KPCZ_HUMAN
ID KPCZ_HUMAN Reviewed; 592 AA.
AC Q05513; A8K4N0; A8MU64; B7Z2J7; E9PCW2; Q15207; Q5SYT5; Q969S4;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 4.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Protein kinase C zeta type;
DE EC=2.7.11.13 {ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659};
DE AltName: Full=nPKC-zeta;
GN Name=PRKCZ; Synonyms=PKC2;
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).
RC TISSUE=Frontal cortex;
RX PubMed=8224878; DOI=10.1016/0378-1119(93)90213-m;
RA Barbee J.L., Loomis C.R., Deutscher S.L., Burns D.J.;
RT "The cDNA sequence encoding human protein kinase C-zeta.";
RL Gene 132:305-306(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, and Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and Ovary;
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 7-592.
RC TISSUE=Hippocampus;
RX PubMed=8375396; DOI=10.1111/j.1432-1033.1993.tb18179.x;
RA Kochs G., Hummel R., Meyer D., Hug H., Marme D., Sarre T.F.;
RT "Activation and substrate specificity of the human protein kinase C alpha
RT and zeta isoenzymes.";
RL Eur. J. Biochem. 216:597-606(1993).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=7597083; DOI=10.1073/pnas.92.13.6072;
RA Stuart R.O., Nigam S.K.;
RT "Regulated assembly of tight junctions by protein kinase C.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:6072-6076(1995).
RN [8]
RP FUNCTION IN ACTIVATION OF MAP2K1/MEK1 AND MAPK1/ERK2.
RX PubMed=9447975; DOI=10.1128/mcb.18.2.790;
RA Schoenwasser D.C., Marais R.M., Marshall C.J., Parker P.J.;
RT "Activation of the mitogen-activated protein kinase/extracellular signal-
RT regulated kinase pathway by conventional, novel, and atypical protein
RT kinase C isotypes.";
RL Mol. Cell. Biol. 18:790-798(1998).
RN [9]
RP INTERACTION WITH SQSTM1, AND SUBCELLULAR LOCATION.
RX PubMed=9566925; DOI=10.1128/mcb.18.5.3069;
RA Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T.;
RT "Localization of atypical protein kinase C isoforms into lysosome-targeted
RT endosomes through interaction with p62.";
RL Mol. Cell. Biol. 18:3069-3080(1998).
RN [10]
RP PHOSPHORYLATION AT THR-410 BY PDPK1.
RX PubMed=9768361; DOI=10.1016/s0960-9822(98)70444-0;
RA Chou M.M., Hou W., Johnson J., Graham L.K., Lee M.H., Chen C.S.,
RA Newton A.C., Schaffhausen B.S., Toker A.;
RT "Regulation of protein kinase C zeta by PI 3-kinase and PDK-1.";
RL Curr. Biol. 8:1069-1077(1998).
RN [11]
RP INTERACTION WITH SQSTM1 AND IKBKB.
RX PubMed=10356400; DOI=10.1093/emboj/18.11.3044;
RA Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J.;
RT "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB
RT activation.";
RL EMBO J. 18:3044-3053(1999).
RN [12]
RP FUNCTION IN ACTIVATION OF MAPK1/ERK2.
RX PubMed=11035106; DOI=10.4049/jimmunol.165.8.4632;
RA Monick M.M., Carter A.B., Flaherty D.M., Peterson M.W., Hunninghake G.W.;
RT "Protein kinase C zeta plays a central role in activation of the p42/44
RT mitogen-activated protein kinase by endotoxin in alveolar macrophages.";
RL J. Immunol. 165:4632-4639(2000).
RN [13]
RP INTERACTION WITH PARD6A; PARD6B AND PARD6G.
RC TISSUE=Neuroblastoma;
RX PubMed=11260256; DOI=10.1046/j.1365-2443.2001.00404.x;
RA Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H.;
RT "Human homologues of the Caenorhabditis elegans cell polarity protein PAR6
RT as an adaptor that links the small GTPases Rac and Cdc42 to atypical
RT protein kinase C.";
RL Genes Cells 6:107-119(2001).
RN [14]
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 [15]
RP FUNCTION IN ACTIVATION OF AKT3.
RX PubMed=12162751; DOI=10.1021/bi026065r;
RA Hodgkinson C.P., Sale E.M., Sale G.J.;
RT "Characterization of PDK2 activity against protein kinase B gamma.";
RL Biochemistry 41:10351-10359(2002).
