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Database: UniProt
Entry: Q04759
LinkDB: Q04759
Original site: Q04759 
ID   KPCT_HUMAN              Reviewed;         706 AA.
AC   Q04759; B4DF52; Q14DH6; Q3MJF1; Q64FY5; Q9H508; Q9H549;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   27-MAR-2002, sequence version 3.
DT   02-JUN-2021, entry version 226.
DE   RecName: Full=Protein kinase C theta type;
DE            EC=2.7.11.13 {ECO:0000269|PubMed:23509302};
DE   AltName: Full=nPKC-theta;
GN   Name=PRKCQ; Synonyms=PRKCT;
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), TISSUE SPECIFICITY, AND VARIANT
RP   LEU-330.
RX   PubMed=7686153;
RA   Chang J.D., Xu Y., Raychowdhury M.K., Ware J.A.;
RT   "Molecular cloning and expression of a cDNA encoding a novel isoenzyme of
RT   protein kinase C (nPKC). A new member of the nPKC family expressed in
RT   skeletal muscle, megakaryoblastic cells, and platelets.";
RL   J. Biol. Chem. 268:14208-14214(1993).
RN   [2]
RP   ERRATUM OF PUBMED:7686153, AND SEQUENCE REVISION.
RX   PubMed=7983077;
RA   Chang J.D., Xu Y., Raychowdhury M.K., Ware J.A.;
RL   J. Biol. Chem. 269:31322-31322(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Blood;
RX   PubMed=8444877;
RA   Baier G., Telford D., Giampa L., Coggeshall K.M., Baier-Bitterlich G.,
RA   Isakov N., Altman A.;
RT   "Molecular cloning and characterization of PKC theta, a novel member of the
RT   protein kinase C (PKC) gene family expressed predominantly in hematopoietic
RT   cells.";
RL   J. Biol. Chem. 268:4997-5004(1993).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT LEU-330.
RA   Li H., Ke R., Zhou G., Shen C., Zhong G., Lin L., Yang S.;
RL   Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Cerebellum;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
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   [8]
RP   FUNCTION IN ACTIVATION OF JUN.
RX   PubMed=8657160; DOI=10.1128/mcb.16.4.1842;
RA   Baier-Bitterlich G., Uberall F., Bauer B., Fresser F., Wachter H.,
RA   Grunicke H., Utermann G., Altman A., Baier G.;
RT   "Protein kinase C-theta isoenzyme selective stimulation of the
RT   transcription factor complex AP-1 in T lymphocytes.";
RL   Mol. Cell. Biol. 16:1842-1850(1996).
RN   [9]
RP   INTERACTION WITH GLRX3.
RX   PubMed=10636891; DOI=10.1074/jbc.275.3.1902;
RA   Witte S., Villalba M., Bi K., Liu Y., Isakov N., Altman A.;
RT   "Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by
RT   PICOT, a novel protein kinase C-interacting protein with a thioredoxin
RT   homology domain.";
RL   J. Biol. Chem. 275:1902-1909(2000).
RN   [10]
RP   PHOSPHORYLATION AT TYR-90, AND MUTAGENESIS OF TYR-90; ALA-148 AND LYS-409.
RX   PubMed=10652356; DOI=10.1074/jbc.275.5.3603;
RA   Liu Y., Witte S., Liu Y.C., Doyle M., Elly C., Altman A.;
RT   "Regulation of protein kinase Ctheta function during T cell activation by
RT   Lck-mediated tyrosine phosphorylation.";
RL   J. Biol. Chem. 275:3603-3609(2000).
RN   [11]
RP   FUNCTION IN PHOSPHORYLATION OF BAD.
RX   PubMed=11342610; DOI=10.4049/jimmunol.166.10.5955;
RA   Villalba M., Bushway P., Altman A.;
RT   "Protein kinase C-theta mediates a selective T cell survival signal via
RT   phosphorylation of BAD.";
RL   J. Immunol. 166:5955-5963(2001).
