InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Prkcb

Summary

InnateDB Protein

IDBP-208978.6

Last Modified

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

Gene Symbol

Prkcb

Protein Name

protein kinase C, beta

Synonyms

A130082F03Rik; PKC-Beta; Pkcb; Prkcb1; Prkcb2;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000070019

InnateDB Gene

IDBG-208976 (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. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. 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 16 experimentally validated interaction(s) in this database.
They are also associated with 52 interaction(s) predicted by orthology.

Experimentally validated
Total	16 [view]
Protein-Protein	16 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	52 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003682	chromatin binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004697	protein kinase C activity
GO:0004713	protein tyrosine kinase activity
GO:0005080	protein kinase C binding
GO:0005246	calcium channel regulator activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
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:0006816	calcium ion transport
GO:0006874	cellular calcium ion homeostasis
GO:0006915	apoptotic process
GO:0010829	negative regulation of glucose transport
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: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

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

MGI:97596

InterPro

IPR000008 C2 domain
IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol binding
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR014375 Protein kinase C, alpha/beta/gamma types
IPR017892 Protein kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00168
PF00069
PF07714
PF00130
PF00433

PRINTS

PR00360
PR00109
PR00008

PIRSF

PIRSF000550

SMART

SM00239
SM00133
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References