RN [16]
RP INTERACTION WITH SQSTM1 AND PAWR.
RX PubMed=11755531; DOI=10.1016/s0014-5793(01)03224-0;
RA Chang S., Kim J.H., Shin J.;
RT "p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-
RT induced PKCzeta inhibition.";
RL FEBS Lett. 510:57-61(2002).
RN [17]
RP INTERACTION WITH PARD3.
RX PubMed=12234671; DOI=10.1016/s0378-1119(02)00681-9;
RA Gao L., Macara I.G., Joberty G.;
RT "Multiple splice variants of Par3 and of a novel related gene, Par3L,
RT produce proteins with different binding properties.";
RL Gene 294:99-107(2002).
RN [18]
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 [19]
RP INTERACTION WITH SQSTM1 AND PARD6B, DOMAIN, AND MUTAGENESIS OF LYS-19;
RP ASP-62 AND ASP-66.
RX PubMed=12887891; DOI=10.1016/s1097-2765(03)00246-6;
RA Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L.;
RT "PB1 domain-mediated heterodimerization in NADPH oxidase and signaling
RT complexes of atypical protein kinase C with Par6 and p62.";
RL Mol. Cell 12:39-50(2003).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF MARK2 AND MARK3, AND CATALYTIC ACTIVITY.
RX PubMed=15084291; DOI=10.1016/j.cub.2004.04.007;
RA Hurov J.B., Watkins J.L., Piwnica-Worms H.;
RT "Atypical PKC phosphorylates PAR-1 kinases to regulate localization and
RT activity.";
RL Curr. Biol. 14:736-741(2004).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF MARK2, AND CATALYTIC ACTIVITY.
RX PubMed=15324659; DOI=10.1016/j.cub.2004.08.021;
RA Suzuki A., Hirata M., Kamimura K., Maniwa R., Yamanaka T., Mizuno K.,
RA Kishikawa M., Hirose H., Amano Y., Izumi N., Miwa Y., Ohno S.;
RT "aPKC acts upstream of PAR-1b in both the establishment and maintenance of
RT mammalian epithelial polarity.";
RL Curr. Biol. 14:1425-1435(2004).
RN [22]
RP PHOSPHORYLATION AT THR-410 BY PI3K.
RX PubMed=15314172; DOI=10.1128/mcb.24.17.7643-7653.2004;
RA Castoria G., Migliaccio A., Di Domenico M., Lombardi M., de Falco A.,
RA Varricchio L., Bilancio A., Barone M.V., Auricchio F.;
RT "Role of atypical protein kinase C in estradiol-triggered G1/S progression
RT of MCF-7 cells.";
RL Mol. Cell. Biol. 24:7643-7653(2004).
RN [23]
RP INTERACTION WITH WDFY2.
RX PubMed=16792529; DOI=10.1042/bj20060511;
RA Fritzius T., Burkard G., Haas E., Heinrich J., Schweneker M., Bosse M.,
RA Zimmermann S., Frey A.D., Caelers A., Bachmann A.S., Moelling K.;
RT "A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.";
RL Biochem. J. 399:9-20(2006).
RN [24]
RP FUNCTION, INTERACTION WITH VAMP2, COMPLEX FORMATION WITH VAMP2 AND WDFY2,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17313651; DOI=10.1111/j.1742-4658.2007.05702.x;
RA Fritzius T., Frey A.D., Schweneker M., Mayer D., Moelling K.;
RT "WD-repeat-propeller-FYVE protein, ProF, binds VAMP2 and protein kinase
RT Czeta.";
RL FEBS J. 274:1552-1566(2007).
RN [25]
RP INTERACTION WITH WWC1 AND DDR1.
RX PubMed=18190796; DOI=10.1016/j.bbamcr.2007.12.007;
RA Hilton H.N., Stanford P.M., Harris J., Oakes S.R., Kaplan W., Daly R.J.,
RA Ormandy C.J.;
RT "KIBRA interacts with discoidin domain receptor 1 to modulate collagen-
RT induced signalling.";
RL Biochim. Biophys. Acta 1783:383-393(2008).
RN [26]
RP RETRACTED PAPER.
RX PubMed=18321849; DOI=10.1074/jbc.m708208200;
RA Song P., Xie Z., Wu Y., Xu J., Dong Y., Zou M.H.;
RT "Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases
RT LKB1 nucleus export and apoptosis in endothelial cells.";
RL J. Biol. Chem. 283:12446-12455(2008).
