Motif 982 (n=85)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A6NNZ2 | TUBB8B | T274 | ochoa | Tubulin beta 8B | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| O14920 | IKBKB | S181 | psp | Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK-2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:9346484}. |
| O14965 | AURKA | T288 | ochoa|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}. |
| O15111 | CHUK | S180 | psp | Inhibitor of nuclear factor kappa-B kinase subunit alpha (I-kappa-B kinase alpha) (IKK-A) (IKK-alpha) (IkBKA) (IkappaB kinase) (EC 2.7.11.10) (Conserved helix-loop-helix ubiquitous kinase) (I-kappa-B kinase 1) (IKK-1) (IKK1) (Nuclear factor NF-kappa-B inhibitor kinase alpha) (NFKBIKA) (Transcription factor 16) (TCF-16) | Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues (PubMed:18626576, PubMed:35952808, PubMed:9244310, PubMed:9252186, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18626576, PubMed:9244310, PubMed:9252186, PubMed:9346484). Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11) (PubMed:21765415). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes (PubMed:20501937). In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Also participates in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities (PubMed:17434128). Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP (PubMed:12789342). Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates AMBRA1 following mitophagy induction, promoting AMBRA1 interaction with ATG8 family proteins and its mitophagic activity (PubMed:30217973). {ECO:0000250|UniProtKB:Q60680, ECO:0000269|PubMed:12789342, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17434128, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20501937, ECO:0000269|PubMed:21765415, ECO:0000269|PubMed:30217973, ECO:0000269|PubMed:35952808, ECO:0000269|PubMed:9244310, ECO:0000269|PubMed:9252186, ECO:0000269|PubMed:9346484, ECO:0000303|PubMed:18626576}. |
| O43781 | DYRK3 | T368 | ochoa | Dual specificity tyrosine-phosphorylation-regulated kinase 3 (EC 2.7.12.1) (Regulatory erythroid kinase) (REDK) | Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:29634919, PubMed:9748265). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity and apoptosis (PubMed:20167603). {ECO:0000269|PubMed:10779429, ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919, ECO:0000269|PubMed:29973724, ECO:0000269|PubMed:9748265}. |
| O43930 | PRKY | T203 | ochoa | Putative serine/threonine-protein kinase PRKY (EC 2.7.11.1) | None |
| O60285 | NUAK1 | T211 | psp | NUAK family SNF1-like kinase 1 (EC 2.7.11.1) (AMPK-related protein kinase 5) (ARK5) (Omphalocele kinase 1) | Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171, ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}. |
| O75116 | ROCK2 | T249 | psp | Rho-associated protein kinase 2 (EC 2.7.11.1) (Rho kinase 2) (Rho-associated, coiled-coil-containing protein kinase 2) (Rho-associated, coiled-coil-containing protein kinase II) (ROCK-II) (p164 ROCK-2) | Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation. {ECO:0000269|PubMed:10579722, ECO:0000269|PubMed:15699075, ECO:0000269|PubMed:16574662, ECO:0000269|PubMed:17015463, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21147781}. |
| O75676 | RPS6KA4 | S196 | ochoa|psp | Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| O75676 | RPS6KA4 | T568 | psp | Ribosomal protein S6 kinase alpha-4 (S6K-alpha-4) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 4) (Nuclear mitogen- and stress-activated protein kinase 2) (Ribosomal protein kinase B) (RSKB) | Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors. {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393, ECO:0000269|PubMed:9792677}. |
| O94806 | PRKD3 | S735 | ochoa|psp | Serine/threonine-protein kinase D3 (EC 2.7.11.13) (Protein kinase C nu type) (Protein kinase EPK2) (nPKC-nu) | Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress (By similarity). {ECO:0000250}. |
| O95747 | OXSR1 | T185 | ochoa|psp | Serine/threonine-protein kinase OSR1 (EC 2.7.11.1) (Oxidative stress-responsive 1 protein) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:17721439, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:17721439). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (PubMed:23386621, PubMed:25362046). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (PubMed:29581290). Phosphorylates RELL1, RELL2 and RELT (PubMed:16389068, PubMed:28688764). Phosphorylates PAK1 (PubMed:14707132). Phosphorylates PLSCR1 in the presence of RELT (PubMed:22052202). {ECO:0000269|PubMed:14707132, ECO:0000269|PubMed:16389068, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:17721439, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:22052202, ECO:0000269|PubMed:23386621, ECO:0000269|PubMed:25362046, ECO:0000269|PubMed:28688764, ECO:0000269|PubMed:29581290, ECO:0000269|PubMed:34289367}. |
| O95835 | LATS1 | S909 | ochoa|psp | Serine/threonine-protein kinase LATS1 (EC 2.7.11.1) (Large tumor suppressor homolog 1) (WARTS protein kinase) (h-warts) | Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:10518011, PubMed:10831611, PubMed:18158288, PubMed:26437443, PubMed:28068668). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288, PubMed:26437443, PubMed:28068668). Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288, PubMed:26437443, PubMed:28068668). Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint (PubMed:15122335, PubMed:19927127). Negatively regulates G2/M transition by down-regulating CDK1 kinase activity (PubMed:9988268). Involved in the control of p53 expression (PubMed:15122335). Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1 (PubMed:15220930). May also play a role in endocrine function. Plays a role in mammary gland epithelial cell differentiation, both through the Hippo signaling pathway and the intracellular estrogen receptor signaling pathway by promoting the degradation of ESR1 (PubMed:28068668). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10518011, ECO:0000269|PubMed:10831611, ECO:0000269|PubMed:15122335, ECO:0000269|PubMed:15220930, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:28068668, ECO:0000269|PubMed:39173637, ECO:0000269|PubMed:9988268}. |
| O96017 | CHEK2 | T383 | ochoa|psp | Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T] (PubMed:37943659). Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}. |
| P04350 | TUBB4A | T274 | ochoa | Tubulin beta-4A chain (Tubulin 5 beta) (Tubulin beta-4 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P07437 | TUBB | T274 | ochoa | Tubulin beta chain (Tubulin beta-5 chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH7 | TUBA3C | T56 | ochoa | Tubulin alpha-3C chain (EC 3.6.5.-) (Alpha-tubulin 2) (Alpha-tubulin 3C) (Tubulin alpha-2 chain) [Cleaved into: Detyrosinated tubulin alpha-3C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P0DPH8 | TUBA3D | T56 | ochoa | Tubulin alpha-3D chain (EC 3.6.5.-) (Alpha-tubulin 3D) [Cleaved into: Detyrosinated tubulin alpha-3D chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| P17612 | PRKACA | T198 | ochoa|psp | cAMP-dependent protein kinase catalytic subunit alpha (PKA C-alpha) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:31112131). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+) (PubMed:17693412). PSMC5/RPT6 activation by phosphorylation stimulates proteasome (PubMed:17565987). Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation (PubMed:15905176). NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding (PubMed:15642694). Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes (By similarity). GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane (By similarity). Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis (PubMed:33934390). Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation (By similarity). May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). Phosphorylates APOBEC3G and AICDA (PubMed:16387847, PubMed:18836454). Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock (PubMed:21085490). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000250|UniProtKB:P05132, ECO:0000250|UniProtKB:P27791, ECO:0000269|PubMed:15642694, ECO:0000269|PubMed:15905176, ECO:0000269|PubMed:16387847, ECO:0000269|PubMed:17333334, ECO:0000269|PubMed:17565987, ECO:0000269|PubMed:17693412, ECO:0000269|PubMed:18836454, ECO:0000269|PubMed:19949837, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21514275, ECO:0000269|PubMed:21812984, ECO:0000269|PubMed:31112131, ECO:0000269|PubMed:33934390}.; FUNCTION: [Isoform 2]: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. {ECO:0000250|UniProtKB:P05132}. |
| P22612 | PRKACG | T198 | ochoa | cAMP-dependent protein kinase catalytic subunit gamma (PKA C-gamma) (EC 2.7.11.11) | Phosphorylates a large number of substrates in the cytoplasm and the nucleus. |
| P22694 | PRKACB | T198 | ochoa | cAMP-dependent protein kinase catalytic subunit beta (PKA C-beta) (EC 2.7.11.11) | Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs (PubMed:12420224, PubMed:21423175, PubMed:31112131). PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux (PubMed:12420224, PubMed:21423175). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131). {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142, ECO:0000269|PubMed:31112131}. |
| P27448 | MARK3 | T211 | ochoa|psp | MAP/microtubule affinity-regulating kinase 3 (EC 2.7.11.1) (C-TAK1) (cTAK1) (Cdc25C-associated protein kinase 1) (ELKL motif kinase 2) (EMK-2) (Protein kinase STK10) (Ser/Thr protein kinase PAR-1) (Par-1a) (Serine/threonine-protein kinase p78) | Serine/threonine-protein kinase (PubMed:16822840, PubMed:16980613, PubMed:23666762). Involved in the specific phosphorylation of microtubule-associated proteins for MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Phosphorylates CDC25C on 'Ser-216' (PubMed:12941695). Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Regulates localization and activity of MITF by mediating its phosphorylation, promoting subsequent interaction between MITF and 14-3-3 and retention in the cytosol (PubMed:16822840). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714). Phosphorylates PKP2 and KSR1 (PubMed:12941695). {ECO:0000269|PubMed:12941695, ECO:0000269|PubMed:16822840, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:28087714}. |
| P36507 | MAP2K2 | S226 | ochoa|psp | Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2) | Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity). Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). {ECO:0000250|UniProtKB:Q63932, ECO:0000269|PubMed:29433126}. |
| P49137 | MAPKAPK2 | T222 | ochoa|psp | 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 | T338 | 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}. |
| P51817 | PRKX | T203 | ochoa | cAMP-dependent protein kinase catalytic subunit PRKX (PrKX) (Protein kinase X) (Protein kinase X-linked) (Serine/threonine-protein kinase PRKX) (EC 2.7.11.1) (Protein kinase PKX1) | Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation. {ECO:0000269|PubMed:12082174, ECO:0000269|PubMed:16236808, ECO:0000269|PubMed:16491121, ECO:0000269|PubMed:17980165, ECO:0000269|PubMed:19367327, ECO:0000269|PubMed:21684272, ECO:0000269|PubMed:9860982}. |
| P53671 | LIMK2 | T505 | psp | LIM domain kinase 2 (LIMK-2) (EC 2.7.11.1) | Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics (PubMed:10436159, PubMed:11018042). Acts downstream of several Rho family GTPase signal transduction pathways (PubMed:10436159, PubMed:11018042). Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP (PubMed:22328514). Displays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro (PubMed:8537403). Suppresses ciliogenesis via multiple pathways; phosphorylation of CFL1, suppression of directional trafficking of ciliary vesicles to the ciliary base, and by facilitating YAP1 nuclear localization where it acts as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). {ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:22328514, ECO:0000269|PubMed:25849865, ECO:0000269|PubMed:8537403}. |
