KPCE_HUMAN
ID KPCE_HUMAN Reviewed; 737 AA.
AC Q02156; B0LPH7; Q32MQ3; Q53SL4; Q53SM5; Q9UE81;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Protein kinase C epsilon type;
DE EC=2.7.11.13 {ECO:0000269|PubMed:34593629};
DE AltName: Full=nPKC-epsilon;
GN Name=PRKCE; Synonyms=PKCE;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1382605; DOI=10.1016/0167-4781(92)90006-l;
RA Basta P., Strickland M.B., Holmes W., Loomis C.R., Ballas L.M., Burns D.J.;
RT "Sequence and expression of human protein kinase C-epsilon.";
RL Biochim. Biophys. Acta 1132:154-160(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF KRT8.
RX PubMed=1374067; DOI=10.1083/jcb.117.3.583;
RA Omary M.B., Baxter G.T., Chou C.F., Riopel C.L., Lin W.Y., Strulovici B.;
RT "PKC epsilon-related kinase associates with and phosphorylates cytokeratin
RT 8 and 18.";
RL J. Cell Biol. 117:583-593(1992).
RN [7]
RP PHOSPHORYLATION AT THR-566 AND SER-729, AND MUTAGENESIS OF LYS-437;
RP THR-566; THR-710 AND SER-729.
RX PubMed=11964154; DOI=10.1042/0264-6021:3630537;
RA Cenni V., Doeppler H., Sonnenburg E.D., Maraldi N., Newton A.C., Toker A.;
RT "Regulation of novel protein kinase C epsilon by phosphorylation.";
RL Biochem. J. 363:537-545(2002).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF TRPV1.
RX PubMed=11884385; DOI=10.1074/jbc.c200104200;
RA Numazaki M., Tominaga T., Toyooka H., Tominaga M.;
RT "Direct phosphorylation of capsaicin receptor VR1 by protein kinase
RT Cepsilon and identification of two target serine residues.";
RL J. Biol. Chem. 277:13375-13378(2002).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF IQGAP1.
RX PubMed=15355962; DOI=10.1074/jbc.m408113200;
RA Grohmanova K., Schlaepfer D., Hess D., Gutierrez P., Beck M.,
RA Kroschewski R.;
RT "Phosphorylation of IQGAP1 modulates its binding to Cdc42, revealing a new
RT type of rho-GTPase regulator.";
RL J. Biol. Chem. 279:48495-48504(2004).
RN [10]
RP INTERACTION WITH DGKQ.
RX PubMed=15632189; DOI=10.1074/jbc.m409301200;
RA van Baal J., de Widt J., Divecha N., van Blitterswijk W.J.;
RT "Translocation of diacylglycerol kinase theta from cytosol to plasma
RT membrane in response to activation of G protein-coupled receptors and
RT protein kinase C.";
RL J. Biol. Chem. 280:9870-9878(2005).
RN [11]
RP FUNCTION.
RX PubMed=16757566; DOI=10.1073/pnas.0600462103;
RA McGettrick A.F., Brint E.K., Palsson-McDermott E.M., Rowe D.C.,
RA Golenbock D.T., Gay N.J., Fitzgerald K.A., O'Neill L.A.J.;
RT "Trif-related adapter molecule is phosphorylated by PKCepsilon during Toll-
RT like receptor 4 signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9196-9201(2006).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF STAT3, AND INTERACTION WITH STAT3.
RX PubMed=17875724; DOI=10.1158/0008-5472.can-07-1604;
RA Aziz M.H., Manoharan H.T., Church D.R., Dreckschmidt N.E., Zhong W.,
RA Oberley T.D., Wilding G., Verma A.K.;
RT "Protein kinase Cepsilon interacts with signal transducers and activators
RT of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its
RT constitutive activation in prostate cancer.";
RL Cancer Res. 67:8828-8838(2007).
RN [13]
RP FUNCTION IN CELL MOTILITY, AND SUBCELLULAR LOCATION.
RX PubMed=17603037; DOI=10.1016/j.exer.2007.05.004;
RA Sharma G.D., Kakazu A., Bazan H.E.;
RT "Protein kinase C alpha and epsilon differentially modulate hepatocyte
RT growth factor-induced epithelial proliferation and migration.";
RL Exp. Eye Res. 85:289-297(2007).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF GABRG2.
