Motif 988 (n=55)

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uniprot	genes	site	source	protein	function
O43293	DAPK3	T180	psp	Death-associated protein kinase 3 (DAP kinase 3) (EC 2.7.11.1) (DAP-like kinase) (Dlk) (MYPT1 kinase) (Zipper-interacting protein kinase) (ZIP-kinase)	Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor. {ECO:0000269\|PubMed:10356987, ECO:0000269\|PubMed:11384979, ECO:0000269\|PubMed:11781833, ECO:0000269\|PubMed:12917339, ECO:0000269\|PubMed:15096528, ECO:0000269\|PubMed:15367680, ECO:0000269\|PubMed:16219639, ECO:0000269\|PubMed:17126281, ECO:0000269\|PubMed:17158456, ECO:0000269\|PubMed:18084323, ECO:0000269\|PubMed:18995835, ECO:0000269\|PubMed:21169990, ECO:0000269\|PubMed:21408167, ECO:0000269\|PubMed:21454679, ECO:0000269\|PubMed:21487036, ECO:0000269\|PubMed:23454120, ECO:0000269\|PubMed:38009294}.
O43930	PRKY	T207	ochoa	Putative serine/threonine-protein kinase PRKY (EC 2.7.11.1)	None
O94806	PRKD3	T739	ochoa	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}.
O96017	CHEK2	T387	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}.
P05129	PRKCG	T518	ochoa	Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13)	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250\|UniProtKB:P63318, ECO:0000250\|UniProtKB:P63319, ECO:0000269\|PubMed:16377624, ECO:0000269\|PubMed:36040231}.
P05771	PRKCB	T504	ochoa	Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13)	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012). Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790). In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116). Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250\|UniProtKB:P68404, ECO:0000269\|PubMed:11598012, ECO:0000269\|PubMed:19176525, ECO:0000269\|PubMed:20228790, ECO:0000269\|PubMed:25313067, ECO:0000269\|PubMed:25982116, ECO:0000269\|PubMed:36040231}.
P17252	PRKCA	T501	ochoa	Protein kinase C alpha type (PKC-A) (PKC-alpha) (EC 2.7.11.13)	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (PubMed:25313067). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000250\|UniProtKB:P20444, ECO:0000269\|PubMed:10848585, ECO:0000269\|PubMed:11909826, ECO:0000269\|PubMed:12724315, ECO:0000269\|PubMed:12832403, ECO:0000269\|PubMed:15016832, ECO:0000269\|PubMed:15504744, ECO:0000269\|PubMed:15526160, ECO:0000269\|PubMed:18056764, ECO:0000269\|PubMed:19176525, ECO:0000269\|PubMed:21576361, ECO:0000269\|PubMed:21806543, ECO:0000269\|PubMed:23990668, ECO:0000269\|PubMed:25313067, ECO:0000269\|PubMed:28028151, ECO:0000269\|PubMed:36040231, ECO:0000269\|PubMed:9738012, ECO:0000269\|PubMed:9830023, ECO:0000269\|PubMed:9873035, ECO:0000269\|PubMed:9927633}.
P17612	PRKACA	T202	ochoa	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	T202	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	T202	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	S215	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}.
P31749	AKT1	T312	ochoa	RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha)	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis (PubMed:11882383, PubMed:15526160, PubMed:15861136, PubMed:21432781, PubMed:21620960, PubMed:31204173). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960, PubMed:29343641, PubMed:31204173). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:11882383, PubMed:15526160, PubMed:21432781, PubMed:21620960). AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271). AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 signaling pathway, and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Part of a positive feedback loop of mTORC2 signaling by mediating phosphorylation of MAPKAP1/SIN1, promoting mTORC2 activation (By similarity). AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075). AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth (By similarity). Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF1 (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062). Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865). Acts as a regulator of mitochondrial calcium uptake by mediating phosphorylation of MICU1 in the mitochondrial intermembrane space, impairing MICU1 maturation (PubMed:30504268). Acts as an inhibitor of tRNA methylation by mediating phosphorylation of the N-terminus of METTL1, thereby inhibiting METTL1 methyltransferase activity (PubMed:15861136). In response to LPAR1 receptor pathway activation, phosphorylates Rabin8/RAB3IP which alters its activity and phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby switching Rab11 vesicular function from preciliary trafficking to endocytic recycling (PubMed:31204173). {ECO:0000250\|UniProtKB:P31750, ECO:0000250\|UniProtKB:P47196, ECO:0000269\|PubMed:10358075, ECO:0000269\|PubMed:10576742, ECO:0000269\|PubMed:10926925, ECO:0000269\|PubMed:11154276, ECO:0000269\|PubMed:11994271, ECO:0000269\|PubMed:12150915, ECO:0000269\|PubMed:12172553, ECO:0000269\|PubMed:12176338, ECO:0000269\|PubMed:12964941, ECO:0000269\|PubMed:15861136, ECO:0000269\|PubMed:16139227, ECO:0000269\|PubMed:16982699, ECO:0000269\|PubMed:17726016, ECO:0000269\|PubMed:18507042, ECO:0000269\|PubMed:19592491, ECO:0000269\|PubMed:19934221, ECO:0000269\|PubMed:20086174, ECO:0000269\|PubMed:20471940, ECO:0000269\|PubMed:20682768, ECO:0000269\|PubMed:23431171, ECO:0000269\|PubMed:30504268, ECO:0000269\|PubMed:31204173, ECO:0000269\|PubMed:31548394, ECO:0000269\|PubMed:32228865, ECO:0000269\|PubMed:32322062, ECO:0000269\|PubMed:33594058, ECO:0000269\|PubMed:9829964, ECO:0000303\|PubMed:11882383, ECO:0000303\|PubMed:15526160, ECO:0000303\|PubMed:21432781, ECO:0000303\|PubMed:21620960}.
P31751	AKT2	T313	ochoa	RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-2) (Protein kinase B beta) (PKB beta) (RAC protein kinase beta) (RAC-PK-beta)	Serine/threonine kinase closely related to AKT1 and AKT3. All 3 enzymes, AKT1, AKT2 and AKT3, are collectively known as AKT kinase. AKT regulates many processes including metabolism, proliferation, cell survival, growth and angiogenesis, through the phosphorylation of a range of downstream substrates. Over 100 substrates have been reported so far, although for most of them, the precise AKT kinase catalyzing the reaction was not specified. AKT regulates glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT also regulates the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT also regulates cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor 1 (IGF1). AKT mediates the antiapoptotic effects of IGF1. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development (PubMed:21432781, PubMed:21620960). In response to lysophosphatidic acid stimulation, inhibits the ciliogenesis cascade. In this context, phosphorylates WDR44, hence stabilizing its interaction with Rab11 and preventing the formation of the ciliogenic Rab11-FIP3-RAB3IP complex. Also phosphorylates RAB3IP/Rabin8, thus may affect RAB3IP guanine nucleotide exchange factor (GEF) activity toward Rab8, which is important for cilia growth (PubMed:31204173). Phosphorylates PKP1, facilitating its interaction with YWHAG and translocation to the nucleus, ultimately resulting in a reduction in keratinocyte intercellular adhesion (By similarity). Phosphorylation of PKP1 increases PKP1 protein stability, translocation to the cytoplasm away from desmosome plaques and PKP1-driven cap-dependent translation (PubMed:23444369). {ECO:0000250\|UniProtKB:Q60823, ECO:0000269\|PubMed:23444369, ECO:0000269\|PubMed:31204173, ECO:0000303\|PubMed:21432781, ECO:0000303\|PubMed:21620960}.; FUNCTION: Several AKT2-specific substrates have been identified, including ANKRD2, C2CD5, CLK2 and PITX2. May play a role in myoblast differentiation. In this context, may act through PITX2 phosphorylation. Unphosphorylated PITX2 associates with an ELAVL1/HuR-containing complex, which stabilizes CCND1 cyclin mRNA, ensuring cell proliferation. Phosphorylation by AKT2 impairs this association, leading to CCND1 mRNA destabilization and progression towards differentiation (By similarity). Also involved in the negative regulation of myogenesis in response to stress conditions. In this context, acts by phosphorylating ANKRD2 (By similarity). May also be a key regulator of glucose uptake. Regulates insulin-stimulated glucose transport by the increase of glucose transporter GLUT4 translocation from intracellular stores to the plasma membrane. In this context, acts by phosphorylating C2CD5/CDP138 on 'Ser-197' in insulin-stimulated adipocytes (By similarity). Through the phosphorylation of CLK2 on 'Thr-343', involved in insulin-regulated suppression of hepatic gluconeogenesis (By similarity). {ECO:0000250\|UniProtKB:Q60823}.
P41743	PRKCI	T416	ochoa\|psp	Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota)	Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis. Involved in early synaptic long term potentiation phase in CA1 hippocampal cells and short term memory formation (By similarity). {ECO:0000250\|UniProtKB:F1M7Y5, ECO:0000269\|PubMed:10356400, ECO:0000269\|PubMed:10467349, ECO:0000269\|PubMed:10906326, ECO:0000269\|PubMed:11042363, ECO:0000269\|PubMed:11724794, ECO:0000269\|PubMed:12871960, ECO:0000269\|PubMed:14684752, ECO:0000269\|PubMed:15994303, ECO:0000269\|PubMed:18270268, ECO:0000269\|PubMed:19327373, ECO:0000269\|PubMed:21189248, ECO:0000269\|PubMed:21419810, ECO:0000269\|PubMed:8226978, ECO:0000269\|PubMed:9346882}.
P49137	MAPKAPK2	T226	ochoa	MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1)	Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269\|PubMed:10383393, ECO:0000269\|PubMed:11844797, ECO:0000269\|PubMed:12456657, ECO:0000269\|PubMed:12565831, ECO:0000269\|PubMed:14499342, ECO:0000269\|PubMed:14517288, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:15629715, ECO:0000269\|PubMed:16278218, ECO:0000269\|PubMed:16456544, ECO:0000269\|PubMed:17481585, ECO:0000269\|PubMed:18021073, ECO:0000269\|PubMed:20932473, ECO:0000269\|PubMed:26616734, ECO:0000269\|PubMed:8093612, ECO:0000269\|PubMed:8280084, ECO:0000269\|PubMed:8774846}.
P51812	RPS6KA3	T231	ochoa	Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2)	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250\|UniProtKB:P18654, ECO:0000269\|PubMed:10436156, ECO:0000269\|PubMed:16213824, ECO:0000269\|PubMed:16223362, ECO:0000269\|PubMed:17360704, ECO:0000269\|PubMed:18722121, ECO:0000269\|PubMed:26158630, ECO:0000269\|PubMed:8250835, ECO:0000269\|PubMed:9770464, ECO:0000303\|PubMed:18508509, ECO:0000303\|PubMed:18813292}.
