 -3 0.802
CAMK1ACAMK1A 0.680 0.075 -3 0.715
SRPK2SRPK2 0.680 0.049 -3 0.735
DNAPKDNAPK 0.679 -0.073 1 0.477
CHK2CHK2 0.679 0.039 -3 0.699
CK1A2CK1A2 0.679 0.038 -3 0.473
TNK2TNK2 0.679 0.309 3 0.569
PKCTPKCT 0.678 -0.008 2 0.585
RIPK2RIPK2 0.677 -0.128 1 0.498
PTK2BPTK2B 0.677 0.316 -1 0.728
PAK6PAK6 0.677 0.072 -2 0.760
PKACAPKACA 0.677 0.097 -2 0.706
STLK3STLK3 0.676 -0.129 1 0.522
KISKIS 0.676 0.072 1 0.643
MERTKMERTK 0.675 0.279 3 0.512
MAPKAPK5MAPKAPK5 0.674 0.021 -3 0.759
MAPKAPK2MAPKAPK2 0.674 0.033 -3 0.775
CK1DCK1D 0.673 0.019 -3 0.469
EPHA6EPHA6 0.673 0.258 -1 0.709
SBKSBK 0.672 0.062 -3 0.646
BRSK2BRSK2 0.672 -0.039 -3 0.841
AKT3AKT3 0.672 0.077 -3 0.686
PAK5PAK5 0.672 0.075 -2 0.723
PHKG1PHKG1 0.672 -0.048 -3 0.851
NUAK1NUAK1 0.671 -0.036 -3 0.829
CK1ECK1E 0.671 0.014 -3 0.524
EPHB4EPHB4 0.670 0.270 -1 0.711
PAK4PAK4 0.670 0.080 -2 0.710
SRMSSRMS 0.670 0.249 1 0.725
TXKTXK 0.669 0.208 1 0.769
LTKLTK 0.668 0.212 3 0.560
EPHB1EPHB1 0.667 0.259 1 0.682
EPHA4EPHA4 0.667 0.247 2 0.819
EPHB2EPHB2 0.666 0.267 -1 0.691
BMXBMX 0.666 0.184 -1 0.758
EPHA7EPHA7 0.666 0.278 2 0.817
TYRO3TYRO3 0.666 0.166 3 0.487
ITKITK 0.666 0.207 -1 0.755
PRKXPRKX 0.666 0.093 -3 0.723
AXLAXL 0.665 0.199 3 0.509
PKG1PKG1 0.665 0.094 -2 0.706
PKN1PKN1 0.664 0.009 -3 0.767
ABL2ABL2 0.664 0.129 -1 0.747
ALKALK 0.664 0.192 3 0.570
BCKDKBCKDK 0.664 -0.202 -1 0.645
EPHB3EPHB3 0.662 0.227 -1 0.707
YES1YES1 0.662 0.105 -1 0.708
PDHK3_TYRPDHK3_TYR 0.662 0.023 4 0.460
EPHA1EPHA1 0.662 0.215 3 0.564
ABL1ABL1 0.662 0.122 -1 0.744
FERFER 0.661 0.125 1 0.733
EPHA3EPHA3 0.661 0.234 2 0.815
INSRRINSRR 0.661 0.132 3 0.496
EPHA5EPHA5 0.660 0.237 2 0.798
EPHA8EPHA8 0.660 0.242 -1 0.688
BLKBLK 0.660 0.137 -1 0.700
TECTEC 0.660 0.122 -1 0.761
TEKTEK 0.660 0.143 3 0.504
PHKG2PHKG2 0.659 -0.039 -3 0.832
MST1RMST1R 0.659 0.121 3 0.521
CSF1RCSF1R 0.657 0.100 3 0.506
LCKLCK 0.657 0.109 -1 0.715
BMPR2_TYRBMPR2_TYR 0.657 0.069 -1 0.690
ROS1ROS1 0.656 0.077 3 0.492
