KPCI_HUMAN
ID KPCI_HUMAN Reviewed; 596 AA.
AC P41743; D3DNQ4; Q8WW06;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 231.
DE RecName: Full=Protein kinase C iota type;
DE EC=2.7.11.13;
DE AltName: Full=Atypical protein kinase C-lambda/iota;
DE Short=PRKC-lambda/iota;
DE Short=aPKC-lambda/iota;
DE AltName: Full=nPKC-iota;
GN Name=PRKCI; Synonyms=DXS1179E;
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], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8226978; DOI=10.1016/s0021-9258(20)80525-0;
RA Selbie L.A., Schmitz-Peiffer C., Sheng Y., Biden T.J.;
RT "Molecular cloning and characterization of PKC iota, an atypical isoform of
RT protein kinase C derived from insulin-secreting cells.";
RL J. Biol. Chem. 268:24296-24302(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Teratocarcinoma;
RX PubMed=7607695; DOI=10.1016/0888-7543(95)80190-w;
RA Mazzarella R., Ciccodicola A., Esposito T., Arcucci A., Migliaccio C.,
RA Jones C., Schlessinger D., D'Urso M., D'Esposito M.;
RT "Human protein kinase C iota gene (PRKCI) is closely linked to the BTK gene
RT in Xq21.3.";
RL Genomics 26:629-631(1995).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 INTERACTION WITH SMG1, AND ACTIVITY REGULATION.
RX PubMed=8524286; DOI=10.1128/mcb.16.1.105;
RA Diaz-Meco M.T., Municio M.M., Sanchez P., Lozano J., Moscat J.;
RT "Lambda-interacting protein, a novel protein that specifically interacts
RT with the zinc finger domain of the atypical protein kinase C isotype
RT lambda/iota and stimulates its kinase activity in vitro and in vivo.";
RL Mol. Cell. Biol. 16:105-114(1996).
RN [6]
RP FUNCTION IN CELL SURVIVAL.
RX PubMed=9346882; DOI=10.1074/jbc.272.44.27521;
RA Murray N.R., Fields A.P.;
RT "Atypical protein kinase C iota protects human leukemia cells against drug-
RT induced apoptosis.";
RL J. Biol. Chem. 272:27521-27524(1997).
RN [7]
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 [8]
RP FUNCTION IN CELL SURVIVAL.
RX PubMed=10467349; DOI=10.1038/sj.cdd.4400548;
RA Wooten M.W., Seibenhener M.L., Zhou G., Vandenplas M.L., Tan T.H.;
RT "Overexpression of atypical PKC in PC12 cells enhances NGF-responsiveness
RT and survival through an NF-kappaB dependent pathway.";
RL Cell Death Differ. 6:753-764(1999).
RN [9]
RP INTERACTION WITH SQSTM1 AND IKBKB, AND FUNCTION.
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 [10]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF LYS-274.
RX PubMed=10906326; DOI=10.1074/jbc.m002742200;
RA Spitaler M., Villunger A., Grunicke H., Uberall F.;
RT "Unique structural and functional properties of the ATP-binding domain of
RT atypical protein kinase C-iota.";
RL J. Biol. Chem. 275:33289-33296(2000).
RN [11]
RP FUNCTION IN CELL SURVIVAL.
RX PubMed=11042363; DOI=10.1016/s0169-328x(00)00187-x;
RA Xie J., Guo Q., Zhu H., Wooten M.W., Mattson M.P.;
RT "Protein kinase C iota protects neural cells against apoptosis induced by
RT amyloid beta-peptide.";
RL Brain Res. Mol. Brain Res. 82:107-113(2000).
RN [12]
RP INTERACTION WITH PARD6A; PARD6B AND PARD6G, AND SUBUNIT OF A COMPLEX
RP CONTAINING PARD6B AND CDC42/RAC1.
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 [13]
RP INTERACTION WITH PARD3 AND PARD6B IN THE TERNARY AKPC/PAR3/PAR6 COMPLEX.
RX PubMed=11257119; DOI=10.1083/jcb.152.6.1183;
RA Suzuki A., Yamanaka T., Hirose T., Manabe N., Mizuno K., Shimizu M.,
RA Akimoto K., Izumi Y., Ohnishi T., Ohno S.;
RT "Atypical protein kinase C is involved in the evolutionarily conserved par
RT protein complex and plays a critical role in establishing epithelia-
RT specific junctional structures.";
RL J. Cell Biol. 152:1183-1196(2001).