| P54646 | PRKAA2 | T172 | ochoa|psp | 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK subunit alpha-2) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (PubMed:7959015). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation (By similarity). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). Upon glucose starvation, promotes ARF6 activation in a kinase-independent manner leading to cell migration (PubMed:36017701). Upon glucose deprivation mediates the phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear localization signal of ACSS2, required for its interaction with KPNA1 and nuclear translocation (PubMed:28552616). Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:Q09137, ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36017701, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:7959015, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| P57059 | SIK1 | T182 | psp | Serine/threonine-protein kinase SIK1 (EC 2.7.11.1) (Salt-inducible kinase 1) (SIK-1) (Serine/threonine-protein kinase SNF1-like kinase 1) (Serine/threonine-protein kinase SNF1LK) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348). Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832, ECO:0000269|PubMed:29211348}. |
| P68363 | TUBA1B | T56 | ochoa | Tubulin alpha-1B chain (EC 3.6.5.-) (Alpha-tubulin ubiquitous) (Tubulin K-alpha-1) (Tubulin alpha-ubiquitous chain) [Cleaved into: Detyrosinated tubulin alpha-1B chain] | Tubulin is the major constituent of microtubules, protein filaments consisting of alpha- and beta-tubulin heterodimers (PubMed:38305685, PubMed:34996871, PubMed:38609661). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:38305685, PubMed:34996871, PubMed:38609661). Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871, PubMed:38609661). {ECO:0000269|PubMed:34996871, ECO:0000269|PubMed:38305685, ECO:0000269|PubMed:38609661}. |
| P68371 | TUBB4B | T274 | ochoa | Tubulin beta-4B chain (Tubulin beta-2 chain) (Tubulin beta-2C chain) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q02750 | MAP2K1 | S222 | ochoa|psp | Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (PubMed:29433126). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of 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. {ECO:0000269|PubMed:14737111, ECO:0000269|PubMed:17101779, ECO:0000269|PubMed:29433126}. |
| Q13131 | PRKAA1 | T183 | ochoa|psp | 5'-AMP-activated protein kinase catalytic subunit alpha-1 (AMPK subunit alpha-1) (EC 2.7.11.1) (Acetyl-CoA carboxylase kinase) (ACACA kinase) (Hydroxymethylglutaryl-CoA reductase kinase) (HMGCR kinase) (EC 2.7.11.31) (Tau-protein kinase PRKAA1) (EC 2.7.11.26) | Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357, PubMed:24563466, PubMed:37821951). In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively (By similarity). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160 (By similarity). Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2 (PubMed:14651849, PubMed:18439900, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process, it also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q5EG47, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:24563466, ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:32029622, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36367943, ECO:0000269|PubMed:36732624, ECO:0000269|PubMed:37079666, ECO:0000269|PubMed:37821951, ECO:0000303|PubMed:17307971, ECO:0000303|PubMed:17712357}. |
| Q13163 | MAP2K5 | T315 | psp | Dual specificity mitogen-activated protein kinase kinase 5 (MAP kinase kinase 5) (MAPKK 5) (EC 2.7.12.2) (MAPK/ERK kinase 5) (MEK 5) | Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). {ECO:0000250|UniProtKB:Q62862, ECO:0000269|PubMed:7759517, ECO:0000269|PubMed:9384584}. |
| Q13873 | BMPR2 | S375 | ochoa | Bone morphogenetic protein receptor type-2 (BMP type-2 receptor) (BMPR-2) (EC 2.7.11.30) (Bone morphogenetic protein receptor type II) (BMP type II receptor) (BMPR-II) | On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Can also mediate signaling through the activation of the p38MAPK cascade (PubMed:12045205). Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but enhanced by the presence of type I receptors for BMPs. Mediates induction of adipogenesis by GDF6. Promotes signaling also by binding to activin A/INHBA (PubMed:24018044). {ECO:0000250|UniProtKB:O35607, ECO:0000269|PubMed:12045205, ECO:0000269|PubMed:24018044}. |
| Q13885 | TUBB2A | T274 | ochoa | Tubulin beta-2A chain (Tubulin beta class IIa) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q13976 | PRKG1 | T517 | ochoa|psp | cGMP-dependent protein kinase 1 (cGK 1) (cGK1) (EC 2.7.11.12) (cGMP-dependent protein kinase I) (cGKI) | Serine/threonine protein kinase that acts as a key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates IRAG1 and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling also alters gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle. {ECO:0000269|PubMed:10567269, ECO:0000269|PubMed:11162591, ECO:0000269|PubMed:11723116, ECO:0000269|PubMed:12082086, ECO:0000269|PubMed:14608379, ECO:0000269|PubMed:15194681, ECO:0000269|PubMed:16990611, ECO:0000269|PubMed:8182057}. |
| Q14012 | CAMK1 | T177 | ochoa|psp | 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}. |
| Q14680 | MELK | T167 | psp | Maternal embryonic leucine zipper kinase (hMELK) (EC 2.7.11.1) (Protein kinase Eg3) (pEg3 kinase) (Protein kinase PK38) (hPK38) (Tyrosine-protein kinase MELK) (EC 2.7.10.2) | Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Has a broad substrate specificity; phosphorylates BCL2L14, CDC25B, MAP3K5/ASK1 and ZNF622. Acts as an activator of apoptosis by phosphorylating and activating MAP3K5/ASK1. Acts as a regulator of cell cycle, notably by mediating phosphorylation of CDC25B, promoting localization of CDC25B to the centrosome and the spindle poles during mitosis. Plays a key role in cell proliferation and carcinogenesis. Required for proliferation of embryonic and postnatal multipotent neural progenitors. Phosphorylates and inhibits BCL2L14, possibly leading to affect mammary carcinogenesis by mediating inhibition of the pro-apoptotic function of BCL2L14. Also involved in the inhibition of spliceosome assembly during mitosis by phosphorylating ZNF622, thereby contributing to its redirection to the nucleus. May also play a role in primitive hematopoiesis. {ECO:0000269|PubMed:11802789, ECO:0000269|PubMed:12400006, ECO:0000269|PubMed:14699119, ECO:0000269|PubMed:15908796, ECO:0000269|PubMed:16216881, ECO:0000269|PubMed:17280616}. |
| Q15139 | PRKD1 | S742 | ochoa|psp | Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response (PubMed:10764790, PubMed:12505989, PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, PubMed:19211839). Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation (PubMed:10523301). Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1 (PubMed:12505989). Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2 (PubMed:18509061). In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling (PubMed:18332134). Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation (PubMed:19211839). In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents (PubMed:10764790). In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity). May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}. |
| Q15208 | STK38 | S281 | ochoa|psp | Serine/threonine-protein kinase 38 (EC 2.7.11.1) (NDR1 protein kinase) (Nuclear Dbf2-related kinase 1) | Serine/threonine-protein kinase that acts as a negative regulator of MAP3K1/2 signaling (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441). Converts MAP3K2 from its phosphorylated form to its non-phosphorylated form and inhibits autophosphorylation of MAP3K2 (PubMed:12493777, PubMed:15197186, PubMed:17906693, PubMed:7761441). Acts as an ufmylation 'reader' in a kinase-independent manner: specifically recognizes and binds mono-ufmylated histone H4 in response to DNA damage, promoting the recruitment of SUV39H1 to the double-strand breaks, resulting in ATM activation (PubMed:32537488). {ECO:0000269|PubMed:12493777, ECO:0000269|PubMed:15197186, ECO:0000269|PubMed:17906693, ECO:0000269|PubMed:32537488, ECO:0000269|PubMed:7761441}. |
| Q16566 | CAMK4 | T200 | ochoa|psp | Calcium/calmodulin-dependent protein kinase type IV (CaMK IV) (EC 2.7.11.17) (CaM kinase-GR) | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. In the thymus, regulates the CD4(+)/CD8(+) double positive thymocytes selection threshold during T-cell ontogeny. In CD4 memory T-cells, is required to link T-cell antigen receptor (TCR) signaling to the production of IL2, IFNG and IL4 (through the regulation of CREB and MEF2). Regulates the differentiation and survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2. Phosphorylates the transcription activator CREB1 on 'Ser-133' in hippocampal neuron nuclei and contribute to memory consolidation and long term potentiation (LTP) in the hippocampus. Can activate the MAP kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate transcription through the phosphorylation of ELK1 and ATF2. Can also phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18. {ECO:0000269|PubMed:10617605, ECO:0000269|PubMed:17909078, ECO:0000269|PubMed:18829949, ECO:0000269|PubMed:7961813, ECO:0000269|PubMed:8065343, ECO:0000269|PubMed:8855261, ECO:0000269|PubMed:8980227, ECO:0000269|PubMed:9154845}. |
| Q16584 | MAP3K11 | S281 | psp | Mitogen-activated protein kinase kinase kinase 11 (EC 2.7.11.25) (Mixed lineage kinase 3) (Src-homology 3 domain-containing proline-rich kinase) | Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle. {ECO:0000269|PubMed:12529434, ECO:0000269|PubMed:15258589, ECO:0000269|PubMed:8195146, ECO:0000269|PubMed:9003778}. |
| Q16644 | MAPKAPK3 | T201 | ochoa|psp | MAP kinase-activated protein kinase 3 (MAPK-activated protein kinase 3) (MAPKAP kinase 3) (MAPKAP-K3) (MAPKAPK-3) (MK-3) (EC 2.7.11.1) (Chromosome 3p kinase) (3pK) | Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling 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. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair 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, such as TTP/ZFP36, leading to regulate 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 transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}. |
| Q3ZCM7 | TUBB8 | T274 | ochoa | Tubulin beta-8 chain (Tubulin beta 8 class VIII) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. TUBB8 has a key role in meiotic spindle assembly and oocyte maturation (PubMed:26789871, PubMed:34509376). {ECO:0000269|PubMed:26789871, ECO:0000269|PubMed:34509376}. |
| Q5S007 | LRRK2 | T2031 | psp | Leucine-rich repeat serine/threonine-protein kinase 2 (EC 2.7.11.1) (EC 3.6.5.-) (Dardarin) | Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:17114044, PubMed:20949042, PubMed:21850687, PubMed:22012985, PubMed:23395371, PubMed:24687852, PubMed:25201882, PubMed:26014385, PubMed:26824392, PubMed:27830463, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB29, RAB35, and RAB43 (PubMed:23395371, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29127255, PubMed:29212815, PubMed:30398148, PubMed:30635421, PubMed:38127736). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent activation of the CaMKK/AMPK signaling pathway (PubMed:22012985). The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes (PubMed:22012985). Phosphorylates PRDX3 (PubMed:21850687). By phosphorylating APP on 'Thr-743', which promotes the production and the nuclear translocation of the APP intracellular domain (AICD), regulates dopaminergic neuron apoptosis (PubMed:28720718). Acts as a positive regulator of innate immunity by mediating phosphorylation of RIPK2 downstream of NOD1 and NOD2, thereby enhancing RIPK2 activation (PubMed:27830463). Independent of its kinase activity, inhibits the proteasomal degradation of MAPT, thus promoting MAPT oligomerization and secretion (PubMed:26014385). In addition, has GTPase activity via its Roc domain which regulates LRRK2 kinase activity (PubMed:18230735, PubMed:26824392, PubMed:28720718, PubMed:29125462, PubMed:29212815). Recruited by RAB29/RAB7L1 to overloaded lysosomes where it phosphorylates and stabilizes RAB8A and RAB10 which promote lysosomal content release and suppress lysosomal enlargement through the EHBP1 and EHBP1L1 effector proteins (PubMed:30209220, PubMed:38227290). {ECO:0000269|PubMed:17114044, ECO:0000269|PubMed:18230735, ECO:0000269|PubMed:20949042, ECO:0000269|PubMed:21850687, ECO:0000269|PubMed:22012985, ECO:0000269|PubMed:23395371, ECO:0000269|PubMed:24687852, ECO:0000269|PubMed:25201882, ECO:0000269|PubMed:26014385, ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:27830463, ECO:0000269|PubMed:28720718, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:29127255, ECO:0000269|PubMed:29212815, ECO:0000269|PubMed:30209220, ECO:0000269|PubMed:30398148, ECO:0000269|PubMed:30635421, ECO:0000269|PubMed:38127736, ECO:0000269|PubMed:38227290}. |
