KPCA_HUMAN
ID KPCA_HUMAN Reviewed; 672 AA.
AC P17252; B5BU22; Q15137; Q32M72; Q96RE4;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 4.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Protein kinase C alpha type;
DE Short=PKC-A;
DE Short=PKC-alpha;
DE EC=2.7.11.13;
GN Name=PRKCA; Synonyms=PKCA, PRKACA;
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], AND VARIANT ILE-568.
RC TISSUE=Blood;
RX PubMed=2336401; DOI=10.1093/nar/18.8.2183;
RA Finkenzeller G., Marme D., Hug H.;
RT "Sequence of human protein kinase C alpha.";
RL Nucleic Acids Res. 18:2183-2183(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-568.
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-568.
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-568.
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 NUCLEOTIDE SEQUENCE [MRNA] OF 15-445.
RX PubMed=1714454; DOI=10.1016/s0021-9258(18)98596-0;
RA McSwine-Kennick R.L., McKeegan E.M., Johnson M.D., Morin M.J.;
RT "Phorbol diester-induced alterations in the expression of protein kinase C
RT isozymes and their mRNAs. Analysis in wild-type and phorbol diester-
RT resistant HL-60 cell clones.";
RL J. Biol. Chem. 266:15135-15143(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-57.
RA Haridasse V., Hackenbruck J., Glazer R.I.;
RT "Homo sapiens protein kinase C alpha 5-flanking sequence.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PROTEIN SEQUENCE OF 2-19.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP FUNCTION IN APOPTOSIS, AND SUBCELLULAR LOCATION.
RX PubMed=9738012; DOI=10.1074/jbc.273.39.25436;
RA Ruvolo P.P., Deng X., Carr B.K., May W.S.;
RT "A functional role for mitochondrial protein kinase Calpha in Bcl2
RT phosphorylation and suppression of apoptosis.";
RL J. Biol. Chem. 273:25436-25442(1998).
RN [10]
RP FUNCTION IN INFLAMMATORY RESPONSE.
RX PubMed=9830023; DOI=10.1074/jbc.273.49.32787;
RA St-Denis A., Chano F., Tremblay P., St-Pierre Y., Descoteaux A.;
RT "Protein kinase C-alpha modulates lipopolysaccharide-induced functions in a
RT murine macrophage cell line.";
RL J. Biol. Chem. 273:32787-32792(1998).
RN [11]
RP FUNCTION IN INFLAMMATORY RESPONSE.
RX PubMed=9873035; DOI=10.1074/jbc.274.2.939;
RA Han Y., Meng T., Murray N.R., Fields A.P., Brasier A.R.;
RT "Interleukin-1-induced nuclear factor-kappaB-IkappaBalpha autoregulatory
RT feedback loop in hepatocytes. A role for protein kinase calpha in post-
RT transcriptional regulation of ikappabalpha resynthesis.";
RL J. Biol. Chem. 274:939-947(1999).
RN [12]
RP FUNCTION IN APOPTOSIS.
RX PubMed=9927633; DOI=10.1124/mol.55.2.396;
RA Shen L., Dean N.M., Glazer R.I.;
RT "Induction of p53-dependent, insulin-like growth factor-binding protein-3-
RT mediated apoptosis in glioblastoma multiforme cells by a protein kinase
RT Calpha antisense oligonucleotide.";
RL Mol. Pharmacol. 55:396-402(1999).
RN [13]
RP FUNCTION IN CELL CYCLE PROGRESSION.
RX PubMed=10848585; DOI=10.1128/mcb.20.13.4580-4590.2000;
RA Besson A., Yong V.W.;
RT "Involvement of p21(Waf1/Cip1) in protein kinase C alpha-induced cell cycle
RT progression.";
RL Mol. Cell. Biol. 20:4580-4590(2000).
RN [14]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=11909826; DOI=10.1161/01.res.0000012503.30315.e8;
RA Wang A., Nomura M., Patan S., Ware J.A.;
RT "Inhibition of protein kinase Calpha prevents endothelial cell migration
RT and vascular tube formation in vitro and myocardial neovascularization in
RT vivo.";
RL Circ. Res. 90:609-616(2002).
RN [15]
RP INTERACTION WITH ADAP1.
RX PubMed=12893243; DOI=10.1016/s0006-291x(03)01187-2;
RA Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D.,
RA Wakefield R.I.D., Johannes F.-J., Aitken A.;
RT "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of
RT protein kinase C.";
RL Biochem. Biophys. Res. Commun. 307:459-465(2003).
