Protein kinase C eta type

NameProtein kinase C eta type
Synonyms
  • 2.7.11.13
  • nPKC-eta
  • PKC-L
  • PKCL
  • PRKCL
Gene NamePRKCH
OrganismHuman
Amino acid sequence
>lcl|BSEQ0008737|Protein kinase C eta type
MSSGTMKFNGYLRVRIGEAVGLQPTRWSLRHSLFKKGHQLLDPYLTVSVDQVRVGQTSTK
QKTNKPTYNEEFCANVTDGGHLELAVFHETPLGYDHFVANCTLQFQELLRTTGASDTFEG
WVDLEPEGKVFVVITLTGSFTEATLQRDRIFKHFTRKRQRAMRRRVHQINGHKFMATYLR
QPTYCSHCREFIWGVFGKQGYQCQVCTCVVHKRCHHLIVTACTCQNNINKVDSKIAEQRF
GINIPHKFSIHNYKVPTFCDHCGSLLWGIMRQGLQCKICKMNVHIRCQANVAPNCGVNAV
ELAKTLAGMGLQPGNISPTSKLVSRSTLRRQGKESSKEGNGIGVNSSNRLGIDNFEFIRV
LGKGSFGKVMLARVKETGDLYAVKVLKKDVILQDDDVECTMTEKRILSLARNHPFLTQLF
CCFQTPDRLFFVMEFVNGGDLMFHIQKSRRFDEARARFYAAEIISALMFLHDKGIIYRDL
KLDNVLLDHEGHCKLADFGMCKEGICNGVTTATFCGTPDYIAPEILQEMLYGPAVDWWAM
GVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLHEDATGILKSFMTKNPTMRLGSL
TQGGEHAILRHPFFKEIDWAQLNHRQIEPPFRPRIKSREDVSNFDPDFIKEEPVLTPIDE
GHLPMINQDEFRNFSYVSPELQP
Number of residues683
Molecular Weight77827.96
Theoretical pINot Available
GO Classification
Functions
  • ATP binding
  • calcium-independent protein kinase C activity
  • metal ion binding
  • enzyme binding
  • protein kinase C activity
Processes
  • positive regulation of B cell receptor signaling pathway
  • signal transduction
  • negative regulation of glial cell apoptotic process
  • positive regulation of glial cell proliferation
  • blood coagulation
  • regulation of bicellular tight junction assembly
  • protein kinase C signaling
  • platelet activation
  • protein phosphorylation
  • positive regulation of macrophage derived foam cell differentiation
  • positive regulation of keratinocyte differentiation
  • positive regulation of NF-kappaB transcription factor activity
Components
  • cytoplasm
  • plasma membrane
  • cytosol
  • extracellular exosome
  • cell-cell junction
General FunctionProtein kinase c activity
Specific FunctionCalcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP24723
UniProtKB Entry NameKPCL_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0013386|Protein kinase C eta type (PRKCH)
ATGTCGTCTGGCACCATGAAGTTCAATGGCTATTTGAGGGTCCGCATCGGTGAGGCAGTG
GGGCTGCAGCCCACCCGCTGGTCCCTGCGCCACTCGCTCTTCAAGAAGGGCCACCAGCTG
CTGGACCCCTATCTGACGGTGAGCGTGGACCAGGTGCGCGTGGGCCAGACCAGCACCAAG
CAGAAGACCAACAAACCCACGTACAACGAGGAGTTTTGCGCTAACGTCACCGACGGCGGC
CACCTCGAGTTGGCCGTCTTCCACGAGACGCCCCTGGGCTACGACCACTTCGTGGCCAAC
TGCACCCTGCAGTTCCAGGAGCTGCTGCGCACGACCGGCGCCTCGGACACCTTCGAGGGT
TGGGTGGATCTCGAGCCAGAGGGGAAAGTATTTGTGGTAATAACCCTTACCGGGAGTTTC
ACTGAAGCTACTCTCCAGAGAGACCGGATCTTCAAACATTTTACCAGGAAGCGCCAAAGG
GCTATGCGAAGGCGAGTCCACCAGATCAATGGACACAAGTTCATGGCCACGTATCTGAGG
CAGCCCACCTACTGCTCTCACTGCAGGGAGTTTATCTGGGGAGTGTTTGGGAAACAGGGT
TATCAGTGCCAAGTGTGCACCTGTGTCGTCCATAAACGCTGCCATCATCTAATTGTTACA
