Target Information
Target General Infomation | |||||
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Target ID |
T49368
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Former ID |
TTDR01404
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Target Name |
mRNA of PKC-delta
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Gene Name |
PRKCD
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Synonyms |
PRKCD (mRNA); Protein kinase C delta type catalytic subunit (mRNA); SDK1 (mRNA); Tyrosine-protein kinase PRKCD (mRNA); nPKC-delta (mRNA); PRKCD
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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 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. Negatively regulates B cell proliferation and also has an important function in self- antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. 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. 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. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. 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). 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. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. 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. Phosphorylates MUC1 in the C- terminal and regulates the interaction between MUC1 and beta- catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) ina sphingosine-dependent fashion (By similarity).
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BioChemical Class |
Kinase
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Target Validation |
T49368
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UniProt ID | |||||
EC Number |
EC 2.7.10.2
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Sequence |
MAPFLRIAFNSYELGSLQAEDEANQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKSTFD
AHIYEGRVIQIVLMRAAEEPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMSVQY FLEDVDCKQSMRSEDEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKDFVW GLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTAANSRDTIFQKERFNIDMPHRFKVHNYMS PTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRASR RSDSASSEPVGIYQGFEKKTGVAGEDMQDNSGTYGKIWEGSSKCNINNFIFHKVLGKGSF GKVLLGELKGRGEYFAIKALKKDVVLIDDDVECTMVEKRVLTLAAENPFLTHLICTFQTK DHLFFVMEFLNGGDLMYHIQDKGRFELYRATFYAAEIMCGLQFLHSKGIIYRDLKLDNVL LDRDGHIKIADFGMCKENIFGESRASTFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYE MLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDILEKLFEREPTKRLGVTGNIKIH PFFKTINWTLLEKRRLEPPFRPKVKSPRDYSNFDQEFLNEKARLSYSDKNLIDSMDQSAF AGFSFVNPKFEHLLED |
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Drugs and Mode of Action | |||||
Inhibitor | 8-Octyl-benzolactam-V9 | Drug Info | [528158] | ||
BALANOL | Drug Info | [551285] | |||
Dicarba-Closo-Dodecaborane analogue | Drug Info | [525598] | |||
Diheptan-3-yl 5-(hydroxymethyl)isophthalate | Drug Info | [530134] | |||
Dihexan-3-yl 5-(hydroxymethyl)isophthalate | Drug Info | [530134] | |||
GF-109203 | Drug Info | [529049] | |||
Go 6983 | Drug Info | [534191] | |||
LY-326449 | Drug Info | [534154] | |||
PROSTRATIN | Drug Info | [527606] | |||
Pathways | |||||
KEGG Pathway | Chemokine signaling pathway | ||||
Vascular smooth muscle contraction | |||||
Tight junction | |||||
Fc epsilon RI signaling pathway | |||||
Fc gamma R-mediated phagocytosis | |||||
Neurotrophin signaling pathway | |||||
Inflammatory mediator regulation of TRP channels | |||||
GnRH signaling pathway | |||||
Estrogen signaling pathway | |||||
Type II diabetes mellitus | |||||
NetPath Pathway | IL2 Signaling Pathway | ||||
PANTHER Pathway | Alpha adrenergic receptor signaling pathway | ||||
Alzheimer disease-amyloid secretase pathway | |||||
Angiogenesis | |||||
Apoptosis signaling pathway | |||||
B cell activation | |||||
EGF receptor signaling pathway | |||||
Endothelin signaling pathway | |||||
FGF signaling pathway | |||||
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated 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 | |||||
Thromboxane A2 receptor signaling | |||||
Role of Calcineurin-dependent NFAT signaling in lymphocytes | |||||
IGF1 pathway | |||||
Ceramide signaling pathway | |||||
IFN-gamma pathway | |||||
ErbB1 downstream signaling | |||||
Syndecan-4-mediated signaling events | |||||
IL6-mediated signaling events | |||||
PDGFR-beta signaling pathway | |||||
Hedgehog signaling events mediated by Gli proteins | |||||
Signaling events mediated by VEGFR1 and VEGFR2 | |||||
PAR1-mediated thrombin signaling events | |||||
Syndecan-2-mediated signaling events | |||||
Validated transcriptional targets of TAp63 isoforms | |||||
p53 pathway | |||||
Trk receptor signaling mediated by the MAPK pathway | |||||
Trk receptor signaling mediated by PI3K and PLC-gamma | |||||
Alpha-synuclein signaling | |||||
Reactome | Apoptotic cleavage of cellular proteins | ||||
Calmodulin induced events | |||||
Effects of PIP2 hydrolysis | |||||
DAG and IP3 signaling | |||||
Role of phospholipids in phagocytosis | |||||
G alpha (z) signalling events | |||||
HuR (ELAVL1) binds and stabilizes mRNA | |||||
VEGFR2 mediated cell proliferation | |||||
CLEC7A (Dectin-1) signaling | |||||
Interferon gamma signaling | |||||
WikiPathways | TCR Signaling Pathway | ||||
Type II interferon signaling (IFNG) | |||||
Calcium Regulation in the Cardiac Cell | |||||
Insulin Signaling | |||||
EGF/EGFR Signaling Pathway | |||||
Wnt Signaling Pathway | |||||
Wnt Signaling Pathway and Pluripotency | |||||
MAPK Signaling Pathway | |||||
IL-6 signaling pathway | |||||
G Protein Signaling Pathways | |||||
Myometrial Relaxation and Contraction Pathways | |||||
Regulation of mRNA Stability by Proteins that Bind AU-rich Elements | |||||
DAG and IP3 signaling | |||||
Alpha 6 Beta 4 signaling pathway | |||||
BDNF signaling pathway | |||||
Oncostatin M Signaling Pathway | |||||
Corticotropin-releasing hormone | |||||
AGE/RAGE pathway | |||||
B Cell Receptor Signaling Pathway | |||||
Signaling Pathways in Glioblastoma | |||||
miRs in Muscle Cell Differentiation | |||||
Opioid Signalling | |||||
GPCR downstream signaling | |||||
Effects of PIP2 hydrolysis | |||||
Apoptotic execution phase | |||||
Type II diabetes mellitus | |||||
References | |||||
Ref 525598 | Bioorg Med Chem Lett. 1999 Sep 6;9(17):2561-4.Protein kinase C modulators bearing dicarba-CLOSO-dodecaborane as a hydrophobic pharmacophore. | ||||
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 530134 | J Med Chem. 2009 Jul 9;52(13):3969-81.Design, synthesis, and biological activity of isophthalic acid derivatives targeted to the C1 domain of protein kinase C. | ||||
Ref 534154 | J Med Chem. 1996 Jul 5;39(14):2664-71.(S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-d ione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C beta. | ||||
Ref 534191 | Inhibition of protein kinase C mu by various inhibitors. Differentiation from protein kinase c isoenzymes. FEBS Lett. 1996 Aug 26;392(2):77-80. | ||||
Ref 549607 | US patent application no. 5,959,096, Antisense oligonucleotides against human protein kinase C. |
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