RN [16]
RP FUNCTION IN PLATELET AGGREGATION.
RX PubMed=12724315; DOI=10.1074/jbc.m212407200;
RA Tabuchi A., Yoshioka A., Higashi T., Shirakawa R., Nishioka H., Kita T.,
RA Horiuchi H.;
RT "Direct demonstration of involvement of protein kinase Calpha in the Ca2+-
RT induced platelet aggregation.";
RL J. Biol. Chem. 278:26374-26379(2003).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF TNNT2/CTNT.
RX PubMed=12832403; DOI=10.1074/jbc.m306325200;
RA Sumandea M.P., Pyle W.G., Kobayashi T., de Tombe P.P., Solaro R.J.;
RT "Identification of a functionally critical protein kinase C phosphorylation
RT residue of cardiac troponin T.";
RL J. Biol. Chem. 278:35135-35144(2003).
RN [18]
RP FUNCTION IN KIT SIGNALING.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF TRPC1.
RX PubMed=15016832; DOI=10.1074/jbc.m313975200;
RA Ahmmed G.U., Mehta D., Vogel S., Holinstat M., Paria B.C., Tiruppathi C.,
RA Malik A.B.;
RT "Protein kinase Calpha phosphorylates the TRPC1 channel and regulates
RT store-operated Ca2+ entry in endothelial cells.";
RL J. Biol. Chem. 279:20941-20949(2004).
RN [20]
RP INTERACTION WITH PICK1.
RX PubMed=15247289; DOI=10.1074/jbc.m404499200;
RA Dev K.K., Nakanishi S., Henley J.M.;
RT "The PDZ domain of PICK1 differentially accepts protein kinase C-alpha and
RT GluR2 as interacting ligands.";
RL J. Biol. Chem. 279:41393-41397(2004).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF CSPG4, AND INTERACTION WITH CSPG4.
RX PubMed=15504744; DOI=10.1074/jbc.m411045200;
RA Makagiansar I.T., Williams S., Dahlin-Huppe K., Fukushi J., Mustelin T.,
RA Stallcup W.B.;
RT "Phosphorylation of NG2 proteoglycan by protein kinase C-alpha regulates
RT polarized membrane distribution and cell motility.";
RL J. Biol. Chem. 279:55262-55270(2004).
RN [22]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [24]
RP INTERACTION WITH TRIM41.
RX PubMed=17893151; DOI=10.1074/jbc.m703320200;
RA Chen D., Gould C., Garza R., Gao T., Hampton R.Y., Newton A.C.;
RT "Amplitude control of protein kinase C by RINCK, a novel E3 ubiquitin
RT ligase.";
RL J. Biol. Chem. 282:33776-33787(2007).
RN [25]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=18056764; DOI=10.1093/cvr/cvm085;
RA Xu H., Czerwinski P., Hortmann M., Sohn H.Y., Foerstermann U., Li H.;
RT "Protein kinase C alpha promotes angiogenic activity of human endothelial
RT cells via induction of vascular endothelial growth factor.";
RL Cardiovasc. Res. 78:349-355(2008).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-638 AND SER-651, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND IDENTIFICATION BY
RP 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 [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [30]
RP FUNCTION.
RX PubMed=19176525; DOI=10.1074/jbc.m808719200;
RA Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K.;
RT "Phosphorylation of activation transcription factor-2 at serine 121 by
RT protein kinase c controls c-Jun-mediated activation of transcription.";
RL J. Biol. Chem. 284:8567-8581(2009).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-628, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226 AND THR-638, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP FUNCTION IN PHOSPHORYLATION OF EIF4G1.
RX PubMed=21576361; DOI=10.1128/mcb.05589-11;
RA Dobrikov M., Dobrikova E., Shveygert M., Gromeier M.;
RT "Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1)
RT by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1.";
RL Mol. Cell. Biol. 31:2947-2959(2011).
RN [36]
RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION.
RX PubMed=12417014; DOI=10.1093/oxfordjournals.jbchem.a003272;
RA Nakashima S.;
RT "Protein kinase C alpha (PKC alpha): regulation and biological function.";
RL J. Biochem. 132:669-675(2002).
RN [37]
RP REVIEW ON FUNCTION.
RX PubMed=19969380; DOI=10.1016/j.tips.2009.10.006;
RA Konopatskaya O., Poole A.W.;
RT "Protein kinase Calpha: disease regulator and therapeutic target.";
RL Trends Pharmacol. Sci. 31:8-14(2010).
RN [38]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [39]
RP FUNCTION IN CELL MIGRATION, AND SUBCELLULAR LOCATION.
