Motif 990 (n=76)
Position-wise Probabilities
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uniprot | genes | site | source | protein | function |
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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}. |
Download
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 |
---|---|---|---|---|
DAPK2 |
0.739 | 0.176 | -3 | 0.877 |
SKMLCK |
0.736 | 0.179 | -2 | 0.849 |
DAPK3 |
0.735 | 0.174 | -3 | 0.837 |
CAMLCK |
0.732 | 0.118 | -2 | 0.845 |
DAPK1 |
0.732 | 0.179 | -3 | 0.818 |
NLK |
0.730 | 0.112 | 1 | 0.725 |
CAMK1B |
0.730 | 0.149 | -3 | 0.880 |
MOS |
0.729 | 0.073 | 1 | 0.784 |
ALK4 |
0.725 | 0.081 | -2 | 0.712 |
VRK2 |
0.725 | -0.022 | 1 | 0.692 |
BMPR1B |
0.725 | 0.153 | 1 | 0.810 |
PRPK |
0.724 | 0.019 | -1 | 0.733 |
BMPR2 |
0.723 | -0.040 | -2 | 0.777 |
NIK |
0.723 | 0.005 | -3 | 0.883 |
ICK |
0.722 | 0.107 | -3 | 0.860 |
PKR |
0.721 | -0.023 | 1 | 0.662 |
P38A |
0.721 | 0.120 | 1 | 0.647 |
PRP4 |
0.721 | 0.101 | -3 | 0.761 |
GAK |
0.720 | 0.023 | 1 | 0.738 |
SMMLCK |
0.720 | 0.105 | -3 | 0.841 |
TGFBR1 |
0.720 | 0.092 | -2 | 0.678 |
MEK1 |
0.720 | -0.032 | 2 | 0.693 |
CDKL1 |
0.720 | 0.071 | -3 | 0.833 |
P38B |
0.719 | 0.121 | 1 | 0.594 |
PAK1 |
0.718 | 0.171 | -2 | 0.824 |
DRAK1 |
0.718 | 0.135 | 1 | 0.716 |
ACVR2B |
0.718 | 0.099 | -2 | 0.677 |
JNK2 |
0.718 | 0.108 | 1 | 0.604 |
BMPR1A |
0.718 | 0.138 | 1 | 0.788 |
COT |
0.718 | 0.099 | 2 | 0.754 |
ERK5 |
0.717 | 0.059 | 1 | 0.672 |
CAMK2G |
0.717 | 0.080 | 2 | 0.821 |
ATR |
0.717 | -0.005 | 1 | 0.667 |
RIPK3 |
0.716 | 0.023 | 3 | 0.435 |
ANKRD3 |
0.716 | -0.057 | 1 | 0.648 |
BRAF |
0.715 | -0.023 | -4 | 0.714 |
MYLK4 |
0.715 | 0.123 | -2 | 0.806 |
HIPK1 |
0.715 | 0.119 | 1 | 0.670 |
CDC7 |
0.714 | 0.069 | 1 | 0.793 |
PAK2 |
0.714 | 0.114 | -2 | 0.811 |
JNK3 |
0.714 | 0.085 | 1 | 0.628 |
PASK |
0.713 | 0.048 | -3 | 0.855 |
ALK2 |
0.713 | 0.045 | -2 | 0.682 |
GRK6 |
0.713 | 0.019 | 1 | 0.730 |
ACVR2A |
0.712 | 0.068 | -2 | 0.655 |
DYRK2 |
0.712 | 0.106 | 1 | 0.659 |
CDK5 |
0.712 | 0.081 | 1 | 0.688 |
RAF1 |
0.712 | -0.062 | 1 | 0.644 |
DYRK1A |
0.712 | 0.118 | 1 | 0.672 |
