KPCD_HUMAN
ID KPCD_HUMAN Reviewed; 676 AA.
AC Q05655; B0KZ81; B2R834; Q15144; Q86XJ6;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Protein kinase C delta type {ECO:0000305};
DE EC=2.7.11.13 {ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:34593629};
DE AltName: Full=Tyrosine-protein kinase PRKCD;
DE EC=2.7.10.2;
DE AltName: Full=nPKC-delta;
DE Contains:
DE RecName: Full=Protein kinase C delta type regulatory subunit;
DE Contains:
DE RecName: Full=Protein kinase C delta type catalytic subunit;
DE AltName: Full=Sphingosine-dependent protein kinase-1;
DE Short=SDK1;
GN Name=PRKCD {ECO:0000312|HGNC:HGNC:9399};
GN Synonyms=PKCD {ECO:0000303|PubMed:17303575};
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] (ISOFORM 1), AND VARIANTS SER-375 AND MET-593.
RC TISSUE=Liver;
RX PubMed=8357834; DOI=10.1016/0167-4781(93)90111-p;
RA Aris J.P., Basta P.V., Holmes W.D., Ballas L.M., Moomaw C., Rankl N.B.,
RA Blobel G., Loomis C.R., Burns D.J.;
RT "Molecular and biochemical characterization of a recombinant human PKC-
RT delta family member.";
RL Biochim. Biophys. Acta 1174:171-181(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-365 (ISOFORM 1).
RC TISSUE=Hippocampus;
RA Hug H.;
RT "Partial cDNA Sequence of human protein kinase C delta.";
RL Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-676 (ISOFORM 1).
RX PubMed=9427282; DOI=10.1046/j.1365-2443.1997.1470346.x;
RA Nomoto S., Watanabe Y., Ninomiya-Tsuji J., Yang L.-X., Kikuchi K.,
RA Hagiwara M., Hidaka H., Matsumoto K., Irie K.;
RT "Functional analyses of mammalian protein kinase C isozymes in budding
RT yeast and mammalian fibroblasts.";
RL Genes Cells 2:601-614(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 224-371 (ISOFORM 2).
RX PubMed=18092819; DOI=10.1021/bi7019782;
RA Jiang K., Apostolatos A.H., Ghansah T., Watson J.E., Vickers T.,
RA Cooper D.R., Epling-Burnette P.K., Patel N.A.;
RT "Identification of a novel antiapoptotic human protein kinase C delta
RT isoform, PKCdeltaVIII in NT2 cells.";
RL Biochemistry 47:787-797(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 432-533 (ISOFORM 1), AND VARIANT VAL-494.
RX PubMed=7988719; DOI=10.1016/0014-5793(94)01202-4;
RA Palmer R.H., Ridden J., Parker P.J.;
RT "Identification of multiple, novel, protein kinase C-related gene
RT products.";
RL FEBS Lett. 356:5-8(1994).
RN [9]
RP FUNCTION.
RX PubMed=11748588; DOI=10.1002/jcp.10022;
RA Bankers-Fulbright J.L., Kita H., Gleich G.J., O'Grady S.M.;
RT "Regulation of human eosinophil NADPH oxidase activity: a central role for
RT PKCdelta.";
RL J. Cell. Physiol. 189:306-315(2001).
RN [10]
RP MUTAGENESIS OF THR-507.
RX PubMed=11772397; DOI=10.1042/bj3610255;
RA Liu Y., Graham C., Li A., Fisher R.J., Shaw S.;
RT "Phosphorylation of the protein kinase C-theta activation loop and
RT hydrophobic motif regulates its kinase activity, but only activation loop
RT phosphorylation is critical to in vivo nuclear-factor-kappaB induction.";
RL Biochem. J. 361:255-265(2002).
RN [11]
RP INTERACTION WITH PDPK1, AND PHOSPHORYLATION.
RX PubMed=11781095; DOI=10.1021/bi010719z;
RA Hodgkinson C.P., Sale G.J.;
RT "Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by
RT a C-terminal PRK2 fragment.";
RL Biochemistry 41:561-569(2002).
RN [12]
RP INTERACTION WITH MUC1, AND FUNCTION.
RX PubMed=11877440; DOI=10.1074/jbc.m200436200;
RA Ren J., Li Y., Kufe D.;
RT "Protein kinase C delta regulates function of the DF3/MUC1 carcinoma
RT antigen in beta-catenin signaling.";
RL J. Biol. Chem. 277:17616-17622(2002).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH PLSC3, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=12649167;
RA Liu J., Chen J., Dai Q., Lee R.M.;
RT "Phospholipid scramblase 3 is the mitochondrial target of protein kinase C
RT delta-induced apoptosis.";
RL Cancer Res. 63:1153-1156(2003).