RN [14]
RP FUNCTION, AND INTERACTION WITH GAPDH.
RX PubMed=11724794; DOI=10.1074/jbc.m109744200;
RA Tisdale E.J.;
RT "Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein
RT kinase Ciota /lambda and plays a role in microtubule dynamics in the early
RT secretory pathway.";
RL J. Biol. Chem. 277:3334-3341(2002).
RN [15]
RP PHOSPHORYLATION AT TYR-265; TYR-280 AND TYR-334, AND MUTAGENESIS OF
RP TYR-265; TYR-280 AND TYR-334.
RX PubMed=11713277; DOI=10.1128/mcb.21.24.8414-8427.2001;
RA Wooten M.W., Vandenplas M.L., Seibenhener M.L., Geetha T., Diaz-Meco M.T.;
RT "Nerve growth factor stimulates multisite tyrosine phosphorylation and
RT activation of the atypical protein kinase C's via a src kinase pathway.";
RL Mol. Cell. Biol. 21:8414-8427(2001).
RN [16]
RP INTERACTION WITH KPNB1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-265,
RP AND MUTAGENESIS OF TYR-265.
RX PubMed=11891849; DOI=10.1002/jcb.10101.abs;
RA White W.O., Seibenhener M.L., Wooten M.W.;
RT "Phosphorylation of tyrosine 256 facilitates nuclear import of atypical
RT protein kinase C.";
RL J. Cell. Biochem. 85:42-53(2002).
RN [17]
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 [18]
RP INTERACTION WITH PARD6B/PAR-6 AND LLGL1.
RX PubMed=12725730; DOI=10.1016/s0960-9822(03)00244-6;
RA Yamanaka T., Horikoshi Y., Sugiyama Y., Ishiyama C., Suzuki A., Hirose T.,
RA Iwamatsu A., Shinohara A., Ohno S.;
RT "Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of
RT PAR-3 to regulate epithelial cell polarity.";
RL Curr. Biol. 13:734-743(2003).
RN [19]
RP FUNCTION.
RX PubMed=12871960; DOI=10.1074/jbc.m305381200;
RA Tisdale E.J., Wang J., Silver R.B., Artalejo C.R.;
RT "Atypical protein kinase C plays a critical role in protein transport from
RT pre-Golgi intermediates.";
RL J. Biol. Chem. 278:38015-38021(2003).
RN [20]
RP INTERACTION WITH RAB2A.
RX PubMed=14570876; DOI=10.1074/jbc.m309343200;
RA Tisdale E.J.;
RT "Rab2 interacts directly with atypical protein kinase C (aPKC) iota/lambda
RT and inhibits aPKCiota/lambda-dependent glyceraldehyde-3-phosphate
RT dehydrogenase phosphorylation.";
RL J. Biol. Chem. 278:52524-52530(2003).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF IRAK1.
RX PubMed=14684752; DOI=10.1074/jbc.c300431200;
RA Mamidipudi V., Lin C., Seibenhener M.L., Wooten M.W.;
RT "Regulation of interleukin receptor-associated kinase (IRAK)
RT phosphorylation and signaling by iota protein kinase C.";
RL J. Biol. Chem. 279:4161-4165(2004).
RN [22]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15994303; DOI=10.1074/jbc.m505402200;
RA Regala R.P., Weems C., Jamieson L., Copland J.A., Thompson E.A.,
RA Fields A.P.;
RT "Atypical protein kinase Ciota plays a critical role in human lung cancer
RT cell growth and tumorigenicity.";
RL J. Biol. Chem. 280:31109-31115(2005).
RN [23]
RP INTERACTION WITH CDK7, AND SUBCELLULAR LOCATION.
RX PubMed=15695176; DOI=10.1016/j.tice.2004.10.004;
RA Bicaku E., Patel R., Acevedo-Duncan M.;
RT "Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota
RT in human glioma cells.";
RL Tissue Cell 37:53-58(2005).
RN [24]
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 [25]
RP INTERACTION WITH RAB2A AND GADPH, PHOSPHORYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16452474; DOI=10.1074/jbc.m513031200;
RA Tisdale E.J., Artalejo C.R.;
RT "Src-dependent protein kinase C iota/lambda (aPKCiota/lambda) tyrosine
RT phosphorylation is required for aPKCiota/lambda association with Rab2 and
RT glyceraldehyde-3-phosphate dehydrogenase on pre-Golgi intermediates.";
RL J. Biol. Chem. 281:8436-8442(2006).