PIM3 |
0.711 | 0.080 | -3 | 0.860 |
LATS1 |
0.711 | 0.035 | -3 | 0.869 |
P38D |
0.711 | 0.121 | 1 | 0.566 |
VRK1 |
0.711 | -0.051 | 2 | 0.728 |
P38G |
0.710 | 0.104 | 1 | 0.571 |
PAK3 |
0.710 | 0.128 | -2 | 0.830 |
MLK2 |
0.710 | -0.035 | 2 | 0.632 |
PIM1 |
0.710 | 0.080 | -3 | 0.821 |
ERK2 |
0.710 | 0.071 | 1 | 0.629 |
TSSK2 |
0.710 | 0.037 | -5 | 0.700 |
RIPK1 |
0.710 | -0.010 | 1 | 0.620 |
CDK14 |
0.710 | 0.107 | 1 | 0.644 |
MPSK1 |
0.709 | 0.023 | 1 | 0.675 |
PDK1 |
0.709 | -0.016 | 1 | 0.578 |
DLK |
0.709 | -0.105 | 1 | 0.658 |
DMPK1 |
0.709 | 0.119 | -3 | 0.804 |
HIPK3 |
0.709 | 0.118 | 1 | 0.630 |
PLK1 |
0.709 | 0.014 | -2 | 0.690 |
TAK1 |
0.709 | -0.041 | 1 | 0.641 |
HIPK4 |
0.709 | 0.090 | 1 | 0.714 |
MEK5 |
0.708 | -0.143 | 2 | 0.665 |
ALPHAK3 |
0.708 | 0.051 | -1 | 0.687 |
ROCK2 |
0.708 | 0.090 | -3 | 0.813 |
JNK1 |
0.708 | 0.086 | 1 | 0.618 |
DCAMKL2 |
0.708 | 0.141 | -3 | 0.846 |
TAO2 |
0.708 | -0.072 | 2 | 0.684 |
CDK18 |
0.707 | 0.129 | 1 | 0.619 |
TTK |
0.707 | 0.015 | -2 | 0.688 |
NEK5 |
0.707 | -0.067 | 1 | 0.625 |
WNK4 |
0.707 | -0.027 | -2 | 0.837 |
P70S6KB |
0.707 | 0.072 | -3 | 0.831 |
WNK3 |
0.707 | -0.021 | 1 | 0.598 |
MASTL |
0.707 | -0.086 | -2 | 0.771 |
CLK3 |
0.707 | 0.065 | 1 | 0.765 |
TAO3 |
0.707 | -0.051 | 1 | 0.597 |
LRRK2 |
0.707 | -0.093 | 2 | 0.707 |
CDK17 |
0.707 | 0.113 | 1 | 0.585 |
TLK2 |
0.707 | -0.009 | 1 | 0.616 |
CDK7 |
0.707 | 0.101 | 1 | 0.664 |
GRK5 |
0.707 | -0.054 | -3 | 0.828 |
CDKL5 |
0.707 | 0.071 | -3 | 0.824 |
MEKK2 |
0.706 | -0.097 | 2 | 0.650 |
DCAMKL1 |
0.706 | 0.088 | -3 | 0.829 |
CHAK2 |
0.706 | -0.036 | -1 | 0.712 |
MAK |
0.706 | 0.141 | -2 | 0.748 |
DYRK1B |
0.706 | 0.104 | 1 | 0.651 |
WNK1 |
0.705 | -0.010 | -2 | 0.841 |
IRAK4 |
0.705 | -0.015 | 1 | 0.592 |
PBK |
0.705 | 0.032 | 1 | 0.645 |
GRK2 |
0.704 | 0.056 | -2 | 0.604 |
CDK8 |
0.704 | 0.105 | 1 | 0.640 |
ERK1 |
0.704 | 0.088 | 1 | 0.585 |
MLK3 |
0.704 | -0.009 | 2 | 0.589 |
MLK1 |
0.704 | -0.077 | 2 | 0.634 |
DYRK3 |
0.704 | 0.114 | 1 | 0.659 |
CLK4 |
0.703 | 0.098 | -3 | 0.815 |
HIPK2 |
0.703 | 0.120 | 1 | 0.614 |
PINK1 |
0.703 | -0.020 | 1 | 0.737 |
