InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCD

Summary

InnateDB Protein

IDBP-40084.5

Last Modified

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

Gene Symbol

PRKCD

Protein Name

protein kinase C, delta

Synonyms

CVID9; MAY1; nPKC-delta; PKCD;

Species

Homo sapiens

Ensembl Protein

ENSP00000331602

InnateDB Gene

IDBG-40082 (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 as well as survival of several cancers, 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. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro- survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). 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 (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm. Cytoplasm, perinuclear region. Nucleus. Endoplasmic reticulum. Mitochondrion. Cell membrane; Peripheral membrane protein.

Disease Associations

Immunodeficiency, common variable, 9 (CVID9) [MIM:615559]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity. {ECO:0000269PubMed:23319571}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 123 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.

Experimentally validated
Total	123 [view]
Protein-Protein	122 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	10 [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:0004699	calcium-independent 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: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:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0007049	cell cycle
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007202	activation of phospholipase C activity
GO:0007596	blood coagulation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010467	gene expression
GO:0010469	regulation of receptor activity
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0018107	peptidyl-threonine phosphorylation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0019221	cytokine-mediated signaling pathway
GO:0023021	termination of signal transduction
GO:0030168	platelet activation
GO:0030837	negative regulation of actin filament polymerization
GO:0032091	negative regulation of protein binding
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:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042119	neutrophil activation
GO:0042742	defense response to bacterium
GO:0043407	negative regulation of MAP kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050728	negative regulation of inflammatory response
GO:0050732	negative regulation of peptidyl-tyrosine phosphorylation
GO:0050821	protein stabilization
GO:0051490	negative regulation of filopodium assembly
GO:0060333	interferon-gamma-mediated signaling pathway
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

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0048471	perinuclear region of cytoplasm
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

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 domain
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