P16054 (KPCE_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 145. History...
Names and origin
|Protein names||Recommended name:|
Protein kinase C epsilon type
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||737 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. 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). 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. Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10 Ref.13
ATP + a protein = ADP + a phosphoprotein.
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.
Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane By similarity. Cytoplasm › perinuclear region. Nucleus. Note: Translocated to plasma membrane in epithelial cells stimulated by HGF By similarity. Associated with the Golgi at the perinuclear site in pre-passage fibroblasts. In passaging cells, translocated to the cell periphery. Translocated to the nucleus in PMA-treated cells. Ref.11
The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.
Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729 By similarity. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB.
Contains 1 AGC-kinase C-terminal domain.
Contains 1 C2 domain.
Contains 2 phorbol-ester/DAG-type zinc fingers.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 737||737||Protein kinase C epsilon type||PRO_0000055698|
|Domain||1 – 99||99||C2|
|Domain||408 – 668||261||Protein kinase|
|Domain||669 – 737||69||AGC-kinase C-terminal|
|Zinc finger||169 – 220||52||Phorbol-ester/DAG-type 1|
|Zinc finger||242 – 292||51||Phorbol-ester/DAG-type 2|
|Nucleotide binding||414 – 422||9||ATP By similarity|
|Motif||223 – 228||6||Interaction with actin|
|Active site||532||1||Proton acceptor By similarity|
|Binding site||437||1||ATP By similarity|
Amino acid modifications
|Modified residue||228||1||Phosphothreonine By similarity|
|Modified residue||234||1||Phosphoserine Ref.12|
|Modified residue||309||1||Phosphothreonine By similarity|
|Modified residue||316||1||Phosphoserine Ref.12|
|Modified residue||329||1||Phosphoserine By similarity|
|Modified residue||346||1||Phosphoserine; by GSK3-beta Ref.13|
|Modified residue||350||1||Phosphoserine; by MAPK11 and MAPK14 Ref.13|
|Modified residue||368||1||Phosphoserine; by autocatalysis Ref.12 Ref.13|
|Modified residue||388||1||Phosphoserine By similarity|
|Modified residue||566||1||Phosphothreonine; by PDPK1 By similarity|
|Modified residue||703||1||Phosphothreonine; by autocatalysis Potential|
|Modified residue||710||1||Phosphothreonine; alternate Ref.6|
|Modified residue||710||1||Phosphothreonine; by autocatalysis; alternate Potential|
|Modified residue||729||1||Phosphoserine; by autocatalysis Probable|
|Mutagenesis||346||1||S → A: Loss of interaction with YWHAB and defects in the completion of cytokinesis. Ref.13|
|Mutagenesis||368||1||S → A: Loss of interaction with YWHAB and defects in the completion of cytokinesis. Ref.13|
|Mutagenesis||729||1||S → A, E or T: Loss of localization to the perinuclear region. Loss of translocation to the nucleus upon PMA stimulation. Ref.11|
|||"Unique substrate specificity and regulatory properties of PKC-epsilon: a rationale for diversity."|
Schaap D., Parker P.J., Bristol A., Kriz R., Knopf J.
FEBS Lett. 243:351-357(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The catalytic domain of PKC-epsilon, in reciprocal PKC-delta and - epsilon chimeras, is responsible for conferring tumorgenicity to NIH3T3 cells, whereas both regulatory and catalytic domains of PKC-epsilon contribute to in vitro transformation."|
Wang Q.J., Acs P., Goodnight J., Blumberg P.M., Mischak H., Mushinski J.F.
Oncogene 16:53-60(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Biochemical and morphogenic effects of the interaction between protein kinase C-epsilon and actin in vitro and in cultured NIH3T3 cells."|
Hernandez R.M., Wescott G.G., Mayhew M.W., McJilton M.A., Terrian D.M.
J. Cell. Biochem. 83:532-546(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACTIN, ACTIN-BINDING MOTIF.
|||"Protein kinase C phosphorylates protein kinase D activation loop Ser744 and Ser748 and releases autoinhibition by the pleckstrin homology domain."|
Waldron R.T., Rozengurt E.