RX PubMed=17875639; DOI=10.1074/jbc.m707233200;
RA Qi Z.H., Song M., Wallace M.J., Wang D., Newton P.M., McMahon T.,
RA Chou W.H., Zhang C., Shokat K.M., Messing R.O.;
RT "Protein kinase C epsilon regulates gamma-aminobutyrate type A receptor
RT sensitivity to ethanol and benzodiazepines through phosphorylation of
RT gamma2 subunits.";
RL J. Biol. Chem. 282:33052-33063(2007).
RN [15]
RP REVIEW ON FUNCTION.
RX PubMed=12473185; DOI=10.1093/oxfordjournals.jbchem.a003296;
RA Akita Y.;
RT "Protein kinase C-epsilon (PKC-epsilon): its unique structure and
RT function.";
RL J. Biochem. 132:847-852(2002).
RN [16]
RP REVIEW ON FUNCTION IN APOPTOSIS.
RX PubMed=16584980;
RA Vitale M., Gobbi G., Mirandola P., Ponti C., Sponzilli I., Rinaldi L.,
RA Manzoli F.A.;
RT "TNF-related apoptosis-inducing ligand (TRAIL) and erythropoiesis: a role
RT for PKC epsilon.";
RL Eur. J. Histochem. 50:15-18(2006).
RN [17]
RP REVIEW ON FUNCTION IN NEURONS.
RX PubMed=18637121; DOI=10.1111/j.1742-4658.2008.06556.x;
RA Shirai Y., Adachi N., Saito N.;
RT "Protein kinase Cepsilon: function in neurons.";
RL FEBS J. 275:3988-3994(2008).
RN [18]
RP REVIEW ON FUNCTION IN CYTOSKELETON.
RX PubMed=18637120; DOI=10.1111/j.1742-4658.2008.06557.x;
RA Akita Y.;
RT "Protein kinase Cepsilon: multiple roles in the function of, and signaling
RT mediated by, the cytoskeleton.";
RL FEBS J. 275:3995-4004(2008).
RN [19]
RP INTERACTION WITH PRPH AND VIM.
RX PubMed=18408015; DOI=10.1074/jbc.m710436200;
RA Sunesson L., Hellman U., Larsson C.;
RT "Protein kinase Cepsilon binds peripherin and induces its aggregation,
RT which is accompanied by apoptosis of neuroblastoma cells.";
RL J. Biol. Chem. 283:16653-16664(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-228; THR-309; SER-329;
RP SER-388 AND THR-710, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-309 AND SER-316, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [22]
RP FUNCTION, INTERACTION WITH NLRP5, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19542546; DOI=10.1093/molehr/gap048;
RA Maraldi T., Riccio M., Sena P., Marzona L., Nicoli A., La Marca A.,
RA Marmiroli S., Bertacchini J., La Sala G., De Pol A.;
RT "MATER protein as substrate of PKCepsilon in human cumulus cells.";
RL Mol. Hum. Reprod. 15:499-506(2009).
RN [23]
RP REVIEW.
RX PubMed=20350291; DOI=10.1042/bj20091302;
RA Newton P.M., Messing R.O.;
RT "The substrates and binding partners of protein kinase Cepsilon.";
RL Biochem. J. 427:189-196(2010).
RN [24]
RP INTERACTION WITH HSP90AB1.
RX PubMed=20353823; DOI=10.1016/j.cellsig.2010.03.012;
RA Cheng M.B., Zhang Y., Zhong X., Sutter B., Cao C.Y., Chen X.S., Cheng X.K.,
RA Zhang Y., Xiao L., Shen Y.F.;
RT "Stat1 mediates an auto-regulation of hsp90beta gene in heat shock
RT response.";
RL Cell. Signal. 22:1206-1213(2010).
RN [25]
RP REVIEW ON FUNCTION IN NEURONS.
RX PubMed=21681677; DOI=10.1007/s11684-011-0119-9;
RA Chen Y., Tian Q.;
RT "The role of protein kinase C epsilon in neural signal transduction and
RT neurogenic diseases.";
RL Front. Med. 5:70-76(2011).
RN [26]
RP REVIEW.
RX PubMed=21810427; DOI=10.1016/j.yjmcc.2011.07.013;
RA Duquesnes N., Lezoualc'h F., Crozatier B.;
RT "PKC-delta and PKC-epsilon: Foes of the same family or strangers?";
RL J. Mol. Cell. Cardiol. 51:665-673(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH PRKCH
RP UPSTREAM OPEN READING FRAME 2.