RN   [12]
RP   PHOSPHORYLATION AT THR-538; SER-676 AND SER-695, AND MUTAGENESIS OF THR-538
RP   AND SER-695.
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   [13]
RP   FUNCTION IN PHOSPHORYLATION OF STK39/SPAK.
RX   PubMed=14988727; DOI=10.1038/sj.emboj.7600125;
RA   Li Y., Hu J., Vita R., Sun B., Tabata H., Altman A.;
RT   "SPAK kinase is a substrate and target of PKCtheta in T-cell receptor-
RT   induced AP-1 activation pathway.";
RL   EMBO J. 23:1112-1122(2004).
RN   [14]
RP   FUNCTION IN PHOSPHORYLATION OF IRS1.
RX   PubMed=15364919; DOI=10.1074/jbc.c400186200;
RA   Li Y., Soos T.J., Li X., Wu J., Degennaro M., Sun X., Littman D.R.,
RA   Birnbaum M.J., Polakiewicz R.D.;
RT   "Protein kinase C Theta inhibits insulin signaling by phosphorylating IRS1
RT   at Ser(1101).";
RL   J. Biol. Chem. 279:45304-45307(2004).
RN   [15]
RP   INTERACTION WITH ECT2.
RX   PubMed=15254234; DOI=10.1128/mcb.24.15.6665-6675.2004;
RA   Liu X.F., Ishida H., Raziuddin R., Miki T.;
RT   "Nucleotide exchange factor ECT2 interacts with the polarity protein
RT   complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta
RT   activity.";
RL   Mol. Cell. Biol. 24:6665-6675(2004).
RN   [16]
RP   FUNCTION, PHOSPHORYLATION AT THR-219; THR-538; SER-676 AND SER-695, AND
RP   MUTAGENESIS OF THR-219; THR-538; SER-676 AND SER-695.
RX   PubMed=16252004; DOI=10.1038/sj.emboj.7600856;
RA   Thuille N., Heit I., Fresser F., Krumbock N., Bauer B., Leuthaeusser S.,
RA   Dammeier S., Graham C., Copeland T.D., Shaw S., Baier G.;
RT   "Critical role of novel Thr-219 autophosphorylation for the cellular
RT   function of PKCtheta in T lymphocytes.";
RL   EMBO J. 24:3869-3880(2005).
RN   [17]
RP   FUNCTION IN PHOSPHORYLATION OF CARD11, AND SUBUNIT.
RX   PubMed=16356855; DOI=10.1016/j.immuni.2005.09.014;
RA   Sommer K., Guo B., Pomerantz J.L., Bandaranayake A.D., Moreno-Garcia M.E.,
RA   Ovechkina Y.L., Rawlings D.J.;
RT   "Phosphorylation of the CARMA1 linker controls NF-kappaB activation.";
RL   Immunity 23:561-574(2005).
RN   [18]
RP   FUNCTION IN ACTIVATION OF BCL-X(L)/BCL2L1.
RX   PubMed=16709830; DOI=10.4049/jimmunol.176.11.6709;
RA   Manicassamy S., Gupta S., Huang Z., Sun Z.;
RT   "Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by
RT   up-regulating Bcl-xL.";
RL   J. Immunol. 176:6709-6716(2006).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-348; SER-685 AND SER-695, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-676 AND SER-695, 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   [21]
RP   FUNCTION IN PHOSPHORYLATION OF CBLB.
RX   PubMed=19549985; DOI=10.1126/scisignal.2000046;
RA   Gruber T., Hermann-Kleiter N., Hinterleitner R., Fresser F., Schneider R.,
RA   Gastl G., Penninger J.M., Baier G.;
RT   "PKC-theta modulates the strength of T cell responses by targeting Cbl-b
RT   for ubiquitination and degradation.";
RL   Sci. Signal. 2:RA30-RA30(2009).
RN   [22]
RP   REVIEW ON FUNCTION.