| Q6P2M8 | PNCK | T171 | psp | Calcium/calmodulin-dependent protein kinase type 1B (EC 2.7.11.17) (CaM kinase I beta) (CaM kinase IB) (CaM-KI beta) (CaMKI-beta) (Pregnancy up-regulated non-ubiquitously-expressed CaM kinase) | Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates CREB1 and SYN1/synapsin I. Phosphorylates and activates CAMK1 (By similarity). {ECO:0000250}. |
| Q6PEY2 | TUBA3E | T56 | ochoa | Tubulin alpha-3E chain (EC 3.6.5.-) (Alpha-tubulin 3E) [Cleaved into: Detyrosinated tubulin alpha-3E chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q71U36 | TUBA1A | T56 | ochoa | Tubulin alpha-1A chain (EC 3.6.5.-) (Alpha-tubulin 3) (Tubulin B-alpha-1) (Tubulin alpha-3 chain) [Cleaved into: Detyrosinated tubulin alpha-1A chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q7KZI7 | MARK2 | T208 | ochoa|psp | Serine/threonine-protein kinase MARK2 (EC 2.7.11.1) (EC 2.7.11.26) (ELKL motif kinase 1) (EMK-1) (MAP/microtubule affinity-regulating kinase 2) (PAR1 homolog) (PAR1 homolog b) (Par-1b) (Par1b) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates CRTC2/TORC2, DCX, HDAC7, KIF13B, MAP2, MAP4 and RAB11FIP2. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Plays a key role in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Regulates epithelial cell polarity by phosphorylating RAB11FIP2. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Regulates axogenesis by phosphorylating KIF13B, promoting interaction between KIF13B and 14-3-3 and inhibiting microtubule-dependent accumulation of KIF13B. Also required for neurite outgrowth and establishment of neuronal polarity. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). Modulates the developmental decision to build a columnar versus a hepatic epithelial cell apparently by promoting a switch from a direct to a transcytotic mode of apical protein delivery. Essential for the asymmetric development of membrane domains of polarized epithelial cells. {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:12429843, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15158914, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:15365179, ECO:0000269|PubMed:16775013, ECO:0000269|PubMed:16980613, ECO:0000269|PubMed:18626018, ECO:0000269|PubMed:20194617, ECO:0000269|PubMed:23666762}. |
| Q86Z02 | HIPK1 | T351 | ochoa | Homeodomain-interacting protein kinase 1 (EC 2.7.11.1) (Nuclear body-associated kinase 2) | Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:24559171). {ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:24559171}. |
| Q8IU85 | CAMK1D | T180 | ochoa|psp | 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}. |
| Q8IW41 | MAPKAPK5 | T182 | ochoa|psp | MAP kinase-activated protein kinase 5 (MAPK-activated protein kinase 5) (MAPKAP kinase 5) (MAPKAP-K5) (MAPKAPK-5) (MK-5) (MK5) (EC 2.7.11.1) (p38-regulated/activated protein kinase) (PRAK) | Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement. {ECO:0000269|PubMed:17254968, ECO:0000269|PubMed:17728103, ECO:0000269|PubMed:19166925, ECO:0000269|PubMed:21329882, ECO:0000269|PubMed:9628874}. |
| Q8IWQ3 | BRSK2 | T174 | psp | Serine/threonine-protein kinase BRSK2 (EC 2.7.11.1) (Brain-selective kinase 2) (EC 2.7.11.26) (Brain-specific serine/threonine-protein kinase 2) (BR serine/threonine-protein kinase 2) (Serine/threonine-protein kinase 29) (Serine/threonine-protein kinase SAD-A) | Serine/threonine-protein kinase that plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:22798068, ECO:0000269|PubMed:23029325}. |
| Q8TDC3 | BRSK1 | T189 | psp | Serine/threonine-protein kinase BRSK1 (EC 2.7.11.1) (Brain-selective kinase 1) (EC 2.7.11.26) (Brain-specific serine/threonine-protein kinase 1) (BR serine/threonine-protein kinase 1) (Serine/threonine-protein kinase SAD-B) (Synapses of Amphids Defective homolog 1) (SAD1 homolog) (hSAD1) | Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma-tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15150265, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311}. |
| Q92630 | DYRK2 | T381 | psp | Dual specificity tyrosine-phosphorylation-regulated kinase 2 (EC 2.7.12.1) | Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro). {ECO:0000269|PubMed:11311121, ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:14593110, ECO:0000269|PubMed:15910284, ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:16611631, ECO:0000269|PubMed:17349958, ECO:0000269|PubMed:18455992, ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19287380, ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:23362280, ECO:0000269|PubMed:9748265}. |
| Q96GD4 | AURKB | T232 | ochoa|psp | Aurora kinase B (EC 2.7.11.1) (Aurora 1) (Aurora- and IPL1-like midbody-associated protein 1) (AIM-1) (Aurora/IPL1-related kinase 2) (ARK-2) (Aurora-related kinase 2) (STK-1) (Serine/threonine-protein kinase 12) (Serine/threonine-protein kinase 5) (Serine/threonine-protein kinase aurora-B) | Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:29449677). The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly (PubMed:11516652, PubMed:12925766, PubMed:14610074, PubMed:14722118, PubMed:26829474). Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis (PubMed:15249581). Required for central/midzone spindle assembly and cleavage furrow formation (PubMed:12458200, PubMed:12686604). Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage: phosphorylates CHMP4C, leading to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis (PubMed:22422861, PubMed:24814515). AURKB phosphorylates the CPC complex subunits BIRC5/survivin, CDCA8/borealin and INCENP (PubMed:11516652, PubMed:12925766, PubMed:14610074). Phosphorylation of INCENP leads to increased AURKB activity (PubMed:11516652, PubMed:12925766, PubMed:14610074). Other known AURKB substrates involved in centromeric functions and mitosis are CENPA, DES/desmin, GPAF, KIF2C, NSUN2, RACGAP1, SEPTIN1, VIM/vimentin, HASPIN, and histone H3 (PubMed:11756469, PubMed:11784863, PubMed:11856369, PubMed:12689593, PubMed:14602875, PubMed:16103226, PubMed:21658950). A positive feedback loop involving HASPIN and AURKB contributes to localization of CPC to centromeres (PubMed:21658950). Phosphorylation of VIM controls vimentin filament segregation in cytokinetic process, whereas histone H3 is phosphorylated at 'Ser-10' and 'Ser-28' during mitosis (H3S10ph and H3S28ph, respectively) (PubMed:11784863, PubMed:11856369). AURKB is also required for kinetochore localization of BUB1 and SGO1 (PubMed:15020684, PubMed:17617734). Phosphorylation of p53/TP53 negatively regulates its transcriptional activity (PubMed:20959462). Key regulator of active promoters in resting B- and T-lymphocytes: acts by mediating phosphorylation of H3S28ph at active promoters in resting B-cells, inhibiting RNF2/RING1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes (By similarity). Acts as an inhibitor of CGAS during mitosis: catalyzes phosphorylation of the N-terminus of CGAS during the G2-M transition, blocking CGAS liquid phase separation and activation, and thereby preventing CGAS-induced autoimmunity (PubMed:33542149). Phosphorylates KRT5 during anaphase and telophase (By similarity). Phosphorylates ATXN10 which promotes phosphorylation of ATXN10 by PLK1 and may play a role in the regulation of cytokinesis and stimulating the proteasomal degradation of ATXN10 (PubMed:25666058). {ECO:0000250|UniProtKB:O70126, ECO:0000269|PubMed:11516652, ECO:0000269|PubMed:11756469, ECO:0000269|PubMed:11784863, ECO:0000269|PubMed:11856369, ECO:0000269|PubMed:12458200, ECO:0000269|PubMed:12686604, ECO:0000269|PubMed:12689593, ECO:0000269|PubMed:12925766, ECO:0000269|PubMed:14602875, ECO:0000269|PubMed:14610074, ECO:0000269|PubMed:14722118, ECO:0000269|PubMed:15020684, ECO:0000269|PubMed:15249581, ECO:0000269|PubMed:16103226, ECO:0000269|PubMed:17617734, ECO:0000269|PubMed:20959462, ECO:0000269|PubMed:21658950, ECO:0000269|PubMed:22422861, ECO:0000269|PubMed:24814515, ECO:0000269|PubMed:25666058, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:29449677, ECO:0000269|PubMed:33542149}. |
| Q96L34 | MARK4 | T214 | ochoa|psp | MAP/microtubule affinity-regulating kinase 4 (EC 2.7.11.1) (MAP/microtubule affinity-regulating kinase-like 1) | Serine/threonine-protein kinase (PubMed:14594945, PubMed:15009667, PubMed:23184942, PubMed:23666762). Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942). Involved in NLRP3 positioning along microtubules by mediating NLRP3 recruitment to microtubule organizing center (MTOC) upon inflammasome activation (PubMed:28656979). {ECO:0000250|UniProtKB:Q8CIP4, ECO:0000269|PubMed:14594945, ECO:0000269|PubMed:15009667, ECO:0000269|PubMed:23184942, ECO:0000269|PubMed:23400999, ECO:0000269|PubMed:23666762, ECO:0000269|PubMed:25123532, ECO:0000269|PubMed:28656979}. |
| Q96RG2 | PASK | T1161 | psp | PAS domain-containing serine/threonine-protein kinase (PAS-kinase) (PASKIN) (hPASK) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation. {ECO:0000269|PubMed:16275910, ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, ECO:0000269|PubMed:21418524}. |
| Q99759 | MAP3K3 | S526 | psp | Mitogen-activated protein kinase kinase kinase 3 (EC 2.7.11.25) (MAPK/ERK kinase kinase 3) (MEK kinase 3) (MEKK 3) | Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators. {ECO:0000269|PubMed:12912994, ECO:0000269|PubMed:14661019, ECO:0000269|PubMed:14743216, ECO:0000269|PubMed:33729480, ECO:0000269|PubMed:33891857, ECO:0000269|PubMed:9006902}. |
| Q9BQE3 | TUBA1C | T56 | ochoa | Tubulin alpha-1C chain (EC 3.6.5.-) (Alpha-tubulin 6) (Tubulin alpha-6 chain) [Cleaved into: Detyrosinated tubulin alpha-1C chain] | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. |
| Q9BUB5 | MKNK1 | T255 | psp | MAP kinase-interacting serine/threonine-protein kinase 1 (EC 2.7.11.1) (MAP kinase signal-integrating kinase 1) (MAPK signal-integrating kinase 1) (Mnk1) | May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. {ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:15350534, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9878069}. |
| Q9BUF5 | TUBB6 | T274 | ochoa | Tubulin beta-6 chain (Tubulin beta class V) | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. {ECO:0000250|UniProtKB:P02557}. |
| Q9BVA1 | TUBB2B | T274 | ochoa | Tubulin beta-2B chain | Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:23001566, PubMed:26732629, PubMed:28013290). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910). {ECO:0000269|PubMed:19465910, ECO:0000269|PubMed:23001566, ECO:0000269|PubMed:26732629, ECO:0000269|PubMed:28013290}. |
| Q9BZL6 | PRKD2 | S710 | ochoa|psp | Serine/threonine-protein kinase D2 (EC 2.7.11.13) (nPKC-D2) | Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion (PubMed:14743217, PubMed:15604256, PubMed:16928771, PubMed:17077180, PubMed:17951978, PubMed:17962809, PubMed:18262756, PubMed:19001381, PubMed:19192391, PubMed:23503467, PubMed:28428613). May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression (By similarity). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (PubMed:15604256, PubMed:28428613). In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 (PubMed:17962809). Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens (By similarity). In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors (PubMed:19192391). In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane (PubMed:14743217). Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis (PubMed:19001381). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, ECO:0000269|PubMed:28428613}. |
