InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCB

Summary

InnateDB Protein

IDBP-749350.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKCB

Protein Name

Synonyms

PKC-beta; PKCB; PRKCB1; PRKCB2;

Species

Homo sapiens

Ensembl Protein

ENSP00000454428

InnateDB Gene

IDBG-20895 (PRKCB)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:11598012, ECO:0000269PubMed:19176525, ECO:0000269PubMed:20228790}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000269PubMed:20228790}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 90 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	90 [view]
Protein-Protein	89 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003682	chromatin binding
GO:0004674	protein serine/threonine kinase activity
GO:0004697	protein kinase C activity
GO:0005080	protein kinase C binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0030374	ligand-dependent nuclear receptor transcription coactivator activity
GO:0035403	histone kinase activity (H3-T6 specific)
GO:0042393	histone binding
GO:0050681	androgen receptor binding

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0007268	synaptic transmission
GO:0007596	blood coagulation
GO:0010829	negative regulation of glucose transport
GO:0030168	platelet activation
GO:0030949	positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0035408	histone H3-T6 phosphorylation
GO:0035556	intracellular signal transduction
GO:0042113	B cell activation
GO:0042953	lipoprotein transport
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