RX   PubMed=11861617; DOI=10.1146/annurev.immunol.20.100301.064807;
RA   Isakov N., Altman A.;
RT   "Protein kinase C(theta) in T cell activation.";
RL   Annu. Rev. Immunol. 20:761-794(2002).
RN   [23]
RP   REVIEW ON FUNCTION.
RX   PubMed=12473184; DOI=10.1093/oxfordjournals.jbchem.a003295;
RA   Altman A., Villalba M.;
RT   "Protein kinase C-theta (PKC theta): a key enzyme in T cell life and
RT   death.";
RL   J. Biochem. 132:841-846(2002).
RN   [24]
RP   REVIEW.
RX   PubMed=15282562; DOI=10.1038/ni1097;
RA   Spitaler M., Cantrell D.A.;
RT   "Protein kinase C and beyond.";
RL   Nat. Immunol. 5:785-790(2004).
RN   [25]
RP   REVIEW ON FUNCTION.
RX   PubMed=16978534;
RA   Manicassamy S., Gupta S., Sun Z.;
RT   "Selective function of PKC-theta in T cells.";
RL   Cell. Mol. Immunol. 3:263-270(2006).
RN   [26]
RP   REVIEW ON FUNCTION.
RX   PubMed=17544292; DOI=10.1016/j.phrs.2007.04.009;
RA   Hayashi K., Altman A.;
RT   "Protein kinase C theta (PKCtheta): a key player in T cell life and
RT   death.";
RL   Pharmacol. Res. 55:537-544(2007).
RN   [27]
RP   REVIEW ON FUNCTION.
RX   PubMed=18328786; DOI=10.1016/j.it.2008.01.005;
RA   Marsland B.J., Kopf M.;
RT   "T-cell fate and function: PKC-theta and beyond.";
RL   Trends Immunol. 29:179-185(2008).
RN   [28]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-685, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [29]
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   [30]
RP   REVIEW ON FUNCTION IN PLATELET ACTIVATION.
RX   PubMed=21944869; DOI=10.1016/j.febslet.2011.09.014;
RA   Cohen S., Braiman A., Shubinsky G., Isakov N.;
RT   "Protein kinase C-theta in platelet activation.";
RL   FEBS Lett. 585:3208-3215(2011).
RN   [31]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-685 AND SER-695, 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   [32]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-676; SER-685 AND SER-695, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [33]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH CCDC88A.
RX   PubMed=23509302; DOI=10.1073/pnas.1303392110;
RA   Lopez-Sanchez I., Garcia-Marcos M., Mittal Y., Aznar N., Farquhar M.G.,
RA   Ghosh P.;
RT   "Protein kinase C-theta (PKCtheta) phosphorylates and inhibits the guanine
RT   exchange factor, GIV/Girdin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:5510-5515(2013).
RN   [34]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695, 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   [35]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 362-706, AND PHOSPHORYLATION AT
RP   THR-538 AND SER-695.
RX   PubMed=15364937; DOI=10.1074/jbc.m409216200;
RA   Xu Z.B., Chaudhary D., Olland S., Wolfrom S., Czerwinski R., Malakian K.,
RA   Lin L., Stahl M.L., Joseph-McCarthy D., Benander C., Fitz L., Greco R.,
RA   Somers W.S., Mosyak L.;
RT   "Catalytic domain crystal structure of protein kinase C-theta (PKCtheta).";
RL   J. Biol. Chem. 279:50401-50409(2004).
RN   [36]
RP   X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF 361-706, AND PHOSPHORYLATION AT
RP   SER-676 AND SER-695.
RA   Stark W., Bitsch F., Berner A., Buelens F., Graff P., Depersin H.,
RA   Fendrich G., Geiser M., Knecht R., Rahuel J., Rummel G., Schlaeppi J.M.,
RA   Schmitz R., Strauss A., Wagner J.;
RT   "The crystal structure of the kinase domain of the protein kinase C theta
RT   in complex with Nvp-Xaa228.";
RL   Submitted (JAN-2007) to the PDB data bank.