| Q9H093 | NUAK2 | T208 | psp | NUAK family SNF1-like kinase 2 (EC 2.7.11.1) (Omphalocele kinase 2) (SNF1/AMP kinase-related kinase) (SNARK) | Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958). {ECO:0000269|PubMed:14575707, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15345718, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:32845958}. |
| Q9H0K1 | SIK2 | T175 | psp | Serine/threonine-protein kinase SIK2 (EC 2.7.11.1) (Qin-induced kinase) (Salt-inducible kinase 2) (SIK-2) (Serine/threonine-protein kinase SNF1-like kinase 2) | Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:23322770, PubMed:26983400). Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:15454081). Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity (PubMed:21084751, PubMed:26983400). In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (PubMed:21084751, PubMed:26983400). Also plays a role in thymic T-cell development (By similarity). {ECO:0000250|UniProtKB:Q8CFH6, ECO:0000269|PubMed:15454081, ECO:0000269|PubMed:21084751, ECO:0000269|PubMed:23322770, ECO:0000269|PubMed:26983400}. |
| Q9H2X6 | HIPK2 | T360 | ochoa|psp | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| Q9H422 | HIPK3 | T358 | ochoa | Homeodomain-interacting protein kinase 3 (EC 2.7.11.1) (Androgen receptor-interacting nuclear protein kinase) (ANPK) (Fas-interacting serine/threonine-protein kinase) (FIST) (Homolog of protein kinase YAK1) | Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}. |
| Q9HAZ1 | CLK4 | T336 | 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}. |
| Q9NRH2 | SNRK | T173 | psp | SNF-related serine/threonine-protein kinase (EC 2.7.11.1) (SNF1-related kinase) | May play a role in hematopoietic cell proliferation or differentiation. Potential mediator of neuronal apoptosis. {ECO:0000250|UniProtKB:Q63553, ECO:0000269|PubMed:12234663, ECO:0000269|PubMed:15733851}. |
| Q9NRM7 | LATS2 | S872 | ochoa|psp | Serine/threonine-protein kinase LATS2 (EC 2.7.11.1) (Kinase phosphorylated during mitosis protein) (Large tumor suppressor homolog 2) (Serine/threonine-protein kinase kpm) (Warts-like kinase) | Negative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:18158288, PubMed:26437443, PubMed:26598551, PubMed:34404733). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:26437443, PubMed:26598551, PubMed:34404733). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:26598551, PubMed:34404733). Also phosphorylates YAP1 in response to cell contact inhibition-driven WWP1 ubiquitination of AMOTL2, which results in LATS2 activation (PubMed:34404733). Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability (PubMed:10871863). Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity (PubMed:12853976). Negative regulator of the androgen receptor (PubMed:15131260). Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities (PubMed:21952048). This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ (PubMed:21952048). Acts as an activator of the NLRP3 inflammasome by mediating phosphorylation of 'Ser-265' of NLRP3 following NLRP3 palmitoylation, promoting NLRP3 activation by NEK7 (PubMed:39173637). {ECO:0000269|PubMed:10871863, ECO:0000269|PubMed:12853976, ECO:0000269|PubMed:15131260, ECO:0000269|PubMed:18158288, ECO:0000269|PubMed:21952048, ECO:0000269|PubMed:26437443, ECO:0000269|PubMed:26598551, ECO:0000269|PubMed:34404733, ECO:0000269|PubMed:39173637}. |
| Q9NYL2 | MAP3K20 | S165 | psp | Mitogen-activated protein kinase kinase kinase 20 (EC 2.7.11.25) (Human cervical cancer suppressor gene 4 protein) (HCCS-4) (Leucine zipper- and sterile alpha motif-containing kinase) (MLK-like mitogen-activated protein triple kinase) (Mitogen-activated protein kinase kinase kinase MLT) (Mixed lineage kinase 7) (Mixed lineage kinase-related kinase) (MLK-related kinase) (MRK) (Sterile alpha motif- and leucine zipper-containing kinase AZK) | Stress-activated component of a protein kinase signal transduction cascade that promotes programmed cell death in response to various stress, such as ribosomal stress, osmotic shock and ionizing radiation (PubMed:10924358, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15350844, PubMed:15737997, PubMed:18331592, PubMed:20559024, PubMed:26999302, PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts by catalyzing phosphorylation of MAP kinase kinases, leading to activation of the JNK (MAPK8/JNK1, MAPK9/JNK2 and/or MAPK10/JNK3) and MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) pathways (PubMed:11042189, PubMed:11836244, PubMed:12220515, PubMed:14521931, PubMed:15172994, PubMed:15737997, PubMed:32289254, PubMed:32610081, PubMed:35857590). Activates JNK through phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7, and MAP kinase p38 gamma (MAPK12) via phosphorylation of MAP2K3/MKK3 and MAP2K6/MKK6 (PubMed:11836244, PubMed:12220515). Involved in stress associated with adrenergic stimulation: contributes to cardiac decompensation during periods of acute cardiac stress (PubMed:15350844, PubMed:21224381, PubMed:27859413). May be involved in regulation of S and G2 cell cycle checkpoint by mediating phosphorylation of CHEK2 (PubMed:15342622). {ECO:0000269|PubMed:10924358, ECO:0000269|PubMed:11042189, ECO:0000269|PubMed:11836244, ECO:0000269|PubMed:12220515, ECO:0000269|PubMed:14521931, ECO:0000269|PubMed:15172994, ECO:0000269|PubMed:15342622, ECO:0000269|PubMed:15350844, ECO:0000269|PubMed:15737997, ECO:0000269|PubMed:18331592, ECO:0000269|PubMed:20559024, ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:26999302, ECO:0000269|PubMed:27859413, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}.; FUNCTION: [Isoform ZAKalpha]: Key component of the stress-activated protein kinase signaling cascade in response to ribotoxic stress or UV-B irradiation (PubMed:32289254, PubMed:32610081, PubMed:35857590). Acts as the proximal sensor of ribosome collisions during the ribotoxic stress response (RSR): directly binds to the ribosome by inserting its flexible C-terminus into the ribosomal intersubunit space, thereby acting as a sentinel for colliding ribosomes (PubMed:32289254, PubMed:32610081). Upon ribosome collisions, activates either the stress-activated protein kinase signal transduction cascade or the integrated stress response (ISR), leading to programmed cell death or cell survival, respectively (PubMed:32610081). Dangerous levels of ribosome collisions trigger the autophosphorylation and activation of MAP3K20, which dissociates from colliding ribosomes and phosphorylates MAP kinase kinases, leading to activation of the JNK and MAP kinase p38 pathways that promote programmed cell death (PubMed:32289254, PubMed:32610081). Less dangerous levels of ribosome collisions trigger the integrated stress response (ISR): MAP3K20 activates EIF2AK4/GCN2 independently of its protein-kinase activity, promoting EIF2AK4/GCN2-mediated phosphorylation of EIF2S1/eIF-2-alpha (PubMed:32610081). Also part of the stress-activated protein kinase signaling cascade triggering the NLRP1 inflammasome in response to UV-B irradiation: ribosome collisions activate MAP3K20, which directly phosphorylates NLRP1, leading to activation of the NLRP1 inflammasome and subsequent pyroptosis (PubMed:35857590). NLRP1 is also phosphorylated by MAP kinase p38 downstream of MAP3K20 (PubMed:35857590). Also acts as a histone kinase by phosphorylating histone H3 at 'Ser-28' (H3S28ph) (PubMed:15684425). {ECO:0000269|PubMed:15684425, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}.; FUNCTION: [Isoform ZAKbeta]: Isoform that lacks the C-terminal region that mediates ribosome-binding: does not act as a sensor of ribosome collisions in response to ribotoxic stress (PubMed:32289254, PubMed:32610081, PubMed:35857590). May act as an antagonist of isoform ZAKalpha: interacts with isoform ZAKalpha, leading to decrease the expression of isoform ZAKalpha (PubMed:27859413). {ECO:0000269|PubMed:27859413, ECO:0000269|PubMed:32289254, ECO:0000269|PubMed:32610081, ECO:0000269|PubMed:35857590}. |
| Q9P0L2 | MARK1 | T215 | ochoa|psp | Serine/threonine-protein kinase MARK1 (EC 2.7.11.1) (EC 2.7.11.26) (MAP/microtubule affinity-regulating kinase 1) (PAR1 homolog c) (Par-1c) (Par1c) | Serine/threonine-protein kinase (PubMed:23666762). Involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2 and MAP4. Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:23666762). Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3). {ECO:0000269|PubMed:11433294, ECO:0000269|PubMed:17573348, ECO:0000269|PubMed:23666762}. |
| Q9UEW8 | STK39 | T231 | ochoa|psp | STE20/SPS1-related proline-alanine-rich protein kinase (Ste-20-related kinase) (EC 2.7.11.1) (DCHT) (Serine/threonine-protein kinase 39) | Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:16669787, PubMed:18270262, PubMed:21321328, PubMed:34289367). Specifically recognizes and binds proteins with a RFXV motif (PubMed:16669787, PubMed:21321328). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (PubMed:21321328). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (PubMed:12740379, PubMed:16669787, PubMed:21321328). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:16669787, PubMed:19665974, PubMed:21321328). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (PubMed:18270262). Mediates the inhibition of SLC4A4, SLC26A6 as well as CFTR activities (By similarity). Phosphorylates RELT (By similarity). {ECO:0000250|UniProtKB:Q9Z1W9, ECO:0000269|PubMed:12740379, ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:19665974, ECO:0000269|PubMed:21321328, ECO:0000269|PubMed:34289367}. |
| Q9UQB9 | AURKC | T198 | ochoa|psp | Aurora kinase C (EC 2.7.11.1) (Aurora 3) (Aurora/IPL1-related kinase 3) (ARK-3) (Aurora-related kinase 3) (Aurora/IPL1/Eg2 protein 2) (Serine/threonine-protein kinase 13) (Serine/threonine-protein kinase aurora-C) | Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Also plays a role in meiosis and more particularly in spermatogenesis. Has redundant cellular functions with AURKB and can rescue an AURKB knockdown. Like AURKB, AURKC phosphorylates histone H3 at 'Ser-10' and 'Ser-28'. AURKC phosphorylates the CPC complex subunits BIRC5/survivin and INCENP leading to increased AURKC activity. Phosphorylates TACC1, another protein involved in cell division, at 'Ser-228'. {ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:15499654, ECO:0000269|PubMed:15670791, ECO:0000269|PubMed:15938719, ECO:0000269|PubMed:21493633, ECO:0000269|PubMed:21531210, ECO:0000269|PubMed:27332895}. |
| Q9Y2H1 | STK38L | S282 | ochoa|psp | 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}. |
| Q9Y2K2 | SIK3 | T221 | psp | Serine/threonine-protein kinase SIK3 (EC 2.7.11.1) (Salt-inducible kinase 3) (SIK-3) (Serine/threonine-protein kinase QSK) | Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. Involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation during skeletogenesis (PubMed:30232230). Negatively regulates cAMP signaling pathway possibly by acting on CRTC2/TORC2 and CRTC3/TORC3 (Probable). Prevents HDAC4 translocation to the nucleus (By similarity). {ECO:0000250|UniProtKB:Q6P4S6, ECO:0000269|PubMed:30232230, ECO:0000305|PubMed:29211348}. |
| Q9Y2U5 | MAP3K2 | S520 | psp | Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2) | Component of a protein kinase signal transduction cascade. Regulates the JNK and ERK5 pathways by phosphorylating and activating MAP2K5 and MAP2K7 (By similarity). Plays a role in caveolae kiss-and-run dynamics. {ECO:0000250, ECO:0000269|PubMed:10713157, ECO:0000269|PubMed:16001074}. |
| Q96PN8 | TSSK3 | T168 | SIGNOR | Testis-specific serine/threonine-protein kinase 3 (TSK-3) (TSSK-3) (Testis-specific kinase 3) (EC 2.7.11.1) (Serine/threonine-protein kinase 22C) | Serine/threonine protein kinase required for spermatid development and male fertility. {ECO:0000250|UniProtKB:Q9D2E1}. |