RN [26]
RP INTERACTION WITH VAMP2.
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 [27]
RP FUNCTION IN PHOSPHORYLATION OF EZR.
RX PubMed=18270268; DOI=10.1242/jcs.016246;
RA Wald F.A., Oriolo A.S., Mashukova A., Fregien N.L., Langshaw A.H.,
RA Salas P.J.;
RT "Atypical protein kinase C (iota) activates ezrin in the apical domain of
RT intestinal epithelial cells.";
RL J. Cell Sci. 121:644-654(2008).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [29]
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 [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP FUNCTION IN APOPTOSIS.
RX PubMed=19327373; DOI=10.1016/j.mvr.2009.01.014;
RA Staiger K., Schatz U., Staiger H., Weyrich P., Haas C., Guirguis A.,
RA Machicao F., Haering H.U., Kellerer M.;
RT "Protein kinase C iota mediates lipid-induced apoptosis of human coronary
RT artery endothelial cells.";
RL Microvasc. Res. 78:40-44(2009).
RN [32]
RP INTERACTION WITH ECT2 AND PARD6A, AND MUTAGENESIS OF ASP-72.
RX PubMed=19617897; DOI=10.1038/onc.2009.217;
RA Justilien V., Fields A.P.;
RT "Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular
RT transformation.";
RL Oncogene 28:3597-3607(2009).
RN [33]
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 [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT PRO-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-3; SER-7; SER-8 AND THR-9, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [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 FUNCTION IN PHOSPHORYLATION OF BAD.
RX PubMed=21419810; DOI=10.1016/j.bbamcr.2011.03.007;
RA Desai S., Pillai P., Win-Piazza H., Acevedo-Duncan M.;
RT "PKC-? promotes glioblastoma cell survival by phosphorylating and
RT inhibiting BAD through a phosphatidylinositol 3-kinase pathway.";
RL Biochim. Biophys. Acta 1813:1190-1197(2011).
RN [37]
RP FUNCTION IN PHOSPHORYLATION OF ECT2.
RX PubMed=21189248; DOI=10.1074/jbc.m110.196113;
RA Justilien V., Jameison L., Der C.J., Rossman K.L., Fields A.P.;
RT "Oncogenic activity of Ect2 is regulated through protein kinase C iota-
RT mediated phosphorylation.";
RL J. Biol. Chem. 286:8149-8157(2011).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-564, AND IDENTIFICATION BY
RP 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 [39]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-564, 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 [41]
RP STRUCTURE BY NMR OF 25-108, INTERACTION WITH SQSTM1 AND MAP2K5, AND
RP MUTAGENESIS OF LYS-29 AND ASP-72.
RX PubMed=15143057; DOI=10.1074/jbc.m403092200;
RA Hirano Y., Yoshinaga S., Ogura K., Yokochi M., Noda Y., Sumimoto H.,
RA Inagaki F.;
RT "Solution structure of atypical protein kinase C PB1 domain and its mode of
RT interaction with ZIP/p62 and MEK5.";
RL J. Biol. Chem. 279:31883-31890(2004).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 25-108 IN COMPLEX WITH PARD6A, AND
RP MUTAGENESIS OF ASP-72; GLU-85 AND ARG-91.
RX PubMed=15590654; DOI=10.1074/jbc.m409823200;
RA Hirano Y., Yoshinaga S., Takeya R., Suzuki N.N., Horiuchi M., Kohjima M.,
RA Sumimoto H., Inagaki F.;
RT "Structure of a cell polarity regulator, a complex between atypical PKC and
RT Par6 PB1 domains.";
RL J. Biol. Chem. 280:9653-9661(2005).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-596, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND PHOSPHORYLATION AT THR-412 AND THR-564.
RX PubMed=16125198; DOI=10.1016/j.jmb.2005.07.060;
RA Messerschmidt A., Macieira S., Velarde M., Baedeker M., Benda C.,
RA Jestel A., Brandstetter H., Neuefeind T., Blaesse M.;
RT "Crystal structure of the catalytic domain of human atypical protein kinase
RT C-iota reveals interaction mode of phosphorylation site in turn motif.";
RL J. Mol. Biol. 352:918-931(2005).
RN [44]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-118 AND CYS-130.