RX PubMed=34593629; DOI=10.1073/pnas.2018899118;
RA Jayaram D.R., Frost S., Argov C., Liju V.B., Anto N.P., Muraleedharan A.,
RA Ben-Ari A., Sinay R., Smoly I., Novoplansky O., Isakov N., Toiber D.,
RA Keasar C., Elkabets M., Yeger-Lotem E., Livneh E.;
RT "Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor
RT of PKCs.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 342-372, AND PHOSPHORYLATION AT
RP SER-346 AND SER-368.
RX PubMed=19662078; DOI=10.1038/embor.2009.150;
RA Kostelecky B., Saurin A.T., Purkiss A., Parker P.J., McDonald N.Q.;
RT "Recognition of an intra-chain tandem 14-3-3 binding site within
RT PKCepsilon.";
RL EMBO Rep. 10:983-989(2009).
RN [30]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-143.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [31]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-333; ARG-389 AND MET-563.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays essential roles in
CC the regulation of multiple cellular processes linked to cytoskeletal
CC proteins, such as cell adhesion, motility, migration and cell cycle,
CC functions in neuron growth and ion channel regulation, and is involved
CC in immune response, cancer cell invasion and regulation of apoptosis.
CC Mediates cell adhesion to the extracellular matrix via integrin-
CC dependent signaling, by mediating angiotensin-2-induced activation of
CC integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS,
CC which phosphorylates and activates PTK2/FAK, leading to the spread of
CC cardiomyocytes. Involved in the control of the directional transport of
CC ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an
CC intermediate filament (IF) protein. In epithelial cells, associates
CC with and phosphorylates keratin-8 (KRT8), which induces targeting of
CC desmoplakin at desmosomes and regulates cell-cell contact.
CC Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-
CC cell detachment prior to migration. In HeLa cells, contributes to
CC hepatocyte growth factor (HGF)-induced cell migration, and in human
CC corneal epithelial cells, plays a critical role in wound healing after
CC activation by HGF. During cytokinesis, forms a complex with YWHAB,
CC which is crucial for daughter cell separation, and facilitates
CC abscission by a mechanism which may implicate the regulation of RHOA.
CC In cardiac myocytes, regulates myofilament function and excitation
CC coupling at the Z-lines, where it is indirectly associated with F-actin
CC via interaction with COPB1. During endothelin-induced cardiomyocyte
CC hypertrophy, mediates activation of PTK2/FAK, which is critical for
CC cardiomyocyte survival and regulation of sarcomere length. Plays a role
CC in the pathogenesis of dilated cardiomyopathy via persistent
CC phosphorylation of troponin I (TNNI3). Involved in nerve growth factor
CC (NFG)-induced neurite outgrowth and neuron morphological change
CC independently of its kinase activity, by inhibition of RHOA pathway,
CC activation of CDC42 and cytoskeletal rearrangement. May be involved in
CC presynaptic facilitation by mediating phorbol ester-induced synaptic
CC potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit
CC gamma-2 (GABRG2), which reduces the response of GABA receptors to
CC ethanol and benzodiazepines and may mediate acute tolerance to the
CC intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the
CC capsaicin- and heat-activated cation channel TRPV1, which is required
CC for bradykinin-induced sensitization of the heat response in
CC nociceptive neurons. Is able to form a complex with PDLIM5 and N-type
CC calcium channel, and may enhance channel activities and potentiates
CC fast synaptic transmission by phosphorylating the pore-forming alpha
CC subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and
CC phosphorylates STAT3, which increases DNA-binding and transcriptional
CC activity of STAT3 and seems to be essential for prostate cancer cell
CC invasion. Downstream of TLR4, plays an important role in the
CC lipopolysaccharide (LPS)-induced immune response by phosphorylating and
CC activating TICAM2/TRAM, which in turn activates the transcription
CC factor IRF3 and subsequent cytokines production. In differentiating
CC erythroid progenitors, is regulated by EPO and controls the protection
CC against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved
CC in the regulation of the insulin-induced phosphorylation and activation
CC of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT
CC pathway activation in cumulus cells (PubMed:19542546).
