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MGP002422

UniProt Annotations

Entry Information
Gene Nameprotein kinase C, beta
Protein EntryKPCB_HUMAN
UniProt IDP05771
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=Beta-I; Synonyms=PRKCB1; IsoId=P05771-1; Sequence=Displayed; Name=Beta-II; Synonyms=PRKCB2; IsoId=P05771-2; Sequence=VSP_004738; Note=Contains a phosphoserine at position 660. Contains a phosphothreonine at position 641.;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein. {ECO:0000269|PubMed:20228790}.
CofactorName=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain. {ECO:0000250};
Enzyme RegulationClassical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615). {ECO:0000269|PubMed:16103100}.
FunctionCalcium-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. 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 (ANDR)-dependent transcription, by being recruited to ANDR 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. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1- MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. 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. {ECO:0000250, ECO:0000269|PubMed:11598012, ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:20228790}.
InteractionO60346:PHLPP1; NbExp=5; IntAct=EBI-5774511, EBI-2511516;
PtmPhosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade (By similarity). {ECO:0000250}.
SimilarityBelongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}.
SimilarityContains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
SimilarityContains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 2 phorbol-ester/DAG-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00226}.
Subcellular LocationCytoplasm {ECO:0000250}. Nucleus {ECO:0000269|PubMed:20228790}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
SubunitInteracts with PDK1 (By similarity). Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR. {ECO:0000250, ECO:0000269|PubMed:17115692, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:20228790}.
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/prkcb1/";
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