FGFR2FGFR2 0.656 0.132 3 0.522
METMET 0.656 0.138 3 0.538
HCKHCK 0.656 0.105 -1 0.730
LIMK2_TYRLIMK2_TYR 0.656 0.044 -3 0.873
PTK2PTK2 0.656 0.228 -1 0.592
EPHA2EPHA2 0.656 0.226 -1 0.685
MAP2K6_TYRMAP2K6_TYR 0.656 -0.012 -1 0.690
PKMYT1_TYRPKMYT1_TYR 0.655 -0.019 3 0.445
FGFR1FGFR1 0.654 0.147 3 0.538
MAP2K4_TYRMAP2K4_TYR 0.654 -0.036 -1 0.714
DDR1DDR1 0.653 0.042 4 0.415
BTKBTK 0.653 0.099 -1 0.783
FESFES 0.653 0.183 -1 0.731
KDRKDR 0.653 0.089 3 0.539
PDHK1_TYRPDHK1_TYR 0.652 -0.011 -1 0.690
FGFR3FGFR3 0.652 0.120 3 0.519
FRKFRK 0.652 0.132 -1 0.738
MAP2K7_TYRMAP2K7_TYR 0.652 -0.112 2 0.744
PDGFRBPDGFRB 0.652 0.093 3 0.522
KITKIT 0.651 0.087 3 0.506
TESK1_TYRTESK1_TYR 0.650 -0.104 3 0.420
FYNFYN 0.650 0.098 -1 0.679
LIMK1_TYRLIMK1_TYR 0.650 -0.064 2 0.725
CSKCSK 0.649 0.169 2 0.832
RETRET 0.649 0.016 1 0.575
PINK1_TYRPINK1_TYR 0.649 -0.118 1 0.682
FLT3FLT3 0.649 0.057 3 0.512
PDHK4_TYRPDHK4_TYR 0.649 -0.096 2 0.729
MATKMATK 0.648 0.098 -1 0.688
NTRK1NTRK1 0.648 0.090 -1 0.700
JAK2JAK2 0.647 0.011 1 0.551
LYNLYN 0.647 0.067 3 0.466
FGFR4FGFR4 0.647 0.169 -1 0.677
DDR2DDR2 0.647 0.085 3 0.554
SRCSRC 0.646 0.083 -1 0.681
WEE1_TYRWEE1_TYR 0.645 0.015 -1 0.763
NTRK3NTRK3 0.645 0.107 -1 0.672
TNK1TNK1 0.645 0.008 3 0.467
NTRK2NTRK2 0.645 0.075 3 0.502
INSRINSR 0.645 0.049 3 0.456
CK1G1CK1G1 0.644 -0.005 -3 0.530
TYK2TYK2 0.642 -0.071 1 0.560
FGRFGR 0.642 -0.010 1 0.697
PTK6PTK6 0.641 -0.020 -1 0.725
IGF1RIGF1R 0.641 0.065 3 0.440
PDGFRAPDGFRA 0.640 0.018 3 0.529
ERBB2ERBB2 0.640 0.030 1 0.561
ERBB4ERBB4 0.639 0.088 1 0.560
JAK3JAK3 0.639 -0.046 1 0.568
EGFREGFR 0.638 0.095 1 0.487
FLT4FLT4 0.637 0.013 3 0.476
CK1ACK1A 0.637 0.067 -3 0.385
JAK1JAK1 0.636 0.018 1 0.476
SYKSYK 0.633 0.089 -1 0.620
CK1G3CK1G3 0.631 0.010 -3 0.338
FLT1FLT1 0.629 -0.035 -1 0.652
MUSKMUSK 0.627 -0.007 1 0.480
NEK10_TYRNEK10_TYR 0.621 -0.139 1 0.486
CK1G2CK1G2 0.620 -0.006 -3 0.439
TNNI3K_TYRTNNI3K_TYR 0.615 -0.137 1 0.564
ZAP70ZAP70 0.615 0.046 -1 0.623