CC {ECO:0000269|PubMed:11884385, ECO:0000269|PubMed:1374067,
CC ECO:0000269|PubMed:15355962, ECO:0000269|PubMed:16757566,
CC ECO:0000269|PubMed:17603037, ECO:0000269|PubMed:17875639,
CC ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:19542546}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC Evidence={ECO:0000269|PubMed:34593629};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000269|PubMed:34593629};
CC -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC calcium-insensitive, but activated by diacylglycerol (DAG) and
CC phosphatidylserine. Three specific sites; Thr-566 (activation loop of
CC the kinase domain), Thr-710 (turn motif) and Ser-729 (hydrophobic
CC region), need to be phosphorylated for its full activation. Inhibited
CC by PRKCH upstream open reading frame 2 (PubMed:34593629).
CC {ECO:0000269|PubMed:34593629}.
CC -!- SUBUNIT: Forms a ternary complex with TRIM63 and RACK1/GN2BL1 (By
CC similarity). Can form a complex with PDLIM5 and N-type calcium channel
CC (By similarity). Interacts with COPB1 (By similarity). Interacts with
CC DGKQ (PubMed:15632189). Interacts with STAT3 (PubMed:17875724).
CC Interacts with YWHAB (By similarity). Interacts with HSP90AB1; promotes
CC functional activation in a heat shock-dependent manner
CC (PubMed:20353823). Interacts (via phorbol-ester/DAG-type 2 domain) with
CC PRPH and VIM (PubMed:18408015). Interacts with NLRP5/MATER
CC (PubMed:19542546). Interacts with PRKCH upstream open reading frame 2;
CC the interaction leads to inhibition of kinase activity
CC (PubMed:34593629). {ECO:0000250|UniProtKB:P09216,
CC ECO:0000250|UniProtKB:P16054, ECO:0000269|PubMed:15632189,
CC ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:18408015,
CC ECO:0000269|PubMed:19542546, ECO:0000269|PubMed:20353823,
CC ECO:0000269|PubMed:34593629}.
CC -!- INTERACTION:
CC Q02156; P05067: APP; NbExp=3; IntAct=EBI-706254, EBI-77613;
CC Q02156; P15056: BRAF; NbExp=3; IntAct=EBI-706254, EBI-365980;
CC Q02156; P08238: HSP90AB1; NbExp=4; IntAct=EBI-706254, EBI-352572;
CC Q02156; C6GKH1: IL32; NbExp=2; IntAct=EBI-706254, EBI-9547476;
CC Q02156; Q9BPZ7: MAPKAP1; NbExp=2; IntAct=EBI-706254, EBI-749938;
CC Q02156; P17252: PRKCA; NbExp=2; IntAct=EBI-706254, EBI-1383528;
CC Q02156; Q15349: RPS6KA2; NbExp=2; IntAct=EBI-706254, EBI-1384149;
CC Q02156; P37840: SNCA; NbExp=3; IntAct=EBI-706254, EBI-985879;
CC Q02156; P63104: YWHAZ; NbExp=7; IntAct=EBI-706254, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17603037,
CC ECO:0000269|PubMed:19542546}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:17603037}. Cell membrane
CC {ECO:0000269|PubMed:17603037}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P16054}. Nucleus {ECO:0000250|UniProtKB:P16054}.
CC Note=Translocated to plasma membrane in epithelial cells stimulated by
CC HGF (PubMed:17603037). Associated with the Golgi at the perinuclear
CC site in pre-passage fibroblasts (By similarity). In passaging cells,
CC translocated to the cell periphery (By similarity). Translocated to the
CC nucleus in PMA-treated cells (By similarity).
CC {ECO:0000250|UniProtKB:P16054, ECO:0000269|PubMed:17603037}.
CC -!- TISSUE SPECIFICITY: Expressed in cumulus cells (at protein level).
CC {ECO:0000269|PubMed:19542546}.
CC -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type region 1
CC (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a
CC non-calcium binding domain.
CC -!- PTM: Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation
CC on Ser-729. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or
CC MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required
CC for interaction with YWHAB. {ECO:0000269|PubMed:11964154,
CC ECO:0000269|PubMed:19662078}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; X65293; CAA46388.1; -; mRNA.
DR EMBL; EU332867; ABY87556.1; -; Genomic_DNA.
DR EMBL; U51244; AAD08855.1; -; Genomic_DNA.
DR EMBL; AC017078; AAY14773.1; -; Genomic_DNA.
DR EMBL; AC017006; AAX93253.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00258.1; -; Genomic_DNA.
DR EMBL; BC109033; AAI09034.1; -; mRNA.