P51812	RPS6KA3	T581	ochoa	Ribosomal protein S6 kinase alpha-3 (S6K-alpha-3) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 3) (p90-RSK 3) (p90RSK3) (Insulin-stimulated protein kinase 1) (ISPK-1) (MAP kinase-activated protein kinase 1b) (MAPK-activated protein kinase 1b) (MAPKAP kinase 1b) (MAPKAPK-1b) (Ribosomal S6 kinase 2) (RSK-2) (pp90RSK2)	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:16213824, PubMed:16223362, PubMed:17360704, PubMed:9770464). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:10436156, PubMed:9770464). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:18508509, PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:18722121). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (By similarity). In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity). Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and YWHAE binding sites and which contribute to the negative regulation of MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Acts as a regulator of osteoblast differentiation by mediating phosphorylation of ATF4, thereby promoting ATF4 transactivation activity (By similarity). {ECO:0000250\|UniProtKB:P18654, ECO:0000269\|PubMed:10436156, ECO:0000269\|PubMed:16213824, ECO:0000269\|PubMed:16223362, ECO:0000269\|PubMed:17360704, ECO:0000269\|PubMed:18722121, ECO:0000269\|PubMed:26158630, ECO:0000269\|PubMed:8250835, ECO:0000269\|PubMed:9770464, ECO:0000303\|PubMed:18508509, ECO:0000303\|PubMed:18813292}.
P51817	PRKX	T207	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}.
P53350	PLK1	T214	ochoa\|psp	Serine/threonine-protein kinase PLK1 (EC 2.7.11.21) (Polo-like kinase 1) (PLK-1) (Serine/threonine-protein kinase 13) (STPK13)	Serine/threonine-protein kinase that performs several important functions throughout M phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Polo-like kinase proteins act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:23455478, PubMed:23509069, PubMed:28512243, PubMed:8991084). Phosphorylates BORA, BUB1B/BUBR1, CCNB1, CDC25C, CEP55, ECT2, ERCC6L, FBXO5/EMI1, FOXM1, KIF20A/MKLP2, CENPU, NEDD1, NINL, NPM1, NUDC, PKMYT1/MYT1, KIZ, MRE11, PPP1R12A/MYPT1, POLQ, PRC1, RACGAP1/CYK4, RAD51, RHNO1, SGO1, STAG2/SA2, TEX14, TOPORS, p73/TP73, TPT1, WEE1 and HNRNPU (PubMed:11202906, PubMed:12207013, PubMed:12447691, PubMed:12524548, PubMed:12738781, PubMed:12852856, PubMed:12939256, PubMed:14532005, PubMed:14734534, PubMed:15070733, PubMed:15148369, PubMed:15469984, PubMed:16198290, PubMed:16247472, PubMed:16980960, PubMed:17081991, PubMed:17218258, PubMed:17351640, PubMed:17376779, PubMed:17617734, PubMed:18174154, PubMed:18331714, PubMed:18418051, PubMed:18477460, PubMed:18521620, PubMed:18615013, PubMed:19160488, PubMed:19351716, PubMed:19468300, PubMed:19468302, PubMed:19473992, PubMed:19509060, PubMed:19597481, PubMed:22325354, PubMed:23455478, PubMed:23509069, PubMed:25986610, PubMed:26811421, PubMed:28512243, PubMed:37440612, PubMed:37674080, PubMed:8991084). Plays a key role in centrosome functions and the assembly of bipolar spindles by phosphorylating KIZ, NEDD1 and NINL (PubMed:16980960, PubMed:19509060). NEDD1 phosphorylation promotes subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). Phosphorylation of NINL component of the centrosome leads to NINL dissociation from other centrosomal proteins (PubMed:12852856). Involved in mitosis exit and cytokinesis by phosphorylating CEP55, ECT2, KIF20A/MKLP2, CENPU, PRC1 and RACGAP1 (PubMed:12939256, PubMed:16247472, PubMed:17351640, PubMed:19468300, PubMed:19468302). Recruited at the central spindle by phosphorylating and docking PRC1 and KIF20A/MKLP2; creates its own docking sites on PRC1 and KIF20A/MKLP2 by mediating phosphorylation of sites subsequently recognized by the POLO box domains (PubMed:12939256, PubMed:17351640). Phosphorylates RACGAP1, thereby creating a docking site for the Rho GTP exchange factor ECT2 that is essential for the cleavage furrow formation (PubMed:19468300, PubMed:19468302). Promotes the central spindle recruitment of ECT2 (PubMed:16247472). Plays a central role in G2/M transition of mitotic cell cycle by phosphorylating CCNB1, CDC25C, FOXM1, CENPU, PKMYT1/MYT1, PPP1R12A/MYPT1 and WEE1 (PubMed:11202906, PubMed:12447691, PubMed:12524548, PubMed:19160488). Part of a regulatory circuit that promotes the activation of CDK1 by phosphorylating the positive regulator CDC25C and inhibiting the negative regulators WEE1 and PKMYT1/MYT1 (PubMed:11202906). Also acts by mediating phosphorylation of cyclin-B1 (CCNB1) on centrosomes in prophase (PubMed:12447691, PubMed:12524548). Phosphorylates FOXM1, a key mitotic transcription regulator, leading to enhance FOXM1 transcriptional activity (PubMed:19160488). Involved in kinetochore functions and sister chromatid cohesion by phosphorylating BUB1B/BUBR1, FBXO5/EMI1 and STAG2/SA2 (PubMed:15148369, PubMed:15469984, PubMed:17376779, PubMed:18331714). PLK1 is high on non-attached kinetochores suggesting a role of PLK1 in kinetochore attachment or in spindle assembly checkpoint (SAC) regulation (PubMed:17617734). Required for kinetochore localization of BUB1B (PubMed:17376779). Regulates the dissociation of cohesin from chromosomes by phosphorylating cohesin subunits such as STAG2/SA2 (By similarity). Phosphorylates SGO1: required for spindle pole localization of isoform 3 of SGO1 and plays a role in regulating its centriole cohesion function (PubMed:18331714). Mediates phosphorylation of FBXO5/EMI1, a negative regulator of the APC/C complex during prophase, leading to FBXO5/EMI1 ubiquitination and degradation by the proteasome (PubMed:15148369, PubMed:15469984). Acts as a negative regulator of p53 family members: phosphorylates TOPORS, leading to inhibit the sumoylation of p53/TP53 and simultaneously enhance the ubiquitination and subsequent degradation of p53/TP53 (PubMed:19473992). Phosphorylates the transactivation domain of the transcription factor p73/TP73, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates BORA, and thereby promotes the degradation of BORA (PubMed:18521620). Contributes to the regulation of AURKA function (PubMed:18615013, PubMed:18662541). Also required for recovery after DNA damage checkpoint and entry into mitosis (PubMed:18615013, PubMed:18662541). Phosphorylates MISP, leading to stabilization of cortical and astral microtubule attachments required for proper spindle positioning (PubMed:23509069). Together with MEIKIN, acts as a regulator of kinetochore function during meiosis I: required both for mono-orientation of kinetochores on sister chromosomes and protection of centromeric cohesin from separase-mediated cleavage (By similarity). Phosphorylates CEP68 and is required for its degradation (PubMed:25503564). Regulates nuclear envelope breakdown during prophase by phosphorylating DCTN1 resulting in its localization in the nuclear envelope (PubMed:20679239). Phosphorylates the heat shock transcription factor HSF1, promoting HSF1 nuclear translocation upon heat shock (PubMed:15661742). Phosphorylates HSF1 also in the early mitotic period; this phosphorylation regulates HSF1 localization to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase complex induicing HSF1 degradation, and hence mitotic progression (PubMed:18794143). Regulates mitotic progression by phosphorylating RIOK2 (PubMed:21880710). Through the phosphorylation of DZIP1 regulates the localization during mitosis of the BBSome, a ciliary protein complex involved in cilium biogenesis (PubMed:27979967). Regulates DNA repair during mitosis by mediating phosphorylation of POLQ and RHNO1, thereby promoting POLQ recruitment to DNA damage sites (PubMed:37440612, PubMed:37674080). Phosphorylates ATXN10 which may play a role in the regulation of cytokinesis and may stimulate the proteasome-mediated degradation of ATXN10 (PubMed:21857149). {ECO:0000250\|UniProtKB:P70032, ECO:0000250\|UniProtKB:Q5F2C3, ECO:0000269\|PubMed:11202906, ECO:0000269\|PubMed:12207013, ECO:0000269\|PubMed:12447691, ECO:0000269\|PubMed:12524548, ECO:0000269\|PubMed:12738781, ECO:0000269\|PubMed:12852856, ECO:0000269\|PubMed:12939256, ECO:0000269\|PubMed:14532005, ECO:0000269\|PubMed:14734534, ECO:0000269\|PubMed:15070733, ECO:0000269\|PubMed:15148369, ECO:0000269\|PubMed:15469984, ECO:0000269\|PubMed:15661742, ECO:0000269\|PubMed:16198290, ECO:0000269\|PubMed:16247472, ECO:0000269\|PubMed:16980960, ECO:0000269\|PubMed:17081991, ECO:0000269\|PubMed:17218258, ECO:0000269\|PubMed:17351640, ECO:0000269\|PubMed:17376779, ECO:0000269\|PubMed:17617734, ECO:0000269\|PubMed:18174154, ECO:0000269\|PubMed:18331714, ECO:0000269\|PubMed:18418051, ECO:0000269\|PubMed:18477460, ECO:0000269\|PubMed:18521620, ECO:0000269\|PubMed:18615013, ECO:0000269\|PubMed:18662541, ECO:0000269\|PubMed:18794143, ECO:0000269\|PubMed:19160488, ECO:0000269\|PubMed:19351716, ECO:0000269\|PubMed:19468300, ECO:0000269\|PubMed:19468302, ECO:0000269\|PubMed:19473992, ECO:0000269\|PubMed:19509060, ECO:0000269\|PubMed:19597481, ECO:0000269\|PubMed:20679239, ECO:0000269\|PubMed:21857149, ECO:0000269\|PubMed:21880710, ECO:0000269\|PubMed:22325354, ECO:0000269\|PubMed:23455478, ECO:0000269\|PubMed:23509069, ECO:0000269\|PubMed:25503564, ECO:0000269\|PubMed:25986610, ECO:0000269\|PubMed:26811421, ECO:0000269\|PubMed:27979967, ECO:0000269\|PubMed:37440612, ECO:0000269\|PubMed:37674080, ECO:0000269\|PubMed:8991084}.
P54646	PRKAA2	S176	ochoa	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	S186	ochoa	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}.
Q04759	PRKCQ	T542	ochoa	Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation (PubMed:21964608). Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity (PubMed:23509302). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231). {ECO:0000269\|PubMed:11342610, ECO:0000269\|PubMed:14988727, ECO:0000269\|PubMed:15364919, ECO:0000269\|PubMed:16252004, ECO:0000269\|PubMed:16356855, ECO:0000269\|PubMed:16709830, ECO:0000269\|PubMed:19549985, ECO:0000269\|PubMed:21964608, ECO:0000269\|PubMed:23509302, ECO:0000269\|PubMed:36040231, ECO:0000269\|PubMed:8657160}.
Q05655	PRKCD	T511	ochoa	Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]	Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21406692, PubMed:21810427). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21406692, PubMed:21810427). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21406692, PubMed:21810427). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21406692, PubMed:21810427). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575). {ECO:0000250\|UniProtKB:P28867, ECO:0000269\|PubMed:11748588, ECO:0000269\|PubMed:11877440, ECO:0000269\|PubMed:12649167, ECO:0000269\|PubMed:15774464, ECO:0000269\|PubMed:16940418, ECO:0000269\|PubMed:17303575, ECO:0000269\|PubMed:18285462, ECO:0000269\|PubMed:19587372, ECO:0000269\|PubMed:19801500, ECO:0000303\|PubMed:21406692, ECO:0000303\|PubMed:21810427}.
Q13131	PRKAA1	S187	ochoa	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}.