RX PubMed=23990668; DOI=10.1093/jnci/djt224;
RA Evensen N.A., Kuscu C., Nguyen H.L., Zarrabi K., Dufour A., Kadam P.,
RA Hu Y.J., Pulkoski-Gross A., Bahou W.F., Zucker S., Cao J.;
RT "Unraveling the role of KIAA1199, a novel endoplasmic reticulum protein, in
RT cancer cell migration.";
RL J. Natl. Cancer Inst. 105:1402-1416(2013).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10 AND SER-226, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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 [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226; THR-638 AND SER-657, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [42]
RP INTERACTION WITH PARD3.
RX PubMed=27925688; DOI=10.1002/humu.23153;
RA Chen X., An Y., Gao Y., Guo L., Rui L., Xie H., Sun M., Lam Hung S.,
RA Sheng X., Zou J., Bao Y., Guan H., Niu B., Li Z., Finnell R.H.,
RA Gusella J.F., Wu B.L., Zhang T.;
RT "Rare deleterious PARD3 variants in the aPKC-binding region are implicated
RT in the pathogenesis of human cranial neural tube defects via disrupting
RT apical tight junction formation.";
RL Hum. Mutat. 38:378-389(2017).
RN [43]
RP FUNCTION.
RX PubMed=28028151; DOI=10.1084/jem.20160068;
RA Xu X., Han L., Zhao G., Xue S., Gao Y., Xiao J., Zhang S., Chen P.,
RA Wu Z.Y., Ding J., Hu R., Wei B., Wang H.;
RT "LRCH1 interferes with DOCK8-Cdc42-induced T cell migration and ameliorates
RT experimental autoimmune encephalomyelitis.";
RL J. Exp. Med. 214:209-226(2017).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 320-672 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=19827831; DOI=10.1021/jm901108b;
RA Wagner J., von Matt P., Sedrani R., Albert R., Cooke N., Ehrhardt C.,
RA Geiser M., Rummel G., Stark W., Strauss A., Cowan-Jacob S.W., Beerli C.,
RA Weckbecker G., Evenou J.P., Zenke G., Cottens S.;
RT "Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-
RT yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein
RT kinase C isotypes.";
RL J. Med. Chem. 52:6193-6196(2009).
RN [45]
RP STRUCTURE BY NMR OF 88-169.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the second phorbol esters/diacylglycerol binding
RT domain of human protein kinase C alpha type.";
RL Submitted (APR-2008) to the PDB data bank.
RN [46]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-98; ASN-467 AND VAL-489.
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-activated, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that is involved in positive
CC and negative regulation of cell proliferation, apoptosis,
CC differentiation, migration and adhesion, tumorigenesis, cardiac
CC hypertrophy, angiogenesis, platelet function and inflammation, by
CC directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT,
CC or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP.
CC Involved in cell proliferation and cell growth arrest by positive and
CC negative regulation of the cell cycle. Can promote cell growth by
CC phosphorylating and activating RAF1, which mediates the activation of
CC the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which
CC facilitates active cyclin-dependent kinase (CDK) complex formation in
CC glioma cells. In intestinal cells stimulated by the phorbol ester PMA,
CC can trigger a cell cycle arrest program which is associated with the
CC accumulation of the hyper-phosphorylated growth-suppressive form of RB1
CC and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-
CC apoptotic function in glioma cells and protects them from apoptosis by
CC suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia
CC cells mediates anti-apoptotic action by phosphorylating BCL2. During
CC macrophage differentiation induced by macrophage colony-stimulating
CC factor (CSF1), is translocated to the nucleus and is associated with
CC macrophage development. After wounding, translocates from focal
CC contacts to lamellipodia and participates in the modulation of
CC desmosomal adhesion. Plays a role in cell motility by phosphorylating
CC CSPG4, which induces association of CSPG4 with extensive lamellipodia
CC at the cell periphery and polarization of the cell accompanied by
CC increases in cell motility. During chemokine-induced CD4(+) T cell
CC migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting
CC in its dissociation from LRCH1 and the activation of GTPase CDC42
CC (PubMed:28028151). Is highly expressed in a number of cancer cells
CC where it can act as a tumor promoter and is implicated in malignant
CC phenotypes of several tumors such as gliomas and breast cancers.
CC Negatively regulates myocardial contractility and positively regulates
CC angiogenesis, platelet aggregation and thrombus formation in arteries.