RN [14]
RP INTERACTION WITH RAD9A.
RX PubMed=12628935; DOI=10.1093/emboj/cdg134;
RA Yoshida K., Wang H.-G., Miki Y., Kufe D.;
RT "Protein kinase Cdelta is responsible for constitutive and DNA damage-
RT induced phosphorylation of Rad9.";
RL EMBO J. 22:1431-1441(2003).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT TYR-155.
RX PubMed=15774464; DOI=10.1074/jbc.m501374200;
RA Okhrimenko H., Lu W., Xiang C., Ju D., Blumberg P.M., Gomel R.,
RA Kazimirsky G., Brodie C.;
RT "Roles of tyrosine phosphorylation and cleavage of protein kinase Cdelta in
RT its protective effect against tumor necrosis factor-related apoptosis
RT inducing ligand-induced apoptosis.";
RL J. Biol. Chem. 280:23643-23652(2005).
RN [16]
RP FUNCTION IN PLATELET AGGREGATION, AND INTERACTION WITH VASP.
RX PubMed=16940418; DOI=10.1182/blood-2006-05-023739;
RA Pula G., Schuh K., Nakayama K., Nakayama K.I., Walter U., Poole A.W.;
RT "PKCdelta regulates collagen-induced platelet aggregation through
RT inhibition of VASP-mediated filopodia formation.";
RL Blood 108:4035-4044(2006).
RN [17]
RP PHOSPHORYLATION AT TYR-313 AND TYR-567.
RX PubMed=17570831; DOI=10.1042/bj20070244;
RA Hall K.J., Jones M.L., Poole A.W.;
RT "Coincident regulation of PKCdelta in human platelets by phosphorylation of
RT Tyr311 and Tyr565 and phospholipase C signalling.";
RL Biochem. J. 406:501-509(2007).
RN [18]
RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-299;
RP SER-302 AND SER-304, AND MUTAGENESIS OF SER-299.
RX PubMed=17603046; DOI=10.1016/j.febslet.2007.06.035;
RA Durgan J., Michael N., Totty N., Parker P.J.;
RT "Novel phosphorylation site markers of protein kinase C delta activation.";
RL FEBS Lett. 581:3377-3381(2007).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17303575; DOI=10.1074/jbc.m609424200;
RA Zeidan Y.H., Hannun Y.A.;
RT "Activation of acid sphingomyelinase by protein kinase Cdelta-mediated
RT phosphorylation.";
RL J. Biol. Chem. 282:11549-11561(2007).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=17579121; DOI=10.1158/1541-7786.mcr-06-0255;
RA Gomel R., Xiang C., Finniss S., Lee H.K., Lu W., Okhrimenko H., Brodie C.;
RT "The localization of protein kinase Cdelta in different subcellular sites
RT affects its proapoptotic and antiapoptotic functions and the activation of
RT distinct downstream signaling pathways.";
RL Mol. Cancer Res. 5:627-639(2007).
RN [21]
RP PHOSPHORYLATION AT THR-50; THR-141; SER-304; THR-451; SER-506; THR-507 AND
RP SER-664, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17965192; DOI=10.1110/ps.072874607;
RA Welman A., Griffiths J.R., Whetton A.D., Dive C.;
RT "Protein kinase C delta is phosphorylated on five novel Ser/Thr sites
RT following inducible overexpression in human colorectal cancer cells.";
RL Protein Sci. 16:2711-2715(2007).
RN [22]
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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; TYR-313; SER-503;
RP SER-654; SER-658 AND SER-664, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [24]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=18285462; DOI=10.1128/mcb.01530-07;
RA Doller A., Akool E.-S., Huwiler A., Mueller R., Radeke H.H.,
RA Pfeilschifter J., Eberhardt W.;
RT "Posttranslational modification of the AU-rich element binding protein HuR
RT by protein kinase Cdelta elicits angiotensin II-induced stabilization and
RT nuclear export of cyclooxygenase 2 mRNA.";
RL Mol. Cell. Biol. 28:2608-2625(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-302; SER-304;
RP SER-307 AND SER-664, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [27]
RP FUNCTION IN PLATELET RESPONSE.
RX PubMed=19587372; DOI=10.1182/blood-2008-11-188516;
RA Chari R., Kim S., Murugappan S., Sanjay A., Daniel J.L., Kunapuli S.P.;
RT "Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense
RT granule secretion.";
RL Blood 114:3056-3063(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-218; TYR-313 AND SER-664, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-313 AND SER-664, AND
RP IDENTIFICATION BY 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 [30]
RP FUNCTION IN PHOSPHORYLATION OF NCF1, AND PHOSPHORYLATION AT THR-507 AND
RP SER-645.