GCCTGTACTTGCCAAAACAATATTAACAAAGTGGATTCAAAGATTGCAGAACAGAGGTTC
GGGATCAACATCCCACACAAGTTCAGCATCCACAACTACAAAGTGCCAACATTCTGCGAT
CACTGTGGCTCACTGCTCTGGGGAATAATGCGACAAGGACTTCAGTGTAAAATATGTAAA
ATGAATGTGCATATTCGATGTCAAGCGAACGTGGCCCCTAACTGTGGGGTAAATGCGGTG
GAACTTGCCAAGACCCTGGCAGGGATGGGTCTCCAACCCGGAAATATTTCTCCAACCTCG
AAACTCGTTTCCAGATCGACCCTAAGACGACAGGGAAAGGAGAGCAGCAAAGAAGGAAAT
GGGATTGGGGTTAATTCTTCCAACCGACTTGGTATCGACAACTTTGAGTTCATCCGAGTG
TTGGGGAAGGGGAGTTTTGGGAAGGTGATGCTTGCAAGAGTAAAAGAAACAGGAGACCTC
TATGCTGTGAAGGTGCTGAAGAAGGACGTGATTCTGCAGGATGATGATGTGGAATGCACC
ATGACCGAGAAAAGGATCCTGTCTCTGGCCCGCAATCACCCCTTCCTCACTCAGTTGTTC
TGCTGCTTTCAGACCCCCGATCGTCTGTTTTTTGTGATGGAGTTTGTGAATGGGGGTGAC
TTGATGTTCCACATTCAGAAGTCTCGTCGTTTTGATGAAGCACGAGCTCGCTTCTATGCT
GCAGAAATCATTTCGGCTCTCATGTTCCTCCATGATAAAGGAATCATCTATAGAGATCTG
AAACTGGACAATGTCCTGTTGGACCACGAGGGTCACTGTAAACTGGCAGACTTCGGAATG
TGCAAGGAGGGGATTTGCAATGGTGTCACCACGGCCACATTCTGTGGCACGCCAGACTAT
ATCGCTCCAGAGATCCTCCAGGAAATGCTGTACGGGCCTGCAGTAGACTGGTGGGCAATG
GGCGTGTTGCTCTATGAGATGCTCTGTGGTCACGCGCCTTTTGAGGCAGAGAACGAAGAT
GACCTCTTTGAGGCCATACTGAATGATGAGGTGGTCTACCCTACCTGGCTCCATGAAGAT
GCCACAGGGATCCTAAAATCTTTCATGACCAAGAACCCCACCATGCGCTTGGGCAGCCTG
ACTCAGGGAGGCGAGCACGCCATCTTGAGACATCCTTTTTTTAAGGAAATCGACTGGGCC
CAGCTGAACCATCGCCAAATAGAACCGCCTTTCAGACCCAGAATCAAATCCCGAGAAGAT
GTCAGTAATTTTGACCCTGACTTCATAAAGGAAGAGCCAGTTTTAACTCCAATTGATGAG
GGACATCTTCCAATGATTAACCAGGATGAGTTTAGAAACTTTTCCTATGTGTCTCCAGAA
TTGCAACCATAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:9403
Chromosome Location14
LocusNot Available
References
  1. Bacher N, Zisman Y, Berent E, Livneh E: Isolation and characterization of PKC-L, a new member of the protein kinase C-related gene family specifically expressed in lung, skin, and heart. Mol Cell Biol. 1991 Jan;11(1):126-33. 1986216
  2. Bacher N, Zisman Y, Berent E, Livneh E: Isolation and characterization of PKC-L, a new member of the protein kinase C-related gene family specifically expressed in lung, skin, and heart. Mol Cell Biol. 1992 Mar;12(3):1404. 1545821
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. 12508121
  5. 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
  6. Palmer RH, Ridden J, Parker PJ: Identification of multiple, novel, protein kinase C-related gene products. FEBS Lett. 1994 Dec 12;356(1):5-8. 7988719
  7. Akkaraju GR, Basu A: Overexpression of protein kinase C-eta attenuates caspase activation and tumor necrosis factor-alpha-induced cell death. Biochem Biophys Res Commun. 2000 Dec 9;279(1):103-7. 11112424
  8. Hussaini IM, Karns LR, Vinton G, Carpenter JE, Redpath GT, Sando JJ, VandenBerg SR: Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific proliferative response in astrocytic tumor cells. J Biol Chem. 2000 Jul 21;275(29):22348-54. 10806212
