PRKCE - Protein kinase C epsilon type - human protein (Function)
 
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PRKCE »  Protein kinase C epsilon type   [ EC 2.7.11.13 ]
 
Protein also known as:  nPKC-epsilon.
Gene name:  PRKCE
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
7
  • CuratedUniProtKB
GO molecular function 
14-3-3 protein bindingdefinition[GO:0071889] silver  
  • IEAOrtholog Compara
Actin monomer bindingdefinition[GO:0003785]  
  • ISSOrtholog Curator
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calcium-independent protein kinase C activitydefinition[GO:0004699] silver  
  • IEAOrtholog Compara
Enzyme activator activitydefinition[GO:0008047]  
1
  • IMPBHF-UCL
Enzyme bindingdefinition[GO:0019899]  
2
  • IPIBHF-UCL
  • IPIUniProtKB
Ethanol bindingdefinition[GO:0035276] silver  
  • IEAOrtholog Compara
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
3
  • IPIIntAct
Protein kinase C activitydefinition[GO:0004697]  
1
  • IDABHF-UCL
Receptor activator activitydefinition[GO:0030546] silver  
  • IEAOrtholog Compara
Signal transducer activitydefinition[GO:0004871]  
2
  • TASPINC
GO biological process 
Apoptotic processdefinition[GO:0006915]  
1
  • TASPINC
Cell adhesiondefinition[GO:0007155]  
  • IEAUniProtKB KW
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
Cell divisiondefinition[GO:0051301]  
  • IEAUniProtKB KW
Cellular response to ethanoldefinition[GO:0071361] silver  
  • IEAOrtholog Compara
Cellular response to hypoxiadefinition[GO:0071456] silver  
  • IEAOrtholog Compara
Intracellular signal transductiondefinition[GO:0035556] silver  
  • IEAInterPro 2 GO
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663]  
  • ISSOrtholog Curator
Locomotory exploration behaviordefinition[GO:0035641] silver  
  • IEAOrtholog Compara
Macrophage activation involved in immune responsedefinition[GO:0002281] silver  
  • IEAOrtholog Compara
Positive regulation of actin filament polymerizationdefinition[GO:0030838]  
  • ISSOrtholog Curator
Positive regulation of cell-substrate adhesiondefinition[GO:0010811] silver  
  • IEAOrtholog Compara
Positive regulation of cellular glucuronidationdefinition[GO:2001031]  
1
  • IMPBHF-UCL
Positive regulation of cytokinesisdefinition[GO:0032467]  
1
  • IMPUniProtKB
Positive regulation of epithelial cell migrationdefinition[GO:0010634]  
1
  • IMPUniProtKB
Positive regulation of fibroblast migrationdefinition[GO:0010763]  
  • ISSOrtholog Curator
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123] silver  
  • IEAOrtholog Compara
Positive regulation of insulin secretiondefinition[GO:0032024] silver  
  • IEAOrtholog Compara
Positive regulation of lipid catabolic processdefinition[GO:0050996] silver  
  • IEAOrtholog Compara
Positive regulation of MAPK cascadedefinition[GO:0043410] silver  
  • IEAOrtholog Compara
Positive regulation of mucus secretiondefinition[GO:0070257] silver  
  • IEAOrtholog Compara
Positive regulation of synaptic transmission, GABAergicdefinition[GO:0032230] silver  
  • IEAOrtholog Compara
Positive regulation of wound healingdefinition[GO:0090303]  
1
  • IMPUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDABHF-UCL
Regulation of insulin secretion involved in cellular response to glucose stimulusdefinition[GO:0061178] silver  
  • IEAOrtholog Compara
Regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050730] silver  
  • IEAOrtholog Compara
Release of sequestered calcium ion into cytosoldefinition[GO:0051209] silver  
  • IEAOrtholog Compara
Response to morphinedefinition[GO:0043278] silver  
  • IEAOrtholog Compara
TRAM-dependent toll-like receptor 4 signaling pathwaydefinition[GO:0035669]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-566 (activation loop of the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic region), need to be phosphorylated for its full activation.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Fc epsilon RI signaling pathway  hsa04664+5581  
Fc gamma R-mediated phagocytosis  hsa04666+5581  
Tight junction  hsa04530+5581  
Type II diabetes mellitus  hsa04930+5581  
Vascular smooth muscle contraction  hsa04270+5581  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Cell adhesion  definition   [KW-0130]
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
Immunity  definition   [KW-0391]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PRKCE
GenomeRNAi: 5581
PRO: PR:Q02156
Chemistry
GuidetoPHARMACOLOGY: 1486