NameProtein kinase C epsilon type
Synonyms
  • 2.7.11.13
  • nPKC-epsilon
  • PKCE
Gene NamePRKCE
OrganismHuman
Amino acid sequence
>lcl|BSEQ0012401|Protein kinase C epsilon type
MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKT
NSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLE
PEGRVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQP
TYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDQVGSQRFSVN
MPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIA
KVLADLGVTPDKITNSGQRRKKLIAGAESPQPASGSSPSEEDRSKSAPTSPCDQEIKELE
NNIRKALSFDNRGEEHRAASSPDGQLMSPGENGEVRQGQAKRLGLDEFNFIKVLGKGSFG
KVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKD
RLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILL
DAEGHCKLADFGMCKEGILNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEM
MAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVASQNGED
AIKQHPFFKEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPVLTLVDEAIVKQI
NQEEFKGFSYFGEDLMP
Number of residues737
Molecular Weight83673.2
Theoretical pI7.13
GO Classification
Functions
  • enzyme activator activity
  • metal ion binding
  • enzyme binding
  • signal transducer activity
  • protein kinase C activity
  • ATP binding
  • calcium-independent protein kinase C activity
  • receptor activator activity
  • actin monomer binding
  • protein serine/threonine kinase activity
  • ethanol binding
Processes
  • apoptotic process
  • regulation of insulin secretion involved in cellular response to glucose stimulus
  • positive regulation of synaptic transmission, GABAergic
  • fibroblast growth factor receptor signaling pathway
  • TRAM-dependent toll-like receptor 4 signaling pathway
  • cellular response to prostaglandin E stimulus
  • neurotrophin TRK receptor signaling pathway
  • positive regulation of cytokinesis
  • protein phosphorylation
  • positive regulation of wound healing
  • intracellular signal transduction
  • cell division
  • release of sequestered calcium ion into cytosol
  • activation of phospholipase C activity
  • cell cycle
  • cellular response to ethanol
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • lipopolysaccharide-mediated signaling pathway
  • platelet activation
  • locomotory exploration behavior
  • regulation of peptidyl-tyrosine phosphorylation
  • cellular response to hypoxia
  • regulation of release of sequestered calcium ion into cytosol
  • signal transduction
  • positive regulation of actin filament polymerization
  • positive regulation of epithelial cell migration
  • positive regulation of cell-substrate adhesion
  • positive regulation of lipid catabolic process
  • cell adhesion
  • peptidyl-serine phosphorylation
  • macrophage activation involved in immune response
  • negative regulation of sodium ion transmembrane transporter activity
  • epidermal growth factor receptor signaling pathway
  • positive regulation of cellular glucuronidation
  • positive regulation of MAPK cascade
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • blood coagulation
  • positive regulation of fibroblast migration
  • response to morphine
  • innate immune response
  • positive regulation of mucus secretion
  • positive regulation of insulin secretion
Components
  • endoplasmic reticulum
  • plasma membrane
  • cytoplasm
  • mitochondrion
  • cell periphery
  • Golgi apparatus
  • cytosol
  • perinuclear region of cytoplasm
  • cytoskeleton
  • nucleus