Q13237	PRKG2	T613	ochoa	cGMP-dependent protein kinase 2 (cGK 2) (cGK2) (EC 2.7.11.12) (cGMP-dependent protein kinase II) (cGKII)	Crucial regulator of intestinal secretion and bone growth. Phosphorylates and activates CFTR on the plasma membrane. Plays a key role in intestinal secretion by regulating cGMP-dependent translocation of CFTR in jejunum (PubMed:33106379). Acts downstream of NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863 (By similarity). Acts as a regulator of gene expression and activator of the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear stress, mediates ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast anabolic response to mechanical stimulation (By similarity). {ECO:0000250\|UniProtKB:Q61410, ECO:0000250\|UniProtKB:Q64595, ECO:0000269\|PubMed:33106379}.
Q13976	PRKG1	T521	ochoa	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}.
Q14680	MELK	S171	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	T746	ochoa	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	T285	ochoa	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}.
Q15418	RPS6KA1	T225	ochoa	Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1)	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269\|PubMed:10679322, ECO:0000269\|PubMed:11684016, ECO:0000269\|PubMed:12213813, ECO:0000269\|PubMed:15117958, ECO:0000269\|PubMed:15342917, ECO:0000269\|PubMed:16213824, ECO:0000269\|PubMed:16223362, ECO:0000269\|PubMed:16763566, ECO:0000269\|PubMed:17360704, ECO:0000269\|PubMed:18722121, ECO:0000269\|PubMed:22017876, ECO:0000269\|PubMed:26158630, ECO:0000269\|PubMed:35772404, ECO:0000269\|PubMed:9430688, ECO:0000303\|PubMed:18508509, ECO:0000303\|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269\|PubMed:30842327}.
Q15418	RPS6KA1	T577	ochoa	Ribosomal protein S6 kinase alpha-1 (S6K-alpha-1) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 1) (p90-RSK 1) (p90RSK1) (p90S6K) (MAP kinase-activated protein kinase 1a) (MAPK-activated protein kinase 1a) (MAPKAP kinase 1a) (MAPKAPK-1a) (Ribosomal S6 kinase 1) (RSK-1)	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1 (PubMed:10679322, PubMed:12213813, PubMed:15117958, PubMed:16223362, PubMed:17360704, PubMed:18722121, PubMed:26158630, PubMed:35772404, PubMed:9430688). In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes (PubMed:18508509, PubMed:18813292). In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP (PubMed:12213813, PubMed:16223362). Upon insulin-derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity (PubMed:18508509, PubMed:18813292). Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the pre-initiation complex (PubMed:17360704). In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation (PubMed:16763566). Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway (PubMed:15342917). Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (PubMed:22017876). Mediates cell survival by phosphorylating the pro-apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic function (PubMed:10679322, PubMed:16213824). Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4) (PubMed:11684016). Mediates induction of hepatocyte prolifration by TGFA through phosphorylation of CEBPB (PubMed:18508509, PubMed:18813292). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression (PubMed:18508509, PubMed:18813292). Phosphorylates EPHA2 at 'Ser-897', the RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). In response to mTORC1 activation, phosphorylates EIF4B at 'Ser-406' and 'Ser-422' which stimulates bicarbonate cotransporter SLC4A7 mRNA translation, increasing SLC4A7 protein abundance and function (PubMed:35772404). {ECO:0000269\|PubMed:10679322, ECO:0000269\|PubMed:11684016, ECO:0000269\|PubMed:12213813, ECO:0000269\|PubMed:15117958, ECO:0000269\|PubMed:15342917, ECO:0000269\|PubMed:16213824, ECO:0000269\|PubMed:16223362, ECO:0000269\|PubMed:16763566, ECO:0000269\|PubMed:17360704, ECO:0000269\|PubMed:18722121, ECO:0000269\|PubMed:22017876, ECO:0000269\|PubMed:26158630, ECO:0000269\|PubMed:35772404, ECO:0000269\|PubMed:9430688, ECO:0000303\|PubMed:18508509, ECO:0000303\|PubMed:18813292}.; FUNCTION: (Microbial infection) Promotes the late transcription and translation of viral lytic genes during Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, when constitutively activated. {ECO:0000269\|PubMed:30842327}.
Q16512	PKN1	T778	ochoa\|psp	Serine/threonine-protein kinase N1 (EC 2.7.11.13) (Protease-activated kinase 1) (PAK-1) (Protein kinase C-like 1) (Protein kinase C-like PKN) (Protein kinase PKN-alpha) (Protein-kinase C-related kinase 1) (Serine-threonine protein kinase N)	PKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro. {ECO:0000269\|PubMed:11104762, ECO:0000269\|PubMed:12514133, ECO:0000269\|PubMed:17332740, ECO:0000269\|PubMed:18066052, ECO:0000269\|PubMed:20188095, ECO:0000269\|PubMed:21224381, ECO:0000269\|PubMed:21754995, ECO:0000269\|PubMed:24248594, ECO:0000269\|PubMed:8557118, ECO:0000269\|PubMed:8621664, ECO:0000269\|PubMed:9175763}.
Q16513	PKN2	T820	ochoa	Serine/threonine-protein kinase N2 (EC 2.7.11.13) (PKN gamma) (Protein kinase C-like 2) (Protein-kinase C-related kinase 2)	PKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c-fos serum response factor (SRF). Involved in the negative regulation of ciliogenesis (PubMed:27104747). {ECO:0000269\|PubMed:10226025, ECO:0000269\|PubMed:10926925, ECO:0000269\|PubMed:11777936, ECO:0000269\|PubMed:11781095, ECO:0000269\|PubMed:15123640, ECO:0000269\|PubMed:15364941, ECO:0000269\|PubMed:17332740, ECO:0000269\|PubMed:20188095, ECO:0000269\|PubMed:20974804, ECO:0000269\|PubMed:21754995, ECO:0000269\|PubMed:27104747, ECO:0000269\|PubMed:9121475}.; FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication. {ECO:0000269\|PubMed:15364941}.
Q6P5Z2	PKN3	T722	ochoa	Serine/threonine-protein kinase N3 (EC 2.7.11.13) (Protein kinase PKN-beta) (Protein-kinase C-related kinase 3)	Contributes to invasiveness in malignant prostate cancer. {ECO:0000269\|PubMed:15282551}.
Q7KZI7	MARK2	S212	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}.
Q8IU85	CAMK1D	T184	ochoa	Calcium/calmodulin-dependent protein kinase type 1D (EC 2.7.11.17) (CaM kinase I delta) (CaM kinase ID) (CaM-KI delta) (CaMKI delta) (CaMKID) (CaMKI-like protein kinase) (CKLiK)	Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta. {ECO:0000269\|PubMed:11050006, ECO:0000269\|PubMed:15840691, ECO:0000269\|PubMed:16324104, ECO:0000269\|PubMed:17056143}.
Q8IW41	MAPKAPK5	T186	ochoa	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}.
Q96L34	MARK4	S218	ochoa	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	T1165	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}.
Q9BZL6	PRKD2	T714	ochoa	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}.
Q9P0L2	MARK1	S219	ochoa	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}.
Q9UK32	RPS6KA6	T236	ochoa	Ribosomal protein S6 kinase alpha-6 (S6K-alpha-6) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 6) (p90-RSK 6) (p90RSK6) (Ribosomal S6 kinase 4) (RSK-4) (pp90RSK4)	Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis. {ECO:0000269\|PubMed:15042092, ECO:0000269\|PubMed:15632195}.
Q9Y243	AKT3	T309	ochoa	RAC-gamma serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase Akt-3) (Protein kinase B gamma) (PKB gamma) (RAC-PK-gamma) (STK-2)	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. {ECO:0000269\|PubMed:18524868, ECO:0000269\|PubMed:21191416}.
Q9Y2H1	STK38L	T286	ochoa	Serine/threonine-protein kinase 38-like (EC 2.7.11.1) (NDR2 protein kinase) (Nuclear Dbf2-related kinase 2)	Involved in the regulation of structural processes in differentiating and mature neuronal cells. {ECO:0000250, ECO:0000269\|PubMed:15037617, ECO:0000269\|PubMed:15067004}.
O00141	SGK1	T260	Sugiyama	Serine/threonine-protein kinase Sgk1 (EC 2.7.11.1) (Serum/glucocorticoid-regulated kinase 1)	Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis. Sustained high levels and activity may contribute to conditions such as hypertension and diabetic nephropathy. Isoform 2 exhibited a greater effect on cell plasma membrane expression of SCNN1A/ENAC and Na(+) transport than isoform 1. {ECO:0000269\|PubMed:11154281, ECO:0000269\|PubMed:11410590, ECO:0000269\|PubMed:11696533, ECO:0000269\|PubMed:12397388, ECO:0000269\|PubMed:12590200, ECO:0000269\|PubMed:12634932, ECO:0000269\|PubMed:12650886, ECO:0000269\|PubMed:12761204, ECO:0000269\|PubMed:12911626, ECO:0000269\|PubMed:14623317, ECO:0000269\|PubMed:14706641, ECO:0000269\|PubMed:15040001, ECO:0000269\|PubMed:15044175, ECO:0000269\|PubMed:15234985, ECO:0000269\|PubMed:15319523, ECO:0000269\|PubMed:15496163, ECO:0000269\|PubMed:15733869, ECO:0000269\|PubMed:15737648, ECO:0000269\|PubMed:15845389, ECO:0000269\|PubMed:15888551, ECO:0000269\|PubMed:16036218, ECO:0000269\|PubMed:16443776, ECO:0000269\|PubMed:16982696, ECO:0000269\|PubMed:17382906, ECO:0000269\|PubMed:18005662, ECO:0000269\|PubMed:18304449, ECO:0000269\|PubMed:18753299, ECO:0000269\|PubMed:19447520, ECO:0000269\|PubMed:19756449, ECO:0000269\|PubMed:20511718, ECO:0000269\|PubMed:20730100, ECO:0000269\|PubMed:21865597}.
O00444	PLK4	T174	Sugiyama	Serine/threonine-protein kinase PLK4 (EC 2.7.11.21) (Polo-like kinase 4) (PLK-4) (Serine/threonine-protein kinase 18) (Serine/threonine-protein kinase Sak)	Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2. Required for the recruitment of STIL to the centriole and for STIL-mediated centriole amplification (PubMed:22020124). Phosphorylates CEP131 at 'Ser-78' and PCM1 at 'Ser-372' which is essential for proper organization and integrity of centriolar satellites (PubMed:30804208). {ECO:0000269\|PubMed:16244668, ECO:0000269\|PubMed:16326102, ECO:0000269\|PubMed:17681131, ECO:0000269\|PubMed:18239451, ECO:0000269\|PubMed:19164942, ECO:0000269\|PubMed:21725316, ECO:0000269\|PubMed:22020124, ECO:0000269\|PubMed:27796307, ECO:0000269\|PubMed:30804208}.
Q13464	ROCK1	T237	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}.
Q13233	MAP3K1	T1412	Sugiyama	Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1) (EC 2.3.2.27)	Component of a protein kinase signal transduction cascade (PubMed:9808624). Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4 (PubMed:9808624). May phosphorylate the MAPK8/JNK1 kinase (PubMed:17761173). Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway (PubMed:9808624). {ECO:0000269\|PubMed:17761173, ECO:0000269\|PubMed:9808624}.