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 plays a general protective role against apoptotic
CC stimuli, is involved in NF-kappa-B activation, cell survival,
CC differentiation and polarity, and contributes to the regulation of
CC microtubule dynamics in the early secretory pathway. Is necessary for
CC BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia
CC cells, protecting leukemia cells against drug-induced apoptosis. In
CC cultured neurons, prevents amyloid beta protein-induced apoptosis by
CC interrupting cell death process at a very early step. In glioblastoma
CC cells, may function downstream of phosphatidylinositol 3-kinase
CC (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating
CC and inhibiting the pro-apoptotic factor BAD. Can form a protein complex
CC in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and
CC regulate ECT2 oncogenic activity by phosphorylation, which in turn
CC promotes transformed growth and invasion. In response to nerve growth
CC factor (NGF), acts downstream of SRC to phosphorylate and activate
CC IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal
CC cell survival. Functions in the organization of the apical domain in
CC epithelial cells by phosphorylating EZR. This step is crucial for
CC activation and normal distribution of EZR at the early stages of
CC intestinal epithelial cell differentiation. Forms a protein complex
CC with LLGL1 and PARD6B independently of PARD3 to regulate epithelial
CC cell polarity. Plays a role in microtubule dynamics in the early
CC secretory pathway through interaction with RAB2A and GAPDH and
CC recruitment to vesicular tubular clusters (VTCs). In human coronary
CC artery endothelial cells (HCAEC), is activated by saturated fatty acids
CC and mediates lipid-induced apoptosis. Involved in early synaptic long
CC term potentiation phase in CA1 hippocampal cells and short term memory
CC formation (By similarity). {ECO:0000250|UniProtKB:F1M7Y5,
CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:10467349,
CC ECO:0000269|PubMed:10906326, ECO:0000269|PubMed:11042363,
CC ECO:0000269|PubMed:11724794, ECO:0000269|PubMed:12871960,
CC ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15994303,
CC ECO:0000269|PubMed:18270268, ECO:0000269|PubMed:19327373,
CC ECO:0000269|PubMed:21189248, ECO:0000269|PubMed:21419810,
CC ECO:0000269|PubMed:8226978, ECO:0000269|PubMed:9346882}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13;
CC -!- 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-412 (activation loop of the kinase domain) and Thr-564 (turn
CC motif), need to be phosphorylated for its full activation (By
CC similarity). Might also be a target for novel lipid activators that are
CC elevated during nutrient-stimulated insulin secretion. {ECO:0000250,
CC ECO:0000269|PubMed:8524286}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.5 uM for ATP (for recombinant purified PRKCI)
CC {ECO:0000269|PubMed:10906326};
CC Vmax=7.4 pmol/min/mg enzyme {ECO:0000269|PubMed:10906326};
CC -!- SUBUNIT: Forms a complex with SQSTM1 and MP2K5 (By similarity).
CC Interacts directly with SQSTM1 (Probable). Interacts with IKBKB.
CC Interacts with PARD6A, PARD6B and PARD6G. Part of a quaternary complex
CC containing aPKC, PARD3, a PARD6 protein (PARD6A, PARD6B or PARD6G) and
CC a GTPase protein (CDC42 or RAC1). Part of a complex with LLGL1 and
CC PARD6B. Interacts with ADAP1/CENTA1. Interaction with SMG1, through the
CC ZN-finger domain, activates the kinase activity. Interacts with CDK7.
CC Forms a complex with RAB2A and GAPDH involved in recruitment onto the
CC membrane of vesicular tubular clusters (VTCs). Interacts with ECT2
CC ('Thr-359' phosphorylated form). Interacts with VAMP2
CC (PubMed:17313651). Interacts with WDFY2 (via WD repeats 1-3)
CC (PubMed:16792529). {ECO:0000250|UniProtKB:Q62074,
CC ECO:0000269|PubMed:10356400, ECO:0000269|PubMed:11257119,
CC ECO:0000269|PubMed:11260256, ECO:0000269|PubMed:11724794,
CC ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:12725730,
CC ECO:0000269|PubMed:12893243, ECO:0000269|PubMed:14570876,
CC ECO:0000269|PubMed:15143057, ECO:0000269|PubMed:15590654,
CC ECO:0000269|PubMed:15695176, ECO:0000269|PubMed:16452474,
CC ECO:0000269|PubMed:16792529, ECO:0000269|PubMed:17313651,
CC ECO:0000269|PubMed:19617897, ECO:0000269|PubMed:8524286,
CC ECO:0000269|PubMed:9566925, ECO:0000305}.