RN [27]
RP RETRACTION NOTICE OF PUBMED:18321849.
RX PubMed=31519760; DOI=10.1074/jbc.w119.010661;
RA Song P., Xie Z., Wu Y., Dong Y., Zou M.H.;
RT "Withdrawal: Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation
RT increases LKB1 nucleus export and apoptosis in endothelial cells.";
RL J. Biol. Chem. 294:13831-13831(2019).
RN [28]
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 [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-560, 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 [30]
RP SUBCELLULAR LOCATION, SUBUNIT, AND PHOSPHORYLATION AT THR-410.
RX PubMed=20332120; DOI=10.1242/jcs.059329;
RA Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G.,
RA Chapon F., Dejana E.;
RT "CCM1 regulates vascular-lumen organization by inducing endothelial
RT polarity.";
RL J. Cell Sci. 123:1073-1080(2010).
RN [31]
RP REVIEW ON FUNCTION.
RX PubMed=12761192; DOI=10.1093/jb/mvg017;
RA Hirai T., Chida K.;
RT "Protein kinase Czeta (PKCzeta): activation mechanisms and cellular
RT functions.";
RL J. Biochem. 133:1-7(2003).
RN [32]
RP REVIEW ON FUNCTION.
RX PubMed=16903823; DOI=10.1134/s0006297906070017;
RA Liu L.Z., He A.B., Liu X.J., Li Y., Chang Y.S., Fang F.D.;
RT "Protein kinase Czeta and glucose uptake.";
RL Biochemistry (Mosc.) 71:701-706(2006).
RN [33]
RP REVIEW ON FUNCTION.
RX PubMed=16322752; DOI=10.1038/sj.cdd.4401823;
RA Moscat J., Rennert P., Diaz-Meco M.T.;
RT "PKCzeta at the crossroad of NF-kappaB and Jak1/Stat6 signaling pathways.";
RL Cell Death Differ. 13:702-711(2006).
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-560, 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 [36]
RP INTERACTION WITH APPL1.
RX PubMed=26583432; DOI=10.18632/oncotarget.6346;
RA Song J., Mu Y., Li C., Bergh A., Miaczynska M., Heldin C.H., Landstroem M.;
RT "APPL proteins promote TGFbeta-induced nuclear transport of the TGFbeta
RT type I receptor intracellular domain.";
RL Oncotarget 7:279-292(2016).
RN [37]
RP VARIANT [LARGE SCALE ANALYSIS] PHE-514.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [38]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-84 AND CYS-519.
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- and diacylglycerol-independent serine/threonine-
CC protein kinase that functions in phosphatidylinositol 3-kinase (PI3K)
CC pathway and mitogen-activated protein (MAP) kinase cascade, and is
CC involved in NF-kappa-B activation, mitogenic signaling, cell
CC proliferation, cell polarity, inflammatory response and maintenance of
CC long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment
CC in macrophages, or following mitogenic stimuli, functions downstream of
CC PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently
CC of RAF1 activation. Required for insulin-dependent activation of AKT3,
CC but may function as an adapter rather than a direct activator. Upon
CC insulin treatment may act as a downstream effector of PI3K and
CC contribute to the activation of translocation of the glucose
CC transporter SLC2A4/GLUT4 and subsequent glucose transport in
CC adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-
CC MAPK7/ERK5 independently of its kinase activity and can activate JUN
CC promoter through MEF2C. Through binding with SQSTM1/p62, functions in
CC interleukin-1 signaling and activation of NF-kappa-B with the specific
CC adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation
CC of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in
CC turn leads to the degradation of NF-kappa-B inhibitors. In migrating
CC astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by
CC CDC42 to function in the establishment of cell polarity along with the
CC microtubule motor and dynein. In association with FEZ1, stimulates
CC neuronal differentiation in PC12 cells. In the inflammatory response,
CC is required for the T-helper 2 (Th2) differentiation process, including
CC interleukin production, efficient activation of JAK1 and the subsequent
CC phosphorylation and nuclear translocation of STAT6. May be involved in
CC development of allergic airway inflammation (asthma), a process
CC dependent on Th2 immune response. In the NF-kappa-B-mediated
CC inflammatory response, can relieve SETD6-dependent repression of NF-
CC kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'.
CC Phosphorylates VAMP2 in vitro (PubMed:17313651).
