InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Prkcd

Summary

InnateDB Protein

IDBP-142856.6

Last Modified

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

Gene Symbol

Prkcd

Protein Name

protein kinase C, delta

Synonyms

AI385711; D14Ertd420e; PKC[d]; Pkcd; PKCdelta;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000022521

InnateDB Gene

IDBG-142854 (Prkcd)

Protein Structure

UniProt Annotation

Function

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor- initiated cell death, is involved in tumor suppression, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death- promoting transcription factor BCLAF1/Btf to trigger BCLAF1- mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl- leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C- terminal and regulates the interaction between MUC1 and beta- catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion. {ECO:0000269PubMed:11976686, ECO:0000269PubMed:11976687, ECO:0000269PubMed:18025218, ECO:0000269PubMed:19917613, ECO:0000269PubMed:9705322}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Nucleus {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Mitochondrion {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.

Disease Associations

Tissue Specificity

Isoform 1 is highly expressed in developing pro- and pre-B-cells and moderately in mature T-cells. Isoform 2 is highly expressed in testis and ovary and at a lower level in thymocytes, brain and kidney.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.
They are also associated with 69 interaction(s) predicted by orthology.

Experimentally validated
Total	18 [view]
Protein-Protein	18 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	69 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0008047	enzyme activator activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019899	enzyme binding
GO:0043560	insulin receptor substrate binding
GO:0046872	metal ion binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007049	cell cycle
GO:0016064	immunoglobulin mediated immune response
GO:0018107	peptidyl-threonine phosphorylation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0023021	termination of signal transduction
GO:0030837	negative regulation of actin filament polymerization
GO:0032613	interleukin-10 production
GO:0032615	interleukin-12 production
GO:0032930	positive regulation of superoxide anion generation
GO:0034351	negative regulation of glial cell apoptotic process
GO:0035307	positive regulation of protein dephosphorylation
GO:0035556	intracellular signal transduction
GO:0042100	B cell proliferation
GO:0042119	neutrophil activation
GO:0042742	defense response to bacterium
GO:0043085	positive regulation of catalytic activity
GO:0043407	negative regulation of MAP kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0050732	negative regulation of peptidyl-tyrosine phosphorylation
GO:0051490	negative regulation of filopodium assembly
GO:0090331	negative regulation of platelet aggregation
GO:0090398	cellular senescence
GO:1900163	positive regulation of phospholipid scramblase activity
GO:2000304	positive regulation of ceramide biosynthetic process
GO:2000753	positive regulation of glucosylceramide catabolic process
GO:2000755	positive regulation of sphingomyelin catabolic process
GO:2001022	positive regulation of response to DNA damage stimulus
GO:2001235	positive regulation of apoptotic signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005911	cell-cell junction
GO:0016020	membrane
GO:0016363	nuclear matrix
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

MGI:97598

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
IPR014376 Protein kinase C, delta/epsilon/eta/theta 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

PIRSF000551

SMART

SM00239
SM00133
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References