CC -!- INTERACTION:
CC P41743; P60953: CDC42; NbExp=5; IntAct=EBI-286199, EBI-81752;
CC P41743; P78545: ELF3; NbExp=2; IntAct=EBI-286199, EBI-1057285;
CC P41743; P08151-1: GLI1; NbExp=3; IntAct=EBI-286199, EBI-16038799;
CC P41743; Q96L34: MARK4; NbExp=2; IntAct=EBI-286199, EBI-302319;
CC P41743; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-286199, EBI-16439278;
CC P41743; Q96RE7: NACC1; NbExp=3; IntAct=EBI-286199, EBI-7950997;
CC P41743; Q8TEW0: PARD3; NbExp=5; IntAct=EBI-286199, EBI-81968;
CC P41743; Q9NPB6: PARD6A; NbExp=17; IntAct=EBI-286199, EBI-81876;
CC P41743; Q9NPB6-2: PARD6A; NbExp=3; IntAct=EBI-286199, EBI-10693102;
CC P41743; Q9BYG5: PARD6B; NbExp=22; IntAct=EBI-286199, EBI-295391;
CC P41743; Q9BYG4: PARD6G; NbExp=7; IntAct=EBI-286199, EBI-295417;
CC P41743; Q8ND90: PNMA1; NbExp=2; IntAct=EBI-286199, EBI-302345;
CC P41743; Q05513: PRKCZ; NbExp=8; IntAct=EBI-286199, EBI-295351;
CC P41743; P63000: RAC1; NbExp=3; IntAct=EBI-286199, EBI-413628;
CC P41743; P48431: SOX2; NbExp=2; IntAct=EBI-286199, EBI-6124081;
CC P41743; Q13501: SQSTM1; NbExp=10; IntAct=EBI-286199, EBI-307104;
CC P41743; Q04917: YWHAH; NbExp=3; IntAct=EBI-286199, EBI-306940;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11891849,
CC ECO:0000269|PubMed:15695176, ECO:0000269|PubMed:9566925}. Membrane
CC {ECO:0000269|PubMed:16452474}. Endosome {ECO:0000269|PubMed:9566925}.
CC Nucleus {ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:15695176}.
CC Note=Transported into the endosome through interaction with SQSTM1/p62.
CC After phosphorylation by SRC, transported into the nucleus through
CC interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and
CC nucleus. Transported to vesicular tubular clusters (VTCs) through
CC interaction with RAB2A. {ECO:0000269|PubMed:15695176,
CC ECO:0000269|PubMed:9566925}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in lung and brain, but also
CC expressed at lower levels in many tissues including pancreatic islets.
CC Highly expressed in non-small cell lung cancers.
CC {ECO:0000269|PubMed:15994303, ECO:0000269|PubMed:7607695,
CC ECO:0000269|PubMed:8226978}.
CC -!- DOMAIN: The PB1 domain mediates interaction with SQSTM1. {ECO:0000250}.
CC -!- DOMAIN: The C1 zinc finger does not bind diacylglycerol (DAG).
CC -!- DOMAIN: The pseudosubstrate motif resembles the sequence around sites
CC phosphorylated on target proteins, except the presence of a non-
CC phosphorylatable residue in place of Ser, it modulates activity by
CC competing with substrates. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-412 in the activation loop is not mandatory
CC for activation (By similarity). Upon neuronal growth factor (NGF)
CC stimulation, phosphorylated by SRC at Tyr-265, Tyr-280 and Tyr-334
CC (PubMed:11713277, PubMed:16452474). Phosphorylation at Tyr-265
CC facilitates binding to KPNB1/importin-beta regulating entry of PRKCI
CC into the nucleus (PubMed:11891849). Phosphorylation on Tyr-334 is
CC important for NF-kappa-B stimulation (PubMed:11713277). Phosphorylated
CC at Thr-564 during the initial phase of long term potentiation (By
CC similarity). {ECO:0000250|UniProtKB:F1M7Y5,
CC ECO:0000250|UniProtKB:Q62074, ECO:0000269|PubMed:11713277,
CC ECO:0000269|PubMed:11891849, ECO:0000269|PubMed:16452474}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60171.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB17011.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH22016.3; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRKCIID41857ch3q26.html";
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DR EMBL; L18964; AAA60171.1; ALT_INIT; mRNA.