RX PubMed=19801500; DOI=10.1189/jlb.0408230;
RA Kilpatrick L.E., Sun S., Li H., Vary T.C., Korchak H.M.;
RT "Regulation of TNF-induced oxygen radical production in human neutrophils:
RT role of delta-PKC.";
RL J. Leukoc. Biol. 87:153-164(2010).
RN [31]
RP REVIEW ON FUNCTION.
RX PubMed=12473183; DOI=10.1093/oxfordjournals.jbchem.a003294;
RA Kikkawa U., Matsuzaki H., Yamamoto T.;
RT "Protein kinase C delta (PKC delta): activation mechanisms and functions.";
RL J. Biochem. 132:831-839(2002).
RN [32]
RP REVIEW ON FUNCTION.
RX PubMed=20002545; DOI=10.1111/j.1538-7836.2009.03722.x;
RA Harper M.T., Poole A.W.;
RT "Diverse functions of protein kinase C isoforms in platelet activation and
RT thrombus formation.";
RL J. Thromb. Haemost. 8:454-462(2010).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304; TYR-374; SER-645 AND
RP SER-664, AND 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 REVIEW ON FUNCTION.
RX PubMed=21103796; DOI=10.1100/tsw.2010.214;
RA Basu A., Pal D.;
RT "Two faces of protein kinase Cdelta: the contrasting roles of PKCdelta in
RT cell survival and cell death.";
RL ScientificWorldJournal 10:2272-2284(2010).
RN [35]
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 [36]
RP REVIEW ON FUNCTION.
RX PubMed=21810427; DOI=10.1016/j.yjmcc.2011.07.013;
RA Duquesnes N., Lezoualc'h F., Crozatier B.;
RT "PKC-delta and PKC-epsilon: Foes of the same family or strangers?";
RL J. Mol. Cell. Cardiol. 51:665-673(2011).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-645, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [38]
RP REVIEW.
RX PubMed=22918451; DOI=10.1007/s00005-012-0188-8;
RA Zhao M., Xia L., Chen G.Q.;
RT "Protein kinase cdelta in apoptosis: a brief overview.";
RL Arch. Immunol. Ther. Exp. 60:361-372(2012).
RN [39]
RP INVOLVEMENT IN ALPS3.
RX PubMed=23319571; DOI=10.1182/blood-2012-10-460741;
RA Salzer E., Santos-Valente E., Klaver S., Ban S.A., Emminger W.,
RA Prengemann N.K., Garncarz W., Mullauer L., Kain R., Boztug H., Heitger A.,
RA Arbeiter K., Eitelberger F., Seidel M.G., Holter W., Pollak A., Pickl W.F.,
RA Forster-Waldl E., Boztug K.;
RT "B-cell deficiency and severe autoimmunity caused by deficiency of protein
RT kinase C delta.";
RL Blood 121:3112-3116(2013).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-141; SER-299; SER-302;
RP SER-304; SER-307; SER-503 AND SER-664, AND IDENTIFICATION BY MASS
RP 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-664, AND IDENTIFICATION BY
RP 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 PRKD2.
RX PubMed=28428613; DOI=10.1038/s41598-017-00800-w;
RA Cobbaut M., Derua R., Doeppler H., Lou H.J., Vandoninck S., Storz P.,
RA Turk B.E., Seufferlein T., Waelkens E., Janssens V., Van Lint J.;
RT "Differential regulation of PKD isoforms in oxidative stress conditions
RT through phosphorylation of a conserved Tyr in the P+1 loop.";
RL Sci. Rep. 7:887-887(2017).
RN [43]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH PRKCH
RP UPSTREAM OPEN READING FRAME 2.
RX PubMed=34593629; DOI=10.1073/pnas.2018899118;
RA Jayaram D.R., Frost S., Argov C., Liju V.B., Anto N.P., Muraleedharan A.,
RA Ben-Ari A., Sinay R., Smoly I., Novoplansky O., Isakov N., Toiber D.,
RA Keasar C., Elkabets M., Yeger-Lotem E., Livneh E.;
RT "Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor
RT of PKCs.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-123 IN COMPLEX WITH
RP PHOSPHOTYROSINE-CONTAINING PEPTIDE, AND INTERACTION WITH CDCP1.
RX PubMed=15851033; DOI=10.1016/j.cell.2005.02.019;
RA Benes C.H., Wu N., Elia A.E.H., Dharia T., Cantley L.C., Soltoff S.P.;
RT "The C2 domain of PKCdelta is a phosphotyrosine binding domain.";
RL Cell 121:271-280(2005).