CC Mediates hypertrophic growth of neonatal cardiomyocytes, in part
CC through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA
CC treatment, is required to induce cardiomyocyte hypertrophy up to heart
CC failure and death, by increasing protein synthesis, protein-DNA ratio
CC and cell surface area. Regulates cardiomyocyte function by
CC phosphorylating cardiac troponin T (TNNT2/CTNT), which induces
CC significant reduction in actomyosin ATPase activity, myofilament
CC calcium sensitivity and myocardial contractility. In angiogenesis, is
CC required for full endothelial cell migration, adhesion to vitronectin
CC (VTN), and vascular endothelial growth factor A (VEGFA)-dependent
CC regulation of kinase activation and vascular tube formation. Involved
CC in the stabilization of VEGFA mRNA at post-transcriptional level and
CC mediates VEGFA-induced cell proliferation. In the regulation of
CC calcium-induced platelet aggregation, mediates signals from the
CC CD36/GP4 receptor for granule release, and activates the integrin
CC heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion.
CC During response to lipopolysaccharides (LPS), may regulate selective
CC LPS-induced macrophage functions involved in host defense and
CC inflammation. But in some inflammatory responses, may negatively
CC regulate NF-kappa-B-induced genes, through IL1A-dependent induction of
CC NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-
CC tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which
CC modulates EIF4G1 binding to MKNK1 and may be involved in the regulation
CC of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of
CC KIT activity. Phosphorylates ATF2 which promotes cooperation between
CC ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-
CC 52' facilitating its ubiquitination and proteosomal degradation (By
CC similarity). {ECO:0000250|UniProtKB:P20444,
CC ECO:0000269|PubMed:10848585, ECO:0000269|PubMed:11909826,
CC ECO:0000269|PubMed:12724315, ECO:0000269|PubMed:12832403,
CC ECO:0000269|PubMed:15016832, ECO:0000269|PubMed:15504744,
CC ECO:0000269|PubMed:15526160, ECO:0000269|PubMed:18056764,
CC ECO:0000269|PubMed:19176525, ECO:0000269|PubMed:21576361,
CC ECO:0000269|PubMed:23990668, ECO:0000269|PubMed:28028151,
CC ECO:0000269|PubMed:9738012, ECO:0000269|PubMed:9830023,
CC ECO:0000269|PubMed:9873035, ECO:0000269|PubMed:9927633}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000250|UniProtKB:P05696};
CC -!- ACTIVITY REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and
CC PRKCG) are activated by calcium and diacylglycerol (DAG) in the
CC presence of phosphatidylserine. Three specific sites; Thr-497
CC (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-
CC 657 (hydrophobic region), need to be phosphorylated for its full
CC activation.
CC -!- SUBUNIT: Recruited in a circadian manner into a nuclear complex which
CC also includes BMAL1 and RACK1 (By similarity). Interacts with
CC ADAP1/CENTA1 (PubMed:12893243). Interacts with CSPG4 (PubMed:15504744).
CC Binds to CAVIN2 in the presence of phosphatidylserine (By similarity).
CC Interacts with PRKCABP/PICK1 (via PDZ domain) (PubMed:15247289).
CC Interacts with TRIM41 (PubMed:17893151). Interacts with PARD3
CC (PubMed:27925688). Interacts with SOCS2 (By similarity).
CC {ECO:0000250|UniProtKB:P05696, ECO:0000250|UniProtKB:P20444,
CC ECO:0000269|PubMed:12893243, ECO:0000269|PubMed:15247289,
CC ECO:0000269|PubMed:15504744, ECO:0000269|PubMed:17893151,
CC ECO:0000269|PubMed:27925688}.