DR EMBL; L33881; AAB17011.1; ALT_INIT; mRNA.
DR EMBL; CH471052; EAW78513.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78515.1; -; Genomic_DNA.
DR EMBL; BC022016; AAH22016.3; ALT_INIT; mRNA.
DR CCDS; CCDS3212.2; -.
DR PIR; A49509; A49509.
DR RefSeq; NP_002731.4; NM_002740.5.
DR PDB; 1VD2; NMR; -; A=25-108.
DR PDB; 1WMH; X-ray; 1.50 A; A=25-108.
DR PDB; 1ZRZ; X-ray; 3.00 A; A=233-596.
DR PDB; 3A8W; X-ray; 2.10 A; A/B=249-588.
DR PDB; 3A8X; X-ray; 2.00 A; A/B=249-588.
DR PDB; 3ZH8; X-ray; 2.74 A; A/B/C=248-594.
DR PDB; 5LI1; X-ray; 2.00 A; A=248-596.
DR PDB; 5LI9; X-ray; 1.79 A; A=248-596.
DR PDB; 5LIH; X-ray; 3.25 A; A/B=248-596.
DR PDB; 6ILZ; X-ray; 3.26 A; A/C/E/G=249-588.
DR PDBsum; 1VD2; -.
DR PDBsum; 1WMH; -.
DR PDBsum; 1ZRZ; -.
DR PDBsum; 3A8W; -.
DR PDBsum; 3A8X; -.
DR PDBsum; 3ZH8; -.
DR PDBsum; 5LI1; -.
DR PDBsum; 5LI9; -.
DR PDBsum; 5LIH; -.
DR PDBsum; 6ILZ; -.
DR AlphaFoldDB; P41743; -.
DR BMRB; P41743; -.
DR SMR; P41743; -.
DR BioGRID; 111570; 252.
DR ComplexPortal; CPX-6183; PAR cell polarity complex, PARD6A-PRKCI variant.
DR ComplexPortal; CPX-6193; PAR cell polarity complex, PARD6B-PRKCI variant.
DR ComplexPortal; CPX-6194; PAR cell polarity complex, PARD6G-PRKCI variant.
DR CORUM; P41743; -.
DR DIP; DIP-31311N; -.
DR ELM; P41743; -.
DR IntAct; P41743; 147.
DR MINT; P41743; -.
DR STRING; 9606.ENSP00000295797; -.
DR BindingDB; P41743; -.
DR ChEMBL; CHEMBL2598; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB03777; Bisindolylmaleimide I.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00675; Tamoxifen.
DR DrugCentral; P41743; -.
DR GuidetoPHARMACOLOGY; 1490; -.
DR iPTMnet; P41743; -.
DR PhosphoSitePlus; P41743; -.
DR BioMuta; PRKCI; -.
DR DMDM; 239938658; -.
DR EPD; P41743; -.
DR jPOST; P41743; -.
DR MassIVE; P41743; -.
DR MaxQB; P41743; -.
DR PaxDb; P41743; -.
DR PeptideAtlas; P41743; -.
DR PRIDE; P41743; -.
DR ProteomicsDB; 55477; -.
DR Antibodypedia; 4271; 233 antibodies from 37 providers.
DR DNASU; 5584; -.
DR Ensembl; ENST00000295797.5; ENSP00000295797.4; ENSG00000163558.13.
DR GeneID; 5584; -.
DR KEGG; hsa:5584; -.
DR MANE-Select; ENST00000295797.5; ENSP00000295797.4; NM_002740.6; NP_002731.4.
DR UCSC; uc003fgs.3; human.
DR CTD; 5584; -.
DR DisGeNET; 5584; -.
DR GeneCards; PRKCI; -.
DR HGNC; HGNC:9404; PRKCI.
DR HPA; ENSG00000163558; Low tissue specificity.
DR MIM; 600539; gene.
DR neXtProt; NX_P41743; -.
DR OpenTargets; ENSG00000163558; -.
DR PharmGKB; PA33768; -.
DR VEuPathDB; HostDB:ENSG00000163558; -.
DR eggNOG; KOG0695; Eukaryota.
DR GeneTree; ENSGT00940000153497; -.
DR HOGENOM; CLU_000288_63_29_1; -.
DR InParanoid; P41743; -.
DR OMA; RIQCFIC; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; P41743; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; P41743; -.
DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR Reactome; R-HSA-209543; p75NTR recruits signalling complexes.