DR EMBL; BC109034; AAI09035.1; -; mRNA.
DR CCDS; CCDS1824.1; -.
DR PIR; S28942; S28942.
DR RefSeq; NP_005391.1; NM_005400.2.
DR RefSeq; XP_005264485.1; XM_005264428.1.
DR PDB; 2WH0; X-ray; 2.25 A; Q/R=342-372.
DR PDB; 5LIH; X-ray; 3.25 A; F/G=149-164.
DR PDBsum; 2WH0; -.
DR PDBsum; 5LIH; -.
DR AlphaFoldDB; Q02156; -.
DR SMR; Q02156; -.
DR BioGRID; 111567; 124.
DR DIP; DIP-34186N; -.
DR ELM; Q02156; -.
DR IntAct; Q02156; 77.
DR MINT; Q02156; -.
DR STRING; 9606.ENSP00000306124; -.
DR BindingDB; Q02156; -.
DR ChEMBL; CHEMBL3582; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB11752; Bryostatin 1.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB06064; KAI-1455.
DR DrugBank; DB00675; Tamoxifen.
DR DrugCentral; Q02156; -.
DR GuidetoPHARMACOLOGY; 1486; -.
DR iPTMnet; Q02156; -.
DR PhosphoSitePlus; Q02156; -.
DR BioMuta; PRKCE; -.
DR DMDM; 400135; -.
DR EPD; Q02156; -.
DR jPOST; Q02156; -.
DR MassIVE; Q02156; -.
DR MaxQB; Q02156; -.
DR PaxDb; Q02156; -.
DR PeptideAtlas; Q02156; -.
DR PRIDE; Q02156; -.
DR ProteomicsDB; 58054; -.
DR Antibodypedia; 4528; 712 antibodies from 43 providers.
DR DNASU; 5581; -.
DR Ensembl; ENST00000306156.8; ENSP00000306124.3; ENSG00000171132.14.
DR GeneID; 5581; -.
DR KEGG; hsa:5581; -.
DR MANE-Select; ENST00000306156.8; ENSP00000306124.3; NM_005400.3; NP_005391.1.
DR UCSC; uc002rut.4; human.
DR CTD; 5581; -.
DR DisGeNET; 5581; -.
DR GeneCards; PRKCE; -.
DR HGNC; HGNC:9401; PRKCE.
DR HPA; ENSG00000171132; Tissue enhanced (brain).
DR MIM; 176975; gene.
DR neXtProt; NX_Q02156; -.
DR OpenTargets; ENSG00000171132; -.
DR PharmGKB; PA33765; -.
DR VEuPathDB; HostDB:ENSG00000171132; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000154711; -.
DR HOGENOM; CLU_000288_54_4_1; -.
DR InParanoid; Q02156; -.
DR OMA; LEEMEYG; -.
DR OrthoDB; 222529at2759; -.
DR PhylomeDB; Q02156; -.
DR TreeFam; TF351133; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; Q02156; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-HSA-1489509; DAG and IP3 signaling.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR SABIO-RK; Q02156; -.
DR SignaLink; Q02156; -.
DR SIGNOR; Q02156; -.
DR BioGRID-ORCS; 5581; 23 hits in 1108 CRISPR screens.
DR ChiTaRS; PRKCE; human.
DR EvolutionaryTrace; Q02156; -.
DR GeneWiki; PRKCE; -.
DR GenomeRNAi; 5581; -.
DR Pharos; Q02156; Tchem.
DR PRO; PR:Q02156; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q02156; protein.
DR Bgee; ENSG00000171132; Expressed in buccal mucosa cell and 153 other tissues.
DR ExpressionAtlas; Q02156; baseline and differential.
DR Genevisible; Q02156; HS.
DR GO; GO:0071944; C:cell periphery; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0071889; F:14-3-3 protein binding; IEA:Ensembl.
DR GO; GO:0003785; F:actin monomer binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0004699; F:calcium-independent protein kinase C activity; IEA:Ensembl.
DR GO; GO:0008047; F:enzyme activator activity; IMP:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IDA:BHF-UCL.
DR GO; GO:0035276; F:ethanol binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; IDA:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0030546; F:signaling receptor activator activity; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0031589; P:cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0070254; P:mucus secretion; IEA:Ensembl.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; TAS:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:2001031; P:positive regulation of cellular glucuronidation; IMP:BHF-UCL.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0050996; P:positive regulation of lipid catabolic process; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0070257; P:positive regulation of mucus secretion; IEA:Ensembl.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IEA:Ensembl.