  9. Hussaini IM, Carpenter JE, Redpath GT, Sando JJ, Shaffrey ME, Vandenberg SR: Protein kinase C-eta regulates resistance to UV- and gamma-irradiation-induced apoptosis in glioblastoma cells by preventing caspase-9 activation. Neuro Oncol. 2002 Jan;4(1):9-21. 11772428
  10. Aeder SE, Martin PM, Soh JW, Hussaini IM: PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene. 2004 Dec 2;23(56):9062-9. 15489897
  11. 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
  12. Uht RM, Amos S, Martin PM, Riggan AE, Hussaini IM: The protein kinase C-eta isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway. Oncogene. 2007 May 3;26(20):2885-93. Epub 2006 Dec 4. 17146445
  13. Oda A, Ono T, Yamamoto M, Goitsuka R, Kitamura D: PKC eta directs induction of IRF-4 expression and Ig kappa gene rearrangement in pre-BCR signaling pathway. Int Immunol. 2008 Nov;20(11):1417-26. doi: 10.1093/intimm/dxn101. Epub 2008 Sep 9. 18780722
  14. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  15. Suzuki T, Elias BC, Seth A, Shen L, Turner JR, Giorgianni F, Desiderio D, Guntaka R, Rao R: PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):61-6. doi: 10.1073/pnas.0802741106. Epub 2008 Dec 29. 19114660
  16. Lee HK, Yeo S, Kim JS, Lee JG, Bae YS, Lee C, Baek SH: Protein kinase C-eta and phospholipase D2 pathway regulates foam cell formation via regulator of G protein signaling 2. Mol Pharmacol. 2010 Sep;78(3):478-85. doi: 10.1124/mol.110.064394. Epub 2010 Jun 17. 20558593
  17. Raveh-Amit H, Hai N, Rotem-Dai N, Shahaf G, Gopas J, Livneh E: Protein kinase Ceta activates NF-kappaB in response to camptothecin-induced DNA damage. Biochem Biophys Res Commun. 2011 Aug 26;412(2):313-7. doi: 10.1016/j.bbrc.2011.07.090. Epub 2011 Jul 28. 21820409
  18. Kashiwagi M, Ohba M, Chida K, Kuroki T: Protein kinase C eta (PKC eta): its involvement in keratinocyte differentiation. J Biochem. 2002 Dec;132(6):853-7. 12473186
  19. Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA: PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell. 2012 Feb 3;148(3):543-55. doi: 10.1016/j.cell.2012.01.016. 22304920
  20. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  21. Littler DR, Walker JR, She YM, Finerty PJ Jr, Newman EM, Dhe-Paganon S: Structure of human protein kinase C eta (PKCeta) C2 domain and identification of phosphorylation sites. Biochem Biophys Res Commun. 2006 Nov 3;349(4):1182-9. Epub 2006 Sep 5. 16973127
  22. Kubo M, Hata J, Ninomiya T, Matsuda K, Yonemoto K, Nakano T, Matsushita T, Yamazaki K, Ohnishi Y, Saito S, Kitazono T, Ibayashi S, Sueishi K, Iida M, Nakamura Y, Kiyohara Y: A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat Genet. 2007 Feb;39(2):212-7. Epub 2007 Jan 7. 17206144
  23. 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