Function: Calcium-activated and phospholipid-dependent serine/threonine-protein kinase involved in various processes such as regulation of the B-cell receptor (BCR) signalosome, apoptosis and transcription regulation. Plays a key role in B-cell activation and function by regulating BCR-induced NF-kappa-B activation and B-cell suvival. Required for recruitment and activation of the IKK kinase to lipid rafts and mediates phosphorylation of CARD11/CARMA1 at 'Ser-564', 'Ser-649' and 'Ser-657', leading to activate the NF-kappa-B signaling. 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. Also involved in triglyceride homeostasis. Serves as the receptor for phorbol esters, a class of tumor promoters.
Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
Cofactor: Binds 3 calcium ions per subunit. The ions are bound to the C2 domain.
Enzyme regulation: Activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. Specifically inhibited by Enzastaurin (LY317615)
Subunit structure: 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
Subcellular location: Cytoplasm. Nucleus
By similarity. Membrane; Peripheral membrane protein.
Post-translational modification: Phosphorylation on Thr-500 of isoform beta-I, 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. Similarly, isoform beta-II is autophosphorylated on 'Thr-641' and 'Ser-660', subsequent to phosphorylation on Thr-500. Autophosphorylated on other sites i.e. in the N-terminal and hinge regions have no effect on PKC activity. Ref.6 Ref.7 Ref.8 Ref.9
Sequence similarities: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.Contains 1 AGC-kinase C-terminal domain.Contains 1 C2 domain.Contains 2 phorbol-ester/DAG-type zinc fingers.Contains 1 protein kinase domain.
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