DR GO; GO:0090303; P:positive regulation of wound healing; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IEA:Ensembl.
DR GO; GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR CDD; cd00029; C1; 2.
DR CDD; cd05591; STKc_nPKC_epsilon; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR IDEAL; IID00066; -.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034669; nPKC_epsilon.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027274; PKC_epsilon.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR014376; Prot_kin_PKC_delta.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000551; PKC_delta; 1.
DR PIRSF; PIRSF501106; Protein_kin_C_epsilon; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell adhesion; Cell cycle; Cell division;
KW Cell membrane; Cytoplasm; Cytoskeleton; Immunity; Kinase; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Zinc; Zinc-finger.
FT CHAIN 1..737
FT /note="Protein kinase C epsilon type"
FT /id="PRO_0000055697"
FT DOMAIN 1..117
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 408..668
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 669..737
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 169..220
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 242..292
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 325..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..398
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 223..228
FT /note="Interaction with actin"
FT /evidence="ECO:0000250"
FT COMPBIAS 330..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 532
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 414..422
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 437
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 228
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 234
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 309
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 346
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000305|PubMed:19662078"
FT MOD_RES 349
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 350
FT /note="Phosphoserine; by MAPK11 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P16054, ECO:0000305"
FT MOD_RES 368
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:19662078,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 566
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:11964154"
FT MOD_RES 703
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 710
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 729
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11964154"
FT VARIANT 143
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs772834505)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035466"
FT VARIANT 333
FT /note="A -> V (in dbSNP:rs55989965)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042307"
FT VARIANT 389
FT /note="P -> R (in dbSNP:rs55767130)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042308"
FT VARIANT 563
FT /note="T -> M (in dbSNP:rs34077350)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042309"
FT VARIANT 654
FT /note="A -> T (in dbSNP:rs35777875)"
FT /id="VAR_050559"
FT MUTAGEN 437
FT /note="K->W: Abolishes activity and S-729 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11964154"
FT MUTAGEN 566
FT /note="T->A: Abolishes phosphorylation by PDK1, and S-729
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:11964154"
FT MUTAGEN 566
FT /note="T->E: No effect on S-729 phosphorylation."
FT /evidence="ECO:0000269|PubMed:11964154"
FT MUTAGEN 710
FT /note="T->E: No effect on activity; no effect on S-729
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:11964154"
FT MUTAGEN 729
FT /note="S->A: Enhances T-566 dephosphorylation."
FT /evidence="ECO:0000269|PubMed:11964154"
SQ SEQUENCE 737 AA; 83674 MW; 85032D0A091A1F7F CRC64;
MVVFNGLLKI KICEAVSLKP TAWSLRHAVG PRPQTFLLDP YIALNVDDSR IGQTATKQKT
NSPAWHDEFV TDVCNGRKIE LAVFHDAPIG YDDFVANCTI QFEELLQNGS RHFEDWIDLE
PEGRVYVIID LSGSSGEAPK DNEERVFRER MRPRKRQGAV RRRVHQVNGH KFMATYLRQP
TYCSHCRDFI WGVIGKQGYQ CQVCTCVVHK RCHELIITKC AGLKKQETPD QVGSQRFSVN
MPHKFGIHNY KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA
KVLADLGVTP DKITNSGQRR KKLIAGAESP QPASGSSPSE EDRSKSAPTS PCDQEIKELE
NNIRKALSFD NRGEEHRAAS SPDGQLMSPG ENGEVRQGQA KRLGLDEFNF IKVLGKGSFG
KVMLAELKGK DEVYAVKVLK KDVILQDDDV DCTMTEKRIL ALARKHPYLT QLYCCFQTKD
RLFFVMEYVN GGDLMFQIQR SRKFDEPRSR FYAAEVTSAL MFLHQHGVIY RDLKLDNILL
DAEGHCKLAD FGMCKEGILN GVTTTTFCGT PDYIAPEILQ ELEYGPSVDW WALGVLMYEM
MAGQPPFEAD NEDDLFESIL HDDVLYPVWL SKEAVSILKA FMTKNPHKRL GCVASQNGED
AIKQHPFFKE IDWVLLEQKK IKPPFKPRIK TKRDVNNFDQ DFTREEPVLT LVDEAIVKQI
NQEEFKGFSY FGEDLMP