Q15349	RPS6KA2	T222	EPSD	Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3)	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269\|PubMed:16878154, ECO:0000269\|PubMed:7623830}.
Q15349	RPS6KA2	T574	Sugiyama	Ribosomal protein S6 kinase alpha-2 (S6K-alpha-2) (EC 2.7.11.1) (90 kDa ribosomal protein S6 kinase 2) (p90-RSK 2) (p90RSK2) (MAP kinase-activated protein kinase 1c) (MAPK-activated protein kinase 1c) (MAPKAP kinase 1c) (MAPKAPK-1c) (Ribosomal S6 kinase 3) (RSK-3) (pp90RSK3)	Serine/threonine-protein kinase that acts downstream of ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of transcription factors, regulates translation, and mediates cellular proliferation, survival, and differentiation. May function as tumor suppressor in epithelial ovarian cancer cells. {ECO:0000269\|PubMed:16878154, ECO:0000269\|PubMed:7623830}.
Q16644	MAPKAPK3	T205	Sugiyama	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}.
Q16816	PHKG1	T187	Sugiyama	Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform (PHK-gamma-M) (EC 2.7.11.19) (Phosphorylase kinase subunit gamma-1) (Serine/threonine-protein kinase PHKG1) (EC 2.7.11.1, EC 2.7.11.26)	Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity). {ECO:0000250}.
Q6P0Q8	MAST2	T688	Sugiyama	Microtubule-associated serine/threonine-protein kinase 2 (EC 2.7.11.1)	Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins. Functions in a multi-protein complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages by forming a complex with TRAF6, resulting in the inhibition of TRAF6 NF-kappa-B activation (By similarity). {ECO:0000250}.
Q9Y2H9	MAST1	T550	Sugiyama	Microtubule-associated serine/threonine-protein kinase 1 (EC 2.7.11.1) (Syntrophin-associated serine/threonine-protein kinase)	Microtubule-associated protein essential for correct brain development (PubMed:30449657). Appears to link the dystrophin/utrophin network with microtubule filaments via the syntrophins. Phosphorylation of DMD or UTRN may modulate their affinities for associated proteins (By similarity). {ECO:0000250\|UniProtKB:Q9R1L5, ECO:0000269\|PubMed:30449657}.
Q9NYY3	PLK2	T243	Sugiyama	Serine/threonine-protein kinase PLK2 (EC 2.7.11.21) (Polo-like kinase 2) (PLK-2) (hPlk2) (Serine/threonine-protein kinase SNK) (hSNK) (Serum-inducible kinase)	Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins that are already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CPAP, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CPAP and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress. {ECO:0000269\|PubMed:15242618, ECO:0000269\|PubMed:19001868, ECO:0000269\|PubMed:20352051, ECO:0000269\|PubMed:20531387}.

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reactome_id	name	p	-log10_p
R-HSA-4420097	VEGFA-VEGFR2 Pathway	1.041389e-13	12.982
R-HSA-194138	Signaling by VEGF	2.693401e-13	12.570
R-HSA-438064	Post NMDA receptor activation events	4.597767e-12	11.337
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	4.953926e-12	11.305
R-HSA-442755	Activation of NMDA receptors and postsynaptic events	2.232914e-11	10.651
R-HSA-111933	Calmodulin induced events	4.186946e-10	9.378
R-HSA-111997	CaM pathway	4.186946e-10	9.378
R-HSA-112315	Transmission across Chemical Synapses	5.814746e-10	9.235
R-HSA-111996	Ca-dependent events	1.178474e-09	8.929
R-HSA-1489509	DAG and IP3 signaling	1.756167e-09	8.755
R-HSA-162582	Signal Transduction	1.633467e-09	8.787
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	1.613353e-09	8.792
R-HSA-112043	PLC beta mediated events	1.061214e-08	7.974
R-HSA-112040	G-protein mediated events	1.868517e-08	7.729
R-HSA-199920	CREB phosphorylation	5.303924e-08	7.275
R-HSA-388396	GPCR downstream signalling	3.850618e-08	7.414
R-HSA-112316	Neuronal System	3.840407e-08	7.416
R-HSA-444257	RSK activation	1.176784e-07	6.929
R-HSA-9010642	ROBO receptors bind AKAP5	1.176784e-07	6.929
R-HSA-9006925	Intracellular signaling by second messengers	1.307727e-07	6.883
R-HSA-372790	Signaling by GPCR	1.494992e-07	6.825
R-HSA-111885	Opioid Signalling	3.303740e-07	6.481
R-HSA-5633007	Regulation of TP53 Activity	4.429762e-07	6.354
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase	6.598128e-07	6.181
R-HSA-6804757	Regulation of TP53 Degradation	7.739840e-07	6.111
R-HSA-6806003	Regulation of TP53 Expression and Degradation	1.074834e-06	5.969
R-HSA-211163	AKT-mediated inactivation of FOXO1A	1.924409e-06	5.716
R-HSA-881907	Gastrin-CREB signalling pathway via PKC and MAPK	2.568755e-06	5.590
R-HSA-392517	Rap1 signalling	2.568755e-06	5.590
R-HSA-111931	PKA-mediated phosphorylation of CREB	3.517812e-06	5.454
R-HSA-975871	MyD88 cascade initiated on plasma membrane	4.273467e-06	5.369
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade	4.273467e-06	5.369
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade	4.273467e-06	5.369
R-HSA-163358	PKA-mediated phosphorylation of key metabolic factors	4.536584e-06	5.343
R-HSA-418597	G alpha (z) signalling events	4.926243e-06	5.307
R-HSA-450294	MAP kinase activation	7.627620e-06	5.118
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	7.363528e-06	5.133
R-HSA-8953897	Cellular responses to stimuli	6.203300e-06	5.207
R-HSA-1227986	Signaling by ERBB2	7.111583e-06	5.148
R-HSA-109581	Apoptosis	6.260349e-06	5.203
R-HSA-975155	MyD88 dependent cascade initiated on endosome	7.716455e-06	5.113
R-HSA-114516	Disinhibition of SNARE formation	8.812011e-06	5.055
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade	9.268176e-06	5.033
R-HSA-450282	MAPK targets/ Nuclear events mediated by MAP kinases	1.125675e-05	4.949
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1.313113e-05	4.882
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade	1.313113e-05	4.882
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade	1.059048e-05	4.975
R-HSA-422475	Axon guidance	9.779830e-06	5.010
R-HSA-448424	Interleukin-17 signaling	1.371246e-05	4.863
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade	1.487811e-05	4.827
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade	1.487811e-05	4.827
R-HSA-198693	AKT phosphorylates targets in the nucleus	1.514382e-05	4.820
R-HSA-198725	Nuclear Events (kinase and transcription factor activation)	1.547167e-05	4.810
R-HSA-3700989	Transcriptional Regulation by TP53	1.601709e-05	4.795
R-HSA-442742	CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1.715562e-05	4.766
R-HSA-9675108	Nervous system development	1.758962e-05	4.755
R-HSA-187037	Signaling by NTRK1 (TRKA)	1.969168e-05	4.706
R-HSA-9614399	Regulation of localization of FOXO transcription factors	2.391625e-05	4.621
R-HSA-8941332	RUNX2 regulates genes involved in cell migration	2.391625e-05	4.621
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR...	2.433780e-05	4.614
R-HSA-8853659	RET signaling	2.506287e-05	4.601
R-HSA-5357801	Programmed Cell Death	2.609226e-05	4.583
R-HSA-198323	AKT phosphorylates targets in the cytosol	3.550479e-05	4.450
R-HSA-5687128	MAPK6/MAPK4 signaling	3.161529e-05	4.500
R-HSA-1358803	Downregulation of ERBB2:ERBB3 signaling	3.550479e-05	4.450
R-HSA-5620912	Anchoring of the basal body to the plasma membrane	4.246169e-05	4.372
R-HSA-6804759	Regulation of TP53 Activity through Association with Co-factors	4.247008e-05	4.372
R-HSA-165159	MTOR signalling	4.490617e-05	4.348
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade	4.499803e-05	4.347
R-HSA-166520	Signaling by NTRKs	4.499803e-05	4.347
R-HSA-9755511	KEAP1-NFE2L2 pathway	4.965800e-05	4.304
R-HSA-8963896	HDL assembly	5.027629e-05	4.299
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production	5.620681e-05	4.250
R-HSA-111447	Activation of BAD and translocation to mitochondria	5.896796e-05	4.229
R-HSA-9755779	SARS-CoV-2 targets host intracellular signalling and regulatory pathways	5.896796e-05	4.229
R-HSA-437239	Recycling pathway of L1	6.481015e-05	4.188
R-HSA-9634600	Regulation of glycolysis by fructose 2,6-bisphosphate metabolism	6.858908e-05	4.164
R-HSA-5099900	WNT5A-dependent internalization of FZD4	6.858908e-05	4.164
R-HSA-69278	Cell Cycle, Mitotic	7.831457e-05	4.106
R-HSA-5683057	MAPK family signaling cascades	8.216233e-05	4.085
R-HSA-9860931	Response of endothelial cells to shear stress	8.568203e-05	4.067
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade	9.284920e-05	4.032
R-HSA-1640170	Cell Cycle	9.757415e-05	4.011