CC {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751,
CC ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659,
CC ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:9447975}.
CC -!- FUNCTION: [Isoform 2]: Involved in late synaptic long term potention
CC phase in CA1 hippocampal cells and long term memory maintenance.
CC {ECO:0000250|UniProtKB:Q02956}.
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:15084291, ECO:0000269|PubMed:15324659};
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:15084291,
CC ECO:0000269|PubMed:15324659};
CC -!- ACTIVITY REGULATION: Atypical PKCs (PRKCI and PRKCZ) exhibit an
CC elevated basal enzymatic activity (that may be due to the interaction
CC with SMG1 or SQSTM1) and are not regulated by diacylglycerol,
CC phosphatidylserine, phorbol esters or calcium ions. Two specific sites,
CC Thr-410 (activation loop of the kinase domain) and Thr-560 (turn
CC motif), need to be phosphorylated for its full activation.
CC Phosphatidylinositol 3,4,5-trisphosphate might be a physiological
CC activator (By similarity). Isoform 2: Constitutively active (By
CC similarity). {ECO:0000250|UniProtKB:Q02956}.
CC -!- SUBUNIT: Forms a ternary complex with SQSTM1 and KCNAB2. Forms another
CC ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and
CC MAP2K5 (By similarity). Interacts with PARD6A, PARD6B, PARD6G and
CC SQSTM1. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and
CC CDC42 or RAC1. Interacts with ADAP1/CENTA1. Forms a ternary complex
CC composed of SQSTM1 and PAWR. Interacts directly with SQSTM1 (Probable).
CC Interacts with IKBKB. Interacts (via the protein kinase domain) with
CC WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly
CC in the absence of collagen. Component of the Par polarity complex,
CC composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts
CC with PDPK1 (via N-terminal region). Interacts with WDFY2 (via WD
CC repeats 1-3) (PubMed:16792529). Interacts with VAMP2 (PubMed:17313651).
CC Forms a complex with WDFY2 and VAMP2 (PubMed:17313651). Interacts with
CC APPL1 (PubMed:26583432). {ECO:0000250|UniProtKB:P09217,
CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:11260256,
CC ECO:0000269|PubMed:11755531, ECO:0000269|PubMed:11781095,
CC ECO:0000269|PubMed:12234671, ECO:0000269|PubMed:12887891,
CC ECO:0000269|PubMed:12893243, ECO:0000269|PubMed:16792529,
CC ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:18190796,
CC ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:26583432,
CC ECO:0000269|PubMed:9566925, ECO:0000305}.
CC -!- INTERACTION:
CC Q05513; Q15109: AGER; NbExp=6; IntAct=EBI-295351, EBI-1646426;
CC Q05513; P31749: AKT1; NbExp=2; IntAct=EBI-295351, EBI-296087;
CC Q05513; O95999: BCL10; NbExp=3; IntAct=EBI-295351, EBI-958922;
CC Q05513; Q07021: C1QBP; NbExp=4; IntAct=EBI-295351, EBI-347528;
CC Q05513; P08238: HSP90AB1; NbExp=2; IntAct=EBI-295351, EBI-352572;
CC Q05513; P14598: NCF1; NbExp=3; IntAct=EBI-295351, EBI-395044;
CC Q05513; P49757-1: NUMB; NbExp=4; IntAct=EBI-295351, EBI-7199607;
CC Q05513; Q9NPB6: PARD6A; NbExp=8; IntAct=EBI-295351, EBI-81876;
CC Q05513; Q9BYG5: PARD6B; NbExp=14; IntAct=EBI-295351, EBI-295391;
CC Q05513; Q9BYG4: PARD6G; NbExp=7; IntAct=EBI-295351, EBI-295417;
CC Q05513; P41743: PRKCI; NbExp=8; IntAct=EBI-295351, EBI-286199;
CC Q05513; Q04759: PRKCQ; NbExp=3; IntAct=EBI-295351, EBI-374762;
CC Q05513; P40337: VHL; NbExp=3; IntAct=EBI-295351, EBI-301246;
CC Q05513; P16554: numb; Xeno; NbExp=2; IntAct=EBI-295351, EBI-429581;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17313651,
CC ECO:0000269|PubMed:9566925}. Endosome {ECO:0000269|PubMed:9566925}.