J. Biol. Chem. 278:154-163(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PRKD1.
|||"Phosphoproteomic analysis of the developing mouse brain."|
Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.
Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-710, MASS SPECTROMETRY.
Tissue: Embryonic brain.
|||"Protein kinase C epsilon mediates angiotensin II-induced activation of beta1-integrins in cardiac fibroblasts."|
Stawowy P., Margeta C., Blaschke F., Lindschau C., Spencer-Haensch C., Leitges M., Biagini G., Fleck E., Graf K.
Cardiovasc. Res. 67:50-59(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"PKCepsilon-mediated phosphorylation of vimentin controls integrin recycling and motility."|
Ivaska J., Vuoriluoto K., Huovinen T., Izawa I., Inagaki M., Parker P.J.
EMBO J. 24:3834-3845(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF VIM.
|||"Partial replacement of cardiac troponin I with a non-phosphorylatable mutant at serines 43/45 attenuates the contractile dysfunction associated with PKCepsilon phosphorylation."|
Scruggs S.B., Walker L.A., Lyu T., Geenen D.L., Solaro R.J., Buttrick P.M., Goldspink P.H.
J. Mol. Cell. Cardiol. 40:465-473(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TNNI3.
|||"Trif-related adapter molecule is phosphorylated by PKCepsilon during Toll-like receptor 4 signaling."|
McGettrick A.F., Brint E.K., Palsson-McDermott E.M., Rowe D.C., Golenbock D.T., Gay N.J., Fitzgerald K.A., O'Neill L.A.J.
Proc. Natl. Acad. Sci. U.S.A. 103:9196-9201(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TICAM2/TRAM.
|||"Phosphorylation at Ser729 specifies a Golgi localisation for protein kinase C epsilon (PKCepsilon) in 3T3 fibroblasts."|
Xu T.R., He G., Dobson K., England K., Rumsby M.
Cell. Signal. 19:1986-1995(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-729, MUTAGENESIS OF SER-729.
|||"The identification and characterization of novel PKCepsilon phosphorylation sites provide evidence for functional cross-talk within the PKC superfamily."|
Durgan J., Cameron A.J., Saurin A.T., Hanrahan S., Totty N., Messing R.O., Parker P.J.
Biochem. J. 411:319-331(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-234; SER-316 AND SER-368.
|||"The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis."|
Saurin A.T., Durgan J., Cameron A.J., Faisal A., Marber M.S., Parker P.J.
Nat. Cell Biol. 10:891-901(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH YWHAB, PHOSPHORYLATION AT SER-346; SER-350 AND SER-368, MUTAGENESIS OF SER-346 AND SER-368.
|+||Additional computationally mapped references.|
|AF028009 mRNA. Translation: AAB84189.1.|
AF325507 mRNA. Translation: AAG53692.1.
|PIR||KIMSCE. S02270. |
|RefSeq||NP_035234.1. NM_011104.3. |
3D structure databases
|SMR||P16054. Positions 1-136, 168-736. |
Protein-protein interaction databases
|BioGrid||202198. 7 interactions.|
|IntAct||P16054. 92 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000097274; ENSMUSP00000094873; ENSMUSG00000045038. |
ENSMUST00000097275; ENSMUSP00000094874; ENSMUSG00000045038.
|UCSC||uc008dug.2. mouse. |
|MGI||MGI:97599. Prkce. |
Enzyme and pathway databases
|BRENDA||188.8.131.52. 3474. |
Gene expression databases
Family and domain databases
|InterPro||IPR000961. AGC-kinase_C. |
|Pfam||PF00130. C1_1. 2 hits. |
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
|PIRSF||PIRSF000551. PKC_delta. 1 hit. |
PIRSF501106. Protein_kin_C_epsilon. 1 hit.
|PRINTS||PR00008. DAGPEDOMAIN. |
|SMART||SM00109. C1. 2 hits. |
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
|SUPFAM||SSF49562. SSF49562. 1 hit. |
SSF56112. SSF56112. 1 hit.
|PROSITE||PS51285. AGC_KINASE_CTER. 1 hit. |
PS50004. C2. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
|ChiTaRS||PRKCE. mouse. |
|Accession||Primary (citable) accession number: P16054|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|