ID:KPCB_HUMAN DESCRIPTION: RecName: Full=Protein kinase C beta type; Short=PKC-B; Short=PKC-beta; EC=2.7.11.13; FUNCTION: 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. 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). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Binds 3 calcium ions per subunit. The ions are bound to the C2 domain (By similarity). ENZYME REGULATION: Classical (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). SUBUNIT: Interacts 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. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus. Membrane; Peripheral membrane protein (By similarity). PTM: Phosphorylation 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). SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 2 phorbol-ester/DAG-type zinc fingers. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/prkcb1/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05771
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC036472 - Homo sapiens protein kinase C, beta, mRNA (cDNA clone MGC:41878 IMAGE:5260547), complete cds. X07109 - Human mRNA for protein kinase C (PKC) type beta II. X06318 - Human mRNA for protein kinase C (PKC) type beta I. M13975 - Homo sapiens protein kinase C beta-II type (PRKCB1) mRNA, complete cds. AB587511 - Synthetic construct DNA, clone: pF1KB9948, Homo sapiens PRKCB gene for protein kinase C, beta, without stop codon, in Flexi system. EU832791 - Synthetic construct Homo sapiens clone HAIB:100067820; DKFZo008C1033 protein kinase C, beta 1 protein (PRKCB1) gene, encodes complete protein. GQ129253 - Synthetic construct Homo sapiens clone HAIB:100068480; DKFZo004C1034 protein kinase C, beta 1 protein (PRKCB1) gene, partial cds. KJ891888 - Synthetic construct Homo sapiens clone ccsbBroadEn_01282 PRKCB gene, encodes complete protein. KJ905287 - Synthetic construct Homo sapiens clone ccsbBroadEn_14789 PRKCB gene, encodes complete protein. DL491573 - Novel nucleic acids. DL490174 - Novel nucleic acids. JD139659 - Sequence 120683 from Patent EP1572962. JD023002 - Sequence 4026 from Patent EP1572962. JD033248 - Sequence 14272 from Patent EP1572962. AL833252 - Homo sapiens mRNA; cDNA DKFZp761J0720 (from clone DKFZp761J0720). BC045175 - Homo sapiens cDNA clone IMAGE:5277735, with apparent retained intron. AK123381 - Homo sapiens cDNA FLJ41387 fis, clone BRCAN2024259, weakly similar to PROTEIN KINASE C, BETA-I TYPE (EC 2.7.1.-). AK057555 - Homo sapiens cDNA FLJ32993 fis, clone THYMU1000103, weakly similar to PROTEIN KINASE C, BETA-I TYPE (EC 2.7.1.-).
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_cxcr4Pathway - CXCR4 Signaling Pathway h_pdgfPathway - PDGF Signaling Pathway h_srcRPTPPathway - Activation of Src by Protein-tyrosine phosphatase alpha h_Par1Pathway - Thrombin signaling and protease-activated receptors h_arenrf2Pathway - Oxidative Stress Induced Gene Expression Via Nrf2 h_bcrPathway - BCR Signaling Pathway h_cblPathway - CBL mediated ligand-induced downregulation of EGF receptors h_pkcPathway - Activation of PKC through G protein coupled receptor h_pparaPathway - Mechanism of Gene Regulation by Peroxisome Proliferators via PPARa(alpha) h_vegfPathway - VEGF, Hypoxia, and Angiogenesis h_keratinocytePathway - Keratinocyte Differentiation h_Ccr5Pathway - Pertussis toxin-insensitive CCR5 Signaling in Macrophage h_calcineurinPathway - Effects of calcineurin in Keratinocyte Differentiation h_cardiacegfPathway - Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy h_erbB4pathway - g-Secretase mediated ErbB4 Signaling Pathway h_plcPathway - Phospholipase C Signaling Pathway h_CCR3Pathway - CCR3 signaling in Eosinophils h_agpcrPathway - Attenuation of GPCR Signaling h_gpcrPathway - Signaling Pathway from G-Protein Families h_ionPathway - Ion Channel and Phorbal Esters Signaling Pathway h_chemicalPathway - Apoptotic Signaling in Response to DNA Damage h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells h_tcrPathway - T Cell Receptor Signaling Pathway h_TPOPathway - TPO Signaling Pathway h_edg1Pathway - Phospholipids as signalling intermediaries h_myosinPathway - PKC-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase h_cdMacPathway - Cadmium induces DNA synthesis and proliferation in macrophages h_egfPathway - EGF Signaling Pathway h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase h_mef2dPathway - Role of MEF2D in T-cell Apoptosis h_nos1Pathway - Nitric Oxide Signaling Pathway h_plcdPathway - Phospholipase C d1 in phospholipid associated cell signaling h_sppaPathway - Aspirin Blocks Signaling Pathway Involved in Platelet Activation h_trkaPathway - Trka Receptor Signaling Pathway h_At1rPathway - Angiotensin II mediated activation of JNK Pathway via Pyk2 dependent signaling h_crebPathway - Transcription factor CREB and its extracellular signals h_ghPathway - Growth Hormone Signaling Pathway h_pyk2Pathway - Links between Pyk2 and Map Kinases h_biopeptidesPathway - Bioactive Peptide Induced Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein P05771 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