RN   [37]
RP   VARIANTS [LARGE SCALE ANALYSIS] ASN-240; VAL-306; LEU-330 AND ASN-354.
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-independent, phospholipid- and diacylglycerol (DAG)-
CC       dependent serine/threonine-protein kinase that mediates non-redundant
CC       functions in T-cell receptor (TCR) signaling, including T-cells
CC       activation, proliferation, differentiation and survival, by mediating
CC       activation of multiple transcription factors such as NF-kappa-B, JUN,
CC       NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required
CC       for the activation of NF-kappa-B and JUN, which in turn are essential
CC       for IL2 production, and participates in the calcium-dependent NFATC1
CC       and NFATC2 transactivation. Mediates the activation of the canonical
CC       NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on
CC       several serine residues, inducing CARD11 association with lipid rafts
CC       and recruitment of the BCL10-MALT1 complex, which then activates IKK
CC       complex, resulting in nuclear translocation and activation of NFKB1.
CC       May also play an indirect role in activation of the non-canonical NF-
CC       kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN
CC       activation, acts by phosphorylating the mediator STK39/SPAK and may not
CC       act through MAP kinases signaling. Plays a critical role in TCR/CD28-
CC       induced NFATC1 and NFATC2 transactivation by participating in the
CC       regulation of reduced inositol 1,4,5-trisphosphate generation and
CC       intracellular calcium mobilization. After costimulation of T-cells
CC       through CD28 can phosphorylate CBLB and is required for the
CC       ubiquitination and subsequent degradation of CBLB, which is a
CC       prerequisite for the activation of TCR. During T-cells differentiation,
CC       plays an important role in the development of T-helper 2 (Th2) cells
CC       following immune and inflammatory responses, and, in the development of
CC       inflammatory autoimmune diseases, is necessary for the activation of
CC       IL17-producing Th17 cells. May play a minor role in Th1 response. Upon
CC       TCR stimulation, mediates T-cell protective survival signal by
CC       phosphorylating BAD, thus protecting T-cells from BAD-induced
CC       apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-
CC       kappa-B and JUN pathways. In platelets, regulates signal transduction
CC       downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors,
CC       playing a positive role in 'outside-in' signaling and granule secretion
CC       signal transduction. May relay signals from the activated ITGA2B
CC       receptor by regulating the uncoupling of WASP and WIPF1, thereby
CC       permitting the regulation of actin filament nucleation and branching
CC       activity of the Arp2/3 complex. May mediate inhibitory effects of free
CC       fatty acids on insulin signaling by phosphorylating IRS1, which in turn
CC       blocks IRS1 tyrosine phosphorylation and downstream activation of the
CC       PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of
CC       phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at
CC       'Ser-504' and 'Ser-532' and negatively regulates its ability to
CC       phosphorylate PKB/AKT1. Phosphorylates CCDC88A/GIV and inhibits its
CC       guanine nucleotide exchange factor activity (PubMed:23509302).
CC       {ECO:0000269|PubMed:11342610, ECO:0000269|PubMed:14988727,
CC       ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:16252004,
CC       ECO:0000269|PubMed:16356855, ECO:0000269|PubMed:16709830,
CC       ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:23509302,
CC       ECO:0000269|PubMed:8657160}.
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:23509302};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.13;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
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-538 (activation loop of
CC       the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic
CC       region), need to be phosphorylated for its full activation.
CC   -!- SUBUNIT: Part of a lipid raft complex composed at least of BCL10,
CC       CARD11, MALT1 and IKBKB (PubMed:16356855). Interacts with GLRX3 (via N-
CC       terminus) (PubMed:10636891). Interacts with ECT2 (PubMed:15254234).
CC       Interacts with CCDC88A/GIV; the interaction leads to phosphorylation of
CC       CCDC88A and inhibition of its guanine nucleotide exchange factor
CC       activity (PubMed:23509302). {ECO:0000269|PubMed:10636891,
CC       ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:16356855,
CC       ECO:0000269|PubMed:23509302}.