CC Cell junction {ECO:0000269|PubMed:7597083}. Membrane
CC {ECO:0000250|UniProtKB:P09217}; Peripheral membrane protein
CC {ECO:0000305}. Note=In the retina, localizes in the terminals of the
CC rod bipolar cells (By similarity). Associates with endosomes
CC (PubMed:9566925). Presence of KRIT1, CDH5 and RAP1B is required for its
CC localization to the cell junction (PubMed:7597083). Colocalizes with
CC VAMP2 and WDFY2 in intracellular vesicles (PubMed:17313651).
CC Transiently translocates to the membrane of CA1 hippocampal cells in
CC response to the induction of long term potentiation (By similarity).
CC {ECO:0000250|UniProtKB:P09217, ECO:0000269|PubMed:17313651,
CC ECO:0000269|PubMed:7597083, ECO:0000269|PubMed:9566925}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000250|UniProtKB:P09217}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q05513-1; Sequence=Displayed;
CC Name=2; Synonyms=PKMzeta {ECO:0000250|UniProtKB:P09217};
CC IsoId=Q05513-2; Sequence=VSP_041904;
CC Name=3;
CC IsoId=Q05513-3; Sequence=VSP_046347;
CC -!- TISSUE SPECIFICITY: Expressed in brain, and to a lesser extent in lung,
CC kidney and testis.
CC -!- DOMAIN: The PB1 domain mediate mutually exclusive interactions with
CC SQSTM1 and PARD6B. {ECO:0000269|PubMed:12887891}.
CC -!- DOMAIN: The C1 domain does not bind the diacylglycerol (DAG).
CC {ECO:0000269|PubMed:12887891}.
CC -!- PTM: CDH5 is required for its phosphorylation at Thr-410.
CC Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by
CC the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at
CC Thr-410 by PI3K activates the kinase. {ECO:0000269|PubMed:11781095,
CC ECO:0000269|PubMed:15314172, ECO:0000269|PubMed:20332120,
CC ECO:0000269|PubMed:9768361}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage.
CC {ECO:0000250|UniProtKB:P09217}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
CC -!- CAUTION: Reported to phosphorylate STK11 leading to nuclear export of
CC STK11, subsequent inhibition of PI3K/Akt signaling, and increased
CC apoptosis in vein endothelial cells treated with the oxidant
CC peroxynitrite (PubMed:18321849). However this paper was withdrawn by
CC the authors due to concerns of image duplication in the figures. Its
CC role in protein phosphorylation has been confirmed in other studies
CC (PubMed:15084291, PubMed:15324659). {ECO:0000269|PubMed:15084291,
CC ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:18321849,
CC ECO:0000305|PubMed:31519760}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA78813.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L14283; AAA36488.1; -; mRNA.
DR EMBL; BT007082; AAP35745.1; -; mRNA.
DR EMBL; AK290995; BAF83684.1; -; mRNA.
DR EMBL; AK294649; BAH11833.1; -; mRNA.
DR EMBL; AK294782; BAH11883.1; -; mRNA.
DR EMBL; AL162271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590822; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL645703; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008058; AAH08058.1; -; mRNA.
DR EMBL; BC014270; AAH14270.1; -; mRNA.
DR EMBL; Z15108; CAA78813.1; ALT_INIT; mRNA.
DR CCDS; CCDS37.1; -. [Q05513-1]
DR CCDS; CCDS41229.1; -. [Q05513-2]
DR CCDS; CCDS55563.1; -. [Q05513-3]
DR PIR; JN0877; JN0877.
DR RefSeq; NP_001028753.1; NM_001033581.1. [Q05513-2]
DR RefSeq; NP_001028754.1; NM_001033582.1. [Q05513-2]
DR RefSeq; NP_001229803.1; NM_001242874.1. [Q05513-3]
DR RefSeq; NP_002735.3; NM_002744.4. [Q05513-1]
DR RefSeq; XP_016857288.1; XM_017001799.1.
DR AlphaFoldDB; Q05513; -.
DR SMR; Q05513; -.
DR BioGRID; 111576; 261.
DR ComplexPortal; CPX-6195; PAR cell polarity complex, PARD6G-PRKCZ variant.
DR ComplexPortal; CPX-6196; PAR cell polarity complex, PARD6B-PRKCZ variant.
DR ComplexPortal; CPX-6197; PAR cell polarity complex, PARD6A-PRKCZ variant.
DR CORUM; Q05513; -.
DR ELM; Q05513; -.
DR IntAct; Q05513; 225.