| Q13464 | ROCK1 | T233 | Sugiyama | Rho-associated protein kinase 1 (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-35) (Rho-associated, coiled-coil-containing protein kinase 1) (Rho-associated, coiled-coil-containing protein kinase I) (ROCK-I) (p160 ROCK-1) (p160ROCK) | Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:8617235, PubMed:9722579). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (PubMed:10436159, PubMed:10652353, PubMed:11018042, PubMed:11283607, PubMed:17158456, PubMed:18573880, PubMed:19131646, PubMed:23093407, PubMed:23355470, PubMed:8617235, PubMed:9722579). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing (PubMed:18694941). Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (PubMed:19036714). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation (PubMed:19181962). Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (PubMed:21072057). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (PubMed:19997641). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity). {ECO:0000250|UniProtKB:P70335, ECO:0000250|UniProtKB:Q8MIT6, ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:10652353, ECO:0000269|PubMed:11018042, ECO:0000269|PubMed:11283607, ECO:0000269|PubMed:17158456, ECO:0000269|PubMed:18573880, ECO:0000269|PubMed:18694941, ECO:0000269|PubMed:19036714, ECO:0000269|PubMed:19131646, ECO:0000269|PubMed:19181962, ECO:0000269|PubMed:19997641, ECO:0000269|PubMed:21072057, ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:8617235, ECO:0000269|PubMed:9722579}. |
| P80192 | MAP3K9 | S308 | GPS6|EPSD | Mitogen-activated protein kinase kinase kinase 9 (EC 2.7.11.25) (Mixed lineage kinase 1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade through the phosphorylation of MAP2K4/MKK4 and MAP2K7/MKK7 which in turn activate the JNKs. The MKK/JNK signaling pathway regulates stress response via activator protein-1 (JUN) and GATA4 transcription factors. Also plays a role in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. {ECO:0000269|PubMed:11416147, ECO:0000269|PubMed:15610029}. |
| Q86SG6 | NEK8 | T162 | iPTMNet | Serine/threonine-protein kinase Nek8 (EC 2.7.11.1) (Never in mitosis A-related kinase 8) (NimA-related protein kinase 8) (Nima-related protein kinase 12a) | Required for renal tubular integrity. May regulate local cytoskeletal structure in kidney tubule epithelial cells. May regulate ciliary biogenesis through targeting of proteins to the cilia (PubMed:37598857). Plays a role in organogenesis, and is involved in the regulation of the Hippo signaling pathway (PubMed:26967905). {ECO:0000269|PubMed:23418306, ECO:0000269|PubMed:26967905, ECO:0000269|PubMed:37598857}. |
| Q8IY84 | NIM1K | T229 | GPS6|EPSD | Serine/threonine-protein kinase NIM1 (EC 2.7.11.1) (NIM1 serine/threonine-protein kinase) | None |
| Q9BXA7 | TSSK1B | T174 | SIGNOR | Testis-specific serine/threonine-protein kinase 1 (TSK-1) (TSK1) (TSSK-1) (Testis-specific kinase 1) (EC 2.7.11.1) (Serine/threonine-protein kinase 22A) | Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates 'Ser-288' of TSKS. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body. {ECO:0000269|PubMed:15733851, ECO:0000269|PubMed:19530700}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-9619483 | Activation of AMPK downstream of NMDARs | 1.110223e-16 | 15.955 |
| R-HSA-389977 | Post-chaperonin tubulin folding pathway | 1.110223e-16 | 15.955 |
| R-HSA-389960 | Formation of tubulin folding intermediates by CCT/TriC | 1.110223e-16 | 15.955 |
| R-HSA-8955332 | Carboxyterminal post-translational modifications of tubulin | 1.110223e-16 | 15.955 |
| R-HSA-380320 | Recruitment of NuMA to mitotic centrosomes | 1.110223e-16 | 15.955 |
| R-HSA-190840 | Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane | 1.110223e-16 | 15.955 |
| R-HSA-438064 | Post NMDA receptor activation events | 1.110223e-16 | 15.955 |
| R-HSA-190872 | Transport of connexons to the plasma membrane | 1.110223e-16 | 15.955 |
| R-HSA-6811436 | COPI-independent Golgi-to-ER retrograde traffic | 1.110223e-16 | 15.955 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 1.110223e-16 | 15.955 |
| R-HSA-9646399 | Aggrephagy | 1.110223e-16 | 15.955 |
| R-HSA-437239 | Recycling pathway of L1 | 1.110223e-16 | 15.955 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 1.110223e-16 | 15.955 |
| R-HSA-190861 | Gap junction assembly | 1.110223e-16 | 15.955 |
| R-HSA-190828 | Gap junction trafficking | 1.110223e-16 | 15.955 |
| R-HSA-9668328 | Sealing of the nuclear envelope (NE) by ESCRT-III | 1.110223e-16 | 15.955 |
| R-HSA-983189 | Kinesins | 1.110223e-16 | 15.955 |
| R-HSA-1445148 | Translocation of SLC2A4 (GLUT4) to the plasma membrane | 1.110223e-16 | 15.955 |
| R-HSA-112315 | Transmission across Chemical Synapses | 1.110223e-16 | 15.955 |
| R-HSA-157858 | Gap junction trafficking and regulation | 1.110223e-16 | 15.955 |
| R-HSA-373760 | L1CAM interactions | 1.110223e-16 | 15.955 |
| R-HSA-9609736 | Assembly and cell surface presentation of NMDA receptors | 1.110223e-16 | 15.955 |
| R-HSA-9833482 | PKR-mediated signaling | 1.110223e-16 | 15.955 |
| R-HSA-8852276 | The role of GTSE1 in G2/M progression after G2 checkpoint | 2.220446e-16 | 15.654 |
| R-HSA-389958 | Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding | 3.330669e-16 | 15.477 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 3.330669e-16 | 15.477 |
| R-HSA-9663891 | Selective autophagy | 4.440892e-16 | 15.353 |
| R-HSA-3371497 | HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of lig... | 5.551115e-16 | 15.256 |
| R-HSA-5620920 | Cargo trafficking to the periciliary membrane | 9.992007e-16 | 15.000 |
| R-HSA-68877 | Mitotic Prometaphase | 3.330669e-15 | 14.477 |
| R-HSA-2995410 | Nuclear Envelope (NE) Reassembly | 3.663736e-15 | 14.436 |
| R-HSA-1632852 | Macroautophagy | 1.454392e-14 | 13.837 |
| R-HSA-983231 | Factors involved in megakaryocyte development and platelet production | 1.509903e-14 | 13.821 |
| R-HSA-112316 | Neuronal System | 2.298162e-14 | 13.639 |
| R-HSA-69275 | G2/M Transition | 3.486100e-14 | 13.458 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 3.586020e-14 | 13.445 |
| R-HSA-453274 | Mitotic G2-G2/M phases | 4.041212e-14 | 13.393 |
| R-HSA-6811434 | COPI-dependent Golgi-to-ER retrograde traffic | 4.329870e-14 | 13.364 |
| R-HSA-6807878 | COPI-mediated anterograde transport | 4.329870e-14 | 13.364 |
| R-HSA-422475 | Axon guidance | 4.418688e-14 | 13.355 |
| R-HSA-5617833 | Cilium Assembly | 4.674039e-14 | 13.330 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 4.873879e-14 | 13.312 |
| R-HSA-9612973 | Autophagy | 5.750955e-14 | 13.240 |
| R-HSA-5610787 | Hedgehog 'off' state | 6.850076e-14 | 13.164 |
| R-HSA-389957 | Prefoldin mediated transfer of substrate to CCT/TriC | 1.112443e-13 | 12.954 |
| R-HSA-9675108 | Nervous system development | 1.632028e-13 | 12.787 |
| R-HSA-390466 | Chaperonin-mediated protein folding | 3.129719e-13 | 12.504 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 5.038192e-13 | 12.298 |
| R-HSA-391251 | Protein folding | 6.308287e-13 | 12.200 |
| R-HSA-2132295 | MHC class II antigen presentation | 9.423573e-13 | 12.026 |
| R-HSA-5620924 | Intraflagellar transport | 1.024625e-12 | 11.989 |
| R-HSA-2467813 | Separation of Sister Chromatids | 1.915024e-12 | 11.718 |
| R-HSA-8856688 | Golgi-to-ER retrograde transport | 2.450151e-12 | 11.611 |
| R-HSA-5358351 | Signaling by Hedgehog | 4.332201e-12 | 11.363 |
| R-HSA-68886 | M Phase | 8.219425e-12 | 11.085 |
| R-HSA-199977 | ER to Golgi Anterograde Transport | 9.344303e-12 | 11.029 |
| R-HSA-68882 | Mitotic Anaphase | 5.743861e-11 | 10.241 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 6.067480e-11 | 10.217 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 1.699372e-10 | 9.770 |
| R-HSA-9609690 | HCMV Early Events | 2.339753e-10 | 9.631 |
| R-HSA-6811442 | Intra-Golgi and retrograde Golgi-to-ER traffic | 2.921285e-10 | 9.534 |
| R-HSA-948021 | Transport to the Golgi and subsequent modification | 3.258854e-10 | 9.487 |
| R-HSA-162582 | Signal Transduction | 3.499102e-10 | 9.456 |
| R-HSA-69278 | Cell Cycle, Mitotic | 4.563357e-10 | 9.341 |
| R-HSA-1640170 | Cell Cycle | 2.506771e-09 | 8.601 |
| R-HSA-9609646 | HCMV Infection | 3.545340e-09 | 8.450 |
| R-HSA-913531 | Interferon Signaling | 6.481460e-09 | 8.188 |
| R-HSA-5633007 | Regulation of TP53 Activity | 6.253172e-08 | 7.204 |
| R-HSA-111933 | Calmodulin induced events | 1.742573e-07 | 6.759 |
| R-HSA-111997 | CaM pathway | 1.742573e-07 | 6.759 |
| R-HSA-1280218 | Adaptive Immune System | 2.768975e-07 | 6.558 |
| R-HSA-8953897 | Cellular responses to stimuli | 2.775568e-07 | 6.557 |
| R-HSA-109582 | Hemostasis | 3.748891e-07 | 6.426 |
| R-HSA-111996 | Ca-dependent events | 4.176325e-07 | 6.379 |
| R-HSA-9010642 | ROBO receptors bind AKAP5 | 5.075317e-07 | 6.295 |
| R-HSA-1489509 | DAG and IP3 signaling | 5.846356e-07 | 6.233 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 6.729215e-07 | 6.172 |
| R-HSA-194138 | Signaling by VEGF | 1.232881e-06 | 5.909 |
| R-HSA-446203 | Asparagine N-linked glycosylation | 1.028115e-06 | 5.988 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 1.797884e-06 | 5.745 |
| R-HSA-112043 | PLC beta mediated events | 2.652782e-06 | 5.576 |
| R-HSA-442720 | CREB1 phosphorylation through the activation of Adenylate Cyclase | 2.822954e-06 | 5.549 |
| R-HSA-8854518 | AURKA Activation by TPX2 | 3.948499e-06 | 5.404 |
| R-HSA-112040 | G-protein mediated events | 4.260853e-06 | 5.371 |
| R-HSA-392517 | Rap1 signalling | 1.088801e-05 | 4.963 |
| R-HSA-2565942 | Regulation of PLK1 Activity at G2/M Transition | 1.346951e-05 | 4.871 |
| R-HSA-163358 | PKA-mediated phosphorylation of key metabolic factors | 1.348609e-05 | 4.870 |
| R-HSA-5663205 | Infectious disease | 1.350353e-05 | 4.870 |
| R-HSA-111931 | PKA-mediated phosphorylation of CREB | 1.487102e-05 | 4.828 |
| R-HSA-199991 | Membrane Trafficking | 1.834860e-05 | 4.736 |
| R-HSA-5620912 | Anchoring of the basal body to the plasma membrane | 2.027961e-05 | 4.693 |
| R-HSA-450294 | MAP kinase activation | 4.445379e-05 | 4.352 |
| R-HSA-1266738 | Developmental Biology | 4.520833e-05 | 4.345 |
| R-HSA-111885 | Opioid Signalling | 4.643843e-05 | 4.333 |
| R-HSA-2262752 | Cellular responses to stress | 4.960458e-05 | 4.304 |
| R-HSA-9824446 | Viral Infection Pathways | 4.995313e-05 | 4.301 |
| R-HSA-380284 | Loss of proteins required for interphase microtubule organization from the centr... | 5.083928e-05 | 4.294 |
| R-HSA-380259 | Loss of Nlp from mitotic centrosomes | 5.083928e-05 | 4.294 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 7.127930e-05 | 4.147 |
| R-HSA-448424 | Interleukin-17 signaling | 7.892971e-05 | 4.103 |
| R-HSA-5673000 | RAF activation | 8.633588e-05 | 4.064 |
| R-HSA-380270 | Recruitment of mitotic centrosome proteins and complexes | 9.409432e-05 | 4.026 |
| R-HSA-187687 | Signalling to ERKs | 9.467360e-05 | 4.024 |
| R-HSA-8853659 | RET signaling | 1.035814e-04 | 3.985 |
| R-HSA-380287 | Centrosome maturation | 1.053845e-04 | 3.977 |
| R-HSA-5602636 | IKBKB deficiency causes SCID | 1.344565e-04 | 3.871 |
| R-HSA-5603027 | IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (E... | 1.344565e-04 | 3.871 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 1.476004e-04 | 3.831 |
| R-HSA-8963896 | HDL assembly | 1.476004e-04 | 3.831 |
| R-HSA-5687128 | MAPK6/MAPK4 signaling | 1.782586e-04 | 3.749 |
| R-HSA-5653656 | Vesicle-mediated transport | 1.809790e-04 | 3.742 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 1.957923e-04 | 3.708 |
| R-HSA-9634600 | Regulation of glycolysis by fructose 2,6-bisphosphate metabolism | 2.008610e-04 | 3.697 |
| R-HSA-5683057 | MAPK family signaling cascades | 2.039759e-04 | 3.690 |
| R-HSA-9660821 | ADORA2B mediated anti-inflammatory cytokines production | 2.292374e-04 | 3.640 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 2.460004e-04 | 3.609 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 2.460004e-04 | 3.609 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 2.460004e-04 | 3.609 |