CC   -!- INTERACTION:
CC       Q04759; Q06187: BTK; NbExp=2; IntAct=EBI-374762, EBI-624835;
CC       Q04759; P06241: FYN; NbExp=7; IntAct=EBI-374762, EBI-515315;
CC       Q04759; O76003: GLRX3; NbExp=5; IntAct=EBI-374762, EBI-374781;
CC       Q04759; Q00613: HSF1; NbExp=2; IntAct=EBI-374762, EBI-719620;
CC       Q04759; P06239: LCK; NbExp=2; IntAct=EBI-374762, EBI-1348;
CC       Q04759; Q8IVH8: MAP4K3; NbExp=4; IntAct=EBI-374762, EBI-1758170;
CC       Q04759; Q05513: PRKCZ; NbExp=3; IntAct=EBI-374762, EBI-295351;
CC       Q04759; P35570: Irs1; Xeno; NbExp=2; IntAct=EBI-374762, EBI-520230;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane
CC       protein. Note=In resting T-cells, mostly localized in cytoplasm. In
CC       response to TCR stimulation, associates with lipid rafts and then
CC       localizes in the immunological synapse.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q04759-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q04759-2; Sequence=VSP_017294;
CC       Name=3;
CC         IsoId=Q04759-3; Sequence=VSP_054550;
CC   -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, T-cells,
CC       megakaryoblastic cells and platelets. {ECO:0000269|PubMed:7686153}.
CC   -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type region 1
CC       (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a
CC       non-calcium binding domain.
CC   -!- PTM: Autophosphorylation at Thr-219 is required for targeting to the
CC       TCR and cellular function of PRKCQ upon antigen receptor ligation.
CC       Following TCR stimulation, phosphorylated at Tyr-90 and Ser-685.
CC       {ECO:0000269|PubMed:10652356, ECO:0000269|PubMed:11772397,
CC       ECO:0000269|PubMed:15364937, ECO:0000269|PubMed:16252004,
CC       ECO:0000269|Ref.36}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. PKC subfamily. {ECO:0000305}.
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DR   EMBL; L01087; AAA75571.1; -; mRNA.
DR   EMBL; L07032; AAA60101.1; -; mRNA.
DR   EMBL; AY702977; AAU29340.1; -; mRNA.
DR   EMBL; AK293935; BAG57313.1; -; mRNA.
DR   EMBL; AL158043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL137145; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC101465; AAI01466.1; -; mRNA.
DR   EMBL; BC113359; AAI13360.1; -; mRNA.
DR   CCDS; CCDS55701.1; -. [Q04759-2]
DR   CCDS; CCDS60482.1; -. [Q04759-3]
DR   CCDS; CCDS7079.1; -. [Q04759-1]
DR   PIR; A45416; A45416.
DR   RefSeq; NP_001229342.1; NM_001242413.2. [Q04759-2]
DR   RefSeq; NP_001269573.1; NM_001282644.1.
DR   RefSeq; NP_001269574.1; NM_001282645.1. [Q04759-3]
DR   RefSeq; NP_001310194.1; NM_001323265.1. [Q04759-1]
DR   RefSeq; NP_001310195.1; NM_001323266.1. [Q04759-3]
DR   RefSeq; NP_006248.1; NM_006257.4. [Q04759-1]
DR   RefSeq; XP_006717528.1; XM_006717465.3.
DR   RefSeq; XP_016871899.1; XM_017016410.1.
DR   RefSeq; XP_016871900.1; XM_017016411.1.
DR   PDB; 1XJD; X-ray; 2.00 A; A=362-706.
DR   PDB; 2ENJ; NMR; -; A=1-125.
DR   PDB; 2ENN; NMR; -; A=144-213.
DR   PDB; 2ENZ; NMR; -; A=227-284.
DR   PDB; 2JED; X-ray; 2.32 A; A/B=361-706.
DR   PDB; 4Q9Z; X-ray; 2.60 A; A/B=374-706.