RN [45]
RP STRUCTURE BY NMR OF 149-218.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first phorbol esters/diacylglycerol binding
RT domain of human protein kinase C, delta.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays contrasting roles
CC in cell death and cell survival by functioning as a pro-apoptotic
CC protein during DNA damage-induced apoptosis, but acting as an anti-
CC apoptotic protein during cytokine receptor-initiated cell death, is
CC involved in tumor suppression as well as survival of several cancers,
CC is required for oxygen radical production by NADPH oxidase and acts as
CC positive or negative regulator in platelet functional responses
CC (PubMed:21810427, PubMed:21406692). Negatively regulates B cell
CC proliferation and also has an important function in self-antigen
CC induced B cell tolerance induction (By similarity). Upon DNA damage,
CC activates the promoter of the death-promoting transcription factor
CC BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and
CC apoptosis (PubMed:21810427, PubMed:21406692). In response to oxidative
CC stress, interact with and activate CHUK/IKKA in the nucleus, causing
CC the phosphorylation of p53/TP53 (PubMed:21810427, PubMed:21406692). In
CC the case of ER stress or DNA damage-induced apoptosis, can form a
CC complex with the tyrosine-protein kinase ABL1 which trigger apoptosis
CC independently of p53/TP53 (PubMed:21810427, PubMed:21406692). In
CC cytosol can trigger apoptosis by activating MAPK11 or MAPK14,
CC inhibiting AKT1 and decreasing the level of X-linked inhibitor of
CC apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the
CC activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is
CC required for the activation of the apoptosis regulators BAX and BAK,
CC which trigger the mitochondrial cell death pathway. Can phosphorylate
CC MCL1 and target it for degradation which is sufficient to trigger for
CC BAX activation and apoptosis. Is required for the control of cell cycle
CC progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate
CC 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S
CC phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the
CC cyclin CCNA2 promoter activity. In response to UV irradiation can
CC phosphorylate CDK1, which is important for the G2/M DNA damage
CC checkpoint activation (By similarity). Can protect glioma cells from
CC the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased
CC phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is
CC highly expressed in a number of cancer cells and promotes cell survival
CC and resistance against chemotherapeutic drugs by inducing cyclin D1
CC (CCND1) and hyperphosphorylation of RB1, and via several pro-survival
CC pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in
CC antifungal immunity by mediating phosphorylation and activation of
CC CARD9 downstream of C-type lectin receptors activation, promoting
CC interaction between CARD9 and BCL10, followed by activation of NF-
CC kappa-B and MAP kinase p38 pathways (By similarity). Can also act as
CC tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-
CC formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required
CC for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase
CC activity, and regulates TNF-elicited superoxide anion production in
CC neutrophils, by direct phosphorylation and activation of NCF1 or
CC indirectly through MAPK1/3 (ERK1/2) signaling pathways
CC (PubMed:19801500). May also play a role in the regulation of NADPH
CC oxidase activity in eosinophil after stimulation with IL5, leukotriene
CC B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation,
CC acts a negative regulator of filopodia formation and actin
CC polymerization by interacting with and negatively regulating VASP
CC phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and
CC CD36/GP4 receptors, regulates differentially platelet dense granule
CC secretion; acts as a positive regulator in PAR-mediated granule
CC secretion, whereas it negatively regulates CD36/GP4-mediated granule
CC release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and
CC regulates the interaction between MUC1 and beta-catenin
CC (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins
CC (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By
CC similarity). Phosphorylates ELAVL1 in response to angiotensin-2
CC treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid
CC scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on
CC the mitochondrial outer membrane which facilitates apoptosis
CC (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion
CC (PubMed:17303575). {ECO:0000250|UniProtKB:P28867,
CC ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440,
CC ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464,
CC ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:17303575,
CC ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372,
CC ECO:0000269|PubMed:19801500, ECO:0000303|PubMed:21406692,
CC ECO:0000303|PubMed:21810427}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC Evidence={ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:34593629};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000269|PubMed:12649167,
CC ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:34593629};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10027};
CC -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC calcium-insensitive, but activated by diacylglycerol (DAG) and
CC phosphatidylserine. Three specific sites; Thr-507 (activation loop of
CC the kinase domain), Ser-645 (turn motif) and Ser-664 (hydrophobic
CC region), need to be phosphorylated for its full activation. Activated
CC by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the
CC pseudosubstrate motif in the regulatory subunit is released from the
CC substrate recognition site of the catalytic subunit, which enables
CC PRKCD to become constitutively activated. The catalytic subunit which
CC displays properties of a sphingosine-dependent protein kinase is
CC activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-
CC erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS),
CC but not by ceramide or Sph-1-P and is strongly inhibited by
CC phosphatidylserine (By similarity). Inhibited by PRKCH upstream open
CC reading frame 2 (PubMed:34593629). {ECO:0000250,
CC ECO:0000269|PubMed:34593629}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.5 nM for PLSC3 {ECO:0000269|PubMed:12649167};
CC -!- SUBUNIT: Interacts with PDPK1 (via N-terminal region)
CC (PubMed:11781095). Interacts with RAD9A (PubMed:12628935). Interacts
CC with CDCP1 (PubMed:15851033). Interacts with MUC1 (PubMed:11877440).