R-HSA-416993	Trafficking of GluR2-containing AMPA receptors	1.034615e-04	3.985
R-HSA-163615	PKA activation	1.034615e-04	3.985
R-HSA-164378	PKA activation in glucagon signalling	1.034615e-04	3.985
R-HSA-9855142	Cellular responses to mechanical stimuli	1.309850e-04	3.883
R-HSA-2559583	Cellular Senescence	1.210706e-04	3.917
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling	1.127898e-04	3.948
R-HSA-166166	MyD88-independent TLR4 cascade	1.127898e-04	3.948
R-HSA-389513	Co-inhibition by CTLA4	1.321406e-04	3.879
R-HSA-5628897	TP53 Regulates Metabolic Genes	1.408860e-04	3.851
R-HSA-198753	ERK/MAPK targets	1.482337e-04	3.829
R-HSA-168898	Toll-like Receptor Cascades	1.618203e-04	3.791
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centr...	1.719070e-04	3.765
R-HSA-380259	Loss of Nlp from mitotic centrosomes	1.719070e-04	3.765
R-HSA-8854518	AURKA Activation by TPX2	2.011187e-04	3.697
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer	2.040111e-04	3.690
R-HSA-392451	G beta:gamma signalling through PI3Kgamma	2.040111e-04	3.690
R-HSA-9634638	Estrogen-dependent nuclear events downstream of ESR-membrane signaling	2.040111e-04	3.690
R-HSA-195721	Signaling by WNT	2.225465e-04	3.653
R-HSA-5621575	CD209 (DC-SIGN) signaling	2.252346e-04	3.647
R-HSA-8963898	Plasma lipoprotein assembly	2.252346e-04	3.647
R-HSA-109582	Hemostasis	2.316496e-04	3.635
R-HSA-212436	Generic Transcription Pathway	2.321997e-04	3.634
R-HSA-5218921	VEGFR2 mediated cell proliferation	2.478380e-04	3.606
R-HSA-450531	Regulation of mRNA stability by proteins that bind AU-rich elements	2.700343e-04	3.569
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes	2.829795e-04	3.548
R-HSA-380287	Centrosome maturation	3.101982e-04	3.508
R-HSA-389357	CD28 dependent PI3K/Akt signaling	2.973365e-04	3.527
R-HSA-399719	Trafficking of AMPA receptors	4.145345e-04	3.382
R-HSA-180024	DARPP-32 events	3.528050e-04	3.452
R-HSA-163685	Integration of energy metabolism	3.194557e-04	3.496
R-HSA-210745	Regulation of gene expression in beta cells	3.528050e-04	3.452
R-HSA-8863795	Downregulation of ERBB2 signaling	3.828692e-04	3.417
R-HSA-3858494	Beta-catenin independent WNT signaling	3.194557e-04	3.496
R-HSA-114452	Activation of BH3-only proteins	3.828692e-04	3.417
R-HSA-9730414	MITF-M-regulated melanocyte development	2.819457e-04	3.550
R-HSA-1266738	Developmental Biology	3.214055e-04	3.493
R-HSA-111465	Apoptotic cleavage of cellular proteins	4.478359e-04	3.349
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition	4.563388e-04	3.341
R-HSA-399721	Glutamate binding, activation of AMPA receptors and synaptic plasticity	4.828084e-04	3.316
R-HSA-6804758	Regulation of TP53 Activity through Acetylation	4.828084e-04	3.316
R-HSA-397795	G-protein beta:gamma signalling	4.828084e-04	3.316
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	5.144012e-04	3.289
R-HSA-163359	Glucagon signaling in metabolic regulation	5.194862e-04	3.284
R-HSA-2262752	Cellular responses to stress	5.395351e-04	3.268
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes	5.559162e-04	3.255
R-HSA-73857	RNA Polymerase II Transcription	6.127872e-04	3.213
R-HSA-163560	Triglyceride catabolism	6.400877e-04	3.194
R-HSA-416476	G alpha (q) signalling events	7.946226e-04	3.100
R-HSA-9711123	Cellular response to chemical stress	8.539840e-04	3.069
R-HSA-422356	Regulation of insulin secretion	8.564962e-04	3.067
R-HSA-8939246	RUNX1 regulates transcription of genes involved in differentiation of myeloid ce...	8.586455e-04	3.066
R-HSA-5218920	VEGFR2 mediated vascular permeability	8.782698e-04	3.056
R-HSA-9607240	FLT3 Signaling	8.782698e-04	3.056
R-HSA-9664433	Leishmania parasite growth and survival	8.867852e-04	3.052
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection	8.867852e-04	3.052
R-HSA-5610783	Degradation of GLI2 by the proteasome	9.317663e-04	3.031
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome	9.317663e-04	3.031
R-HSA-5610780	Degradation of GLI1 by the proteasome	9.317663e-04	3.031
R-HSA-76002	Platelet activation, signaling and aggregation	9.493921e-04	3.023
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	9.872871e-04	3.006
R-HSA-450520	HuR (ELAVL1) binds and stabilizes mRNA	1.019332e-03	2.992
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins	1.166289e-03	2.933
R-HSA-69275	G2/M Transition	1.184551e-03	2.926
R-HSA-75153	Apoptotic execution phase	1.230199e-03	2.910
R-HSA-453274	Mitotic G2-G2/M phases	1.236216e-03	2.908
R-HSA-418594	G alpha (i) signalling events	1.281490e-03	2.892
R-HSA-5617833	Cilium Assembly	1.289533e-03	2.890
R-HSA-9634597	GPER1 signaling	1.364549e-03	2.865
R-HSA-389356	Co-stimulation by CD28	1.364549e-03	2.865
R-HSA-373760	L1CAM interactions	1.632103e-03	2.787
R-HSA-376176	Signaling by ROBO receptors	1.678615e-03	2.775
R-HSA-8948751	Regulation of PTEN stability and activity	1.739786e-03	2.760
R-HSA-1852241	Organelle biogenesis and maintenance	1.981456e-03	2.703
R-HSA-109606	Intrinsic Pathway for Apoptosis	1.992952e-03	2.701
R-HSA-2980766	Nuclear Envelope Breakdown	2.082161e-03	2.681
R-HSA-9664323	FCGR3A-mediated IL10 synthesis	2.188899e-03	2.660
R-HSA-418457	cGMP effects	2.259701e-03	2.646
R-HSA-8979227	Triglyceride metabolism	2.267951e-03	2.644
R-HSA-186712	Regulation of beta-cell development	2.267951e-03	2.644
R-HSA-1280218	Adaptive Immune System	2.348055e-03	2.629
R-HSA-1660661	Sphingolipid de novo biosynthesis	2.364579e-03	2.626
R-HSA-445717	Aquaporin-mediated transport	2.463725e-03	2.608
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	2.511538e-03	2.600
R-HSA-171007	p38MAPK events	2.511538e-03	2.600
R-HSA-1280215	Cytokine Signaling in Immune system	2.870643e-03	2.542
R-HSA-74160	Gene expression (Transcription)	2.956800e-03	2.529
R-HSA-450302	activated TAK1 mediates p38 MAPK activation	4.972590e-03	2.303
R-HSA-156711	Polo-like kinase mediated events	3.644158e-03	2.438
R-HSA-4419969	Depolymerization of the Nuclear Lamina	3.644158e-03	2.438
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane	3.857702e-03	2.414
R-HSA-68886	M Phase	4.559433e-03	2.341
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in ...	5.334581e-03	2.273
R-HSA-167044	Signalling to RAS	4.622458e-03	2.335
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	4.972590e-03	2.303
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	5.164034e-03	2.287
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activ...	3.598446e-03	2.444
R-HSA-388841	Regulation of T cell activation by CD28 family	4.258379e-03	2.371
R-HSA-4086398	Ca2+ pathway	3.857702e-03	2.414
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry	3.726693e-03	2.429
R-HSA-9824443	Parasitic Infection Pathways	6.107857e-03	2.214
R-HSA-9658195	Leishmania infection	6.107857e-03	2.214
R-HSA-69202	Cyclin E associated events during G1/S transition	3.472945e-03	2.459
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs	5.820137e-03	2.235
R-HSA-168249	Innate Immune System	4.932696e-03	2.307
R-HSA-4086400	PCP/CE pathway	4.554824e-03	2.342
R-HSA-168256	Immune System	3.135807e-03	2.504
R-HSA-449147	Signaling by Interleukins	3.280185e-03	2.484
R-HSA-5621481	C-type lectin receptors (CLRs)	6.278077e-03	2.202
R-HSA-8986944	Transcriptional Regulation by MECP2	6.894251e-03	2.162
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance	7.276707e-03	2.138
R-HSA-9619483	Activation of AMPK downstream of NMDARs	7.750380e-03	2.111
R-HSA-392154	Nitric oxide stimulates guanylate cyclase	8.192801e-03	2.087
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK	8.646349e-03	2.063
R-HSA-1474151	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	8.646349e-03	2.063
R-HSA-1250196	SHC1 events in ERBB2 signaling	8.646349e-03	2.063
R-HSA-9614085	FOXO-mediated transcription	8.931173e-03	2.049
R-HSA-68877	Mitotic Prometaphase	9.142426e-03	2.039
R-HSA-5610787	Hedgehog 'off' state	9.152183e-03	2.038
R-HSA-70171	Glycolysis	9.152183e-03	2.038
R-HSA-9009391	Extra-nuclear estrogen signaling	9.376383e-03	2.028
R-HSA-2559580	Oxidative Stress Induced Senescence	9.603781e-03	2.018
R-HSA-114508	Effects of PIP2 hydrolysis	1.057004e-02	1.976
R-HSA-9768919	NPAS4 regulates expression of target genes	1.107789e-02	1.956
R-HSA-187687	Signalling to ERKs	1.159635e-02	1.936
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex	1.266471e-02	1.897
R-HSA-9648002	RAS processing	1.377445e-02	1.861
R-HSA-9007101	Rab regulation of trafficking	1.425325e-02	1.846