DR Reactome; R-HSA-420029; Tight junction interactions.
DR SABIO-RK; P41743; -.
DR SignaLink; P41743; -.
DR SIGNOR; P41743; -.
DR BioGRID-ORCS; 5584; 32 hits in 1116 CRISPR screens.
DR ChiTaRS; PRKCI; human.
DR EvolutionaryTrace; P41743; -.
DR GeneWiki; PRKCI; -.
DR GenomeRNAi; 5584; -.
DR Pharos; P41743; Tchem.
DR PRO; PR:P41743; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P41743; protein.
DR Bgee; ENSG00000163558; Expressed in buccal mucosa cell and 204 other tissues.
DR Genevisible; P41743; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0005923; C:bicellular tight junction; IEA:Ensembl.
DR GO; GO:0031252; C:cell leading edge; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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:0000139; C:Golgi membrane; IEA:GOC.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0120157; C:PAR polarity complex; IPI:ComplexPortal.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IEA:Ensembl.
DR GO; GO:0070160; C:tight junction; IC:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; TAS:UniProtKB.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004697; F:protein kinase C activity; ISS:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IEA:Ensembl.
DR GO; GO:0045216; P:cell-cell junction organization; IMP:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:BHF-UCL.
DR GO; GO:0007010; P:cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0035089; P:establishment of apical/basal cell polarity; IEA:Ensembl.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IDA:ComplexPortal.
DR GO; GO:0042462; P:eye photoreceptor cell development; IEA:Ensembl.
DR GO; GO:0048194; P:Golgi vesicle budding; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0061024; P:membrane organization; NAS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:WormBase.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; TAS:Reactome.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; NAS:UniProtKB.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IEA:Ensembl.
DR GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR GO; GO:0046903; P:secretion; NAS:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; TAS:UniProtKB.
DR CDD; cd00029; C1; 1.
DR CDD; cd06404; PB1_aPKC; 1.
DR CDD; cd05618; STKc_aPKC_iota; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR034661; aPKC_iota.
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 3D-structure; Acetylation; ATP-binding; Cytoplasm; Endosome; Kinase;
KW Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Tumor suppressor; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CHAIN 2..596
FT /note="Protein kinase C iota type"
FT /id="PRO_0000055710"
FT DOMAIN 25..108
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 254..522
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 523..594
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 140..190
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..253
FT /note="Regulatory domain"
FT REGION 2..28
FT /note="Required for interaction with RAB2"
FT REGION 72..91
FT /note="Interaction with PARD6A"
FT REGION 220..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 125..134
FT /note="Pseudosubstrate"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 378
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 260..268
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 283
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylproline"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 9
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 265
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:11713277,
FT ECO:0000269|PubMed:11891849"
FT MOD_RES 280
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:11713277"
FT MOD_RES 334
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:11713277"
FT MOD_RES 412
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000305|PubMed:16125198"
FT MOD_RES 564
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16125198,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT VARIANT 118
FT /note="P -> L (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042322"
FT VARIANT 130
FT /note="R -> C (in dbSNP:rs56154494)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042323"
FT MUTAGEN 29
FT /note="K->A: No effect on interaction with SQSTM1."
FT /evidence="ECO:0000269|PubMed:15143057"
FT MUTAGEN 72
FT /note="D->A: Loss of interaction with ECT2, PARD6A and with
FT SQSTM1."
FT /evidence="ECO:0000269|PubMed:15143057,
FT ECO:0000269|PubMed:15590654, ECO:0000269|PubMed:19617897"
FT MUTAGEN 85
FT /note="E->A: Slight decrease of interaction with PARD6A.
FT Loss of interaction with PARD6A; when associated with A-
FT 91."
FT /evidence="ECO:0000269|PubMed:15590654"
FT MUTAGEN 91
FT /note="R->A: Slight decrease of interaction with PARD6A.
FT Loss of interaction with PARD6A; when associated with A-
FT 85."
FT /evidence="ECO:0000269|PubMed:15590654"
FT MUTAGEN 265
FT /note="Y->F: No effect on the SRC-mediated phosphorylation
FT state. No effect on SRC-induced enzyme activity. Little
FT effect on TRAF6-mediated activation of NF-kappa-B.
FT Decreased binding to KPNB1/importin-beta."
FT /evidence="ECO:0000269|PubMed:11713277,
FT ECO:0000269|PubMed:11891849"
FT MUTAGEN 274
FT /note="K->R: No effect on activity."