NEK8 |
0.702 | -0.104 | 2 | 0.674 |
MST3 |
0.702 | -0.060 | 2 | 0.626 |
MLK4 |
0.702 | -0.018 | 2 | 0.569 |
TSSK1 |
0.702 | 0.027 | -3 | 0.887 |
PDHK4 |
0.702 | -0.169 | 1 | 0.659 |
ATM |
0.702 | 0.005 | 1 | 0.618 |
PKCD |
0.702 | 0.030 | 2 | 0.644 |
PIM2 |
0.702 | 0.060 | -3 | 0.790 |
MAP3K15 |
0.702 | -0.052 | 1 | 0.529 |
LKB1 |
0.702 | -0.064 | -3 | 0.813 |
DYRK4 |
0.702 | 0.111 | 1 | 0.619 |
GSK3B |
0.701 | -0.031 | 4 | 0.234 |
MEKK6 |
0.701 | -0.066 | 1 | 0.579 |
STK33 |
0.701 | 0.130 | 2 | 0.775 |
TTBK2 |
0.701 | 0.099 | 2 | 0.777 |
PLK3 |
0.700 | 0.044 | 2 | 0.814 |
CDK2 |
0.700 | 0.040 | 1 | 0.703 |
AMPKA1 |
0.700 | -0.018 | -3 | 0.867 |
BIKE |
0.700 | 0.035 | 1 | 0.643 |
PKN3 |
0.700 | -0.001 | -3 | 0.857 |
PKACG |
0.700 | 0.099 | -2 | 0.804 |
GRK1 |
0.700 | 0.035 | -2 | 0.691 |
GSK3A |
0.699 | -0.011 | 4 | 0.236 |
IRE1 |
0.699 | -0.051 | 1 | 0.618 |
NEK11 |
0.699 | -0.108 | 1 | 0.583 |
TNIK |
0.699 | -0.090 | 3 | 0.398 |
NEK1 |
0.699 | -0.086 | 1 | 0.582 |
MINK |
0.699 | -0.099 | 1 | 0.560 |
MELK |
0.699 | 0.041 | -3 | 0.832 |
CAMKK1 |
0.699 | -0.118 | -2 | 0.700 |
MEKK1 |
0.699 | -0.143 | 1 | 0.588 |
MRCKB |
0.699 | 0.089 | -3 | 0.778 |
NEK9 |
0.699 | -0.087 | 2 | 0.658 |
HPK1 |
0.699 | -0.059 | 1 | 0.590 |
MEK2 |
0.699 | -0.089 | 2 | 0.658 |
TGFBR2 |
0.698 | -0.005 | -2 | 0.674 |
MEKK3 |
0.698 | -0.125 | 1 | 0.601 |
AURB |
0.698 | 0.090 | -2 | 0.716 |
MARK4 |
0.698 | -0.048 | 4 | 0.457 |
YSK4 |
0.698 | -0.108 | 1 | 0.554 |
SSTK |
0.698 | 0.036 | 4 | 0.442 |
CDK1 |
0.698 | 0.057 | 1 | 0.661 |
PKN2 |
0.698 | 0.019 | -3 | 0.845 |
CDK13 |
0.698 | 0.064 | 1 | 0.635 |
SGK3 |
0.697 | 0.081 | -3 | 0.786 |
CDK3 |
0.697 | 0.074 | 1 | 0.607 |
CDK16 |
0.697 | 0.090 | 1 | 0.602 |
PLK4 |
0.697 | 0.044 | 2 | 0.655 |
AKT2 |
0.697 | 0.090 | -3 | 0.745 |
CDK12 |
0.697 | 0.074 | 1 | 0.607 |
NDR1 |
0.697 | 0.053 | -3 | 0.854 |
GCK |
0.697 | -0.104 | 1 | 0.621 |
TBK1 |
0.697 | -0.056 | 1 | 0.485 |
MARK2 |
0.697 | -0.009 | 4 | 0.418 |
GRK7 |
0.697 | -0.016 | 1 | 0.669 |
MST2 |
0.697 | -0.083 | 1 | 0.601 |
RSK2 |
0.697 | 0.081 | -3 | 0.817 |
IRE2 |
0.697 | -0.064 | 2 | 0.634 |