CC -!- INTERACTION:
CC P17252; Q15027: ACAP1; NbExp=3; IntAct=EBI-1383528, EBI-751746;
CC P17252; Q06481-5: APLP2; NbExp=3; IntAct=EBI-1383528, EBI-25646567;
CC P17252; Q66PJ3-4: ARL6IP4; NbExp=3; IntAct=EBI-1383528, EBI-5280499;
CC P17252; Q13072: BAGE; NbExp=3; IntAct=EBI-1383528, EBI-25884811;
CC P17252; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-1383528, EBI-11524452;
CC P17252; Q96A33: CCDC47; NbExp=3; IntAct=EBI-1383528, EBI-720151;
CC P17252; Q96LY2-2: CCDC74B; NbExp=3; IntAct=EBI-1383528, EBI-17967022;
CC P17252; P15169: CPN1; NbExp=3; IntAct=EBI-1383528, EBI-2116369;
CC P17252; P43234: CTSO; NbExp=3; IntAct=EBI-1383528, EBI-2874283;
CC P17252; O95424: DEXI; NbExp=3; IntAct=EBI-1383528, EBI-724515;
CC P17252; O43598: DNPH1; NbExp=3; IntAct=EBI-1383528, EBI-748674;
CC P17252; P21728: DRD1; NbExp=3; IntAct=EBI-1383528, EBI-6624459;
CC P17252; P00533: EGFR; NbExp=3; IntAct=EBI-1383528, EBI-297353;
CC P17252; P60228: EIF3E; NbExp=3; IntAct=EBI-1383528, EBI-347740;
CC P17252; Q96J88-3: EPSTI1; NbExp=3; IntAct=EBI-1383528, EBI-25885343;
CC P17252; Q8IVH2-2: FOXP4; NbExp=3; IntAct=EBI-1383528, EBI-25885364;
CC P17252; Q96NE9-2: FRMD6; NbExp=3; IntAct=EBI-1383528, EBI-13213391;
CC P17252; O14926: FSCN2; NbExp=3; IntAct=EBI-1383528, EBI-21017948;
CC P17252; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-1383528, EBI-9088619;
CC P17252; P19440-3: GGT1; NbExp=3; IntAct=EBI-1383528, EBI-21558069;
CC P17252; Q9UJ42: GPR160; NbExp=3; IntAct=EBI-1383528, EBI-25885139;
CC P17252; P62805: H4C9; NbExp=3; IntAct=EBI-1383528, EBI-302023;
CC P17252; Q9UBN7: HDAC6; NbExp=2; IntAct=EBI-1383528, EBI-301697;
CC P17252; P52597: HNRNPF; NbExp=3; IntAct=EBI-1383528, EBI-352986;
CC P17252; Q92826: HOXB13; NbExp=3; IntAct=EBI-1383528, EBI-11317274;
CC P17252; Q02363: ID2; NbExp=3; IntAct=EBI-1383528, EBI-713450;
CC P17252; Q96FT9-2: IFT43; NbExp=3; IntAct=EBI-1383528, EBI-11944538;
CC P17252; P17936: IGFBP3; NbExp=3; IntAct=EBI-1383528, EBI-715709;
CC P17252; P26951: IL3RA; NbExp=3; IntAct=EBI-1383528, EBI-1757512;
CC P17252; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-1383528, EBI-9996449;
CC P17252; Q9Y234: LIPT1; NbExp=3; IntAct=EBI-1383528, EBI-727376;
CC P17252; P51884: LUM; NbExp=3; IntAct=EBI-1383528, EBI-725780;
CC P17252; Q9H213: MAGEH1; NbExp=3; IntAct=EBI-1383528, EBI-473834;
CC P17252; P80192: MAP3K9; NbExp=3; IntAct=EBI-1383528, EBI-3951604;
CC P17252; Q15759: MAPK11; NbExp=3; IntAct=EBI-1383528, EBI-298304;
CC P17252; A0JLT2-2: MED19; NbExp=3; IntAct=EBI-1383528, EBI-13288755;
CC P17252; Q9H8H3: METTL7A; NbExp=3; IntAct=EBI-1383528, EBI-1390168;
CC P17252; Q8N983-3: MRPL43; NbExp=3; IntAct=EBI-1383528, EBI-11109389;
CC P17252; P49821: NDUFV1; NbExp=3; IntAct=EBI-1383528, EBI-748312;
CC P17252; Q2M1J6: OXA1L; NbExp=3; IntAct=EBI-1383528, EBI-9978021;
CC P17252; Q9BRX2: PELO; NbExp=3; IntAct=EBI-1383528, EBI-1043580;
CC P17252; Q9Y6X2: PIAS3; NbExp=3; IntAct=EBI-1383528, EBI-2803703;
CC P17252; P11309-2: PIM1; NbExp=2; IntAct=EBI-1383528, EBI-1018633;
CC P17252; Q6P1J6-2: PLB1; NbExp=3; IntAct=EBI-1383528, EBI-10694821;
CC P17252; Q9UNA4: POLI; NbExp=3; IntAct=EBI-1383528, EBI-741774;
CC P17252; Q02156: PRKCE; NbExp=2; IntAct=EBI-1383528, EBI-706254;
CC P17252; P07225: PROS1; NbExp=3; IntAct=EBI-1383528, EBI-2803380;