| R-HSA-6802949 | Signaling by RAS mutants | 2.460004e-04 | 3.609 |
| R-HSA-163615 | PKA activation | 3.018528e-04 | 3.520 |
| R-HSA-164378 | PKA activation in glucagon signalling | 3.018528e-04 | 3.520 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 3.621859e-04 | 3.441 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 3.679598e-04 | 3.434 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 3.679598e-04 | 3.434 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 3.679598e-04 | 3.434 |
| R-HSA-416572 | Sema4D induced cell migration and growth-cone collapse | 3.845662e-04 | 3.415 |
| R-HSA-9860931 | Response of endothelial cells to shear stress | 4.687378e-04 | 3.329 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 5.065578e-04 | 3.295 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 5.320562e-04 | 3.274 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 5.675388e-04 | 3.246 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 5.890422e-04 | 3.230 |
| R-HSA-9022535 | Loss of phosphorylation of MECP2 at T308 | 7.215907e-04 | 3.142 |
| R-HSA-400685 | Sema4D in semaphorin signaling | 7.159185e-04 | 3.145 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 6.111518e-04 | 3.214 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 8.975393e-04 | 3.047 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 6.111518e-04 | 3.214 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 8.975393e-04 | 3.047 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 6.812275e-04 | 3.167 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 7.571564e-04 | 3.121 |
| R-HSA-5621575 | CD209 (DC-SIGN) signaling | 6.514334e-04 | 3.186 |
| R-HSA-9855142 | Cellular responses to mechanical stimuli | 7.058719e-04 | 3.151 |
| R-HSA-8963898 | Plasma lipoprotein assembly | 6.514334e-04 | 3.186 |
| R-HSA-5603029 | IkBA variant leads to EDA-ID | 9.391076e-04 | 3.027 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 9.391076e-04 | 3.027 |
| R-HSA-9860276 | SLC15A4:TASL-dependent IRF5 activation | 9.391076e-04 | 3.027 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 9.905754e-04 | 3.004 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 9.905754e-04 | 3.004 |
| R-HSA-180024 | DARPP-32 events | 1.014088e-03 | 2.994 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 1.235399e-03 | 2.908 |
| R-HSA-163359 | Glucagon signaling in metabolic regulation | 1.483974e-03 | 2.829 |
| R-HSA-163685 | Integration of energy metabolism | 1.659333e-03 | 2.780 |
| R-HSA-163560 | Triglyceride catabolism | 1.821719e-03 | 2.740 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 1.838494e-03 | 2.736 |
| R-HSA-168256 | Immune System | 1.857143e-03 | 2.731 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 1.944068e-03 | 2.711 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 2.359376e-03 | 2.627 |
| R-HSA-166520 | Signaling by NTRKs | 2.359376e-03 | 2.627 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 2.387036e-03 | 2.622 |
| R-HSA-1643685 | Disease | 2.554886e-03 | 2.593 |
| R-HSA-5674135 | MAP2K and MAPK activation | 2.632296e-03 | 2.580 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 2.632296e-03 | 2.580 |
| R-HSA-5610783 | Degradation of GLI2 by the proteasome | 2.632296e-03 | 2.580 |
| R-HSA-5610785 | GLI3 is processed to GLI3R by the proteasome | 2.632296e-03 | 2.580 |
| R-HSA-5610780 | Degradation of GLI1 by the proteasome | 2.632296e-03 | 2.580 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 2.632296e-03 | 2.580 |
| R-HSA-381676 | Glucagon-like Peptide-1 (GLP1) regulates insulin secretion | 2.785712e-03 | 2.555 |
| R-HSA-933543 | NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 | 2.814802e-03 | 2.551 |
| R-HSA-3928662 | EPHB-mediated forward signaling | 3.108831e-03 | 2.507 |
| R-HSA-422356 | Regulation of insulin secretion | 3.245579e-03 | 2.489 |
| R-HSA-432040 | Vasopressin regulates renal water homeostasis via Aquaporins | 3.278655e-03 | 2.484 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 3.454067e-03 | 2.462 |
| R-HSA-9020702 | Interleukin-1 signaling | 3.573049e-03 | 2.447 |
| R-HSA-937039 | IRAK1 recruits IKK complex | 3.650248e-03 | 2.438 |
| R-HSA-975144 | IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation | 3.650248e-03 | 2.438 |
| R-HSA-9005895 | Pervasive developmental disorders | 3.650248e-03 | 2.438 |
| R-HSA-9697154 | Disorders of Nervous System Development | 3.650248e-03 | 2.438 |
| R-HSA-9005891 | Loss of function of MECP2 in Rett syndrome | 3.650248e-03 | 2.438 |
| R-HSA-9634597 | GPER1 signaling | 3.821885e-03 | 2.418 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 4.013165e-03 | 2.397 |
| R-HSA-170968 | Frs2-mediated activation | 4.106071e-03 | 2.387 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 4.182081e-03 | 2.379 |
| R-HSA-5578768 | Physiological factors | 4.586914e-03 | 2.338 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 4.586914e-03 | 2.338 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 7.916679e-03 | 2.101 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 9.994343e-03 | 2.000 |
| R-HSA-9758274 | Regulation of NF-kappa B signaling | 5.622524e-03 | 2.250 |
| R-HSA-1810476 | RIP-mediated NFkB activation via ZBP1 | 5.092491e-03 | 2.293 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 9.994343e-03 | 2.000 |
| R-HSA-2028269 | Signaling by Hippo | 6.754839e-03 | 2.170 |
| R-HSA-168927 | TICAM1, RIP1-mediated IKK complex recruitment | 5.092491e-03 | 2.293 |
| R-HSA-937041 | IKK complex recruitment mediated by RIP1 | 7.981656e-03 | 2.098 |
| R-HSA-169893 | Prolonged ERK activation events | 5.622524e-03 | 2.250 |
| R-HSA-171007 | p38MAPK events | 5.092491e-03 | 2.293 |
| R-HSA-9664323 | FCGR3A-mediated IL10 synthesis | 7.957621e-03 | 2.099 |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs | 7.356571e-03 | 2.133 |
| R-HSA-445144 | Signal transduction by L1 | 8.629824e-03 | 2.064 |
| R-HSA-9675151 | Disorders of Developmental Biology | 6.176731e-03 | 2.209 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 6.754839e-03 | 2.170 |
| R-HSA-445717 | Aquaporin-mediated transport | 6.791524e-03 | 2.168 |
| R-HSA-168898 | Toll-like Receptor Cascades | 6.333004e-03 | 2.198 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 6.754839e-03 | 2.170 |
| R-HSA-167044 | Signalling to RAS | 9.300808e-03 | 2.031 |
| R-HSA-373755 | Semaphorin interactions | 7.341274e-03 | 2.134 |
| R-HSA-75893 | TNF signaling | 5.527467e-03 | 2.257 |
| R-HSA-8979227 | Triglyceride metabolism | 6.267144e-03 | 2.203 |
| R-HSA-1660661 | Sphingolipid de novo biosynthesis | 6.526181e-03 | 2.185 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 1.071016e-02 | 1.970 |
| R-HSA-933542 | TRAF6 mediated NF-kB activation | 1.220763e-02 | 1.913 |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR... | 1.307409e-02 | 1.884 |
| R-HSA-3928663 | EPHA-mediated growth cone collapse | 1.461452e-02 | 1.835 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 1.461452e-02 | 1.835 |
| R-HSA-446652 | Interleukin-1 family signaling | 1.491695e-02 | 1.826 |
| R-HSA-380972 | Energy dependent regulation of mTOR by LKB1-AMPK | 1.720820e-02 | 1.764 |
| R-HSA-2682334 | EPH-Ephrin signaling | 1.927287e-02 | 1.715 |
| R-HSA-174824 | Plasma lipoprotein assembly, remodeling, and clearance | 1.927287e-02 | 1.715 |
| R-HSA-597592 | Post-translational protein modification | 2.122724e-02 | 1.673 |
| 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-168638 | NOD1/2 Signaling Pathway | 2.192809e-02 | 1.659 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 2.217118e-02 | 1.654 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 2.217118e-02 | 1.654 |
| R-HSA-9860927 | Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZ... | 2.292948e-02 | 1.640 |
| R-HSA-70171 | Glycolysis | 2.397994e-02 | 1.620 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 2.510306e-02 | 1.600 |
| R-HSA-5602358 | Diseases associated with the TLR signaling cascade | 2.821070e-02 | 1.550 |
| R-HSA-5260271 | Diseases of Immune System | 2.821070e-02 | 1.550 |
| R-HSA-165159 | MTOR signalling | 3.159072e-02 | 1.500 |
| R-HSA-418594 | G alpha (i) signalling events | 3.159380e-02 | 1.500 |
| R-HSA-376176 | Signaling by ROBO receptors | 3.504630e-02 | 1.455 |
| R-HSA-70326 | Glucose metabolism | 3.646653e-02 | 1.438 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 3.755726e-02 | 1.425 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 4.261512e-02 | 1.370 |
| R-HSA-9931269 | AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274) | 4.391740e-02 | 1.357 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 4.391740e-02 | 1.357 |
| R-HSA-174178 | APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ... | 4.523441e-02 | 1.345 |
| R-HSA-5576891 | Cardiac conduction | 4.843088e-02 | 1.315 |
| R-HSA-2980767 | Activation of NIMA Kinases NEK9, NEK6, NEK7 | 4.853863e-02 | 1.314 |
| R-HSA-8857538 | PTK6 promotes HIF1A stabilization | 4.853863e-02 | 1.314 |
| R-HSA-199920 | CREB phosphorylation | 4.853863e-02 | 1.314 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 5.064578e-02 | 1.295 |
| R-HSA-114516 | Disinhibition of SNARE formation | 5.378586e-02 | 1.269 |
| R-HSA-442729 | CREB1 phosphorylation through the activation of CaMKII/CaMKK/CaMKIV cascasde | 5.900448e-02 | 1.229 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 6.063804e-02 | 1.217 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 6.419464e-02 | 1.193 |
| R-HSA-163680 | AMPK inhibits chREBP transcriptional activation activity | 6.419464e-02 | 1.193 |
| R-HSA-9613354 | Lipophagy | 6.419464e-02 | 1.193 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 6.419464e-02 | 1.193 |
| R-HSA-450520 | HuR (ELAVL1) binds and stabilizes mRNA | 6.419464e-02 | 1.193 |
| R-HSA-9679191 | Potential therapeutics for SARS | 6.667395e-02 | 1.176 |
| R-HSA-449147 | Signaling by Interleukins | 6.682382e-02 | 1.175 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 6.935649e-02 | 1.159 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 6.935649e-02 | 1.159 |
| R-HSA-111932 | CaMK IV-mediated phosphorylation of CREB | 6.935649e-02 | 1.159 |
| R-HSA-2179392 | EGFR Transactivation by Gastrin | 6.935649e-02 | 1.159 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 6.969135e-02 | 1.157 |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA | 6.969135e-02 | 1.157 |
| R-HSA-73887 | Death Receptor Signaling | 7.046009e-02 | 1.152 |
| R-HSA-174143 | APC/C-mediated degradation of cell cycle proteins | 7.124118e-02 | 1.147 |
| R-HSA-453276 | Regulation of mitotic cell cycle | 7.124118e-02 | 1.147 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 7.280227e-02 | 1.138 |
| R-HSA-388396 | GPCR downstream signalling | 7.299184e-02 | 1.137 |
| R-HSA-4086398 | Ca2+ pathway | 7.437443e-02 | 1.129 |
| R-HSA-209560 | NF-kB is activated and signals survival | 7.959588e-02 | 1.099 |
| R-HSA-416482 | G alpha (12/13) signalling events | 8.239560e-02 | 1.084 |
| 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-9824443 | Parasitic Infection Pathways | 8.597883e-02 | 1.066 |
| R-HSA-9658195 | Leishmania infection | 8.597883e-02 | 1.066 |
| R-HSA-418555 | G alpha (s) signalling events | 8.865331e-02 | 1.052 |
| R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex | 8.972386e-02 | 1.047 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 9.246799e-02 | 1.034 |
| R-HSA-418457 | cGMP effects | 9.474645e-02 | 1.023 |
| R-HSA-1433559 | Regulation of KIT signaling | 9.474645e-02 | 1.023 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 9.574679e-02 | 1.019 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 9.833371e-02 | 1.007 |
| R-HSA-2559583 | Cellular Senescence | 9.842141e-02 | 1.007 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 9.974164e-02 | 1.001 |
| R-HSA-193639 | p75NTR signals via NF-kB | 9.974164e-02 | 1.001 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 9.974164e-02 | 1.001 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 9.974164e-02 | 1.001 |
| R-HSA-1236974 | ER-Phagosome pathway | 1.026403e-01 | 0.989 |
| R-HSA-202424 | Downstream TCR signaling | 1.043848e-01 | 0.981 |