General FunctionSignal transducer activity
Specific FunctionCalcium-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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ02156
UniProtKB Entry NameKPCE_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0012402|Protein kinase C epsilon type (PRKCE)
ATGGTAGTGTTCAATGGCCTTCTTAAGATCAAAATCTGCGAGGCCGTGAGCTTGAAGCCC
ACAGCCTGGTCGCTGCGCCATGCGGTGGGACCCCGGCCGCAGACTTTCCTTCTCGACCCC
TACATTGCCCTCAATGTGGACGACTCGCGCATCGGCCAAACGGCCACCAAGCAGAAGACC
AACAGCCCGGCCTGGCACGACGAGTTCGTCACCGATGTGTGCAACGGACGCAAGATCGAG
CTGGCTGTCTTTCACGATGCCCCCATAGGCTACGACGACTTCGTGGCCAACTGCACCATC
CAGTTTGAGGAGCTGCTGCAGAACGGGAGCCGCCACTTCGAGGACTGGATTGATCTGGAG
CCAGAAGGAAGAGTGTATGTGATCATCGATCTCTCAGGGTCGTCGGGTGAAGCCCCTAAA
GACAATGAAGAGCGTGTGTTCAGGGAACGCATGCGGCCGAGGAAGCGGCAGGGGGCCGTC
AGGCGCAGGGTCCATCAGGTCAACGGCCACAAGTTCATGGCCACCTATCTTCGGCAGCCC
ACCTACTGCTCCCATTGCAGAGACTTCATCTGGGGTGTCATAGGAAAGCAGGGATACCAG
TGTCAAGTCTGCACCTGCGTGGTCCACAAGCGGTGCCACGAGCTCATAATCACAAAGTGT
GCTGGGTTAAAGAAGCAGGAGACCCCCGACCAGGTGGGCTCCCAGCGGTTCAGCGTCAAC
ATGCCCCACAAGTTCGGTATCCACAACTACAAGGTCCCTACCTTCTGCGATCACTGTGGG
TCCCTGCTCTGGGGACTCTTGCGGCAGGGTTTGCAGTGTAAAGTCTGCAAAATGAATGTT
CACCGTCGATGTGAGACCAACGTGGCTCCCAACTGTGGAGTGGATGCCAGAGGAATCGCC
AAAGTACTGGCCGACCTGGGCGTTACCCCAGACAAAATCACCAACAGCGGCCAGAGAAGG
AAAAAGCTCATTGCTGGTGCCGAGTCCCCGCAGCCTGCTTCTGGAAGCTCACCATCTGAG
GAAGATCGATCCAAGTCAGCACCCACCTCCCCTTGTGACCAGGAAATAAAAGAACTTGAG
AACAACATTCGGAAAGCCTTGTCATTTGACAACCGAGGAGAGGAGCACCGGGCAGCATCG
TCTCCTGATGGCCAGCTGATGAGCCCCGGTGAGAATGGCGAAGTCCGGCAAGGCCAGGCC
AAGCGCCTGGGCCTGGATGAGTTCAACTTCATCAAGGTGTTGGGCAAAGGCAGCTTTGGC
AAGGTCATGTTGGCAGAACTCAAGGGCAAAGATGAAGTATATGCTGTGAAGGTCTTAAAG
AAGGACGTCATCCTTCAGGATGATGACGTGGACTGCACAATGACAGAGAAGAGGATTTTG
GCTCTGGCACGGAAACACCCGTACCTTACCCAACTCTACTGCTGCTTCCAGACCAAGGAC
CGCCTCTTTTTCGTCATGGAATATGTAAATGGTGGAGACCTCATGTTTCAGATTCAGCGC
TCCCGAAAATTCGACGAGCCTCGTTCACGGTTCTATGCTGCAGAGGTCACATCGGCCCTC
ATGTTCCTCCACCAGCATGGAGTCATCTACAGGGATTTGAAACTGGACAACATCCTTCTG
GATGCAGAAGGTCACTGCAAGCTGGCTGACTTCGGGATGTGCAAGGAAGGGATTCTGAAT
GGTGTGACGACCACCACGTTCTGTGGGACTCCTGACTACATAGCTCCTGAGATCCTGCAG
GAGTTGGAGTATGGCCCCTCCGTGGACTGGTGGGCCCTGGGGGTGCTGATGTACGAGATG
ATGGCTGGACAGCCTCCCTTTGAGGCCGACAATGAGGACGACCTATTTGAGTCCATCCTC
CATGACGACGTGCTGTACCCAGTCTGGCTCAGCAAGGAGGCTGTCAGCATCTTGAAAGCT
TTCATGACGAAGAATCCCCACAAGCGCCTGGGCTGTGTGGCATCGCAGAATGGCGAGGAC
GCCATCAAGCAGCACCCATTCTTCAAAGAGATTGACTGGGTGCTCCTGGAGCAGAAGAAG
ATCAAGCCACCCTTCAAACCACGCATTAAAACCAAAAGAGACGTCAATAATTTTGACCAA
GACTTTACCCGGGAAGAGCCGGTACTCACCCTTGTGGACGAAGCAATTGTAAAGCAGATC
AACCAGGAGGAATTCAAAGGTTTCTCCTACTTTGGTGAAGACCTGATGCCCTGA
GenBank Gene IDX65293
GeneCard IDNot Available
GenAtlas IDPRKCE
HGNC IDHGNC:9401
Chromosome Location2
LocusNot Available
References
  1. Basta P, Strickland MB, Holmes W, Loomis CR, Ballas LM, Burns DJ: Sequence and expression of human protein kinase C-epsilon. Biochim Biophys Acta. 1992 Sep 24;1132(2):154-60. 1382605
  2. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Omary MB, Baxter GT, Chou CF, Riopel CL, Lin WY, Strulovici B: PKC epsilon-related kinase associates with and phosphorylates cytokeratin 8 and 18. J Cell Biol. 1992 May;117(3):583-93. 1374067
  5. Cenni V, Doppler H, Sonnenburg ED, Maraldi N, Newton AC, Toker A: Regulation of novel protein kinase C epsilon by phosphorylation. Biochem J. 2002 May 1;363(Pt 3):537-45. 11964154
  6. Numazaki M, Tominaga T, Toyooka H, Tominaga M: Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues. J Biol Chem. 2002 Apr 19;277(16):13375-8. Epub 2002 Mar 7. 11884385