SMG1 |
0.696 | 0.001 | 1 | 0.607 |
MOK |
0.696 | 0.093 | 1 | 0.673 |
YANK3 |
0.696 | 0.197 | 2 | 0.709 |
HGK |
0.696 | -0.107 | 3 | 0.404 |
BUB1 |
0.696 | 0.038 | -5 | 0.689 |
PKG2 |
0.695 | 0.105 | -2 | 0.751 |
ULK2 |
0.695 | -0.064 | 2 | 0.680 |
NEK4 |
0.695 | -0.122 | 1 | 0.558 |
ROCK1 |
0.695 | 0.069 | -3 | 0.790 |
CDK6 |
0.695 | 0.052 | 1 | 0.618 |
LOK |
0.695 | -0.055 | -2 | 0.790 |
ZAK |
0.695 | -0.122 | 1 | 0.555 |
NUAK2 |
0.695 | -0.016 | -3 | 0.861 |
CAMKK2 |
0.694 | -0.138 | -2 | 0.717 |
NIM1 |
0.694 | -0.028 | 3 | 0.417 |
AURA |
0.694 | 0.097 | -2 | 0.665 |
MYO3A |
0.694 | -0.057 | 1 | 0.569 |
CAMK2D |
0.694 | 0.031 | -3 | 0.852 |
DSTYK |
0.694 | -0.057 | 2 | 0.708 |
CDK4 |
0.693 | 0.056 | 1 | 0.602 |
HUNK |
0.693 | -0.095 | 2 | 0.718 |
PERK |
0.693 | -0.143 | -2 | 0.720 |
CAMK2B |
0.693 | 0.054 | 2 | 0.775 |
CAMK1D |
0.693 | 0.078 | -3 | 0.746 |
CAMK1G |
0.693 | 0.074 | -3 | 0.810 |
IRAK1 |
0.693 | -0.097 | -1 | 0.721 |
CHAK1 |
0.692 | -0.102 | 2 | 0.648 |
SRPK1 |
0.692 | 0.048 | -3 | 0.797 |
NEK7 |
0.692 | -0.091 | -3 | 0.793 |
EEF2K |
0.692 | -0.124 | 3 | 0.380 |
PKCZ |
0.692 | -0.024 | 2 | 0.624 |
MRCKA |
0.692 | 0.053 | -3 | 0.794 |
TLK1 |
0.691 | -0.089 | -2 | 0.700 |
CAMK4 |
0.691 | 0.003 | -3 | 0.842 |
NEK2 |
0.691 | -0.088 | 2 | 0.634 |
PDHK1 |
0.691 | -0.195 | 1 | 0.607 |
PLK2 |
0.691 | 0.091 | -3 | 0.786 |
MYO3B |
0.691 | -0.067 | 2 | 0.631 |
CLK1 |
0.691 | 0.089 | -3 | 0.796 |
CDK19 |
0.691 | 0.092 | 1 | 0.612 |
AURC |
0.691 | 0.102 | -2 | 0.716 |
OSR1 |
0.691 | -0.076 | 2 | 0.610 |
HASPIN |
0.690 | -0.003 | -1 | 0.635 |
QIK |
0.690 | -0.048 | -3 | 0.836 |
HRI |
0.690 | -0.171 | -2 | 0.748 |
GRK4 |
0.690 | -0.046 | -2 | 0.697 |
KHS1 |
0.690 | -0.094 | 1 | 0.543 |
IKKE |
0.690 | -0.081 | 1 | 0.480 |
KHS2 |
0.690 | -0.081 | 1 | 0.579 |
CHK1 |
0.690 | -0.029 | -3 | 0.839 |
PRKD3 |
0.690 | 0.057 | -3 | 0.793 |
P90RSK |
0.690 | 0.039 | -3 | 0.821 |
MST1 |
0.690 | -0.133 | 1 | 0.564 |
RSK3 |
0.689 | 0.069 | -3 | 0.814 |
CAMK2A |
0.689 | 0.055 | 2 | 0.756 |
MTOR |
0.689 | -0.121 | 1 | 0.601 |
ERK7 |
0.689 | -0.003 | 2 | 0.396 |
AMPKA2 |
0.689 | -0.026 | -3 | 0.842 |
