InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCA

Summary

InnateDB Protein

IDBP-383572.5

Last Modified

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

Gene Symbol

PRKCA

Protein Name

protein kinase C, alpha

Synonyms

AAG6; PKC-alpha; PKCA; PRKACA;

Species

Homo sapiens

Ensembl Protein

ENSP00000408695

InnateDB Gene

IDBG-65194 (PRKCA)

Protein Structure

UniProt Annotation

Function

Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)- dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B- ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF- kappa-B-induced genes, through IL1A-dependent induction of NF- kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O- tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. {ECO:0000269PubMed:10848585, ECO:0000269PubMed:11909826, ECO:0000269PubMed:12724315, ECO:0000269PubMed:12832403, ECO:0000269PubMed:15016832, ECO:0000269PubMed:15504744, ECO:0000269PubMed:15526160, ECO:0000269PubMed:18056764, ECO:0000269PubMed:19176525, ECO:0000269PubMed:21576361, ECO:0000269PubMed:23990668, ECO:0000269PubMed:9738012, ECO:0000269PubMed:9830023, ECO:0000269PubMed:9873035, ECO:0000269PubMed:9927633}.

Subcellular Localization

Cytoplasm. Cell membrane; Peripheral membrane protein. Mitochondrion membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. Nucleus.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 148 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	148 [view]
Protein-Protein	148 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [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:0004698	calcium-dependent protein kinase C activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019899	enzyme binding
GO:0035403	histone kinase activity (H3-T6 specific)

Biological Process

GO:0000188	inactivation of MAPK activity
GO:0001525	angiogenesis
GO:0001933	negative regulation of protein phosphorylation
GO:0001934	positive regulation of protein phosphorylation
GO:0001938	positive regulation of endothelial cell proliferation
GO:0002026	regulation of the force of heart contraction
GO:0002062	chondrocyte differentiation
GO:0002159	desmosome assembly
GO:0006112	energy reserve metabolic process
GO:0006468	protein phosphorylation
GO:0006469	negative regulation of protein kinase activity
GO:0006874	cellular calcium ion homeostasis
GO:0006937	regulation of muscle contraction
GO:0007155	cell adhesion
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007190	activation of adenylate cyclase activity
GO:0007194	negative regulation of adenylate cyclase activity
GO:0007202	activation of phospholipase C activity
GO:0007268	synaptic transmission
GO:0007596	blood coagulation
GO:0007603	phototransduction, visible light
GO:0008285	negative regulation of cell proliferation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0010467	gene expression
GO:0010595	positive regulation of endothelial cell migration
GO:0010613	positive regulation of cardiac muscle hypertrophy
GO:0016056	rhodopsin mediated signaling pathway
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0022400	regulation of rhodopsin mediated signaling pathway
GO:0030168	platelet activation
GO:0030198	extracellular matrix organization
GO:0030335	positive regulation of cell migration
GO:0030593	neutrophil chemotaxis
GO:0031666	positive regulation of lipopolysaccharide-mediated signaling pathway
GO:0034351	negative regulation of glial cell apoptotic process
GO:0035408	histone H3-T6 phosphorylation
GO:0035556	intracellular signal transduction
GO:0036289	peptidyl-serine autophosphorylation
GO:0043536	positive regulation of blood vessel endothelial cell migration
GO:0044281	small molecule metabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045651	positive regulation of macrophage differentiation
GO:0045766	positive regulation of angiogenesis
GO:0045785	positive regulation of cell adhesion
GO:0045931	positive regulation of mitotic cell cycle
GO:0046325	negative regulation of glucose import
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050729	positive regulation of inflammatory response
GO:0050730	regulation of peptidyl-tyrosine phosphorylation
GO:0050796	regulation of insulin secretion
GO:0050930	induction of positive chemotaxis
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070555	response to interleukin-1
GO:0071322	cellular response to carbohydrate stimulus
GO:0090330	regulation of platelet aggregation
GO:0097190	apoptotic signaling pathway
GO:0097193	intrinsic apoptotic signaling pathway
GO:2000707	positive regulation of dense core granule biogenesis

Cellular Component

GO:0001750	photoreceptor outer segment
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0030425	dendrite
GO:0031966	mitochondrial membrane
GO:0043025	neuronal cell body
GO:0045177	apical part of cell
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
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