ID:KPCB_MOUSE 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) (By similarity). SUBUNIT: Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By similarity). INTERACTION: Q13873:BMPR2 (xeno); NbExp=4; IntAct=EBI-397048, EBI-527196; P56537:EIF6 (xeno); NbExp=2; IntAct=EBI-397048, EBI-372243; SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity). 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 (By similarity). Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade. DISRUPTION PHENOTYPE: Mice develop an immunodeficiency characterized by impaired humoral immune responses and reduced cellular responses of B-cells similar to X-linked immunodeficiency (Xid). Mice are unable to activate NF-kappa-B and promote cell survival in B-cells upon BCR signaling, or even in mast cells. B- cells fail to recruit the I-kappa-B kinase (IKK) complex into lipid rafts, activate IKK, degrade I-kappa-B or up-regulate NF- kappa-B-dependent survival signals. Moreover, mutant animals are hyperphagic and exhibit higher food intake and reduced feed efficiency versus wild type. Mice are considerably leaner and display markedly decreased size of white fat depots. Triglyceride content in the liver and skeletal muscle is also significantly low. 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.
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 P68404
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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.
Biological Process: GO:0001666 response to hypoxia GO:0002250 adaptive immune response GO:0002376 immune system process GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006468 protein phosphorylation GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006915 apoptotic process GO:0010829 negative regulation of glucose transport GO:0014059 regulation of dopamine secretion GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway GO:0035408 histone H3-T6 phosphorylation GO:0035556 intracellular signal transduction GO:0040008 regulation of growth GO:0042113 B cell activation GO:0042493 response to drug GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0045766 positive regulation of angiogenesis GO:0046627 negative regulation of insulin receptor signaling pathway GO:0050853 B cell receptor signaling pathway GO:0050861 positive regulation of B cell receptor signaling pathway GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0071322 cellular response to carbohydrate stimulus