Target Information
Target General Infomation | |||||
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Target ID |
T93262
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Former ID |
TTDR01401
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Target Name |
mRNA of PKC-epsilon
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Gene Name |
PRKCE
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Synonyms |
PRKCE (mRNA); nPKC-epsilon (mRNA); PRKCE
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Target Type |
Discontinued
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Disease | Human immunodeficiency virus infection [ICD9: 279.3; ICD10: B20-B26] | ||||
Function |
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activatesPTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanismwhich may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F- actin via interactionwith COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to theintoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat responsein nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL- mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1.
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BioChemical Class |
Kinase
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Target Validation |
T93262
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UniProt ID | |||||
EC Number |
EC 2.7.11.13
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Sequence |
MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKT
NSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLE PEGRVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQP TYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDQVGSQRFSVN MPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIA KVLADLGVTPDKITNSGQRRKKLIAGAESPQPASGSSPSEEDRSKSAPTSPCDQEIKELE NNIRKALSFDNRGEEHRAASSPDGQLMSPGENGEVRQGQAKRLGLDEFNFIKVLGKGSFG KVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKD RLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILL DAEGHCKLADFGMCKEGILNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEM MAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVASQNGED AIKQHPFFKEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPVLTLVDEAIVKQI NQEEFKGFSYFGEDLMP |
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Drugs and Mode of Action | |||||
Pathways | |||||
KEGG Pathway | cGMP-PKG signaling pathway | ||||
Sphingolipid signaling pathway | |||||
Vascular smooth muscle contraction | |||||
Tight junction | |||||
Fc epsilon RI signaling pathway | |||||
Fc gamma R-mediated phagocytosis | |||||
Inflammatory mediator regulation of TRP channels | |||||
Type II diabetes mellitus | |||||
MicroRNAs in cancer | |||||
NetPath Pathway | IL2 Signaling Pathway | ||||
PANTHER Pathway | Alpha adrenergic receptor signaling pathway | ||||
Alzheimer disease-amyloid secretase pathway | |||||
Angiogenesis | |||||
Apoptosis signaling pathway | |||||
EGF receptor signaling pathway | |||||
Endothelin signaling pathway | |||||
FGF signaling pathway | |||||
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
Inflammation mediated by chemokine and cytokine signaling pathway | |||||
Muscarinic acetylcholine receptor 1 and 3 signaling pathway | |||||
VEGF signaling pathway | |||||
Wnt signaling pathway | |||||
5HT2 type receptor mediated signaling pathway | |||||
Histamine H1 receptor mediated signaling pathway | |||||
Oxytocin receptor mediated signaling pathway | |||||
Thyrotropin-releasing hormone receptor signaling pathway | |||||
CCKR signaling map ST | |||||
Pathway Interaction Database | Endothelins | ||||
LPA receptor mediated events | |||||
TCR signaling in na& | |||||
#xef | |||||
ve CD4+ T cells | |||||
LPA4-mediated signaling events | |||||
CDC42 signaling events | |||||
TCR signaling in na& | |||||
ve CD8+ T cells | |||||
Thromboxane A2 receptor signaling | |||||
Role of Calcineurin-dependent NFAT signaling in lymphocytes | |||||
IL2-mediated signaling events | |||||
PDGFR-beta signaling pathway | |||||
IL8- and CXCR1-mediated signaling events | |||||
Regulation of Ras family activation | |||||
Downstream signaling in na& | |||||
Reactome | Effects of PIP2 hydrolysis | ||||
DAG and IP3 signaling | |||||
Role of phospholipids in phagocytosis | |||||
G alpha (z) signalling events | |||||
WikiPathways | Hypothetical Network for Drug Addiction | ||||
Calcium Regulation in the Cardiac Cell | |||||
Wnt Signaling Pathway | |||||
Wnt Signaling Pathway and Pluripotency | |||||
G Protein Signaling Pathways | |||||
Myometrial Relaxation and Contraction Pathways | |||||
Oncostatin M Signaling Pathway | |||||
miRs in Muscle Cell Differentiation | |||||
GPCR downstream signaling | |||||
Effects of PIP2 hydrolysis | |||||
Physiological and Pathological Hypertrophy of the Heart | |||||
References | |||||
Ref 527221 | Bioorg Med Chem Lett. 2004 Oct 18;14(20):5171-4.Synthesis of anilino-monoindolylmaleimides as potent and selective PKCbeta inhibitors. | ||||
Ref 527606 | J Med Chem. 1992 May 29;35(11):1978-86.A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. | ||||
Ref 528158 | J Med Chem. 2006 May 4;49(9):2681-8.Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase C epsilon and eta. | ||||
Ref 529049 | J Biol Chem. 2007 Nov 9;282(45):33052-63. Epub 2007 Sep 17.Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. | ||||
Ref 529213 | Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. |
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