LipidDB ID

LipidDB-9606-01371

Entry Name

UniProt Accession

Q02156; B0LPH7; Q32MQ3; Q53SL4; Q53SM5; Q9UE81;

Theoretical PI

6.73

Molecular Weight

83673.8

Genbank Protein ID

CAA46388.1; ABY87556.1; AAD08855.1; AAY14773.1; AAX93253.1; EAX00258.1; AAI09034.1; AAI09035.1;

Genbank Nucleotide ID

X65293; EU332867; U51244; AC017078; AC017006; CH471053; BC109033; BC109034;

Protein Name

Protein kinase C epsilon type

Protein Synonyms/Alias

2.7.11.13; nPKC-epsilon;

Gene Name

PRKCE

Gene Synonyms/Alias

PKCE;

Created Date

01-JUL-1993

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Dasgupta S, Bhattacharya S, Maitra S, Pal D, Majumdar SS, Datta A,Bhattacharya S. Mechanism of lipid induced insulin resistance: activated PKCε is a key regulator. Biochim Biophys Acta. 2011 Apr;1812(4):495-506. doi:10.1016/j.bbadis.2011.01.001. Epub 2011 Jan 12.[PMID:21236337]
[2] Martin DD, Vilas GL, Prescher JA, Rajaiah G, Falck JR, Bertozzi CR, BerthiaumeLG. Rapid detection, discovery, and identification of post-translationallymyristoylated proteins during apoptosis using a bio-orthogonal azidomyristateanalog. FASEB J. 2008 Mar;22(3):797-806. Epub 2007 Oct 10.[PMID:17932026]

Functional Description

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.

Sequence Annotation

Domain: 1 99 C2.
Domain: 408 668 Protein kinase.
Domain: 669 737 AGC-kinase C-terminal.
Nucleotide-binding: 414 422 ATP.
Motif: 223 228 Interaction with actin.
Active site: 532 532 Proton acceptor.
Binding site: 437 437 ATP.
Modified residue: 228 228 Phosphothreonine.
Modified residue: 234 234 Phosphoserine.
Modified residue: 309 309 Phosphothreonine.
Modified residue: 316 316 Phosphoserine.
Modified residue: 329 329 Phosphoserine.
Modified residue: 346 346 Phosphoserine; by GSK3-beta.
Modified residue: 350 350 Phosphoserine; by MAPK11 and MAPK14.
Modified residue: 368 368 Phosphoserine; by autocatalysis.
Modified residue: 388 388 Phosphoserine.
Modified residue: 566 566 Phosphothreonine; by PDPK1.
Modified residue: 703 703 Phosphothreonine; by autocatalysis.
Modified residue: 710 710 Phosphothreonine.
Modified residue: 729 729 Phosphoserine; by autocatalysis.

Protein Length

737 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0071944; C:cell periphery; ISS:UniProtKB
GO:0005737; C:cytoplasm; IDA:UniProtKB
GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW
GO:0005829; C:cytosol; IDA:UniProtKB
GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL
GO:0005794; C:Golgi apparatus; IEA:Ensembl
GO:0005739; C:mitochondrion; IEA:Ensembl
GO:0005634; C:nucleus; IEA:UniProtKB-KW
GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB
GO:0005886; C:plasma membrane; IDA:UniProtKB
GO:0003785; F:actin monomer binding; ISS:UniProtKB
GO:0005524; F:ATP binding; IEA:UniProtKB-KW
GO:0004699; F:calcium-independent protein kinase C activity; IEA:Ensembl
GO:0008047; F:enzyme activator activity; IMP:BHF-UCL
GO:0019899; F:enzyme binding; IPI:UniProtKB
GO:0035276; F:ethanol binding; IEA:Ensembl
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW
GO:0004697; F:protein kinase C activity; IDA:BHF-UCL
GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB
GO:0030546; F:receptor activator activity; IEA:Ensembl
GO:0004871; F:signal transducer activity; TAS:ProtInc
GO:0007202; P:activation of phospholipase C activity; TAS:Reactome
GO:0006915; P:apoptotic process; TAS:ProtInc
GO:0007596; P:blood coagulation; TAS:Reactome
GO:0007155; P:cell adhesion; IEA:UniProtKB-KW
GO:0007049; P:cell cycle; IEA:UniProtKB-KW
GO:0051301; P:cell division; IEA:UniProtKB-KW
GO:0071361; P:cellular response to ethanol; IEA:Ensembl
GO:0071456; P:cellular response to hypoxia; IEA:Ensembl
GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome
GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome
GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome
GO:0045087; P:innate immune response; TAS:Reactome
GO:0035556; P:intracellular signal transduction; IEA:InterPro
GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB
GO:0035641; P:locomotory exploration behavior; IEA:Ensembl
GO:0002281; P:macrophage activation involved in immune response; IEA:Ensembl
GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; TAS:BHF-UCL
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome
GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB
GO:0030168; P:platelet activation; TAS:Reactome
GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB
GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl
GO:2001031; P:positive regulation of cellular glucuronidation; IMP:BHF-UCL
GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB
GO:0010634; P:positive regulation of epithelial cell migration; IMP:UniProtKB
GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB
GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl
GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl
GO:0050996; P:positive regulation of lipid catabolic process; IEA:Ensembl
GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl
GO:0070257; P:positive regulation of mucus secretion; IEA:Ensembl
GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IEA:Ensembl
GO:0090303; P:positive regulation of wound healing; IMP:UniProtKB
GO:0006468; P:protein phosphorylation; IDA:BHF-UCL
GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl
GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl
GO:0051209; P:release of sequestered calcium ion into cytosol; IEA:Ensembl
GO:0043278; P:response to morphine; IEA:Ensembl
GO:0007165; P:signal transduction; TAS:Reactome
GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; ISS:UniProtKB

Interpro

InterPro; IPR000961; AGC-kinase_C
InterPro; IPR000008; C2_dom
InterPro; IPR020454; DAG/PE-bd
InterPro; IPR011009; Kinase-like_dom
InterPro; IPR002219; PE/DAG-bd
InterPro; IPR027274; PKC_epsilon
InterPro; IPR017892; Pkinase_C
InterPro; IPR014376; Prot_kin_PKC_delta
InterPro; IPR000719; Prot_kinase_dom
InterPro; IPR017441; Protein_kinase_ATP_BS
InterPro; IPR002290; Ser/Thr_dual-sp_kinase
InterPro; IPR008271; Ser/Thr_kinase_AS

Pfam

Pfam; PF00130; C1_1;
Pfam; PF00168; C2;
Pfam; PF00069; Pkinase;
Pfam; PF00433; Pkinase_C;

SMART

SMART; SM00109; C1;
SMART; SM00239; C2;
SMART; SM00133; S_TK_X;
SMART; SM00220; S_TKc;

PROSITE

PROSITE; PS51285; AGC_KINASE_CTER;
PROSITE; PS50004; C2;
PROSITE; PS00107; PROTEIN_KINASE_ATP;
PROSITE; PS50011; PROTEIN_KINASE_DOM;
PROSITE; PS00108; PROTEIN_KINASE_ST;
PROSITE; PS00479; ZF_DAG_PE_1;
PROSITE; PS50081; ZF_DAG_PE_2;

PRINTS

PRINTS; PR00008; DAGPEDOMAIN;