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 27-MAR-2024, entry version 250. DE RecName: Full=Protein kinase C alpha type; DE Short=PKC-A; DE Short=PKC-alpha; DE EC=2.7.11.13 {ECO:0000269|PubMed:25313067}; 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 FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=25313067; DOI=10.1073/pnas.1418342111; RA Shibata S., Arroyo J.P., Castaneda-Bueno M., Puthumana J., Zhang J., RA Uchida S., Stone K.L., Lam T.T., Lifton R.P.; RT "Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, RT preventing WNK4 degradation."; RL Proc. Natl. Acad. Sci. U.S.A. 111:15556-15561(2014). RN [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 proteasomal degradation (By CC similarity). Phosphorylates KLHL3 in response to angiotensin II CC signaling, decreasing the interaction between KLHL3 and WNK4 CC (PubMed:25313067). {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:25313067, CC ECO:0000269|PubMed:28028151, ECO:0000269|PubMed:9738012, CC ECO:0000269|PubMed:9830023, ECO:0000269|PubMed:9873035, CC 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; Evidence={ECO:0000269|PubMed:25313067}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC 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; 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-36513929; 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; Q9H8H3: TMT1A; NbExp=3; IntAct=EBI-1383528, EBI-1390168; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 333. DR CORUM; P17252; -. DR DIP; DIP-531N; -. DR IntAct; P17252; 134. 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; DB04209; Dequalinium. 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; DB02010; Staurosporine. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00163; Vitamin E. DR DrugCentral; P17252; -. DR GuidetoPHARMACOLOGY; 1482; -. DR GlyGen; P17252; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P17252; -. DR MetOSite; P17252; -. DR PhosphoSitePlus; P17252; -. DR SwissPalm; P17252; -. DR BioMuta; PRKCA; -. DR DMDM; 317373571; -. DR CPTAC; CPTAC-1615; -. DR CPTAC; CPTAC-3172; -. DR CPTAC; CPTAC-3173; -. DR EPD; P17252; -. DR jPOST; P17252; -. DR MassIVE; P17252; -. DR MaxQB; P17252; -. DR PaxDb; 9606-ENSP00000408695; -. DR PeptideAtlas; P17252; -. DR ProteomicsDB; 53464; -. DR Pumba; P17252; -. DR Antibodypedia; 1464; 1412 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 AGR; HGNC:9393; -. 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; VHEIKSH; -. DR OrthoDB; 841660at2759; -. 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; Depolymerization 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; 13 hits in 1191 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 192 other cell types or tissues. DR ExpressionAtlas; P17252; baseline and differential. DR GO; GO:0035866; C:alphav-beta3 integrin-PKCalpha complex; ISS:BHF-UCL. DR GO; GO:0036064; C:ciliary basal body; IDA:UniProt. 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,diacylglycerol-dependent serine/threonine kinase activity; IDA:UniProt. DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IDA:BHF-UCL. DR GO; GO:0035403; F:histone H3T6 kinase activity; 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: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; TAS:ARUK-UCL. 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:0110063; P:positive regulation of angiotensin-activated signaling pathway; IDA:UniProt. 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; cd20833; C1_cPKC_rpt1; 1. DR CDD; cd20836; C1_cPKC_rpt2; 1. DR CDD; cd04026; C2_PKC_alpha_gamma; 1. DR CDD; cd05615; STKc_cPKC_alpha; 1. DR Gene3D; 3.30.60.20; -; 2. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24356:SF193; PROTEIN KINASE C ALPHA TYPE; 1. DR PANTHER; PTHR24356; SERINE/THREONINE-PROTEIN KINASE; 1. 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; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. 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. DR Genevisible; P17252; HS. 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 //