| R-HSA-5099900 | WNT5A-dependent internalization of FZD4 | 1.047096e-01 | 0.980 |
| R-HSA-399997 | Acetylcholine regulates insulin secretion | 1.096504e-01 | 0.960 |
| R-HSA-6804114 | TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest | 1.096504e-01 | 0.960 |
| R-HSA-372790 | Signaling by GPCR | 1.124796e-01 | 0.949 |
| R-HSA-168928 | DDX58/IFIH1-mediated induction of interferon-alpha/beta | 1.150181e-01 | 0.939 |
| R-HSA-392499 | Metabolism of proteins | 1.163682e-01 | 0.934 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 1.186227e-01 | 0.926 |
| R-HSA-416993 | Trafficking of GluR2-containing AMPA receptors | 1.194513e-01 | 0.923 |
| R-HSA-4419969 | Depolymerization of the Nuclear Lamina | 1.194513e-01 | 0.923 |
| R-HSA-6804760 | Regulation of TP53 Activity through Methylation | 1.194513e-01 | 0.923 |
| R-HSA-428157 | Sphingolipid metabolism | 1.227937e-01 | 0.911 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 1.243117e-01 | 0.905 |
| R-HSA-168249 | Innate Immune System | 1.249320e-01 | 0.903 |
| R-HSA-397014 | Muscle contraction | 1.376212e-01 | 0.861 |
| R-HSA-1236975 | Antigen processing-Cross presentation | 1.426961e-01 | 0.846 |
| R-HSA-202403 | TCR signaling | 1.464883e-01 | 0.834 |
| R-HSA-200425 | Carnitine shuttle | 1.482185e-01 | 0.829 |
| R-HSA-3000170 | Syndecan interactions | 1.482185e-01 | 0.829 |
| R-HSA-5674400 | Constitutive Signaling by AKT1 E17K in Cancer | 1.482185e-01 | 0.829 |
| R-HSA-212436 | Generic Transcription Pathway | 1.574388e-01 | 0.803 |
| R-HSA-5218921 | VEGFR2 mediated cell proliferation | 1.575994e-01 | 0.802 |
| R-HSA-5628897 | TP53 Regulates Metabolic Genes | 1.579868e-01 | 0.801 |
| R-HSA-9931510 | Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene... | 1.622516e-01 | 0.790 |
| R-HSA-1592230 | Mitochondrial biogenesis | 1.637992e-01 | 0.786 |
| R-HSA-201451 | Signaling by BMP | 1.668783e-01 | 0.778 |
| R-HSA-68875 | Mitotic Prophase | 1.696499e-01 | 0.770 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 1.714797e-01 | 0.766 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 1.755104e-01 | 0.756 |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | 1.760560e-01 | 0.754 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 1.760560e-01 | 0.754 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 1.760560e-01 | 0.754 |
| R-HSA-1250196 | SHC1 events in ERBB2 signaling | 1.806073e-01 | 0.743 |
| R-HSA-399719 | Trafficking of AMPA receptors | 1.851338e-01 | 0.733 |
| R-HSA-111465 | Apoptotic cleavage of cellular proteins | 1.896355e-01 | 0.722 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 1.941127e-01 | 0.712 |
| R-HSA-399721 | Glutamate binding, activation of AMPA receptors and synaptic plasticity | 1.941127e-01 | 0.712 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 1.941127e-01 | 0.712 |
| R-HSA-390471 | Association of TriC/CCT with target proteins during biosynthesis | 1.985654e-01 | 0.702 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 2.029937e-01 | 0.693 |
| 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-3858494 | Beta-catenin independent WNT signaling | 2.074199e-01 | 0.683 |
| R-HSA-6804757 | Regulation of TP53 Degradation | 2.117780e-01 | 0.674 |
| R-HSA-9679506 | SARS-CoV Infections | 2.137731e-01 | 0.670 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 2.215658e-01 | 0.654 |
| R-HSA-69541 | Stabilization of p53 | 2.247752e-01 | 0.648 |
| R-HSA-6806003 | Regulation of TP53 Expression and Degradation | 2.247752e-01 | 0.648 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 2.256232e-01 | 0.647 |
| R-HSA-5676590 | NIK-->noncanonical NF-kB signaling | 2.333220e-01 | 0.632 |
| R-HSA-9820841 | M-decay: degradation of maternal mRNAs by maternally stored factors | 2.333220e-01 | 0.632 |
| R-HSA-73857 | RNA Polymerase II Transcription | 2.362946e-01 | 0.627 |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling | 2.417756e-01 | 0.617 |
| R-HSA-1433557 | Signaling by SCF-KIT | 2.459678e-01 | 0.609 |
| R-HSA-5654743 | Signaling by FGFR4 | 2.459678e-01 | 0.609 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 2.501371e-01 | 0.602 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 2.541542e-01 | 0.595 |
| R-HSA-5607761 | Dectin-1 mediated noncanonical NF-kB signaling | 2.542836e-01 | 0.595 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 2.542836e-01 | 0.595 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 2.542836e-01 | 0.595 |
| R-HSA-5654741 | Signaling by FGFR3 | 2.542836e-01 | 0.595 |
| R-HSA-2514859 | Inactivation, recovery and regulation of the phototransduction cascade | 2.584074e-01 | 0.588 |
| R-HSA-75153 | Apoptotic execution phase | 2.584074e-01 | 0.588 |
| 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-2514856 | The phototransduction cascade | 2.786906e-01 | 0.555 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 2.848185e-01 | 0.545 |
| R-HSA-418597 | G alpha (z) signalling events | 2.945214e-01 | 0.531 |
| R-HSA-5578775 | Ion homeostasis | 2.984252e-01 | 0.525 |
| R-HSA-5654736 | Signaling by FGFR1 | 2.984252e-01 | 0.525 |
| R-HSA-6791312 | TP53 Regulates Transcription of Cell Cycle Genes | 3.023075e-01 | 0.520 |
| 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-6790901 | rRNA modification in the nucleus and cytosol | 3.251596e-01 | 0.488 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 3.251596e-01 | 0.488 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 3.251596e-01 | 0.488 |
| R-HSA-8848021 | Signaling by PTK6 | 3.251596e-01 | 0.488 |
| R-HSA-5693606 | DNA Double Strand Break Response | 3.399815e-01 | 0.469 |
| R-HSA-389948 | Co-inhibition by PD-1 | 3.416434e-01 | 0.466 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 3.476640e-01 | 0.459 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 3.544814e-01 | 0.450 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 3.580569e-01 | 0.446 |
| R-HSA-69473 | G2/M DNA damage checkpoint | 3.651492e-01 | 0.438 |
| R-HSA-3000171 | Non-integrin membrane-ECM interactions | 3.686663e-01 | 0.433 |
| R-HSA-4086400 | PCP/CE pathway | 3.791023e-01 | 0.421 |
| R-HSA-5654738 | Signaling by FGFR2 | 3.859647e-01 | 0.413 |
| R-HSA-2151201 | Transcriptional activation of mitochondrial biogenesis | 3.893677e-01 | 0.410 |
| R-HSA-5668541 | TNFR2 non-canonical NF-kB pathway | 3.961179e-01 | 0.402 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 3.990012e-01 | 0.399 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 4.061050e-01 | 0.391 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 4.061050e-01 | 0.391 |
| R-HSA-74160 | Gene expression (Transcription) | 4.203779e-01 | 0.376 |
| R-HSA-9837999 | Mitochondrial protein degradation | 4.382306e-01 | 0.358 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 4.521558e-01 | 0.345 |
| R-HSA-190236 | Signaling by FGFR | 4.536429e-01 | 0.343 |
| R-HSA-69620 | Cell Cycle Checkpoints | 4.558538e-01 | 0.341 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 4.566748e-01 | 0.340 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 4.596901e-01 | 0.338 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 4.656711e-01 | 0.332 |
| R-HSA-418346 | Platelet homeostasis | 4.803386e-01 | 0.318 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 4.916365e-01 | 0.308 |
| R-HSA-6798695 | Neutrophil degranulation | 4.944332e-01 | 0.306 |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer | 5.193232e-01 | 0.285 |
| R-HSA-195721 | Signaling by WNT | 5.267076e-01 | 0.278 |
| R-HSA-3371556 | Cellular response to heat stress | 5.272930e-01 | 0.278 |
| R-HSA-9759194 | Nuclear events mediated by NFE2L2 | 5.272930e-01 | 0.278 |
| R-HSA-9816359 | Maternal to zygotic transition (MZT) | 5.325334e-01 | 0.274 |
| R-HSA-69481 | G2/M Checkpoints | 5.453846e-01 | 0.263 |
| R-HSA-9909396 | Circadian clock | 5.603456e-01 | 0.252 |
| R-HSA-76005 | Response to elevated platelet cytosolic Ca2+ | 5.627914e-01 | 0.250 |
| R-HSA-2187338 | Visual phototransduction | 6.001421e-01 | 0.222 |
| R-HSA-556833 | Metabolism of lipids | 6.022608e-01 | 0.220 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 6.077589e-01 | 0.216 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 6.089757e-01 | 0.215 |
| R-HSA-2142753 | Arachidonate metabolism | 6.111537e-01 | 0.214 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 6.133198e-01 | 0.212 |
| R-HSA-9006936 | Signaling by TGFB family members | 6.281518e-01 | 0.202 |
| R-HSA-109581 | Apoptosis | 6.322852e-01 | 0.199 |
| R-HSA-6791226 | Major pathway of rRNA processing in the nucleolus and cytosol | 6.503304e-01 | 0.187 |
| R-HSA-983169 | Class I MHC mediated antigen processing & presentation | 6.571194e-01 | 0.182 |
| R-HSA-9824439 | Bacterial Infection Pathways | 6.663842e-01 | 0.176 |
| R-HSA-8868773 | rRNA processing in the nucleus and cytosol | 6.838345e-01 | 0.165 |
| R-HSA-8978868 | Fatty acid metabolism | 6.880568e-01 | 0.162 |
| R-HSA-5357801 | Programmed Cell Death | 7.141610e-01 | 0.146 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 7.266986e-01 | 0.139 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 7.459222e-01 | 0.127 |
| R-HSA-72312 | rRNA processing | 7.543376e-01 | 0.122 |
| R-HSA-416476 | G alpha (q) signalling events | 7.947757e-01 | 0.100 |
| R-HSA-9711123 | Cellular response to chemical stress | 7.993432e-01 | 0.097 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 8.060066e-01 | 0.094 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 8.276509e-01 | 0.082 |
| R-HSA-8953854 | Metabolism of RNA | 8.580620e-01 | 0.066 |
| R-HSA-1474244 | Extracellular matrix organization | 8.593392e-01 | 0.066 |
| R-HSA-73894 | DNA Repair | 8.806157e-01 | 0.055 |
| R-HSA-382551 | Transport of small molecules | 9.206294e-01 | 0.036 |
| R-HSA-9709957 | Sensory Perception | 9.992823e-01 | 0.000 |
| R-HSA-1430728 | Metabolism | 9.996113e-01 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
GSK3B |
0.675 | 0.274 | 4 | 0.752 |
GSK3A |
0.663 | 0.248 | 4 | 0.750 |
PDK1 |
0.661 | 0.173 | 1 | 0.739 |
CAMKK2 |
0.657 | 0.147 | -2 | 0.702 |
GAK |
0.656 | 0.094 | 1 | 0.664 |
P70S6KB |
0.655 | 0.204 | -3 | 0.729 |
NLK |
0.655 | 0.134 | 1 | 0.689 |
MST3 |
0.655 | 0.079 | 2 | 0.457 |
VRK1 |
0.654 | 0.182 | 2 | 0.577 |
TAK1 |
0.653 | 0.098 | 1 | 0.665 |
LKB1 |
0.653 | 0.152 | -3 | 0.727 |
CAMKK1 |
0.653 | 0.119 | -2 | 0.694 |
PASK |
0.652 | 0.076 | -3 | 0.713 |
ROCK2 |
0.651 | 0.165 | -3 | 0.720 |
NEK5 |
0.651 | 0.086 | 1 | 0.653 |
JNK2 |
0.650 | 0.089 | 1 | 0.553 |
ICK |
0.650 | 0.122 | -3 | 0.737 |
DAPK1 |
0.650 | 0.109 | -3 | 0.715 |
NEK1 |
0.650 | 0.088 | 1 | 0.647 |
NEK11 |
0.650 | 0.043 | 1 | 0.722 |
NEK8 |
0.650 | 0.064 | 2 | 0.468 |
SGK3 |
0.650 | 0.166 | -3 | 0.724 |
HPK1 |
0.649 | 0.050 | 1 | 0.711 |
NIK |
0.649 | 0.078 | -3 | 0.740 |
DAPK2 |
0.649 | 0.090 | -3 | 0.760 |
CAMLCK |
0.649 | 0.082 | -2 | 0.697 |
NEK4 |
0.649 | 0.068 | 1 | 0.649 |
MEKK3 |
0.649 | 0.042 | 1 | 0.708 |
PKR |
0.649 | 0.102 | 1 | 0.604 |
DLK |
0.648 | 0.056 | 1 | 0.706 |
BRAF |
0.648 | 0.042 | -4 | 0.747 |
VRK2 |
0.648 | 0.059 | 1 | 0.677 |
ERK5 |
0.648 | 0.121 | 1 | 0.692 |
LRRK2 |
0.648 | 0.028 | 2 | 0.489 |
TAO3 |
0.647 | 0.074 | 1 | 0.698 |
GCK |
0.647 | 0.033 | 1 | 0.710 |
JNK3 |
0.647 | 0.076 | 1 | 0.570 |
KHS2 |
0.646 | 0.043 | 1 | 0.697 |
EEF2K |
0.646 | 0.001 | 3 | 0.232 |
MINK |
0.646 | 0.027 | 1 | 0.691 |
TAO2 |
0.646 | 0.016 | 2 | 0.475 |
GRK6 |
0.645 | 0.121 | 1 | 0.691 |
P70S6K |
0.645 | 0.177 | -3 | 0.698 |
PKN3 |
0.644 | 0.137 | -3 | 0.736 |
SGK1 |
0.644 | 0.144 | -3 | 0.620 |
MRCKA |
0.644 | 0.139 | -3 | 0.709 |
ANKRD3 |
0.644 | 0.035 | 1 | 0.707 |
MAP3K15 |
0.644 | 0.025 | 1 | 0.696 |
PLK1 |
0.644 | 0.100 | -2 | 0.516 |
MEK5 |
0.644 | -0.023 | 2 | 0.437 |
CAMK1B |
0.643 | 0.085 | -3 | 0.756 |
ALK4 |
0.643 | 0.038 | -2 | 0.580 |
PBK |
0.643 | 0.089 | 1 | 0.606 |
RAF1 |
0.643 | 0.099 | 1 | 0.705 |
ROCK1 |
0.643 | 0.131 | -3 | 0.708 |
SMMLCK |
0.643 | 0.059 | -3 | 0.745 |
ASK1 |
0.643 | 0.023 | 1 | 0.687 |
MEK1 |
0.642 | -0.010 | 2 | 0.432 |
CDKL1 |
0.642 | 0.081 | -3 | 0.718 |
MEKK1 |
0.642 | 0.040 | 1 | 0.662 |
DRAK1 |
0.642 | 0.078 | 1 | 0.713 |
AKT1 |
0.642 | 0.142 | -3 | 0.695 |
AKT2 |
0.642 | 0.133 | -3 | 0.684 |
ZAK |
0.642 | 0.023 | 1 | 0.682 |