CC Interacts with VASP (PubMed:16940418). Interacts with CAVIN3 (By
CC similarity). Interacts with PRKD2 (via N-terminus and zing-finger
CC domain 1 and 2) in response to oxidative stress; the interaction is
CC independent of PRKD2 tyrosine phosphorylation (PubMed:28428613).
CC Interacts with PLSC3; interaction is enhanced by UV irradiation
CC (PubMed:12649167). Interacts with PRKCH upstream open reading frame 2;
CC the interaction leads to inhibition of kinase activity
CC (PubMed:34593629). {ECO:0000250|UniProtKB:P28867,
CC ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:11877440,
CC ECO:0000269|PubMed:12628935, ECO:0000269|PubMed:12649167,
CC ECO:0000269|PubMed:15851033, ECO:0000269|PubMed:16940418,
CC ECO:0000269|PubMed:28428613, ECO:0000269|PubMed:34593629}.
CC -!- INTERACTION:
CC Q05655; P05067: APP; NbExp=3; IntAct=EBI-704279, EBI-77613;
CC Q05655; Q9BXL7: CARD11; NbExp=7; IntAct=EBI-704279, EBI-7006141;
CC Q05655; Q9NR28: DIABLO; NbExp=4; IntAct=EBI-704279, EBI-517508;
CC Q05655; P06241: FYN; NbExp=5; IntAct=EBI-704279, EBI-515315;
CC Q05655; P17677: GAP43; NbExp=4; IntAct=EBI-704279, EBI-1267511;
CC Q05655; C6GKH1: IL32; NbExp=3; IntAct=EBI-704279, EBI-9547476;
CC Q05655; P24001-2: IL32; NbExp=7; IntAct=EBI-704279, EBI-8800907;
CC Q05655; P19878: NCF2; NbExp=3; IntAct=EBI-704279, EBI-489611;
CC Q05655; P11388: TOP2A; NbExp=10; IntAct=EBI-704279, EBI-539628;
CC Q05655; P04637: TP53; NbExp=4; IntAct=EBI-704279, EBI-366083;
CC Q05655; Q9H3D4: TP63; NbExp=2; IntAct=EBI-704279, EBI-2337775;
CC Q05655; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-704279, EBI-11141397;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15774464,
CC ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:17603046,
CC ECO:0000269|PubMed:18285462}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:12649167, ECO:0000269|PubMed:15774464,
CC ECO:0000269|PubMed:17603046}. Nucleus {ECO:0000269|PubMed:15774464,
CC ECO:0000269|PubMed:17603046, ECO:0000269|PubMed:18285462}. Cell
CC membrane {ECO:0000269|PubMed:17303575, ECO:0000269|PubMed:17603046};
CC Peripheral membrane protein {ECO:0000305|PubMed:17603046}.
CC Mitochondrion {ECO:0000269|PubMed:12649167}. Endomembrane system
CC {ECO:0000269|PubMed:17303575}. Note=Translocates to the mitochondria
CC upon apoptotic stimulation. Upon activation, translocates to the plasma
CC membrane followed by partial location to the endolysosomes
CC (PubMed:17303575). {ECO:0000269|PubMed:12649167,
CC ECO:0000269|PubMed:17303575}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q05655-1; Sequence=Displayed;
CC Name=2; Synonyms=PKCdeltaVIII;
CC IsoId=Q05655-2; Sequence=VSP_043899;
CC -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type region 1
CC (C1A) and 2 (C1B), is the diacylglycerol sensor.
CC -!- DOMAIN: The C2 domain is a non-calcium binding domain. It binds
CC proteins containing phosphotyrosine in a sequence-specific manner.