R-HSA-70326	Glucose metabolism	1.425325e-02	1.846
R-HSA-2219528	PI3K/AKT Signaling in Cancer	1.454290e-02	1.837
R-HSA-8878166	Transcriptional regulation by RUNX2	1.483589e-02	1.829
R-HSA-8878171	Transcriptional regulation by RUNX1	1.505548e-02	1.822
R-HSA-68875	Mitotic Prophase	1.513222e-02	1.820
R-HSA-68881	Mitotic Metaphase/Anaphase Transition	1.528475e-02	1.816
R-HSA-69206	G1/S Transition	1.698060e-02	1.770
R-HSA-199418	Negative regulation of the PI3K/AKT network	1.861354e-02	1.730
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade	1.861367e-02	1.730
R-HSA-76005	Response to elevated platelet cytosolic Ca2+	1.998075e-02	1.699
R-HSA-2514856	The phototransduction cascade	2.195012e-02	1.659
R-HSA-5358351	Signaling by Hedgehog	2.213327e-02	1.655
R-HSA-6807070	PTEN Regulation	2.250391e-02	1.648
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	2.264508e-02	1.645
R-HSA-9634815	Transcriptional Regulation by NPAS4	2.264508e-02	1.645
R-HSA-165181	Inhibition of TSC complex formation by PKB	2.284070e-02	1.641
R-HSA-453279	Mitotic G1 phase and G1/S transition	2.559124e-02	1.592
R-HSA-6791312	TP53 Regulates Transcription of Cell Cycle Genes	2.625400e-02	1.581
R-HSA-69242	S Phase	2.639702e-02	1.578
R-HSA-9022535	Loss of phosphorylation of MECP2 at T308	2.659725e-02	1.575
R-HSA-165158	Activation of AKT2	2.659725e-02	1.575
R-HSA-9856651	MITF-M-dependent gene expression	2.721636e-02	1.565
R-HSA-109703	PKB-mediated events	3.033960e-02	1.518
R-HSA-165160	PDE3B signalling	3.033960e-02	1.518
R-HSA-176417	Phosphorylation of Emi1	3.033960e-02	1.518
R-HSA-1257604	PIP3 activates AKT signaling	3.333263e-02	1.477
R-HSA-2980767	Activation of NIMA Kinases NEK9, NEK6, NEK7	3.406778e-02	1.468
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet fun...	3.494269e-02	1.457
R-HSA-418555	G alpha (s) signalling events	3.711939e-02	1.430
R-HSA-8978934	Metabolism of cofactors	3.748136e-02	1.426
R-HSA-428890	Role of ABL in ROBO-SLIT signaling	3.778186e-02	1.423
R-HSA-983231	Factors involved in megakaryocyte development and platelet production	3.909378e-02	1.408
R-HSA-8849469	PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1	4.148190e-02	1.382
R-HSA-163680	AMPK inhibits chREBP transcriptional activation activity	4.516793e-02	1.345
R-HSA-9613354	Lipophagy	4.516793e-02	1.345
R-HSA-418889	Caspase activation via Dependence Receptors in the absence of ligand	4.516793e-02	1.345
R-HSA-2151209	Activation of PPARGC1A (PGC-1alpha) by phosphorylation	4.884001e-02	1.311
R-HSA-2179392	EGFR Transactivation by Gastrin	4.884001e-02	1.311
R-HSA-141424	Amplification of signal from the kinetochores	5.117025e-02	1.291
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory si...	5.117025e-02	1.291
R-HSA-9909615	Regulation of PD-L1(CD274) Post-translational modification	5.117025e-02	1.291
R-HSA-9662834	CD163 mediating an anti-inflammatory response	5.249820e-02	1.280
R-HSA-428157	Sphingolipid metabolism	5.319895e-02	1.274
R-HSA-68884	Mitotic Telophase/Cytokinesis	5.614255e-02	1.251
R-HSA-9005891	Loss of function of MECP2 in Rett syndrome	5.977310e-02	1.223
R-HSA-9005895	Pervasive developmental disorders	5.977310e-02	1.223
R-HSA-9697154	Disorders of Nervous System Development	5.977310e-02	1.223
R-HSA-209543	p75NTR recruits signalling complexes	5.977310e-02	1.223
R-HSA-162658	Golgi Cisternae Pericentriolar Stack Reorganization	6.338992e-02	1.198
R-HSA-75035	Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6.338992e-02	1.198
R-HSA-1433559	Regulation of KIT signaling	6.699304e-02	1.174
R-HSA-69618	Mitotic Spindle Checkpoint	6.848339e-02	1.164
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	7.058253e-02	1.151
R-HSA-193639	p75NTR signals via NF-kB	7.058253e-02	1.151
R-HSA-9705683	SARS-CoV-2-host interactions	7.075574e-02	1.150
R-HSA-176412	Phosphorylation of the APC/C	7.415843e-02	1.130
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA	7.415843e-02	1.130
R-HSA-418346	Platelet homeostasis	7.610105e-02	1.119
R-HSA-8939211	ESR-mediated signaling	7.689196e-02	1.114
R-HSA-399997	Acetylcholine regulates insulin secretion	7.772079e-02	1.109
R-HSA-9675151	Disorders of Developmental Biology	7.772079e-02	1.109
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation	7.944527e-02	1.100
R-HSA-6804760	Regulation of TP53 Activity through Methylation	8.480510e-02	1.072
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	8.832715e-02	1.054
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse	9.183587e-02	1.037
R-HSA-69620	Cell Cycle Checkpoints	9.208522e-02	1.036
R-HSA-2500257	Resolution of Sister Chromatid Cohesion	9.563096e-02	1.019
R-HSA-200425	Carnitine shuttle	1.057384e-01	0.976
R-HSA-3000170	Syndecan interactions	1.057384e-01	0.976
R-HSA-933542	TRAF6 mediated NF-kB activation	1.091811e-01	0.962
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives	1.111149e-01	0.954
R-HSA-420029	Tight junction interactions	1.126109e-01	0.948
R-HSA-400685	Sema4D in semaphorin signaling	1.126109e-01	0.948
R-HSA-70221	Glycogen breakdown (glycogenolysis)	1.126109e-01	0.948
R-HSA-5357769	Caspase activation via extrinsic apoptotic signalling pathway	1.160276e-01	0.935
R-HSA-9931510	Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock gene...	1.160276e-01	0.935
R-HSA-5673001	RAF/MAP kinase cascade	1.165830e-01	0.933
R-HSA-3928663	EPHA-mediated growth cone collapse	1.194314e-01	0.923
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)	1.194314e-01	0.923
R-HSA-5684996	MAPK1/MAPK3 signaling	1.224277e-01	0.912
R-HSA-1632852	Macroautophagy	1.240079e-01	0.907
R-HSA-2187338	Visual phototransduction	1.330131e-01	0.876
R-HSA-9022692	Regulation of MECP2 expression and activity	1.395850e-01	0.855
R-HSA-354192	Integrin signaling	1.395850e-01	0.855
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition	1.395850e-01	0.855
R-HSA-73887	Death Receptor Signaling	1.421643e-01	0.847
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis	1.428996e-01	0.845
R-HSA-9612973	Autophagy	1.448038e-01	0.839
R-HSA-5673000	RAF activation	1.462015e-01	0.835
R-HSA-203615	eNOS activation	1.462015e-01	0.835
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers	1.515611e-01	0.819
R-HSA-2467813	Separation of Sister Chromatids	1.554634e-01	0.808
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants	1.560325e-01	0.807
R-HSA-202131	Metabolism of nitric oxide: NOS3 activation and regulation	1.592847e-01	0.798
R-HSA-69541	Stabilization of p53	1.625245e-01	0.789
R-HSA-9604323	Negative regulation of NOTCH4 signaling	1.657521e-01	0.781
R-HSA-8982491	Glycogen metabolism	1.657521e-01	0.781
R-HSA-9909648	Regulation of PD-L1(CD274) expression	1.676320e-01	0.776
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated gene...	1.689674e-01	0.772
R-HSA-9694516	SARS-CoV-2 Infection	1.698730e-01	0.770
R-HSA-5674135	MAP2K and MAPK activation	1.721705e-01	0.764
R-HSA-9656223	Signaling by RAF1 mutants	1.721705e-01	0.764
R-HSA-5675221	Negative regulation of MAPK pathway	1.721705e-01	0.764
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	1.753615e-01	0.756
R-HSA-1433557	Signaling by SCF-KIT	1.785404e-01	0.748
R-HSA-9679506	SARS-CoV Infections	1.812731e-01	0.742
R-HSA-3928662	EPHB-mediated forward signaling	1.817072e-01	0.741
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)	1.817072e-01	0.741
R-HSA-373752	Netrin-1 signaling	1.817072e-01	0.741
R-HSA-201681	TCF dependent signaling in response to WNT	1.827216e-01	0.738
R-HSA-9006931	Signaling by Nuclear Receptors	1.832141e-01	0.737
R-HSA-69613	p53-Independent G1/S DNA Damage Checkpoint	1.848620e-01	0.733
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A	1.848620e-01	0.733
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation	1.848620e-01	0.733
R-HSA-76009	Platelet Aggregation (Plug Formation)	1.848620e-01	0.733
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF	1.880049e-01	0.726
R-HSA-9649948	Signaling downstream of RAS mutants	1.880049e-01	0.726
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants	1.880049e-01	0.726
R-HSA-6802949	Signaling by RAS mutants	1.880049e-01	0.726
R-HSA-2299718	Condensation of Prophase Chromosomes	1.880049e-01	0.726
R-HSA-5357905	Regulation of TNFR1 signaling	1.880049e-01	0.726
R-HSA-9031628	NGF-stimulated transcription	1.942548e-01	0.712
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling	1.952162e-01	0.709