DAPK3 |
0.642 | 0.075 | -3 | 0.720 |
P38A |
0.642 | 0.058 | 1 | 0.615 |
SKMLCK |
0.642 | 0.106 | -2 | 0.718 |
RIPK3 |
0.642 | 0.068 | 3 | 0.227 |
KHS1 |
0.642 | 0.025 | 1 | 0.691 |
NEK9 |
0.642 | 0.116 | 2 | 0.488 |
JNK1 |
0.641 | 0.069 | 1 | 0.542 |
MPSK1 |
0.641 | 0.086 | 1 | 0.576 |
MEKK2 |
0.641 | -0.026 | 2 | 0.455 |
MRCKB |
0.641 | 0.135 | -3 | 0.708 |
NEK2 |
0.641 | 0.095 | 2 | 0.483 |
GRK7 |
0.641 | 0.112 | 1 | 0.700 |
ERK2 |
0.641 | 0.045 | 1 | 0.588 |
MEK2 |
0.641 | 0.033 | 2 | 0.456 |
CLK4 |
0.640 | 0.128 | -3 | 0.717 |
LOK |
0.640 | 0.051 | -2 | 0.602 |
PAK2 |
0.640 | 0.092 | -2 | 0.677 |
YSK1 |
0.640 | 0.034 | 2 | 0.456 |
LATS1 |
0.640 | 0.090 | -3 | 0.691 |
MEKK6 |
0.639 | -0.006 | 1 | 0.664 |
YSK4 |
0.639 | 0.039 | 1 | 0.694 |
DMPK1 |
0.639 | 0.101 | -3 | 0.711 |
WNK1 |
0.639 | 0.079 | -2 | 0.716 |
PAK1 |
0.639 | 0.122 | -2 | 0.684 |
MASTL |
0.638 | 0.086 | -2 | 0.619 |
PKN2 |
0.638 | 0.101 | -3 | 0.742 |
WNK4 |
0.638 | 0.025 | -2 | 0.695 |
IRAK4 |
0.637 | 0.032 | 1 | 0.588 |
HGK |
0.637 | -0.014 | 3 | 0.243 |
HIPK1 |
0.637 | 0.085 | 1 | 0.571 |
ERK7 |
0.637 | 0.065 | 2 | 0.381 |
P38B |
0.637 | 0.050 | 1 | 0.580 |
RIPK1 |
0.637 | 0.035 | 1 | 0.649 |
IRAK1 |
0.636 | 0.024 | -1 | 0.825 |
TNIK |
0.636 | -0.014 | 3 | 0.249 |
RSK2 |
0.636 | 0.158 | -3 | 0.708 |
CAMK2G |
0.636 | 0.071 | 2 | 0.384 |
CRIK |
0.636 | 0.106 | -3 | 0.686 |
DCAMKL1 |
0.636 | 0.122 | -3 | 0.717 |
MLK2 |
0.636 | 0.053 | 2 | 0.446 |
GRK1 |
0.636 | 0.190 | -2 | 0.661 |
DYRK2 |
0.636 | 0.106 | 1 | 0.558 |
ERK1 |
0.636 | 0.059 | 1 | 0.574 |
MAK |
0.636 | 0.115 | -2 | 0.703 |
MLK1 |
0.636 | 0.031 | 2 | 0.452 |
MST4 |
0.635 | 0.098 | 2 | 0.429 |
GRK5 |
0.635 | 0.091 | -3 | 0.645 |
DSTYK |
0.635 | 0.084 | 2 | 0.464 |
HUNK |
0.634 | 0.042 | 2 | 0.497 |
CDK14 |
0.634 | 0.045 | 1 | 0.562 |
RSK4 |
0.634 | 0.149 | -3 | 0.671 |
PIM1 |
0.634 | 0.115 | -3 | 0.695 |
MSK1 |
0.634 | 0.139 | -3 | 0.692 |
PAK6 |
0.634 | 0.156 | -2 | 0.653 |
MST1 |
0.633 | -0.035 | 1 | 0.693 |
TAO1 |
0.633 | 0.026 | 1 | 0.660 |
MYLK4 |
0.633 | 0.074 | -2 | 0.679 |
CDKL5 |
0.633 | 0.097 | -3 | 0.721 |
P90RSK |
0.633 | 0.139 | -3 | 0.709 |
PIM2 |
0.633 | 0.093 | -3 | 0.716 |
PERK |
0.633 | 0.083 | -2 | 0.614 |
HIPK3 |
0.633 | 0.067 | 1 | 0.606 |
MST2 |
0.633 | -0.026 | 1 | 0.704 |
BMPR2 |
0.632 | -0.085 | -2 | 0.631 |
DCAMKL2 |
0.632 | 0.072 | -3 | 0.743 |
MOS |
0.632 | 0.048 | 1 | 0.612 |
PRPK |
0.631 | -0.037 | -1 | 0.799 |
P38G |
0.631 | 0.052 | 1 | 0.498 |
MOK |
0.631 | 0.102 | 1 | 0.564 |
CLK1 |
0.631 | 0.117 | -3 | 0.719 |
PAK3 |
0.631 | 0.093 | -2 | 0.684 |
NEK3 |
0.631 | 0.078 | 1 | 0.659 |
DYRK1A |
0.631 | 0.082 | 1 | 0.597 |
COT |
0.631 | 0.125 | 2 | 0.509 |
PKACG |
0.630 | 0.141 | -2 | 0.614 |
DYRK3 |
0.630 | 0.106 | 1 | 0.562 |
RIPK2 |
0.630 | -0.002 | 1 | 0.685 |
SLK |
0.630 | 0.023 | -2 | 0.544 |
TGFBR1 |
0.630 | 0.042 | -2 | 0.556 |
AURA |
0.630 | 0.115 | -2 | 0.538 |
P38D |
0.630 | 0.068 | 1 | 0.458 |
CDK4 |
0.630 | 0.042 | 1 | 0.515 |
PKCI |
0.630 | 0.084 | 2 | 0.469 |
PDHK4 |
0.630 | 0.039 | 1 | 0.713 |
CHAK1 |
0.630 | 0.023 | 2 | 0.442 |
AURB |
0.630 | 0.113 | -2 | 0.566 |
PKG2 |
0.629 | 0.125 | -2 | 0.574 |
PAK4 |
0.629 | 0.164 | -2 | 0.585 |
PKCH |
0.629 | 0.067 | 2 | 0.443 |
MTOR |
0.629 | 0.081 | 1 | 0.735 |
PAK5 |
0.629 | 0.159 | -2 | 0.590 |
MLK3 |
0.628 | 0.021 | 2 | 0.414 |
CDK6 |
0.628 | 0.025 | 1 | 0.543 |
NEK7 |
0.628 | 0.093 | -3 | 0.736 |
TTBK2 |
0.628 | 0.051 | 2 | 0.445 |
DYRK1B |
0.628 | 0.074 | 1 | 0.547 |
CAMK4 |
0.628 | 0.093 | -3 | 0.735 |
PIM3 |
0.628 | 0.106 | -3 | 0.703 |
BIKE |
0.628 | 0.033 | 1 | 0.574 |
PKCD |
0.628 | 0.069 | 2 | 0.435 |
MYO3B |
0.628 | -0.017 | 2 | 0.458 |
AKT3 |
0.628 | 0.129 | -3 | 0.633 |
CHAK2 |
0.628 | 0.036 | -1 | 0.866 |
PRP4 |
0.627 | 0.007 | -3 | 0.567 |
CAMK2D |
0.627 | 0.124 | -3 | 0.755 |
WNK3 |
0.627 | -0.004 | 1 | 0.658 |
PKCZ |
0.627 | 0.075 | 2 | 0.482 |
CDK10 |
0.627 | 0.060 | 1 | 0.541 |
IKKB |
0.627 | 0.137 | -2 | 0.627 |
ATR |
0.627 | -0.027 | 1 | 0.582 |
AMPKA1 |
0.626 | 0.047 | -3 | 0.748 |
MELK |
0.626 | 0.086 | -3 | 0.740 |
PKCE |
0.626 | 0.073 | 2 | 0.434 |
OSR1 |
0.626 | -0.009 | 2 | 0.429 |
STK33 |
0.626 | 0.001 | 2 | 0.336 |
RSK3 |
0.625 | 0.131 | -3 | 0.707 |
ALK2 |
0.625 | -0.030 | -2 | 0.581 |
MYO3A |
0.625 | -0.059 | 1 | 0.614 |
TBK1 |
0.625 | 0.066 | 1 | 0.708 |
NDR1 |
0.625 | 0.123 | -3 | 0.716 |
ULK2 |
0.625 | 0.089 | 2 | 0.461 |
MLK4 |
0.624 | -0.020 | 2 | 0.414 |
PLK3 |
0.624 | 0.030 | 2 | 0.385 |
MSK2 |
0.624 | 0.109 | -3 | 0.685 |
NUAK2 |
0.623 | 0.031 | -3 | 0.760 |
ULK1 |
0.623 | 0.077 | -3 | 0.695 |
DYRK4 |
0.623 | 0.074 | 1 | 0.514 |
IKKE |
0.622 | 0.066 | 1 | 0.695 |
PDHK1 |
0.622 | 0.011 | 1 | 0.701 |
CDK2 |
0.622 | -0.014 | 1 | 0.628 |
PKN1 |
0.621 | 0.103 | -3 | 0.725 |
NEK6 |
0.621 | 0.112 | -2 | 0.581 |
CLK2 |
0.621 | 0.125 | -3 | 0.683 |
CAMK2B |
0.621 | 0.093 | 2 | 0.348 |
PKCA |
0.621 | 0.057 | 2 | 0.417 |
CDC7 |
0.621 | 0.049 | 1 | 0.594 |
CAMK2A |
0.621 | 0.093 | 2 | 0.344 |
CDK1 |
0.621 | 0.020 | 1 | 0.541 |
MNK1 |
0.621 | 0.127 | -2 | 0.647 |
AURC |
0.620 | 0.136 | -2 | 0.573 |
DNAPK |
0.620 | 0.003 | 1 | 0.556 |
CHK2 |
0.620 | 0.063 | -3 | 0.657 |
HRI |
0.620 | -0.051 | -2 | 0.596 |
GRK4 |
0.620 | 0.075 | -2 | 0.611 |
CLK3 |
0.620 | 0.071 | 1 | 0.627 |
GRK2 |
0.620 | 0.008 | -2 | 0.541 |
STLK3 |
0.620 | -0.059 | 1 | 0.657 |
AMPKA2 |
0.620 | 0.055 | -3 | 0.733 |
PLK4 |
0.619 | 0.038 | 2 | 0.438 |
TTBK1 |
0.619 | 0.022 | 2 | 0.392 |
CDK5 |
0.619 | 0.010 | 1 | 0.561 |
PKCG |
0.619 | 0.049 | 2 | 0.437 |
MNK2 |
0.619 | 0.125 | -2 | 0.644 |
PKCB |
0.618 | 0.050 | 2 | 0.435 |
ALPHAK3 |
0.618 | -0.066 | -1 | 0.761 |
CAMK1G |
0.618 | 0.051 | -3 | 0.723 |
ACVR2B |
0.618 | -0.025 | -2 | 0.541 |
HIPK2 |
0.617 | 0.081 | 1 | 0.485 |
TTK |
0.617 | -0.106 | -2 | 0.542 |
HASPIN |
0.617 | 0.019 | -1 | 0.726 |
PKACA |
0.617 | 0.121 | -2 | 0.537 |
PINK1 |
0.617 | -0.045 | 1 | 0.581 |
BMPR1B |
0.617 | -0.015 | 1 | 0.614 |
PKACB |
0.617 | 0.124 | -2 | 0.570 |
MAPKAPK3 |
0.617 | 0.101 | -3 | 0.719 |
NIM1 |
0.617 | 0.006 | 3 | 0.204 |
ACVR2A |
0.616 | -0.034 | -2 | 0.516 |
CDK9 |
0.616 | 0.024 | 1 | 0.564 |
PKCT |
0.616 | 0.051 | 2 | 0.445 |
IRE1 |
0.616 | -0.025 | 1 | 0.559 |
PLK2 |
0.615 | 0.023 | -3 | 0.534 |
IKKA |
0.614 | 0.084 | -2 | 0.601 |
CDK3 |
0.614 | 0.013 | 1 | 0.499 |
CAMK1D |
0.614 | 0.062 | -3 | 0.693 |
CDK7 |
0.613 | 0.036 | 1 | 0.553 |
PRKX |
0.613 | 0.152 | -3 | 0.654 |
TGFBR2 |
0.613 | 0.004 | -2 | 0.534 |
HIPK4 |
0.612 | 0.074 | 1 | 0.561 |
MAPKAPK5 |
0.612 | 0.079 | -3 | 0.704 |
CDK8 |
0.612 | 0.048 | 1 | 0.562 |
SRPK3 |
0.612 | 0.035 | -3 | 0.660 |
TLK2 |
0.612 | -0.021 | 1 | 0.576 |
PHKG1 |
0.612 | 0.077 | -3 | 0.722 |
YANK3 |
0.611 | -0.020 | 2 | 0.193 |
CDK17 |
0.611 | 0.014 | 1 | 0.494 |
CDK16 |
0.611 | 0.015 | 1 | 0.498 |
PRKD3 |
0.611 | 0.064 | -3 | 0.723 |
CDK12 |
0.610 | 0.015 | 1 | 0.536 |
CDK13 |
0.610 | 0.009 | 1 | 0.545 |
GCN2 |
0.609 | 0.112 | 2 | 0.446 |
BUB1 |
0.609 | -0.014 | -5 | 0.468 |
SNRK |
0.609 | -0.023 | 2 | 0.376 |
AAK1 |
0.609 | 0.030 | 1 | 0.500 |
QIK |
0.608 | -0.045 | -3 | 0.768 |
TSSK2 |
0.608 | -0.071 | -5 | 0.482 |
NDR2 |
0.607 | 0.113 | -3 | 0.694 |
GRK3 |
0.607 | 0.035 | -2 | 0.507 |
SRPK1 |
0.607 | 0.059 | -3 | 0.686 |
LATS2 |
0.607 | 0.079 | -5 | 0.581 |
CHK1 |
0.606 | -0.013 | -3 | 0.704 |
CDK18 |
0.606 | 0.016 | 1 | 0.517 |
IRE2 |
0.606 | -0.087 | 2 | 0.481 |
BMPR1A |
0.605 | -0.038 | 1 | 0.588 |
CK1A2 |
0.604 | 0.020 | -3 | 0.328 |
TLK1 |
0.603 | -0.096 | -2 | 0.568 |
PRKD2 |
0.603 | 0.096 | -3 | 0.715 |
SMG1 |
0.603 | -0.036 | 1 | 0.524 |
MARK4 |
0.603 | -0.079 | 4 | 0.310 |
PHKG2 |
0.603 | 0.061 | -3 | 0.738 |
CAMK1A |
0.602 | 0.055 | -3 | 0.650 |
CDK19 |
0.602 | 0.044 | 1 | 0.538 |
TSSK1 |
0.602 | -0.038 | -3 | 0.750 |
CK2A1 |
0.602 | 0.039 | 1 | 0.484 |
YANK2 |
0.601 | -0.039 | 2 | 0.188 |
PRKD1 |
0.601 | 0.072 | -3 | 0.725 |
MAPKAPK2 |
0.600 | 0.087 | -3 | 0.664 |
ATM |
0.600 | -0.058 | 1 | 0.519 |
SBK |
0.600 | 0.060 | -3 | 0.607 |
BCKDK |
0.598 | -0.018 | -1 | 0.769 |
CK1E |
0.597 | 0.027 | -3 | 0.357 |
CK1D |
0.597 | 0.009 | -3 | 0.318 |
CK2A2 |
0.597 | 0.009 | 1 | 0.493 |
MARK1 |
0.597 | -0.079 | 4 | 0.275 |
SRPK2 |
0.596 | 0.060 | -3 | 0.641 |
PKG1 |
0.595 | 0.088 | -2 | 0.497 |
MARK2 |
0.594 | -0.086 | 4 | 0.225 |
QSK |
0.593 | -0.051 | 4 | 0.276 |
NUAK1 |
0.593 | -0.008 | -3 | 0.731 |
SSTK |
0.592 | -0.074 | 4 | 0.263 |
MARK3 |
0.592 | -0.067 | 4 | 0.266 |
BRSK2 |
0.591 | -0.012 | -3 | 0.751 |
BRSK1 |
0.590 | -0.010 | -3 | 0.729 |
SIK |
0.588 | -0.025 | -3 | 0.711 |
CK1G3 |
0.582 | 0.018 | -3 | 0.200 |
CK1G1 |
0.579 | 0.035 | -3 | 0.331 |
CK1G2 |
0.575 | 0.026 | -3 | 0.267 |
FAM20C |
0.574 | -0.036 | 2 | 0.229 |
KIS |
0.572 | 0.004 | 1 | 0.567 |
CK1A |
0.563 | 0.047 | -3 | 0.234 |
PDHK3_TYR |
0.551 | 0.088 | 4 | 0.450 |
PINK1_TYR |
0.547 | -0.019 | 1 | 0.684 |
MAP2K4_TYR |
0.546 | 0.032 | -1 | 0.825 |
BMPR2_TYR |
0.546 | 0.019 | -1 | 0.821 |
TESK1_TYR |
0.544 | -0.040 | 3 | 0.263 |
PDHK4_TYR |
0.544 | -0.002 | 2 | 0.392 |
MAP2K7_TYR |
0.544 | -0.068 | 2 | 0.432 |
MAP2K6_TYR |
0.544 | -0.026 | -1 | 0.842 |
PKMYT1_TYR |
0.542 | -0.038 | 3 | 0.264 |
DDR1 |
0.542 | -0.035 | 4 | 0.352 |
EPHB4 |
0.542 | -0.022 | -1 | 0.817 |
LIMK2_TYR |
0.542 | 0.016 | -3 | 0.735 |
PDHK1_TYR |
0.540 | -0.055 | -1 | 0.842 |
RET |
0.539 | -0.040 | 1 | 0.689 |
NEK10_TYR |
0.538 | 0.049 | 1 | 0.624 |
ABL2 |
0.538 | 0.027 | -1 | 0.758 |
LIMK1_TYR |
0.537 | -0.053 | 2 | 0.467 |
TNK2 |
0.537 | -0.045 | 3 | 0.188 |
TNK1 |
0.537 | 0.006 | 3 | 0.226 |
MST1R |
0.537 | -0.069 | 3 | 0.230 |
EPHB1 |
0.536 | -0.047 | 1 | 0.699 |
ABL1 |
0.536 | 0.031 | -1 | 0.746 |
TYK2 |
0.535 | -0.064 | 1 | 0.684 |
EPHA6 |
0.534 | -0.068 | -1 | 0.811 |
ROS1 |
0.534 | -0.092 | 3 | 0.216 |
JAK2 |
0.534 | -0.062 | 1 | 0.692 |
TYRO3 |
0.533 | -0.105 | 3 | 0.221 |
PDGFRB |
0.533 | -0.082 | 3 | 0.211 |
JAK1 |
0.532 | 0.001 | 1 | 0.699 |
INSRR |
0.532 | -0.093 | 3 | 0.186 |
NTRK1 |
0.532 | -0.029 | -1 | 0.764 |
CSF1R |
0.532 | -0.085 | 3 | 0.206 |
KDR |
0.532 | -0.083 | 3 | 0.188 |
EPHB2 |
0.531 | -0.055 | -1 | 0.802 |
FLT4 |
0.531 | -0.057 | 3 | 0.227 |
DDR2 |
0.531 | -0.022 | 3 | 0.166 |
JAK3 |
0.530 | -0.064 | 1 | 0.695 |
FGFR2 |
0.530 | -0.101 | 3 | 0.207 |
YES1 |
0.530 | -0.080 | -1 | 0.763 |
NTRK2 |
0.530 | -0.063 | 3 | 0.204 |
ITK |
0.530 | -0.064 | -1 | 0.797 |
MERTK |
0.530 | -0.071 | 3 | 0.217 |
PDGFRA |
0.529 | -0.069 | 3 | 0.223 |
SRMS |
0.529 | -0.052 | 1 | 0.685 |
EPHB3 |
0.529 | -0.068 | -1 | 0.802 |
AXL |
0.529 | -0.091 | 3 | 0.206 |
EPHA4 |
0.529 | -0.068 | 2 | 0.356 |
MUSK |
0.528 | 0.011 | 1 | 0.673 |
ERBB2 |
0.528 | -0.062 | 1 | 0.714 |
HCK |
0.528 | -0.060 | -1 | 0.766 |
LTK |
0.528 | -0.068 | 3 | 0.201 |
BTK |
0.527 | -0.064 | -1 | 0.762 |
FLT1 |
0.527 | -0.049 | -1 | 0.815 |
INSR |
0.526 | -0.070 | 3 | 0.195 |
FLT3 |
0.526 | -0.102 | 3 | 0.205 |
FGFR1 |
0.526 | -0.112 | 3 | 0.201 |
WEE1_TYR |
0.526 | -0.054 | -1 | 0.746 |
EPHA3 |
0.525 | -0.086 | 2 | 0.356 |
EPHA7 |
0.525 | -0.082 | 2 | 0.385 |
FGFR3 |
0.525 | -0.104 | 3 | 0.190 |
TEC |
0.524 | -0.071 | -1 | 0.709 |
FGR |
0.524 | -0.090 | 1 | 0.711 |
ALK |
0.523 | -0.110 | 3 | 0.171 |
TEK |
0.523 | -0.132 | 3 | 0.180 |
TXK |
0.523 | -0.044 | 1 | 0.659 |
FYN |
0.523 | -0.025 | -1 | 0.708 |
BMX |
0.523 | -0.048 | -1 | 0.691 |
EPHA1 |
0.522 | -0.104 | 3 | 0.193 |
KIT |
0.522 | -0.113 | 3 | 0.202 |
PTK6 |
0.522 | -0.023 | -1 | 0.718 |
MET |
0.521 | -0.100 | 3 | 0.201 |
BLK |
0.521 | -0.055 | -1 | 0.765 |
EPHA5 |
0.521 | -0.080 | 2 | 0.354 |
TNNI3K_TYR |
0.521 | -0.040 | 1 | 0.634 |
LCK |
0.520 | -0.067 | -1 | 0.756 |
FER |
0.519 | -0.162 | 1 | 0.683 |
NTRK3 |
0.519 | -0.067 | -1 | 0.706 |
FRK |
0.519 | -0.085 | -1 | 0.790 |
PTK2B |
0.518 | -0.075 | -1 | 0.711 |
EGFR |
0.518 | -0.022 | 1 | 0.671 |
SRC |
0.517 | -0.059 | -1 | 0.705 |
CSK |
0.517 | -0.082 | 2 | 0.375 |
EPHA8 |
0.517 | -0.074 | -1 | 0.782 |
FGFR4 |
0.516 | -0.061 | -1 | 0.745 |
LYN |
0.516 | -0.089 | 3 | 0.203 |
IGF1R |
0.515 | -0.088 | 3 | 0.168 |
SYK |
0.514 | 0.011 | -1 | 0.728 |
EPHA2 |
0.513 | -0.074 | -1 | 0.761 |
PTK2 |
0.513 | -0.032 | -1 | 0.741 |
ERBB4 |
0.512 | -0.040 | 1 | 0.651 |
MATK |
0.505 | -0.104 | -1 | 0.706 |
FES |
0.501 | -0.097 | -1 | 0.659 |
ZAP70 |
0.491 | -0.027 | -1 | 0.655 |