CC -!- PTM: Autophosphorylated and/or phosphorylated at Thr-507, within the
CC activation loop; phosphorylation at Thr-507 is not a prerequisite for
CC enzymatic activity (PubMed:19801500). Autophosphorylated at Ser-299,
CC Ser-302 and Ser-304 (PubMed:17603046). Upon TNFSF10/TRAIL treatment,
CC phosphorylated at Tyr-155; phosphorylation is required for its
CC translocation to the endoplasmic reticulum and cleavage by caspase-3
CC (PubMed:15774464). Phosphorylated at Tyr-313, Tyr-334 and Tyr-567;
CC phosphorylation of Tyr-313 and Tyr-567 following thrombin or zymosan
CC stimulation potentiates its kinase activity (PubMed:17570831).
CC Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by
CC the apoptotic C-terminal cleavage product of PKN2 (PubMed:11781095).
CC Phosphorylated at Tyr-313 through a SYK and SRC mechanism downstream of
CC C-type lectin receptors activation, promoting its activation (By
CC similarity). {ECO:0000250|UniProtKB:P28867,
CC ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15774464,
CC ECO:0000269|PubMed:17570831, ECO:0000269|PubMed:17603046,
CC ECO:0000269|PubMed:19801500}.
CC -!- PTM: Proteolytically cleaved into a catalytic subunit and a regulatory
CC subunit by caspase-3 during apoptosis which results in kinase
CC activation. {ECO:0000250}.
CC -!- DISEASE: Autoimmune lymphoproliferative syndrome 3 (ALPS3)
CC [MIM:615559]: A primary immunodeficiency characterized by antibody
CC deficiency, hypogammaglobulinemia, recurrent bacterial infections and
CC an inability to mount an antibody response to antigen. The defect
CC results from a failure of B-cell differentiation and impaired secretion
CC of immunoglobulins; the numbers of circulating B-cells is usually in
CC the normal range, but can be low. CVID9 patients have B-cell deficiency
CC and severe autoimmunity. {ECO:0000269|PubMed:23319571}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Antiapoptotic isoform, resistant to
CC caspase-3 cleavage. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRKCDID42901ch3p21.html";
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DR EMBL; L07860; AAA03176.1; -; mRNA.
DR EMBL; L07861; AAA03175.1; -; mRNA.
DR EMBL; AK313216; BAG36031.1; -; mRNA.
DR EMBL; CH471055; EAW65279.1; -; Genomic_DNA.
DR EMBL; BC043350; AAH43350.1; -; mRNA.
DR EMBL; Z22521; CAA80249.1; -; mRNA.
DR EMBL; D10495; BAA01381.1; -; mRNA.
DR EMBL; DQ516383; ABF68960.1; -; mRNA.
DR CCDS; CCDS2870.1; -. [Q05655-1]
DR PIR; S35704; S35704.
DR RefSeq; NP_001303256.1; NM_001316327.1. [Q05655-1]
DR RefSeq; NP_006245.2; NM_006254.3. [Q05655-1]
DR RefSeq; NP_997704.1; NM_212539.1. [Q05655-1]
DR RefSeq; XP_006713322.1; XM_006713259.2.
DR RefSeq; XP_016862344.1; XM_017006855.1.
DR RefSeq; XP_016862345.1; XM_017006856.1.
DR PDB; 1YRK; X-ray; 1.70 A; A=1-123.
DR PDB; 2YUU; NMR; -; A=149-218.
DR PDBsum; 1YRK; -.
DR PDBsum; 2YUU; -.
DR AlphaFoldDB; Q05655; -.
DR SMR; Q05655; -.
DR BioGRID; 111566; 142.
DR CORUM; Q05655; -.
DR DIP; DIP-29954N; -.
DR ELM; Q05655; -.
DR IntAct; Q05655; 53.
DR MINT; Q05655; -.
DR STRING; 9606.ENSP00000378217; -.
DR BindingDB; Q05655; -.
DR ChEMBL; CHEMBL2996; -.
DR DrugBank; DB04376; 13-Acetylphorbol.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB05013; Ingenol mebutate.
DR DrugBank; DB00675; Tamoxifen.
DR DrugCentral; Q05655; -.
DR GuidetoPHARMACOLOGY; 1485; -.
DR iPTMnet; Q05655; -.
DR PhosphoSitePlus; Q05655; -.
DR BioMuta; PRKCD; -.
DR DMDM; 205371776; -.
DR CPTAC; CPTAC-1743; -.
DR EPD; Q05655; -.
DR jPOST; Q05655; -.
DR MassIVE; Q05655; -.
DR MaxQB; Q05655; -.
DR PaxDb; Q05655; -.
DR PeptideAtlas; Q05655; -.
DR PRIDE; Q05655; -.
DR ProteomicsDB; 58342; -. [Q05655-1]
DR ProteomicsDB; 58343; -. [Q05655-2]
DR Antibodypedia; 664; 1203 antibodies from 45 providers.
DR DNASU; 5580; -.