MST4 |
0.688 | -0.064 | 2 | 0.622 |
MARK1 |
0.688 | -0.027 | 4 | 0.419 |
ASK1 |
0.688 | -0.105 | 1 | 0.521 |
CDK9 |
0.688 | 0.044 | 1 | 0.627 |
YSK1 |
0.688 | -0.108 | 2 | 0.613 |
MARK3 |
0.688 | -0.018 | 4 | 0.415 |
IKKB |
0.688 | -0.067 | -2 | 0.692 |
MSK1 |
0.687 | 0.071 | -3 | 0.780 |
PKCB |
0.687 | 0.001 | 2 | 0.563 |
NDR2 |
0.687 | 0.046 | -3 | 0.857 |
SGK1 |
0.687 | 0.082 | -3 | 0.667 |
GRK3 |
0.687 | 0.049 | -2 | 0.556 |
CDK10 |
0.687 | 0.068 | 1 | 0.643 |
SRPK3 |
0.686 | 0.010 | -3 | 0.772 |
FAM20C |
0.686 | 0.063 | 2 | 0.592 |
MAPKAPK3 |
0.686 | 0.018 | -3 | 0.808 |
PKACB |
0.685 | 0.097 | -2 | 0.745 |
PKCH |
0.685 | -0.029 | 2 | 0.579 |
MSK2 |
0.685 | 0.050 | -3 | 0.782 |
PKCG |
0.685 | -0.002 | 2 | 0.621 |
AKT1 |
0.685 | 0.070 | -3 | 0.753 |
QSK |
0.685 | -0.029 | 4 | 0.431 |
CLK2 |
0.685 | 0.087 | -3 | 0.808 |
MNK2 |
0.684 | 0.048 | -2 | 0.819 |
CK2A2 |
0.684 | 0.029 | 1 | 0.750 |
PRKD2 |
0.684 | 0.063 | -3 | 0.816 |
RSK4 |
0.684 | 0.074 | -3 | 0.789 |
IKKA |
0.684 | -0.020 | -2 | 0.658 |
SNRK |
0.683 | -0.020 | 2 | 0.675 |
PKCA |
0.683 | -0.017 | 2 | 0.570 |
AAK1 |
0.683 | 0.043 | 1 | 0.567 |
CRIK |
0.683 | 0.050 | -3 | 0.749 |
PRKD1 |
0.683 | 0.019 | -3 | 0.849 |
YANK2 |
0.683 | 0.168 | 2 | 0.717 |
NEK6 |
0.682 | -0.099 | -2 | 0.746 |
TTBK1 |
0.682 | 0.117 | 2 | 0.802 |
SLK |
0.682 | -0.095 | -2 | 0.723 |
GCN2 |
0.682 | -0.112 | 2 | 0.651 |
BRSK1 |
0.681 | 0.025 | -3 | 0.829 |
LATS2 |
0.681 | 0.021 | -5 | 0.753 |
PKCE |
0.680 | 0.013 | 2 | 0.585 |
ULK1 |
0.680 | -0.095 | -3 | 0.796 |
NEK3 |
0.680 | -0.078 | 1 | 0.508 |
TAO1 |
0.680 | -0.107 | 1 | 0.483 |
P70S6K |
0.680 | 0.039 | -3 | 0.749 |
MNK1 |
0.680 | 0.024 | -2 | 0.822 |
PKCI |
0.680 | -0.015 | 2 | 0.589 |
CK2A1 |
0.680 | 0.028 | 1 | 0.736 |
SIK |
0.680 | -0.010 | -3 | 0.802 |
CAMK1A |
0.680 | 0.075 | -3 | 0.715 |
SRPK2 |
0.680 | 0.049 | -3 | 0.735 |
DNAPK |
0.679 | -0.073 | 1 | 0.477 |
CHK2 |
0.679 | 0.039 | -3 | 0.699 |
CK1A2 |
0.679 | 0.038 | -3 | 0.473 |
TNK2 |
0.679 | 0.309 | 3 | 0.569 |
PKCT |
0.678 | -0.008 | 2 | 0.585 |
RIPK2 |
0.677 | -0.128 | 1 | 0.498 |
PTK2B |
0.677 | 0.316 | -1 | 0.728 |