DR MINT; Q05513; -.
DR STRING; 9606.ENSP00000367830; -.
DR BindingDB; Q05513; -.
DR ChEMBL; CHEMBL3438; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB00675; Tamoxifen.
DR DrugCentral; Q05513; -.
DR GuidetoPHARMACOLOGY; 1491; -.
DR MoonDB; Q05513; Predicted.
DR GlyGen; Q05513; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q05513; -.
DR PhosphoSitePlus; Q05513; -.
DR BioMuta; PRKCZ; -.
DR DMDM; 68067736; -.
DR EPD; Q05513; -.
DR jPOST; Q05513; -.
DR MassIVE; Q05513; -.
DR MaxQB; Q05513; -.
DR PaxDb; Q05513; -.
DR PeptideAtlas; Q05513; -.
DR PRIDE; Q05513; -.
DR ProteomicsDB; 19529; -.
DR ProteomicsDB; 58330; -. [Q05513-1]
DR ProteomicsDB; 58331; -. [Q05513-2]
DR Antibodypedia; 3869; 854 antibodies from 45 providers.
DR DNASU; 5590; -.
DR Ensembl; ENST00000378567.8; ENSP00000367830.3; ENSG00000067606.17. [Q05513-1]
DR Ensembl; ENST00000400921.6; ENSP00000383712.2; ENSG00000067606.17. [Q05513-2]
DR Ensembl; ENST00000461106.6; ENSP00000426412.1; ENSG00000067606.17. [Q05513-3]
DR GeneID; 5590; -.
DR KEGG; hsa:5590; -.
DR MANE-Select; ENST00000378567.8; ENSP00000367830.3; NM_002744.6; NP_002735.3.
DR UCSC; uc001aiq.3; human. [Q05513-1]
DR CTD; 5590; -.
DR DisGeNET; 5590; -.
DR GeneCards; PRKCZ; -.
DR HGNC; HGNC:9412; PRKCZ.
DR HPA; ENSG00000067606; Tissue enhanced (brain).
DR MIM; 176982; gene.
DR neXtProt; NX_Q05513; -.
DR OpenTargets; ENSG00000067606; -.
DR Orphanet; 1606; 1p36 deletion syndrome.
DR PharmGKB; PA33775; -.
DR VEuPathDB; HostDB:ENSG00000067606; -.
DR eggNOG; KOG0695; Eukaryota.
DR GeneTree; ENSGT00940000153497; -.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; Q05513; -.
DR OMA; IPEEPGM; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; Q05513; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; Q05513; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-2173791; TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
DR Reactome; R-HSA-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-9634635; Estrogen-stimulated signaling through PRKCZ.
DR SignaLink; Q05513; -.
DR SIGNOR; Q05513; -.
DR BioGRID-ORCS; 5590; 23 hits in 1116 CRISPR screens.
DR ChiTaRS; PRKCZ; human.
DR GeneWiki; Protein_kinase_M_zeta/Protein_kinase_C_zeta; -.
DR GenomeRNAi; 5590; -.
DR Pharos; Q05513; Tchem.
DR PRO; PR:Q05513; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q05513; protein.
DR Bgee; ENSG00000067606; Expressed in right hemisphere of cerebellum and 166 other tissues.
DR ExpressionAtlas; Q05513; baseline and differential.
DR Genevisible; Q05513; HS.
DR GO; GO:0045179; C:apical cortex; IEA:Ensembl.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0043203; C:axon hillock; IEA:Ensembl.
DR GO; GO:0005923; C:bicellular tight junction; IEA:Ensembl.
DR GO; GO:0030054; C:cell junction; TAS:Reactome.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005815; C:microtubule organizing center; IEA:Ensembl.
DR GO; GO:0035748; C:myelin sheath abaxonal region; IEA:Ensembl.
DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
DR GO; GO:0016363; C:nuclear matrix; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0001725; C:stress fiber; IEA:Ensembl.
DR GO; GO:0070160; C:tight junction; IC:ComplexPortal.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IEA:Ensembl.
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:0043560; F:insulin receptor substrate binding; IC:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043274; F:phospholipase binding; IEA:Ensembl.
DR GO; GO:0015459; F:potassium channel regulator activity; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0004697; F:protein kinase C activity; EXP:Reactome.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0031584; P:activation of phospholipase D activity; IEA:Ensembl.