R-HSA-69580	p53-Dependent G1/S DNA damage checkpoint	1.973621e-01	0.705
R-HSA-69563	p53-Dependent G1 DNA Damage Response	1.973621e-01	0.705
R-HSA-109704	PI3K Cascade	2.004575e-01	0.698
R-HSA-1169091	Activation of NF-kappaB in B cells	2.035411e-01	0.691
R-HSA-389948	Co-inhibition by PD-1	2.064146e-01	0.685
R-HSA-5663205	Infectious disease	2.094581e-01	0.679
R-HSA-174178	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins ...	2.096734e-01	0.678
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling	2.106332e-01	0.676
R-HSA-5578775	Ion homeostasis	2.187849e-01	0.660
R-HSA-176814	Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	2.187849e-01	0.660
R-HSA-75893	TNF signaling	2.187849e-01	0.660
R-HSA-112399	IRS-mediated signalling	2.217990e-01	0.654
R-HSA-556833	Metabolism of lipids	2.222289e-01	0.653
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at...	2.277929e-01	0.642
R-HSA-68882	Mitotic Anaphase	2.304292e-01	0.637
R-HSA-2555396	Mitotic Metaphase and Anaphase	2.318489e-01	0.635
R-HSA-8953854	Metabolism of RNA	2.330399e-01	0.633
R-HSA-2428928	IRS-related events triggered by IGF1R	2.337414e-01	0.631
R-HSA-8852276	The role of GTSE1 in G2/M progression after G2 checkpoint	2.366987e-01	0.626
R-HSA-176408	Regulation of APC/C activators between G1/S and early anaphase	2.366987e-01	0.626
R-HSA-6790901	rRNA modification in the nucleus and cytosol	2.396448e-01	0.620
R-HSA-373755	Semaphorin interactions	2.396448e-01	0.620
R-HSA-69615	G1/S DNA Damage Checkpoints	2.396448e-01	0.620
R-HSA-9006927	Signaling by Non-Receptor Tyrosine Kinases	2.396448e-01	0.620
R-HSA-8848021	Signaling by PTK6	2.396448e-01	0.620
R-HSA-2428924	IGF1R signaling cascade	2.425797e-01	0.615
R-HSA-74751	Insulin receptor signalling cascade	2.425797e-01	0.615
R-HSA-6802952	Signaling by BRAF and RAF1 fusions	2.455035e-01	0.610
R-HSA-2404192	Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	2.455035e-01	0.610
R-HSA-5693606	DNA Double Strand Break Response	2.513178e-01	0.600
R-HSA-199991	Membrane Trafficking	2.567325e-01	0.591
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)	2.599566e-01	0.585
R-HSA-174143	APC/C-mediated degradation of cell cycle proteins	2.628143e-01	0.580
R-HSA-453276	Regulation of mitotic cell cycle	2.628143e-01	0.580
R-HSA-157118	Signaling by NOTCH	2.646245e-01	0.577
R-HSA-69473	G2/M DNA damage checkpoint	2.713226e-01	0.567
R-HSA-9013694	Signaling by NOTCH4	2.713226e-01	0.567
R-HSA-3000171	Non-integrin membrane-ECM interactions	2.741372e-01	0.562
R-HSA-416482	G alpha (12/13) signalling events	2.825168e-01	0.549
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells	2.852888e-01	0.545
R-HSA-6802957	Oncogenic MAPK signaling	3.017010e-01	0.520
R-HSA-390466	Chaperonin-mediated protein folding	3.097675e-01	0.509
R-HSA-9663891	Selective autophagy	3.124359e-01	0.505
R-HSA-202424	Downstream TCR signaling	3.177422e-01	0.498
R-HSA-1912408	Pre-NOTCH Transcription and Translation	3.203803e-01	0.494
R-HSA-74752	Signaling by Insulin receptor	3.256263e-01	0.487
R-HSA-2682334	EPH-Ephrin signaling	3.256263e-01	0.487
R-HSA-391251	Protein folding	3.256263e-01	0.487
R-HSA-9837999	Mitochondrial protein degradation	3.308325e-01	0.480
R-HSA-168928	DDX58/IFIH1-mediated induction of interferon-alpha/beta	3.334208e-01	0.477
R-HSA-5607764	CLEC7A (Dectin-1) signaling	3.385678e-01	0.470
R-HSA-193704	p75 NTR receptor-mediated signalling	3.462150e-01	0.461
R-HSA-3371453	Regulation of HSF1-mediated heat shock response	3.537752e-01	0.451
R-HSA-2672351	Stimuli-sensing channels	3.710829e-01	0.431
R-HSA-202403	TCR signaling	3.759436e-01	0.425
R-HSA-2871796	FCERI mediated MAPK activation	3.807674e-01	0.419
R-HSA-1912422	Pre-NOTCH Expression and Processing	3.831655e-01	0.417
R-HSA-2029485	Role of phospholipids in phagocytosis	3.926668e-01	0.406
R-HSA-5653656	Vesicle-mediated transport	3.967555e-01	0.401
R-HSA-1592230	Mitochondrial biogenesis	3.973634e-01	0.401
R-HSA-3371556	Cellular response to heat stress	4.066495e-01	0.391
R-HSA-9759194	Nuclear events mediated by NFE2L2	4.066495e-01	0.391
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	4.112396e-01	0.386
R-HSA-69481	G2/M Checkpoints	4.225626e-01	0.374
R-HSA-5576891	Cardiac conduction	4.336713e-01	0.363
R-HSA-9909396	Circadian clock	4.358677e-01	0.361
R-HSA-196854	Metabolism of vitamins and cofactors	4.368910e-01	0.360
R-HSA-2871837	FCERI mediated NF-kB activation	4.657511e-01	0.332
R-HSA-9679191	Potential therapeutics for SARS	4.780763e-01	0.321
R-HSA-9820448	Developmental Cell Lineages of the Exocrine Pancreas	4.821222e-01	0.317
R-HSA-2142753	Arachidonate metabolism	4.821222e-01	0.317
R-HSA-5693532	DNA Double-Strand Break Repair	4.841335e-01	0.315
R-HSA-8978868	Fatty acid metabolism	4.931669e-01	0.307
R-HSA-983705	Signaling by the B Cell Receptor (BCR)	4.940756e-01	0.306
R-HSA-877300	Interferon gamma signaling	4.960413e-01	0.304
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	5.190513e-01	0.285
R-HSA-2029480	Fcgamma receptor (FCGR) dependent phagocytosis	5.264891e-01	0.279
R-HSA-382551	Transport of small molecules	5.438707e-01	0.265
R-HSA-8868773	rRNA processing in the nucleus and cytosol	5.516411e-01	0.258
R-HSA-6798695	Neutrophil degranulation	5.527765e-01	0.257
R-HSA-983712	Ion channel transport	5.533865e-01	0.257
R-HSA-397014	Muscle contraction	5.933274e-01	0.227
R-HSA-72312	rRNA processing	6.239097e-01	0.205
R-HSA-421270	Cell-cell junction organization	6.508619e-01	0.187
R-HSA-9824446	Viral Infection Pathways	6.531496e-01	0.185
R-HSA-9734767	Developmental Cell Lineages	6.668955e-01	0.176
R-HSA-1643685	Disease	6.796453e-01	0.168
R-HSA-446728	Cell junction organization	6.859218e-01	0.164
R-HSA-1500931	Cell-Cell communication	7.294665e-01	0.137
R-HSA-1474244	Extracellular matrix organization	7.449693e-01	0.128
R-HSA-73894	DNA Repair	7.725036e-01	0.112
R-HSA-913531	Interferon Signaling	7.930611e-01	0.101
R-HSA-1430728	Metabolism	8.140510e-01	0.089
R-HSA-9709957	Sensory Perception	9.596437e-01	0.018
R-HSA-392499	Metabolism of proteins	9.995266e-01	0.000

Download

kinase	JSD_mean	pearson_surrounding	kinase_max_IC_position	max_position_JSD
JNK1	0.516	0.450	1	0.810
P38D	0.508	0.432	1	0.855
P38B	0.505	0.408	1	0.831
JNK3	0.497	0.416	1	0.808
JNK2	0.495	0.408	1	0.834
P38G	0.493	0.419	1	0.851
ERK1	0.493	0.404	1	0.839
P38A	0.492	0.399	1	0.765
DYRK4	0.489	0.415	1	0.833
ERK2	0.489	0.407	1	0.776
DYRK1B	0.488	0.420	1	0.779
HIPK1	0.486	0.374	1	0.745
CDK17	0.485	0.427	1	0.829
DYRK2	0.481	0.389	1	0.764
CDK16	0.481	0.412	1	0.813
CDK8	0.481	0.421	1	0.806
CDK1	0.480	0.390	1	0.792
CDK9	0.478	0.414	1	0.802
CDK7	0.477	0.396	1	0.787
CDK12	0.476	0.403	1	0.823
HIPK2	0.476	0.371	1	0.816
CDK4	0.475	0.361	1	0.823
CDK3	0.475	0.349	1	0.825
CDK6	0.474	0.357	1	0.801
CDK14	0.474	0.392	1	0.783
HIPK3	0.474	0.332	1	0.735
CDK18	0.473	0.410	1	0.811
CDK19	0.473	0.405	1	0.833
CDK13	0.470	0.390	1	0.801
MAK	0.469	0.217	-2	0.253
MOK	0.468	0.210	1	0.649
PRP4	0.466	0.209	-3	0.375
CDK5	0.466	0.358	1	0.754
DYRK3	0.465	0.268	1	0.722
HIPK4	0.464	0.278	1	0.559
DYRK1A	0.463	0.290	1	0.716
NLK	0.462	0.332	1	0.577
CDK2	0.461	0.289	1	0.694
MARK2	0.459	0.186	4	0.782
CDK10	0.459	0.345	1	0.789
ASK1	0.457	0.072	1	0.262
DNAPK	0.455	0.099	1	0.240
ERK5	0.455	0.208	1	0.530
MAP3K15	0.454	0.076	1	0.265
MARK4	0.452	0.192	4	0.683
MPSK1	0.451	0.056	1	0.256
KIS	0.450	0.372	1	0.793
MARK1	0.449	0.152	4	0.704
ALPHAK3	0.448	0.033	-1	0.253
ICK	0.448	0.137	-3	0.434
PDK1	0.448	0.013	1	0.253
MEK1	0.447	0.014	2	0.469
TAO3	0.447	0.050	1	0.259
PINK1	0.447	0.111	1	0.384
MARK3	0.447	0.161	4	0.736
LKB1	0.447	-0.005	-3	0.551
HPK1	0.447	0.022	1	0.242
VRK2	0.446	-0.025	1	0.333
MINK	0.446	-0.005	1	0.238
CAMKK2	0.446	-0.058	-2	0.282
GAK	0.446	-0.016	1	0.243
NEK4	0.446	-0.012	1	0.226
MEK2	0.445	-0.008	2	0.417
MEKK3	0.445	0.017	1	0.250
MEKK6	0.445	0.023	1	0.267
LRRK2	0.445	0.018	2	0.435
BRAF	0.445	-0.045	-4	0.296
NEK1	0.444	-0.018	1	0.211
PBK	0.444	0.002	1	0.231
KHS2	0.443	0.023	1	0.250
MEK5	0.443	-0.032	2	0.423
MTOR	0.443	0.294	1	0.387
NEK11	0.443	0.003	1	0.259
PRPK	0.442	0.047	-1	0.279
MEKK2	0.441	-0.019	2	0.398
QIK	0.441	0.131	-3	0.480
MEKK1	0.441	-0.030	1	0.267
QSK	0.441	0.140	4	0.706
GCK	0.441	-0.013	1	0.235
CK1G3	0.440	0.142	-3	0.231
KHS1	0.440	-0.007	1	0.252
ATR	0.439	0.015	1	0.251
BMPR2	0.439	-0.089	-2	0.263
TAO2	0.439	-0.027	2	0.451
MST3	0.439	0.001	2	0.396
CK1A2	0.439	0.098	-3	0.306
PDHK4	0.438	0.094	1	0.286
CK1D	0.438	0.089	-3	0.316