FT /evidence="ECO:0000269|PubMed:10906326"
FT MUTAGEN 274
FT /note="K->W: Abolishes activity."
FT /evidence="ECO:0000269|PubMed:10906326"
FT MUTAGEN 280
FT /note="Y->F: No effect on the SRC-mediated phosphorylation
FT state. No effect on SRC-induced enzyme activity. No effect
FT on TRAF6-mediated activation of NF-kappa-B."
FT /evidence="ECO:0000269|PubMed:11713277"
FT MUTAGEN 334
FT /note="Y->F: No effect on the SRC-mediated phosphorylation
FT state. Significant reduction of SRC-induced enzyme
FT activity. Greatly reduced TRAF6-mediated activation of NF-
FT kappa-B. Reduces NGF-dependent cell survival."
FT /evidence="ECO:0000269|PubMed:11713277"
FT CONFLICT 485
FT /note="L -> M (in Ref. 4; AAH22016)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="H -> L (in Ref. 4; AAH22016)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="P -> R (in Ref. 4; AAH22016)"
FT /evidence="ECO:0000305"
FT STRAND 26..32
FT /evidence="ECO:0007829|PDB:1WMH"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:1WMH"
FT HELIX 47..57
FT /evidence="ECO:0007829|PDB:1WMH"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1WMH"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:1VD2"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1WMH"
FT HELIX 83..95
FT /evidence="ECO:0007829|PDB:1WMH"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:1WMH"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 254..262
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 264..273
FT /evidence="ECO:0007829|PDB:5LI9"
FT TURN 274..277
FT /evidence="ECO:0007829|PDB:3A8X"
FT STRAND 279..286
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 287..289
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 293..309
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 310..315
FT /evidence="ECO:0007829|PDB:6ILZ"
FT STRAND 318..323
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 325..332
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:6ILZ"
FT HELIX 340..347
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 352..371
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 384..386
FT /evidence="ECO:0007829|PDB:5LI9"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:3ZH8"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:3A8X"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 422..425
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 433..448
FT /evidence="ECO:0007829|PDB:5LI9"
FT TURN 452..457
FT /evidence="ECO:0007829|PDB:3A8X"
FT HELIX 467..476
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 487..496
FT /evidence="ECO:0007829|PDB:5LI9"
FT TURN 501..503
FT /evidence="ECO:0007829|PDB:5LI9"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:1ZRZ"
FT TURN 509..511
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 512..517
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 520..522
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 527..531
FT /evidence="ECO:0007829|PDB:5LI9"
FT TURN 545..547
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 549..551
FT /evidence="ECO:0007829|PDB:3A8X"
FT HELIX 554..557
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 568..571
FT /evidence="ECO:0007829|PDB:5LI9"
FT HELIX 576..579
FT /evidence="ECO:0007829|PDB:5LI9"
SQ SEQUENCE 596 AA; 68262 MW; 1E3F8C1D4BFC734F CRC64;
MPTQRDSSTM SHTVAGGGSG DHSHQVRVKA YYRGDIMITH FEPSISFEGL CNEVRDMCSF
DNEQLFTMKW IDEEGDPCTV SSQLELEEAF RLYELNKDSE LLIHVFPCVP ERPGMPCPGE
DKSIYRRGAR RWRKLYCANG HTFQAKRFNR RAHCAICTDR IWGLGRQGYK CINCKLLVHK
KCHKLVTIEC GRHSLPQEPV MPMDQSSMHS DHAQTVIPYN PSSHESLDQV GEEKEAMNTR
ESGKASSSLG LQDFDLLRVI GRGSYAKVLL VRLKKTDRIY AMKVVKKELV NDDEDIDWVQ
TEKHVFEQAS NHPFLVGLHS CFQTESRLFF VIEYVNGGDL MFHMQRQRKL PEEHARFYSA
EISLALNYLH ERGIIYRDLK LDNVLLDSEG HIKLTDYGMC KEGLRPGDTT STFCGTPNYI
APEILRGEDY GFSVDWWALG VLMFEMMAGR SPFDIVGSSD NPDQNTEDYL FQVILEKQIR
IPRSLSVKAA SVLKSFLNKD PKERLGCHPQ TGFADIQGHP FFRNVDWDMM EQKQVVPPFK
PNISGEFGLD NFDSQFTNEP VQLTPDDDDI VRKIDQSEFE GFEYINPLLM SAEECV