PAK6 |
0.677 | 0.072 | -2 | 0.760 |
PKACA |
0.677 | 0.097 | -2 | 0.706 |
STLK3 |
0.676 | -0.129 | 1 | 0.522 |
KIS |
0.676 | 0.072 | 1 | 0.643 |
MERTK |
0.675 | 0.279 | 3 | 0.512 |
MAPKAPK5 |
0.674 | 0.021 | -3 | 0.759 |
MAPKAPK2 |
0.674 | 0.033 | -3 | 0.775 |
CK1D |
0.673 | 0.019 | -3 | 0.469 |
EPHA6 |
0.673 | 0.258 | -1 | 0.709 |
SBK |
0.672 | 0.062 | -3 | 0.646 |
BRSK2 |
0.672 | -0.039 | -3 | 0.841 |
AKT3 |
0.672 | 0.077 | -3 | 0.686 |
PAK5 |
0.672 | 0.075 | -2 | 0.723 |
PHKG1 |
0.672 | -0.048 | -3 | 0.851 |
NUAK1 |
0.671 | -0.036 | -3 | 0.829 |
CK1E |
0.671 | 0.014 | -3 | 0.524 |
EPHB4 |
0.670 | 0.270 | -1 | 0.711 |
PAK4 |
0.670 | 0.080 | -2 | 0.710 |
SRMS |
0.670 | 0.249 | 1 | 0.725 |
TXK |
0.669 | 0.208 | 1 | 0.769 |
LTK |
0.668 | 0.212 | 3 | 0.560 |
EPHB1 |
0.667 | 0.259 | 1 | 0.682 |
EPHA4 |
0.667 | 0.247 | 2 | 0.819 |
EPHB2 |
0.666 | 0.267 | -1 | 0.691 |
BMX |
0.666 | 0.184 | -1 | 0.758 |
EPHA7 |
0.666 | 0.278 | 2 | 0.817 |
TYRO3 |
0.666 | 0.166 | 3 | 0.487 |
ITK |
0.666 | 0.207 | -1 | 0.755 |
PRKX |
0.666 | 0.093 | -3 | 0.723 |
AXL |
0.665 | 0.199 | 3 | 0.509 |
PKG1 |
0.665 | 0.094 | -2 | 0.706 |
PKN1 |
0.664 | 0.009 | -3 | 0.767 |
ABL2 |
0.664 | 0.129 | -1 | 0.747 |
ALK |
0.664 | 0.192 | 3 | 0.570 |
BCKDK |
0.664 | -0.202 | -1 | 0.645 |
EPHB3 |
0.662 | 0.227 | -1 | 0.707 |
YES1 |
0.662 | 0.105 | -1 | 0.708 |
PDHK3_TYR |
0.662 | 0.023 | 4 | 0.460 |
EPHA1 |
0.662 | 0.215 | 3 | 0.564 |
ABL1 |
0.662 | 0.122 | -1 | 0.744 |
FER |
0.661 | 0.125 | 1 | 0.733 |
EPHA3 |
0.661 | 0.234 | 2 | 0.815 |
INSRR |
0.661 | 0.132 | 3 | 0.496 |
EPHA5 |
0.660 | 0.237 | 2 | 0.798 |
EPHA8 |
0.660 | 0.242 | -1 | 0.688 |
BLK |
0.660 | 0.137 | -1 | 0.700 |
TEC |
0.660 | 0.122 | -1 | 0.761 |
TEK |
0.660 | 0.143 | 3 | 0.504 |
PHKG2 |
0.659 | -0.039 | -3 | 0.832 |
MST1R |
0.659 | 0.121 | 3 | 0.521 |
CSF1R |
0.657 | 0.100 | 3 | 0.506 |
LCK |
0.657 | 0.109 | -1 | 0.715 |
BMPR2_TYR |
0.657 | 0.069 | -1 | 0.690 |
ROS1 |
0.656 | 0.077 | 3 | 0.492 |
FGFR2 |
0.656 | 0.132 | 3 | 0.522 |
MET |
0.656 | 0.138 | 3 | 0.538 |
HCK |
0.656 | 0.105 | -1 | 0.730 |
LIMK2_TYR |
0.656 | 0.044 | -3 | 0.873 |