DR Ensembl; ENST00000330452.8; ENSP00000331602.3; ENSG00000163932.15. [Q05655-1]
DR Ensembl; ENST00000394729.6; ENSP00000378217.2; ENSG00000163932.15. [Q05655-1]
DR Ensembl; ENST00000650739.1; ENSP00000498623.1; ENSG00000163932.15. [Q05655-1]
DR Ensembl; ENST00000652449.1; ENSP00000498400.1; ENSG00000163932.15. [Q05655-1]
DR Ensembl; ENST00000654719.1; ENSP00000499558.1; ENSG00000163932.15. [Q05655-1]
DR GeneID; 5580; -.
DR KEGG; hsa:5580; -.
DR MANE-Select; ENST00000330452.8; ENSP00000331602.3; NM_006254.4; NP_006245.2.
DR UCSC; uc003dgl.4; human. [Q05655-1]
DR CTD; 5580; -.
DR DisGeNET; 5580; -.
DR GeneCards; PRKCD; -.
DR HGNC; HGNC:9399; PRKCD.
DR HPA; ENSG00000163932; Low tissue specificity.
DR MalaCards; PRKCD; -.
DR MIM; 176977; gene.
DR MIM; 615559; phenotype.
DR neXtProt; NX_Q05655; -.
DR OpenTargets; ENSG00000163932; -.
DR Orphanet; 3261; Autoimmune lymphoproliferative syndrome.
DR Orphanet; 300345; Autosomal systemic lupus erythematosus.
DR Orphanet; 1572; Common variable immunodeficiency.
DR PharmGKB; PA33763; -.
DR VEuPathDB; HostDB:ENSG00000163932; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000155327; -.
DR HOGENOM; CLU_000288_54_4_1; -.
DR InParanoid; Q05655; -.
DR OMA; YPEWKSS; -.
DR OrthoDB; 222529at2759; -.
DR PhylomeDB; Q05655; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; Q05655; -.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-111933; Calmodulin induced events.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-HSA-1489509; DAG and IP3 signaling.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR SABIO-RK; Q05655; -.
DR SignaLink; Q05655; -.
DR SIGNOR; Q05655; -.
DR BioGRID-ORCS; 5580; 17 hits in 1111 CRISPR screens.
DR ChiTaRS; PRKCD; human.
DR EvolutionaryTrace; Q05655; -.
DR GeneWiki; PRKCD; -.
DR GenomeRNAi; 5580; -.
DR Pharos; Q05655; Tclin.
DR PRO; PR:Q05655; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q05655; protein.
DR Bgee; ENSG00000163932; Expressed in monocyte and 148 other tissues.
DR ExpressionAtlas; Q05655; baseline and differential.
DR Genevisible; Q05655; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0036019; C:endolysosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016363; C:nuclear matrix; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
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:0004699; F:calcium-independent protein kinase C activity; TAS:BHF-UCL.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IDA:BHF-UCL.
DR GO; GO:0043560; F:insulin receptor substrate binding; ISS:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; EXP:Reactome.
DR GO; GO:0106310; F:protein serine kinase activity; IDA:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0042100; P:B cell proliferation; IEA:Ensembl.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1904385; P:cellular response to angiotensin; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:ParkinsonsUK-UCL.
DR GO; GO:0071447; P:cellular response to hydroperoxide; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; TAS:ParkinsonsUK-UCL.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0051490; P:negative regulation of filopodium assembly; ISS:UniProtKB.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; TAS:BHF-UCL.
DR GO; GO:0042119; P:neutrophil activation; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0032079; P:positive regulation of endodeoxyribonuclease activity; IMP:UniProtKB.
DR GO; GO:2000753; P:positive regulation of glucosylceramide catabolic process; IMP:BHF-UCL.
DR GO; GO:1900163; P:positive regulation of phospholipid scramblase activity; IMP:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:BHF-UCL.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:2000755; P:positive regulation of sphingomyelin catabolic process; IMP:BHF-UCL.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; 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:0050821; P:protein stabilization; NAS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:CACAO.
DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; IDA:UniProtKB.
DR GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
DR GO; GO:0010469; P:regulation of signaling receptor activity; TAS:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0023021; P:termination of signal transduction; IMP:BHF-UCL.
DR CDD; cd00029; C1; 2.
DR CDD; cd05620; STKc_nPKC_delta; 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; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034667; nPKC_delta.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027436; PKC_delta.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR014376; Prot_kin_PKC_delta.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000551; PKC_delta; 1.
DR PIRSF; PIRSF501104; Protein_kin_C_delta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
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; Alternative splicing; Apoptosis; ATP-binding; Cell cycle;
KW Cell membrane; Cytoplasm; Kinase; Membrane; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor; Zinc;
KW Zinc-finger.