MYO3A	0.438	-0.009	1	0.235
CLK4	0.437	0.151	-3	0.338
CAMKK1	0.437	-0.107	-2	0.268
TAK1	0.437	-0.127	1	0.211
GSK3A	0.437	0.104	4	0.099
HGK	0.437	-0.039	3	0.213
CK1G2	0.437	0.137	-3	0.264
ZAK	0.436	-0.039	1	0.263
YSK1	0.436	-0.020	2	0.387
ERK7	0.436	0.096	2	0.202
PDHK1	0.435	0.017	1	0.295
TNIK	0.435	-0.036	3	0.218
BIKE	0.435	-0.030	1	0.220
CAMK2G	0.435	0.034	2	0.619
RAF1	0.435	-0.003	1	0.230
NEK3	0.434	-0.023	1	0.272
ALK4	0.434	-0.061	-2	0.250
NEK5	0.434	-0.069	1	0.218
ATM	0.434	0.015	1	0.205
YANK2	0.434	0.045	2	0.302
PASK	0.434	-0.026	-3	0.441
ACVR2A	0.434	-0.033	-2	0.259
TAO1	0.433	-0.027	1	0.250
NUAK2	0.433	0.105	-3	0.404
CLK3	0.433	0.184	1	0.520
ALK2	0.432	-0.052	-2	0.229
ANKRD3	0.432	-0.095	1	0.256
PKR	0.432	-0.120	1	0.233
BMPR1B	0.432	-0.017	1	0.174
MST2	0.431	-0.078	1	0.241
CDKL1	0.431	0.046	-3	0.407
ACVR2B	0.431	-0.041	-2	0.263
SRPK3	0.431	0.089	-3	0.331
IRAK1	0.431	-0.036	-1	0.145
NIM1	0.431	0.150	3	0.280
CAMK1B	0.431	-0.027	-3	0.447
WNK4	0.430	-0.045	-2	0.272
CAMLCK	0.430	-0.059	-2	0.242
BMPR1A	0.430	-0.018	1	0.163
NIK	0.430	-0.080	-3	0.461
DAPK2	0.430	-0.064	-3	0.471
TGFBR1	0.430	-0.037	-2	0.250
AAK1	0.429	-0.015	1	0.215
TLK2	0.429	-0.060	1	0.209
SIK	0.429	0.104	-3	0.351
MASTL	0.429	-0.004	-2	0.259
MYO3B	0.429	-0.057	2	0.398
DLK	0.428	-0.126	1	0.250
MST1	0.428	-0.106	1	0.234
STLK3	0.428	-0.104	1	0.242
SMG1	0.428	-0.016	1	0.231
AMPKA1	0.427	0.022	-3	0.411
TLK1	0.427	-0.070	-2	0.227
NEK8	0.427	-0.114	2	0.377
MOS	0.426	-0.048	1	0.236
WNK1	0.426	-0.013	-2	0.295
SMMLCK	0.426	-0.050	-3	0.420
RIPK1	0.426	-0.048	1	0.206
RIPK2	0.426	-0.049	1	0.241
DSTYK	0.425	-0.002	2	0.546
VRK1	0.425	-0.162	2	0.373
STK33	0.424	-0.018	2	0.335
PLK3	0.424	-0.024	2	0.534
PLK2	0.424	0.001	-3	0.394
HUNK	0.423	0.008	2	0.424
TTK	0.423	-0.090	-2	0.249
CLK2	0.423	0.167	-3	0.285
HASPIN	0.422	-0.037	-1	0.165
GRK2	0.422	-0.032	-2	0.174
YSK4	0.422	-0.119	1	0.228
NEK2	0.422	-0.044	2	0.387
EEF2K	0.422	-0.099	3	0.232
GRK7	0.421	0.001	1	0.207
MST4	0.421	0.023	2	0.456
NEK7	0.421	-0.041	-3	0.626
CLK1	0.421	0.140	-3	0.325
GRK6	0.420	-0.056	1	0.207
GSK3B	0.420	0.008	4	0.098
AMPKA2	0.420	0.019	-3	0.375
DAPK3	0.420	-0.058	-3	0.360
CDKL5	0.419	0.033	-3	0.402
OSR1	0.419	-0.114	2	0.400
SKMLCK	0.419	-0.053	-2	0.248
YANK3	0.418	0.026	2	0.279
CK1G1	0.418	0.115	-3	0.301
PERK	0.418	-0.126	-2	0.294
HRI	0.418	-0.127	-2	0.284
CK2A2	0.418	0.013	1	0.114
IKKB	0.417	0.005	-2	0.293
BRSK2	0.417	0.056	-3	0.404
CK2A1	0.417	0.019	1	0.103
WNK3	0.417	-0.087	1	0.224
LOK	0.417	-0.111	-2	0.254
BRSK1	0.417	0.057	-3	0.355
SSTK	0.417	0.011	4	0.671
FAM20C	0.417	0.167	2	0.758
DAPK1	0.417	-0.045	-3	0.364
CAMK2D	0.417	-0.017	-3	0.461
NEK9	0.417	-0.112	2	0.423
GRK5	0.417	-0.084	-3	0.497
CDC7	0.416	-0.027	1	0.192
CK1E	0.416	0.058	-3	0.329
MLK1	0.416	-0.100	2	0.387
SRPK1	0.416	0.101	-3	0.338
IKKE	0.416	-0.044	1	0.241
TBK1	0.415	-0.061	1	0.235
SBK	0.415	0.042	-3	0.206
DMPK1	0.414	-0.054	-3	0.324
RIPK3	0.414	-0.090	3	0.361
CRIK	0.414	-0.025	-3	0.310
PLK1	0.413	-0.102	-2	0.239
TSSK2	0.413	-0.062	-5	0.557
MLK2	0.413	-0.160	2	0.423
GRK4	0.412	-0.062	-2	0.218
GRK3	0.412	-0.015	-2	0.144
SLK	0.412	-0.096	-2	0.235
PLK4	0.412	-0.007	2	0.284
CK1A	0.412	0.107	-3	0.257
PAK2	0.411	-0.059	-2	0.234
CHAK2	0.411	-0.102	-1	0.144
ROCK2	0.409	-0.075	-3	0.345
GRK1	0.409	-0.040	-2	0.207
BCKDK	0.409	-0.031	-1	0.234
DRAK1	0.408	-0.059	1	0.134
TTBK1	0.408	-0.038	2	0.322
MYLK4	0.408	-0.059	-2	0.223
SGK1	0.408	-0.005	-3	0.228
TSSK1	0.407	-0.045	-3	0.416
CAMK2B	0.406	-0.009	2	0.697
LATS1	0.406	-0.076	-3	0.400
IRAK4	0.406	-0.142	1	0.208
PIM2	0.406	-0.046	-3	0.341
TTBK2	0.405	-0.082	2	0.373
P70S6KB	0.405	-0.051	-3	0.372
SGK3	0.405	-0.030	-3	0.343
NUAK1	0.405	0.029	-3	0.351
NEK6	0.405	-0.076	-2	0.229
PIM1	0.405	-0.040	-3	0.334
TGFBR2	0.404	-0.087	-2	0.237
BUB1	0.404	-0.087	-5	0.585
DCAMKL1	0.404	-0.054	-3	0.319
ROCK1	0.403	-0.072	-3	0.319
IKKA	0.403	-0.039	-2	0.271
CHAK1	0.403	-0.130	2	0.362
SNRK	0.403	-0.023	2	0.293
MRCKB	0.403	-0.067	-3	0.325
COT	0.403	-0.061	2	0.506
AKT2	0.403	-0.029	-3	0.296
SRPK2	0.402	0.076	-3	0.282
DCAMKL2	0.401	-0.056	-3	0.362
MRCKA	0.401	-0.070	-3	0.332
MLK4	0.400	-0.122	2	0.326
IRE1	0.400	-0.099	1	0.204
CAMK2A	0.400	-0.025	2	0.653
CAMK1D	0.400	-0.054	-3	0.299
ULK2	0.399	-0.129	2	0.389
PKCA	0.399	-0.029	2	0.325
PKCI	0.399	-0.052	2	0.305
RSK2	0.398	-0.026	-3	0.352
MAPKAPK5	0.398	-0.048	-3	0.353
CAMK1G	0.397	-0.048	-3	0.363
AKT1	0.397	-0.042	-3	0.301
P90RSK	0.397	-0.025	-3	0.351
MLK3	0.397	-0.095	2	0.348
PKN3	0.397	-0.083	-3	0.395
PKCD	0.397	-0.064	2	0.390
CHK1	0.396	-0.103	-3	0.355
AURA	0.396	-0.057	-2	0.119
PKN2	0.395	-0.081	-3	0.406
PIM3	0.395	-0.091	-3	0.379
PAK3	0.395	-0.091	-2	0.242
PKACG	0.395	-0.052	-2	0.170
IRE2	0.394	-0.115	2	0.296
PAK1	0.394	-0.081	-2	0.229
MSK2	0.393	-0.048	-3	0.353
GCN2	0.393	-0.087	2	0.451
NDR1	0.393	-0.045	-3	0.382
P70S6K	0.393	-0.049	-3	0.328
PKCG	0.391	-0.041	2	0.326
PKCH	0.390	-0.074	2	0.297
PKCZ	0.390	-0.094	2	0.357
PKCE	0.390	-0.058	2	0.301
MSK1	0.390	-0.061	-3	0.333
ULK1	0.389	-0.121	-3	0.529
RSK4	0.388	-0.030	-3	0.314
CHK2	0.388	-0.074	-3	0.247
MELK	0.388	-0.109	-3	0.375
PKCT	0.387	-0.071	2	0.313
CAMK4	0.385	-0.137	-3	0.396
AURB	0.385	-0.088	-2	0.143
PKCB	0.384	-0.065	2	0.327
RSK3	0.383	-0.044	-3	0.334
PRKD3	0.382	-0.082	-3	0.341
PKACB	0.382	-0.045	-2	0.150
PRKD1	0.382	-0.074	-3	0.401
PKG2	0.381	-0.094	-2	0.152
MAPKAPK3	0.380	-0.112	-3	0.349
AKT3	0.380	-0.043	-3	0.245
CAMK1A	0.380	-0.076	-3	0.248
NDR2	0.380	-0.044	-3	0.390
PHKG1	0.379	-0.102	-3	0.387
PKACA	0.377	-0.059	-2	0.132
PAK5	0.377	-0.079	-2	0.175
PAK6	0.376	-0.077	-2	0.215
MNK1	0.374	-0.093	-2	0.233
PKMYT1_TYR	0.373	0.269	3	0.326
PRKD2	0.372	-0.081	-3	0.336
MNK2	0.372	-0.103	-2	0.234
PKN1	0.372	-0.082	-3	0.346
PAK4	0.371	-0.073	-2	0.165
LATS2	0.370	-0.097	-5	0.607
MAPKAPK2	0.368	-0.073	-3	0.287
AURC	0.368	-0.086	-2	0.145
PRKX	0.368	-0.042	-3	0.251
PHKG2	0.366	-0.114	-3	0.362
PKG1	0.366	-0.092	-2	0.149
FGFR4	0.362	0.055	-1	0.216
PDHK1_TYR	0.362	0.124	-1	0.218
MAP2K4_TYR	0.361	0.146	-1	0.287
MAP2K7_TYR	0.359	0.108	2	0.503
LYN	0.358	0.020	3	0.422
BMPR2_TYR	0.358	0.042	-1	0.256
MAP2K6_TYR	0.357	0.094	-1	0.255
JAK2	0.355	-0.032	1	0.301
LIMK1_TYR	0.355	0.073	2	0.465
PDHK4_TYR	0.354	0.076	2	0.549
ERBB2	0.354	-0.017	1	0.226
KIT	0.353	-0.023	3	0.351
PDHK3_TYR	0.352	0.009	4	0.400
TEK	0.351	-0.005	3	0.335
SRC	0.351	0.008	-1	0.156
TESK1_TYR	0.351	0.012	3	0.263
FYN	0.350	0.002	-1	0.143
TYK2	0.350	-0.078	1	0.268
FER	0.350	-0.067	1	0.225
FGFR1	0.350	-0.031	3	0.303
MST1R	0.349	-0.076	3	0.306
FLT4	0.349	-0.012	3	0.428
ERBB4	0.348	-0.014	1	0.200
EPHA4	0.348	-0.032	2	0.544
FGFR3	0.348	-0.021	3	0.316
EPHA3	0.348	-0.040	2	0.509
JAK1	0.348	-0.032	1	0.272
PINK1_TYR	0.347	-0.040	1	0.257
CSF1R	0.347	-0.056	3	0.336
YES1	0.347	-0.017	-1	0.162
HCK	0.347	-0.060	-1	0.150
DDR1	0.346	-0.055	4	0.404
FGFR2	0.346	-0.046	3	0.308
BMX	0.346	-0.044	-1	0.207
NTRK3	0.346	-0.050	-1	0.227
FLT1	0.345	-0.032	-1	0.179
CSK	0.345	-0.049	2	0.508
LIMK2_TYR	0.345	-0.015	-3	0.501
NTRK2	0.345	-0.079	3	0.346
FLT3	0.344	-0.089	3	0.313
NTRK1	0.344	-0.066	-1	0.218
INSR	0.344	-0.056	3	0.320
LTK	0.344	-0.062	3	0.352
IGF1R	0.344	-0.034	3	0.349
KDR	0.344	-0.047	3	0.352
EPHB2	0.344	-0.084	-1	0.149
EPHA2	0.344	-0.040	-1	0.166
MET	0.343	-0.069	3	0.288
EPHA7	0.343	-0.062	2	0.517
ROS1	0.343	-0.093	3	0.304
ITK	0.343	-0.082	-1	0.160
EPHB1	0.343	-0.108	1	0.242
INSRR	0.342	-0.063	3	0.304
EPHA8	0.342	-0.053	-1	0.150
FGR	0.342	-0.070	1	0.218
SRMS	0.341	-0.101	1	0.211
ABL1	0.341	-0.085	-1	0.205
FES	0.340	-0.051	-1	0.211
MATK	0.340	-0.038	-1	0.223
BLK	0.340	-0.059	-1	0.137
TNNI3K_TYR	0.339	-0.050	1	0.340
ABL2	0.339	-0.091	-1	0.207
EGFR	0.339	-0.045	1	0.208
SYK	0.339	-0.032	-1	0.164
EPHA5	0.339	-0.064	2	0.541
TEC	0.339	-0.086	-1	0.161
RET	0.338	-0.145	1	0.271
LCK	0.338	-0.082	-1	0.144
JAK3	0.338	-0.111	1	0.255
PTK6	0.337	-0.109	-1	0.192
BTK	0.337	-0.121	-1	0.152
WEE1_TYR	0.337	-0.066	-1	0.250
EPHB3	0.337	-0.119	-1	0.144
EPHA6	0.337	-0.127	-1	0.162
ALK	0.336	-0.108	3	0.294
EPHB4	0.336	-0.133	-1	0.169
PTK2	0.336	-0.033	-1	0.133
PDGFRB	0.336	-0.126	3	0.303
NEK10_TYR	0.335	-0.081	1	0.210
TYRO3	0.335	-0.151	3	0.286
PDGFRA	0.334	-0.126	3	0.310
MERTK	0.333	-0.111	3	0.352
PTK2B	0.333	-0.086	-1	0.156
TNK1	0.333	-0.073	3	0.325
TXK	0.333	-0.103	1	0.201
FRK	0.331	-0.113	-1	0.136
DDR2	0.330	-0.056	3	0.284
AXL	0.329	-0.145	3	0.308
TNK2	0.328	-0.142	3	0.262
ZAP70	0.328	-0.027	-1	0.229
EPHA1	0.327	-0.138	3	0.306
MUSK	0.320	-0.103	1	0.178