InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCE

Summary

InnateDB Protein

IDBP-50154.6

Last Modified

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

Gene Symbol

PRKCE

Protein Name

protein kinase C, epsilon

Synonyms

nPKC-epsilon; PKCE;

Species

Homo sapiens

Ensembl Protein

ENSP00000306124

InnateDB Gene

IDBG-50152 (PRKCE)

Protein Structure

UniProt Annotation

Function

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F- actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL- mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. {ECO:0000269PubMed:11884385, ECO:0000269PubMed:1374067, ECO:0000269PubMed:15355962, ECO:0000269PubMed:16757566, ECO:0000269PubMed:17603037, ECO:0000269PubMed:17875639, ECO:0000269PubMed:17875724}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:17603037}. Cytoplasm, cytoskeleton {ECO:0000269PubMed:17603037}. Cell membrane {ECO:0000269PubMed:17603037}. Cytoplasm, perinuclear region {ECO:0000250}. Nucleus {ECO:0000250}. Note=Translocated to plasma membrane in epithelial cells stimulated by HGF. Associated with the Golgi at the perinuclear site in pre-passage fibroblasts (By similarity). In passaging cells, translocated to the cell periphery (By similarity). Translocated to the nucleus in PMA- treated cells (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 69 experimentally validated interaction(s) in this database.
They are also associated with 15 interaction(s) predicted by orthology.

Experimentally validated
Total	69 [view]
Protein-Protein	67 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	15 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003785	actin monomer binding
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:0004871	signal transducer 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:0030546	receptor activator activity
GO:0035276	ethanol binding
GO:0046872	metal ion binding
GO:0071889	14-3-3 protein binding

Biological Process

GO:0002281	macrophage activation involved in immune response
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007049	cell cycle
GO:0007155	cell adhesion
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:0010634	positive regulation of epithelial cell migration
GO:0010763	positive regulation of fibroblast migration
GO:0010811	positive regulation of cell-substrate adhesion
GO:0019216	regulation of lipid metabolic process
GO:0030168	platelet activation
GO:0030838	positive regulation of actin filament polymerization
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032024	positive regulation of insulin secretion
GO:0032230	positive regulation of synaptic transmission, GABAergic
GO:0032467	positive regulation of cytokinesis
GO:0035556	intracellular signal transduction
GO:0035641	locomotory exploration behavior
GO:0035669	TRAM-dependent toll-like receptor 4 signaling pathway
GO:0038096	Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043278	response to morphine
GO:0043410	positive regulation of MAPK cascade
GO:0045087	innate immune response (InnateDB)
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050730	regulation of peptidyl-tyrosine phosphorylation
GO:0050996	positive regulation of lipid catabolic process
GO:0051209	release of sequestered calcium ion into cytosol
GO:0051301	cell division
GO:0061178	regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0070257	positive regulation of mucus secretion
GO:0071361	cellular response to ethanol
GO:0071456	cellular response to hypoxia
GO:0090303	positive regulation of wound healing
GO:2000273	positive regulation of receptor activity
GO:2001031	positive regulation of cellular glucuronidation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0048471	perinuclear region of cytoplasm
GO:0071944	cell periphery

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