DR   PDB; 4RA5; X-ray; 2.61 A; A/B=374-706.
DR   PDB; 5F9E; X-ray; 2.00 A; A/B=361-706.
DR   PDBsum; 1XJD; -.
DR   PDBsum; 2ENJ; -.
DR   PDBsum; 2ENN; -.
DR   PDBsum; 2ENZ; -.
DR   PDBsum; 2JED; -.
DR   PDBsum; 4Q9Z; -.
DR   PDBsum; 4RA5; -.
DR   PDBsum; 5F9E; -.
DR   SMR; Q04759; -.
DR   BioGRID; 111574; 39.
DR   IntAct; Q04759; 23.
DR   MINT; Q04759; -.
DR   STRING; 9606.ENSP00000263125; -.
DR   BindingDB; Q04759; -.
DR   ChEMBL; CHEMBL3920; -.
DR   DrugBank; DB04522; Dexfosfoserine.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugBank; DB02482; Phosphonothreonine.
DR   DrugBank; DB02010; Staurosporine.
DR   DrugBank; DB00675; Tamoxifen.
DR   DrugCentral; Q04759; -.
DR   GuidetoPHARMACOLOGY; 1488; -.
DR   CarbonylDB; Q04759; -.
DR   iPTMnet; Q04759; -.
DR   PhosphoSitePlus; Q04759; -.
DR   BioMuta; PRKCQ; -.
DR   DMDM; 20141582; -.
DR   EPD; Q04759; -.
DR   jPOST; Q04759; -.
DR   MassIVE; Q04759; -.
DR   MaxQB; Q04759; -.
DR   PaxDb; Q04759; -.
DR   PeptideAtlas; Q04759; -.
DR   PRIDE; Q04759; -.
DR   ProteomicsDB; 4008; -.
DR   ProteomicsDB; 58279; -. [Q04759-1]
DR   ProteomicsDB; 58280; -. [Q04759-2]
DR   Antibodypedia; 10940; 826 antibodies.
DR   DNASU; 5588; -.
DR   Ensembl; ENST00000263125; ENSP00000263125; ENSG00000065675. [Q04759-1]
DR   Ensembl; ENST00000397176; ENSP00000380361; ENSG00000065675. [Q04759-2]
DR   Ensembl; ENST00000539722; ENSP00000441752; ENSG00000065675. [Q04759-3]
DR   GeneID; 5588; -.
DR   KEGG; hsa:5588; -.
DR   UCSC; uc001ijj.3; human. [Q04759-1]
DR   CTD; 5588; -.
DR   DisGeNET; 5588; -.
DR   GeneCards; PRKCQ; -.
DR   HGNC; HGNC:9410; PRKCQ.
DR   HPA; ENSG00000065675; Group enriched (blood, lymphoid tissue, skeletal muscle).
DR   MalaCards; PRKCQ; -.
DR   MIM; 600448; gene.
DR   neXtProt; NX_Q04759; -.
DR   OpenTargets; ENSG00000065675; -.
DR   PharmGKB; PA33773; -.
DR   VEuPathDB; HostDB:ENSG00000065675.14; -.
DR   eggNOG; KOG0694; Eukaryota.
DR   GeneTree; ENSGT00940000157638; -.
DR   HOGENOM; CLU_000288_54_4_1; -.
DR   InParanoid; Q04759; -.
DR   OMA; MFHIQNC; -.
DR   OrthoDB; 222529at2759; -.
DR   PhylomeDB; Q04759; -.
DR   TreeFam; TF102004; -.
DR   BRENDA; 2.7.11.13; 2681.
DR   PathwayCommons; Q04759; -.
DR   Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR   Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR   Reactome; R-HSA-202424; Downstream TCR signaling.
DR   Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR   Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR   Reactome; R-HSA-373752; Netrin-1 signaling.
DR   Reactome; R-HSA-418597; G alpha (z) signalling events.
DR   Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR   Reactome; R-HSA-9648002; RAS processing.