CC P17252; Q3YEC7-3: RABL6; NbExp=3; IntAct=EBI-1383528, EBI-25885259;
CC P17252; O94844: RHOBTB1; NbExp=3; IntAct=EBI-1383528, EBI-6426999;
CC P17252; Q9NWS8-3: RMND1; NbExp=3; IntAct=EBI-1383528, EBI-25884400;
CC P17252; Q9ULK6-3: RNF150; NbExp=3; IntAct=EBI-1383528, EBI-23640835;
CC P17252; P18077: RPL35A; NbExp=3; IntAct=EBI-1383528, EBI-353383;
CC P17252; P31431: SDC4; NbExp=2; IntAct=EBI-1383528, EBI-3913237;
CC P17252; Q99643: SDHC; NbExp=3; IntAct=EBI-1383528, EBI-1224539;
CC P17252; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-1383528, EBI-745901;
CC P17252; Q01105-2: SET; NbExp=3; IntAct=EBI-1383528, EBI-7481343;
CC P17252; P37840: SNCA; NbExp=3; IntAct=EBI-1383528, EBI-985879;
CC P17252; Q9Y5X0: SNX10; NbExp=3; IntAct=EBI-1383528, EBI-10329478;
CC P17252; P56693: SOX10; NbExp=3; IntAct=EBI-1383528, EBI-1167533;
CC P17252; Q9BRW5: SP2; NbExp=3; IntAct=EBI-1383528, EBI-25868254;
CC P17252; O43761: SYNGR3; NbExp=3; IntAct=EBI-1383528, EBI-11321949;
CC P17252; P15884: TCF4; NbExp=3; IntAct=EBI-1383528, EBI-533224;
CC P17252; Q3YBM2: TMEM176B; NbExp=3; IntAct=EBI-1383528, EBI-2821479;
CC P17252; P0CG48: UBC; NbExp=2; IntAct=EBI-1383528, EBI-3390054;
CC P17252; P13051-2: UNG; NbExp=3; IntAct=EBI-1383528, EBI-25834258;
CC P17252; Q8NB14: USP38; NbExp=3; IntAct=EBI-1383528, EBI-2512509;
CC P17252; O95498: VNN2; NbExp=3; IntAct=EBI-1383528, EBI-21494555;
CC P17252; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-1383528, EBI-12040603;
CC P17252; Q9BQ24: ZFYVE21; NbExp=3; IntAct=EBI-1383528, EBI-2849569;
CC P17252; Q05CR2: ZNF248; NbExp=3; IntAct=EBI-1383528, EBI-25835471;
CC P17252; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-1383528, EBI-12010736;
CC P17252; O15535: ZSCAN9; NbExp=3; IntAct=EBI-1383528, EBI-751531;
CC P17252; Q24008: inaD; Xeno; NbExp=2; IntAct=EBI-1383528, EBI-195326;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23990668}. Cell
CC membrane {ECO:0000269|PubMed:23990668}; Peripheral membrane protein
CC {ECO:0000305|PubMed:23990668}. Mitochondrion membrane
CC {ECO:0000269|PubMed:9738012}; Peripheral membrane protein
CC {ECO:0000305|PubMed:9738012}. Nucleus {ECO:0000250|UniProtKB:P20444}.
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; X52479; CAA36718.1; -; mRNA.
DR EMBL; AB451258; BAG70072.1; -; mRNA.
DR EMBL; AB451383; BAG70197.1; -; mRNA.
DR EMBL; AC005918; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC005988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006947; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC009452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC060796; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89014.1; -; Genomic_DNA.
DR EMBL; BC109273; AAI09274.1; -; mRNA.
DR EMBL; BC109274; AAI09275.1; -; mRNA.
DR EMBL; M22199; AAA60098.1; -; mRNA.
DR EMBL; AF395829; AAK84184.1; -; Genomic_DNA.
DR CCDS; CCDS11664.1; -.
DR PIR; S09496; KIHUCA.
DR RefSeq; NP_002728.1; NM_002737.2.
DR PDB; 2ELI; NMR; -; A=93-169.
DR PDB; 3IW4; X-ray; 2.80 A; A/B/C=320-672.
DR PDB; 4DNL; X-ray; 1.90 A; A=155-293.
DR PDB; 4RA4; X-ray; 2.63 A; A=318-672.
DR PDBsum; 2ELI; -.
DR PDBsum; 3IW4; -.
DR PDBsum; 4DNL; -.
DR PDBsum; 4RA4; -.
DR AlphaFoldDB; P17252; -.
DR BMRB; P17252; -.
DR SMR; P17252; -.
DR BioGRID; 111564; 289.
DR CORUM; P17252; -.
DR DIP; DIP-531N; -.
DR IntAct; P17252; 133.
DR MINT; P17252; -.