DR GO; GO:0032148; P:activation of protein kinase B activity; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0051899; P:membrane depolarization; IEA:Ensembl.
DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; IEA:Ensembl.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:BHF-UCL.
DR GO; GO:1990138; P:neuron projection extension; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; ISS:UniProtKB.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0051222; P:positive regulation of protein transport; IEA:Ensembl.
DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:UniProtKB.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISS:UniProtKB.
DR GO; GO:0070528; P:protein kinase C signaling; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0047496; P:vesicle transport along microtubule; IEA:Ensembl.
DR CDD; cd00029; C1; 1.
DR CDD; cd06404; PB1_aPKC; 1.
DR CDD; cd05617; STKc_aPKC_zeta; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR034662; aPKC_zeta.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034877; PB1_aPKC.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR012233; PKC.
DR InterPro; IPR017892; Pkinase_C.
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; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000554; PKC_zeta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS51745; PB1; 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; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Alternative promoter usage; Alternative splicing; ATP-binding;
KW Cell junction; Cytoplasm; Endosome; Inflammatory response; Kinase;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..592
FT /note="Protein kinase C zeta type"
FT /id="PRO_0000055701"
FT DOMAIN 15..98
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 252..518
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 519..590
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 130..180
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 79..145
FT /note="Interaction with SQSTM1"
FT /evidence="ECO:0000250"
FT ACT_SITE 376
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 258..266
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 281
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 410
FT /note="Phosphothreonine; by PDPK1 and PI3K"
FT /evidence="ECO:0000269|PubMed:15314172,
FT ECO:0000269|PubMed:20332120, ECO:0000269|PubMed:9768361"
FT MOD_RES 560
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 591
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09217"
FT VAR_SEQ 1..183
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041904"
FT VAR_SEQ 1..112
FT /note="MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQ
FT QHPLTLKWVDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGED
FT K -> MLTPRTDE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046347"
FT VARIANT 49
FT /note="R -> H (in dbSNP:rs35271800)"
FT /id="VAR_050560"
FT VARIANT 84
FT /note="R -> H (in dbSNP:rs56017162)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042310"
FT VARIANT 514
FT /note="S -> F (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035467"
FT VARIANT 519
FT /note="R -> C (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs376894109)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042311"
FT MUTAGEN 19
FT /note="K->A: No effect on interaction with SQSTM1 and
FT PARD6B."
FT /evidence="ECO:0000269|PubMed:12887891"
FT MUTAGEN 62
FT /note="D->A: Loss of interaction with SQSTM1 and PARD6B."
FT /evidence="ECO:0000269|PubMed:12887891"
FT MUTAGEN 66
FT /note="D->A: Loss of interaction with SQSTM1 and PARD6B."
FT /evidence="ECO:0000269|PubMed:12887891"
FT CONFLICT 6
FT /note="G -> D (in Ref. 1; AAA36488)"
FT /evidence="ECO:0000305"
FT CONFLICT 198
FT /note="K -> R (in Ref. 3; BAF83684)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="S -> T (in Ref. 1; AAA36488)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="K -> R (in Ref. 3; BAH11883)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="F -> L (in Ref. 3; BAF83684)"
FT /evidence="ECO:0000305"
FT CONFLICT 500
FT /note="R -> G (in Ref. 3; BAF83684)"
FT /evidence="ECO:0000305"
FT CONFLICT 522
FT /note="D -> G (in Ref. 3; BAF83684)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 592 AA; 67660 MW; 88CCD0577E6A596C CRC64;
MPSRTGPKME GSGGRVRLKA HYGGDIFITS VDAATTFEEL CEEVRDMCRL HQQHPLTLKW
VDSEGDPCTV SSQMELEEAF RLARQCRDEG LIIHVFPSTP EQPGLPCPGE DKSIYRRGAR
RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHGLVPLTC
RKHMDSVMPS QEPPVDDKNE DADLPSEETD GIAYISSSRK HDSIKDDSED LKPVIDGMDG
IKISQGLGLQ DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE EHARFYAAEI
CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE GLGPGDTTST FCGTPNYIAP
EILRGEEYGF SVDWWALGVL MFEMMAGRSP FDIITDNPDM NTEDYLFQVI LEKPIRIPRF
LSVKASHVLK GFLNKDPKER LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ ALPPFQPQIT
DDYGLDNFDT QFTSEPVQLT PDDEDAIKRI DQSEFEGFEY INPLLLSTEE SV