PTK2 |
0.656 | 0.228 | -1 | 0.592 |
EPHA2 |
0.656 | 0.226 | -1 | 0.685 |
MAP2K6_TYR |
0.656 | -0.012 | -1 | 0.690 |
PKMYT1_TYR |
0.655 | -0.019 | 3 | 0.445 |
FGFR1 |
0.654 | 0.147 | 3 | 0.538 |
MAP2K4_TYR |
0.654 | -0.036 | -1 | 0.714 |
DDR1 |
0.653 | 0.042 | 4 | 0.415 |
BTK |
0.653 | 0.099 | -1 | 0.783 |
FES |
0.653 | 0.183 | -1 | 0.731 |
KDR |
0.653 | 0.089 | 3 | 0.539 |
PDHK1_TYR |
0.652 | -0.011 | -1 | 0.690 |
FGFR3 |
0.652 | 0.120 | 3 | 0.519 |
FRK |
0.652 | 0.132 | -1 | 0.738 |
MAP2K7_TYR |
0.652 | -0.112 | 2 | 0.744 |
PDGFRB |
0.652 | 0.093 | 3 | 0.522 |
KIT |
0.651 | 0.087 | 3 | 0.506 |
TESK1_TYR |
0.650 | -0.104 | 3 | 0.420 |
FYN |
0.650 | 0.098 | -1 | 0.679 |
LIMK1_TYR |
0.650 | -0.064 | 2 | 0.725 |
CSK |
0.649 | 0.169 | 2 | 0.832 |
RET |
0.649 | 0.016 | 1 | 0.575 |
PINK1_TYR |
0.649 | -0.118 | 1 | 0.682 |
FLT3 |
0.649 | 0.057 | 3 | 0.512 |
PDHK4_TYR |
0.649 | -0.096 | 2 | 0.729 |
MATK |
0.648 | 0.098 | -1 | 0.688 |
NTRK1 |
0.648 | 0.090 | -1 | 0.700 |
JAK2 |
0.647 | 0.011 | 1 | 0.551 |
LYN |
0.647 | 0.067 | 3 | 0.466 |
FGFR4 |
0.647 | 0.169 | -1 | 0.677 |
DDR2 |
0.647 | 0.085 | 3 | 0.554 |
SRC |
0.646 | 0.083 | -1 | 0.681 |
WEE1_TYR |
0.645 | 0.015 | -1 | 0.763 |
NTRK3 |
0.645 | 0.107 | -1 | 0.672 |
TNK1 |
0.645 | 0.008 | 3 | 0.467 |
NTRK2 |
0.645 | 0.075 | 3 | 0.502 |
INSR |
0.645 | 0.049 | 3 | 0.456 |
CK1G1 |
0.644 | -0.005 | -3 | 0.530 |
TYK2 |
0.642 | -0.071 | 1 | 0.560 |
FGR |
0.642 | -0.010 | 1 | 0.697 |
PTK6 |
0.641 | -0.020 | -1 | 0.725 |
IGF1R |
0.641 | 0.065 | 3 | 0.440 |
PDGFRA |
0.640 | 0.018 | 3 | 0.529 |
ERBB2 |
0.640 | 0.030 | 1 | 0.561 |
ERBB4 |
0.639 | 0.088 | 1 | 0.560 |
JAK3 |
0.639 | -0.046 | 1 | 0.568 |
EGFR |
0.638 | 0.095 | 1 | 0.487 |
FLT4 |
0.637 | 0.013 | 3 | 0.476 |
CK1A |
0.637 | 0.067 | -3 | 0.385 |
JAK1 |
0.636 | 0.018 | 1 | 0.476 |
SYK |
0.633 | 0.089 | -1 | 0.620 |
CK1G3 |
0.631 | 0.010 | -3 | 0.338 |
FLT1 |
0.629 | -0.035 | -1 | 0.652 |
MUSK |
0.627 | -0.007 | 1 | 0.480 |
NEK10_TYR |
0.621 | -0.139 | 1 | 0.486 |
CK1G2 |
0.620 | -0.006 | -3 | 0.439 |
TNNI3K_TYR |
0.615 | -0.137 | 1 | 0.564 |
ZAP70 |
0.615 | 0.046 | -1 | 0.623 |