DR STRING; 9606.ENSP00000408695; -.
DR BindingDB; P17252; -.
DR ChEMBL; CHEMBL299; -.
DR DrugBank; DB14001; alpha-Tocopherol succinate.
DR DrugBank; DB06451; Aprinocarsen.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB11752; Bryostatin 1.
DR DrugBank; DB14002; D-alpha-Tocopherol acetate.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB05013; Ingenol mebutate.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB06641; Perifosine.
DR DrugBank; DB00144; Phosphatidyl serine.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB00163; Vitamin E.
DR DrugCentral; P17252; -.
DR GuidetoPHARMACOLOGY; 1482; -.
DR iPTMnet; P17252; -.
DR MetOSite; P17252; -.
DR PhosphoSitePlus; P17252; -.
DR SwissPalm; P17252; -.
DR BioMuta; PRKCA; -.
DR DMDM; 317373571; -.
DR CPTAC; CPTAC-1615; -.
DR EPD; P17252; -.
DR jPOST; P17252; -.
DR MassIVE; P17252; -.
DR MaxQB; P17252; -.
DR PaxDb; P17252; -.
DR PeptideAtlas; P17252; -.
DR PRIDE; P17252; -.
DR ProteomicsDB; 53464; -.
DR Antibodypedia; 1464; 1252 antibodies from 47 providers.
DR DNASU; 5578; -.
DR Ensembl; ENST00000413366.8; ENSP00000408695.3; ENSG00000154229.12.
DR GeneID; 5578; -.
DR KEGG; hsa:5578; -.
DR MANE-Select; ENST00000413366.8; ENSP00000408695.3; NM_002737.3; NP_002728.2.
DR UCSC; uc002jfp.2; human.
DR CTD; 5578; -.
DR DisGeNET; 5578; -.
DR GeneCards; PRKCA; -.
DR HGNC; HGNC:9393; PRKCA.
DR HPA; ENSG00000154229; Tissue enhanced (brain).
DR MIM; 176960; gene.
DR neXtProt; NX_P17252; -.
DR OpenTargets; ENSG00000154229; -.
DR PharmGKB; PA33759; -.
DR VEuPathDB; HostDB:ENSG00000154229; -.
DR eggNOG; KOG0696; Eukaryota.
DR GeneTree; ENSGT00940000156104; -.
DR HOGENOM; CLU_000288_54_2_1; -.
DR InParanoid; P17252; -.
DR OMA; EGEFYNI; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; P17252; -.
DR TreeFam; TF351133; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; P17252; -.
DR Reactome; R-HSA-111933; Calmodulin induced events.
DR Reactome; R-HSA-114516; Disinhibition of SNARE formation.
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-1433559; Regulation of KIT signaling.
DR Reactome; R-HSA-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR Reactome; R-HSA-3000170; Syndecan interactions.
DR Reactome; R-HSA-399997; Acetylcholine regulates insulin secretion.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-HSA-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-76005; Response to elevated platelet cytosolic Ca2+.
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-9010642; ROBO receptors bind AKAP5.
DR SABIO-RK; P17252; -.
DR SignaLink; P17252; -.
DR SIGNOR; P17252; -.
DR BioGRID-ORCS; 5578; 12 hits in 1109 CRISPR screens.
DR ChiTaRS; PRKCA; human.
DR EvolutionaryTrace; P17252; -.
DR GeneWiki; PKC_alpha; -.
DR GenomeRNAi; 5578; -.
DR Pharos; P17252; Tchem.
DR PRO; PR:P17252; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P17252; protein.
DR Bgee; ENSG00000154229; Expressed in CA1 field of hippocampus and 190 other tissues.
DR ExpressionAtlas; P17252; baseline and differential.
DR Genevisible; P17252; HS.
DR GO; GO:0035866; C:alphav-beta3 integrin-PKCalpha complex; ISS:BHF-UCL.
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:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA: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:0019899; F:enzyme binding; IDA:BHF-UCL.
DR GO; GO:0035403; F:histone kinase activity (H3-T6 specific); IDA:UniProtKB.
DR GO; GO:0005178; F:integrin binding; ISS:BHF-UCL.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; EXP:Reactome.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0002159; P:desmosome assembly; IMP:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007077; P:mitotic nuclear membrane disassembly; TAS:Reactome.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0106071; P:positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:DFLAT.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:BHF-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:UniProtKB.
DR GO; GO:2000707; P:positive regulation of dense core granule biogenesis; ISS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
DR GO; GO:0090330; P:regulation of platelet aggregation; IDA:UniProtKB.