  7. Grohmanova K, Schlaepfer D, Hess D, Gutierrez P, Beck M, Kroschewski R: Phosphorylation of IQGAP1 modulates its binding to Cdc42, revealing a new type of rho-GTPase regulator. J Biol Chem. 2004 Nov 19;279(47):48495-504. Epub 2004 Sep 7. 15355962
  8. van Baal J, de Widt J, Divecha N, van Blitterswijk WJ: Translocation of diacylglycerol kinase theta from cytosol to plasma membrane in response to activation of G protein-coupled receptors and protein kinase C. J Biol Chem. 2005 Mar 18;280(11):9870-8. Epub 2005 Jan 4. 15632189
  9. McGettrick AF, Brint EK, Palsson-McDermott EM, Rowe DC, Golenbock DT, Gay NJ, Fitzgerald KA, O'Neill LA: Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9196-201. Epub 2006 Jun 6. 16757566
  10. Aziz MH, Manoharan HT, Church DR, Dreckschmidt NE, Zhong W, Oberley TD, Wilding G, Verma AK: Protein kinase Cepsilon interacts with signal transducers and activators of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its constitutive activation in prostate cancer. Cancer Res. 2007 Sep 15;67(18):8828-38. 17875724
  11. Sharma GD, Kakazu A, Bazan HE: Protein kinase C alpha and epsilon differentially modulate hepatocyte growth factor-induced epithelial proliferation and migration. Exp Eye Res. 2007 Aug;85(2):289-97. Epub 2007 May 26. 17603037
  12. Qi ZH, Song M, Wallace MJ, Wang D, Newton PM, McMahon T, Chou WH, Zhang C, Shokat KM, Messing RO: Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor sensitivity to ethanol and benzodiazepines through phosphorylation of gamma2 subunits. J Biol Chem. 2007 Nov 9;282(45):33052-63. Epub 2007 Sep 17. 17875639
  13. Akita Y: Protein kinase C-epsilon (PKC-epsilon): its unique structure and function. J Biochem. 2002 Dec;132(6):847-52. 12473185
  14. Vitale M, Gobbi G, Mirandola P, Ponti C, Sponzilli I, Rinaldi L, Manzoli FA: TNF-related apoptosis-inducing ligand (TRAIL) and erythropoiesis: a role for PKC epsilon. Eur J Histochem. 2006 Jan-Mar;50(1):15-8. 16584980
  15. Shirai Y, Adachi N, Saito N: Protein kinase Cepsilon: function in neurons. FEBS J. 2008 Aug;275(16):3988-94. doi: 10.1111/j.1742-4658.2008.06556.x. Epub 2008 Jul 11. 18637121
  16. Akita Y: Protein kinase Cepsilon: multiple roles in the function of, and signaling mediated by, the cytoskeleton. FEBS J. 2008 Aug;275(16):3995-4004. doi: 10.1111/j.1742-4658.2008.06557.x. Epub 2008 Jul 11. 18637120
  17. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  18. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  19. Newton PM, Messing RO: The substrates and binding partners of protein kinase Cepsilon. Biochem J. 2010 Mar 29;427(2):189-96. doi: 10.1042/BJ20091302. 20350291
  20. Chen Y, Tian Q: The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases. Front Med. 2011 Mar;5(1):70-6. doi: 10.1007/s11684-011-0119-9. Epub 2011 Mar 17. 21681677
  21. Duquesnes N, Lezoualc'h F, Crozatier B: PKC-delta and PKC-epsilon: foes of the same family or strangers? J Mol Cell Cardiol. 2011 Nov;51(5):665-73. doi: 10.1016/j.yjmcc.2011.07.013. Epub 2011 Jul 23. 21810427
  22. Kostelecky B, Saurin AT, Purkiss A, Parker PJ, McDonald NQ: Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon. EMBO Rep. 2009 Sep;10(9):983-9. doi: 10.1038/embor.2009.150. Epub 2009 Aug 7. 19662078
  23. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974
  24. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. 17344846