Names & Taxonomy
- Uniprot ID:
- P05771
- Entry Name:
- KPCB_HUMAN
- Status:
- reviewed
- Protein Names:
- Protein kinase C beta type (PKC-B) (PKC-beta) (EC 2.7.11.13)
- Gene Names:
- PRKCB PKCB PRKCB1
- Gene Names Primary:
- PRKCB
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 671
- Sequence:
- MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGFGKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGSLLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDRDVLIVLVRDAKNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRLSVEIWDWDLTSRNDFMGSLSFGISELQKASVDGWFKLLSQEEGEYFNVPVPPEGSEANEELRQKFERAKISQGTKVPEEKTTNTVSKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSERKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFFRYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGFSYTNPEFVINV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
Function
- 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). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
- Enzyme Regulation:
- 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).
- Active Site:
- ACT_SITE 466 466 Proton acceptor.
- Cross Reference Drug Bank:
- DB00675 DB00163
- Gene Ontology Go:
- cytoplasm
cytosol
extracellular exosome
nucleoplasm
nucleus
plasma membrane
androgen receptor binding
ATP binding
calcium channel regulator activity
chromatin binding
histone binding
histone kinase activity (H3-T6 specific)
ligand-dependent nuclear receptor transcription coactivator activity
protein kinase C activity
protein kinase C binding
protein serine/threonine kinase activity
zinc ion binding
adaptive immune response
apoptotic process
B cell activation
B cell receptor signaling pathway
blood coagulation
calcium ion transport
cellular calcium ion homeostasis
cellular response to carbohydrate stimulus
histone H3-T6 phosphorylation
intracellular signal transduction
lipoprotein transport
mitotic cell cycle
mitotic nuclear envelope disassembly
negative regulation of glucose transport
negative regulation of insulin receptor signaling pathway
peptidyl-serine phosphorylation
platelet activation
positive regulation of angiogenesis
positive regulation of B cell receptor signaling pathway
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of NF-kappaB transcription factor activity
positive regulation of vascular endothelial growth factor receptor signaling pathway
protein phosphorylation
regulation of transcription from RNA polymerase II promoter
response to hypoxia
signal transduction
synaptic transmission
transcription, DNA-templated
vascular endothelial growth factor receptor signaling pathway - Gene Ontology Biological Process:
- adaptive immune response
apoptotic process
B cell activation
B cell receptor signaling pathway
blood coagulation
calcium ion transport
cellular calcium ion homeostasis
cellular response to carbohydrate stimulus
histone H3-T6 phosphorylation
intracellular signal transduction
lipoprotein transport
mitotic cell cycle
mitotic nuclear envelope disassembly
negative regulation of glucose transport
negative regulation of insulin receptor signaling pathway
peptidyl-serine phosphorylation
platelet activation
positive regulation of angiogenesis
positive regulation of B cell receptor signaling pathway
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of NF-kappaB transcription factor activity
positive regulation of vascular endothelial growth factor receptor signaling pathway
protein phosphorylation
regulation of transcription from RNA polymerase II promoter
response to hypoxia
signal transduction
synaptic transmission
transcription, DNA-templated
vascular endothelial growth factor receptor signaling pathway - Gene Ontology Molecular Function:
- androgen receptor binding
ATP binding
calcium channel regulator activity
chromatin binding
histone binding
histone kinase activity (H3-T6 specific)
ligand-dependent nuclear receptor transcription coactivator activity
protein kinase C activity
protein kinase C binding
protein serine/threonine kinase activity
zinc ion binding - Gene Ontology Cellular Component:
- cytoplasm
cytosol
extracellular exosome
nucleoplasm
nucleus
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Acetylation
Adaptive immunity
Alternative splicing
Apoptosis
Calcium
Chromatin regulator
Complete proteome
Cytoplasm
Direct protein sequencing
Immunity
Kinase
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Zinc
Zinc-finger - Interacts With:
- O60346; Q8NEM2; Q9BSI4