DR GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL.
DR CDD; cd00029; C1; 2.
DR CDD; cd05615; STKc_cPKC_alpha; 1.
DR Gene3D; 2.60.40.150; -; 1.
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; IPR034663; cPKC_alpha.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014375; Protein_kinase_C_a/b/g.
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; PIRSF000550; PKC_alpha; 1.
DR PRINTS; PR00360; C2DOMAIN.
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; Acetylation; Angiogenesis; Apoptosis; ATP-binding; Calcium;
KW Cell adhesion; Cell membrane; Cytoplasm; Direct protein sequencing; Kinase;
KW Membrane; Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22814378"
FT CHAIN 2..672
FT /note="Protein kinase C alpha type"
FT /id="PRO_0000055679"
FT DOMAIN 158..275
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 339..597
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 598..668
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 36..86
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 101..151
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 463
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 195
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 245
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT BINDING 345..353
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 368
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05696"
FT MOD_RES 494
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 495
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04409"
FT MOD_RES 497
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P04409, ECO:0000305"
FT MOD_RES 501
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P05771"
FT MOD_RES 628
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 631
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P68403, ECO:0000255"
FT MOD_RES 638
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 658
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250|UniProtKB:P20444"
FT VARIANT 98
FT /note="P -> S (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042301"
FT VARIANT 467
FT /note="D -> N (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042302"
FT VARIANT 489
FT /note="M -> V (in dbSNP:rs34406842)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042303"
FT VARIANT 568
FT /note="V -> I (in dbSNP:rs6504459)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19054851, ECO:0000269|PubMed:2336401,
FT ECO:0000269|Ref.4"
FT /id="VAR_050558"
FT CONFLICT 50
FT /note="C -> S (in Ref. 6; AAA60098)"
FT /evidence="ECO:0000305"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:2ELI"
FT TURN 141..146
FT /evidence="ECO:0007829|PDB:2ELI"
FT STRAND 161..169
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 172..182
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 194..202
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:4DNL"
FT HELIX 233..237
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 254..262
FT /evidence="ECO:0007829|PDB:4DNL"
FT HELIX 263..268
FT /evidence="ECO:0007829|PDB:4DNL"
FT STRAND 271..276
FT /evidence="ECO:0007829|PDB:4DNL"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:4DNL"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 339..350
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 352..361
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 364..371
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 372..377
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 381..392
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 403..408
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 410..417
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:3IW4"
FT HELIX 425..432
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 437..456
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:4RA4"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 507..510
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 518..533
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 543..552
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 563..572
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 577..579
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 587..593
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 595..597
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 602..606
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 642..646
FT /evidence="ECO:0007829|PDB:4RA4"
FT HELIX 650..653
FT /evidence="ECO:0007829|PDB:4RA4"
SQ SEQUENCE 672 AA; 76750 MW; 9EB157789A062349 CRC64;
MADVFPGNDS TASQDVANRF ARKGALRQKN VHEVKDHKFI ARFFKQPTFC SHCTDFIWGF
GKQGFQCQVC CFVVHKRCHE FVTFSCPGAD KGPDTDDPRS KHKFKIHTYG SPTFCDHCGS
LLYGLIHQGM KCDTCDMNVH KQCVINVPSL CGMDHTEKRG RIYLKAEVAD EKLHVTVRDA
KNLIPMDPNG LSDPYVKLKL IPDPKNESKQ KTKTIRSTLN PQWNESFTFK LKPSDKDRRL
SVEIWDWDRT TRNDFMGSLS FGVSELMKMP ASGWYKLLNQ EEGEYYNVPI PEGDEEGNME
LRQKFEKAKL GPAGNKVISP SEDRKQPSNN LDRVKLTDFN FLMVLGKGSF GKVMLADRKG
TEELYAIKIL KKDVVIQDDD VECTMVEKRV LALLDKPPFL TQLHSCFQTV DRLYFVMEYV
NGGDLMYHIQ QVGKFKEPQA VFYAAEISIG LFFLHKRGII YRDLKLDNVM LDSEGHIKIA
DFGMCKEHMM DGVTTRTFCG TPDYIAPEII AYQPYGKSVD WWAYGVLLYE MLAGQPPFDG
EDEDELFQSI MEHNVSYPKS LSKEAVSVCK GLMTKHPAKR LGCGPEGERD VREHAFFRRI
DWEKLENREI QPPFKPKVCG KGAENFDKFF TRGQPVLTPP DQLVIANIDQ SDFEGFSYVN
PQFVHPILQS AV
