Names & Taxonomy

Uniprot ID:
Q02156
Entry Name:
KPCE_HUMAN
Status:
reviewed
Protein Names:
Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)
Gene Names:
PRKCE PKCE
Gene Names Primary:
PRKCE
Organism:
Homo sapiens (Human)

Structure

Length:
737
Sequence:
MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKTNSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLEPEGRVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQPTYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDQVGSQRFSVNMPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIAKVLADLGVTPDKITNSGQRRKKLIAGAESPQPASGSSPSEEDRSKSAPTSPCDQEIKELENNIRKALSFDNRGEEHRAASSPDGQLMSPGENGEVRQGQAKRLGLDEFNFIKVLGKGSFGKVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKDRLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILLDAEGHCKLADFGMCKEGILNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVASQNGEDAIKQHPFFKEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPVLTLVDEAIVKQINQEEFKGFSYFGEDLMP
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

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.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 532 532 Proton acceptor.
Cross Reference Drug Bank:
DB00675
Gene Ontology Go:
cell periphery
cytoplasm
cytoskeleton
cytosol
endoplasmic reticulum
Golgi apparatus
mitochondrion
nucleus
perinuclear region of cytoplasm
plasma membrane
actin monomer binding
ATP binding
calcium-independent protein kinase C activity
enzyme activator activity
enzyme binding
ethanol binding
metal ion binding
protein kinase C activity
protein serine/threonine kinase activity
receptor activator activity
signal transducer activity
activation of phospholipase C activity
apoptotic process
blood coagulation
cell adhesion
cell cycle
cell division
cellular response to ethanol
cellular response to hypoxia
cellular response to prostaglandin E stimulus
epidermal growth factor receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
innate immune response
intracellular signal transduction
lipopolysaccharide-mediated signaling pathway
locomotory exploration behavior
macrophage activation involved in immune response
negative regulation of protein ubiquitination
negative regulation of sodium ion transmembrane transporter activity
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
platelet activation
positive regulation of actin filament polymerization
positive regulation of cell-substrate adhesion
positive regulation of cellular glucuronidation
positive regulation of cytokinesis
positive regulation of epithelial cell migration
positive regulation of fibroblast migration
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of insulin secretion
positive regulation of lipid catabolic process
positive regulation of MAPK cascade
positive regulation of mucus secretion
positive regulation of synaptic transmission, GABAergic
positive regulation of wound healing
protein phosphorylation
regulation of insulin secretion involved in cellular response to glucose stimulus
regulation of peptidyl-tyrosine phosphorylation
regulation of release of sequestered calcium ion into cytosol
release of sequestered calcium ion into cytosol
response to morphine
signal transduction
TRAM-dependent toll-like receptor 4 signaling pathway
Gene Ontology Biological Process:
activation of phospholipase C activity
apoptotic process
blood coagulation
cell adhesion
cell cycle
cell division
cellular response to ethanol
cellular response to hypoxia
cellular response to prostaglandin E stimulus
epidermal growth factor receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
innate immune response
intracellular signal transduction
lipopolysaccharide-mediated signaling pathway
locomotory exploration behavior
macrophage activation involved in immune response
negative regulation of protein ubiquitination
negative regulation of sodium ion transmembrane transporter activity
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
platelet activation
positive regulation of actin filament polymerization
positive regulation of cell-substrate adhesion
positive regulation of cellular glucuronidation
positive regulation of cytokinesis
positive regulation of epithelial cell migration
positive regulation of fibroblast migration
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of insulin secretion
positive regulation of lipid catabolic process
positive regulation of MAPK cascade
positive regulation of mucus secretion
positive regulation of synaptic transmission, GABAergic
positive regulation of wound healing
protein phosphorylation
regulation of insulin secretion involved in cellular response to glucose stimulus
regulation of peptidyl-tyrosine phosphorylation
regulation of release of sequestered calcium ion into cytosol
release of sequestered calcium ion into cytosol
response to morphine
signal transduction
TRAM-dependent toll-like receptor 4 signaling pathway
Gene Ontology Molecular Function:
actin monomer binding
ATP binding
calcium-independent protein kinase C activity
enzyme activator activity
enzyme binding
ethanol binding
metal ion binding
protein kinase C activity
protein serine/threonine kinase activity
receptor activator activity
signal transducer activity
Gene Ontology Cellular Component:
cell periphery
cytoplasm
cytoskeleton
cytosol
endoplasmic reticulum
Golgi apparatus
mitochondrion
nucleus
perinuclear region of cytoplasm
plasma membrane
Keywords:
3D-structure
ATP-binding
Cell adhesion
Cell cycle
Cell division
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Immunity
Kinase
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger
Interacts With:
P08238; C6GKH1; Q15349; P63104

Publication

PubMed ID:
1382605 15815621 15489334 1374067 11964154 11884385 15355962 15632189 16757566 17875724 17603037 17875639 12473185 16584980 18637121 18637120 18691976 18669648 20350291 21681677 21810427 19662078 16959974 17344846