| Comment type | Description |
|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=Beta-I; IsoId=P68404-1; Sequence=Displayed; Name=Beta-II; IsoId=P68404-2; Sequence=VSP_041812; Note=Contains a phosphothreonine at position 641.; |
| Catalytic Activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Name=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}; |
| 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. {ECO:0000269|PubMed:12118249, ECO:0000269|PubMed:17962198, ECO:0000269|PubMed:8670417}. |
| 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). {ECO:0000250}. |
| 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. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). {ECO:0000250}. |
| Interaction | Q13873:BMPR2 (xeno); NbExp=4; IntAct=EBI-397048, EBI-527196; P56537:EIF6 (xeno); NbExp=2; IntAct=EBI-397048, EBI-372243; |
| 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. {ECO:0000250, ECO:0000269|PubMed:12881490}. |
| Similarity | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}. |
| Similarity | Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}. |
| Similarity | Contains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}. |
| Similarity | Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}. |
| Similarity | Contains 2 phorbol-ester/DAG-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00226}. |
| Subcellular Location | Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. |
| 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). {ECO:0000250}. |