FT CHAIN 1..676
FT /note="Protein kinase C delta type"
FT /id="PRO_0000055694"
FT CHAIN 1..329
FT /note="Protein kinase C delta type regulatory subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421667"
FT CHAIN 330..676
FT /note="Protein kinase C delta type catalytic subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421668"
FT DOMAIN 1..106
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 349..603
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 604..675
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 158..208
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 230..280
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 473
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 355..363
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 378
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 48
FT /note="Interaction with phosphotyrosine-containing peptide"
FT SITE 62
FT /note="Interaction with phosphotyrosine-containing peptide"
FT SITE 67
FT /note="Interaction with phosphotyrosine-containing peptide"
FT SITE 123
FT /note="Interaction with phosphotyrosine-containing peptide"
FT SITE 329..330
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 43
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P28867"
FT MOD_RES 50
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17965192"
FT MOD_RES 64
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P09215"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 141
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17965192,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 155
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15774464"
FT MOD_RES 218
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 299
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17603046,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 302
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17603046,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 304
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17603046,
FT ECO:0000269|PubMed:17965192, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 313
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17570831,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 334
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P09215"
FT MOD_RES 374
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 451
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:17965192"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17965192"
FT MOD_RES 507
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17965192,
FT ECO:0000305|PubMed:19801500"
FT MOD_RES 567
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17570831"
FT MOD_RES 645
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19801500,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 654
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17965192,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 328
FT /note="Q -> QGEAGSIAPLRFLFPLRPKKGDCPPFHCQVRQ (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:18092819"
FT /id="VSP_043899"
FT VARIANT 348
FT /note="N -> S (in dbSNP:rs33911937)"
FT /id="VAR_035347"
FT VARIANT 375
FT /note="F -> S (in dbSNP:rs1056998)"
FT /evidence="ECO:0000269|PubMed:8357834"
FT /id="VAR_006175"
FT VARIANT 410
FT /note="L -> F (in dbSNP:rs34502209)"
FT /id="VAR_035348"
FT VARIANT 483
FT /note="R -> W (in dbSNP:rs35891605)"
FT /id="VAR_046009"
FT VARIANT 494
FT /note="M -> V"
FT /evidence="ECO:0000269|PubMed:7988719"
FT /id="VAR_020610"
FT VARIANT 593
FT /note="V -> M"
FT /evidence="ECO:0000269|PubMed:8357834"
FT /id="VAR_006176"
FT MUTAGEN 299
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:17603046"
FT MUTAGEN 507
FT /note="T->A: No effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:11772397"
FT CONFLICT 524
FT /note="K -> R (in Ref. 2; BAG36031)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="S -> A (in Ref. 8; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 1..13
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 27..38
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 68..76
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:1YRK"
FT HELIX 88..96
FT /evidence="ECO:0007829|PDB:1YRK"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 101..107
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:1YRK"
FT STRAND 113..123
FT /evidence="ECO:0007829|PDB:1YRK"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:2YUU"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:2YUU"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:2YUU"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:2YUU"
FT STRAND 186..189
FT /evidence="ECO:0007829|PDB:2YUU"
FT TURN 190..192
FT /evidence="ECO:0007829|PDB:2YUU"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:2YUU"
SQ SEQUENCE 676 AA; 77505 MW; 013F4314A2EE331A CRC64;
MAPFLRIAFN SYELGSLQAE DEANQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKSTFD
AHIYEGRVIQ IVLMRAAEEP VSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMSVQY
FLEDVDCKQS MRSEDEAKFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKDFVW
GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TAANSRDTIF QKERFNIDMP HRFKVHNYMS
PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQRASR
RSDSASSEPV GIYQGFEKKT GVAGEDMQDN SGTYGKIWEG SSKCNINNFI FHKVLGKGSF
GKVLLGELKG RGEYFAIKAL KKDVVLIDDD VECTMVEKRV LTLAAENPFL THLICTFQTK
DHLFFVMEFL NGGDLMYHIQ DKGRFELYRA TFYAAEIMCG LQFLHSKGII YRDLKLDNVL
LDRDGHIKIA DFGMCKENIF GESRASTFCG TPDYIAPEIL QGLKYTFSVD WWSFGVLLYE
MLIGQSPFHG DDEDELFESI RVDTPHYPRW ITKESKDILE KLFEREPTKR LGVTGNIKIH
PFFKTINWTL LEKRRLEPPF RPKVKSPRDY SNFDQEFLNE KARLSYSDKN LIDSMDQSAF
AGFSFVNPKF EHLLED