DR   SABIO-RK; Q04759; -.
DR   SignaLink; Q04759; -.
DR   SIGNOR; Q04759; -.
DR   BioGRID-ORCS; 5588; 7 hits in 1023 CRISPR screens.
DR   ChiTaRS; PRKCQ; human.
DR   EvolutionaryTrace; Q04759; -.
DR   GeneWiki; PRKCQ; -.
DR   GenomeRNAi; 5588; -.
DR   Pharos; Q04759; Tchem.
DR   PRO; PR:Q04759; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q04759; protein.
DR   Bgee; ENSG00000065675; Expressed in vastus lateralis and 191 other tissues.
DR   ExpressionAtlas; Q04759; baseline and differential.
DR   Genevisible; Q04759; HS.
DR   GO; GO:0016235; C:aggresome; IDA:HPA.
DR   GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004697; F:protein kinase C activity; EXP:Reactome.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR   GO; GO:0106311; F:protein threonine kinase activity; IEA:RHEA.
DR   GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR   GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR   GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0000165; P:MAPK cascade; TAS:Reactome.
DR   GO; GO:0006509; P:membrane protein ectodomain proteolysis; ISS:BHF-UCL.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR   GO; GO:0070233; P:negative regulation of T cell apoptotic process; IMP:UniProtKB.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR   GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR   GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB.
DR   GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl.
DR   GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR   GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0050870; P:positive regulation of T cell activation; ISS:UniProtKB.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl.
DR   GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; ISS:UniProtKB.
DR   GO; GO:2000570; P:positive regulation of T-helper 2 cell activation; ISS:UniProtKB.
DR   GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL.
DR   GO; GO:1904355; P:positive regulation of telomere capping; IMP:BHF-UCL.
DR   GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR   GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
DR   GO; GO:0045652; P:regulation of megakaryocyte differentiation; TAS:Reactome.
DR   GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
DR   CDD; cd00029; C1; 2.
DR   CDD; cd05619; STKc_nPKC_theta; 1.
DR   Gene3D; 2.60.40.150; -; 1.
DR   InterPro; IPR000961; AGC-kinase_C.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR020454; DAG/PE-bd.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR034668; nPKC_theta.
DR   InterPro; IPR002219; PE/DAG-bd.
DR   InterPro; IPR027264; PKC_theta.
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; PIRSF501105; Protein_kin_C_theta; 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; SSF56112; SSF56112; 1.
DR   PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR   PROSITE; PS50004; C2; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR   PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR   PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell membrane; Cytoplasm;
KW   Immunity; Inflammatory response; Kinase; Magnesium; Membrane;
KW   Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT   CHAIN           1..706
FT                   /note="Protein kinase C theta type"
FT                   /id="PRO_0000055708"
FT   DOMAIN          1..107
FT                   /note="C2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          380..634
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          635..706
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   ZN_FING         159..209
FT                   /note="Phorbol-ester/DAG-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT   ZN_FING         231..281
FT                   /note="Phorbol-ester/DAG-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT   NP_BIND         386..394
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ACT_SITE        504
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         409
FT                   /note="ATP"
FT   MOD_RES         90
FT                   /note="Phosphotyrosine; by LCK"
FT                   /evidence="ECO:0000269|PubMed:10652356"
FT   MOD_RES         219
FT                   /note="Phosphothreonine; by autocatalysis"
FT                   /evidence="ECO:0000269|PubMed:16252004"
FT   MOD_RES         348
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976"
FT   MOD_RES         538
FT                   /note="Phosphothreonine; by PDPK1"
FT                   /evidence="ECO:0000305|PubMed:11772397,
FT                   ECO:0000305|PubMed:15364937, ECO:0000305|PubMed:16252004"
FT   MOD_RES         676
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11772397,
FT                   ECO:0000269|PubMed:16252004, ECO:0000269|Ref.36,
FT                   ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT   MOD_RES         685
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         695
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:11772397,
FT                   ECO:0000269|PubMed:15364937, ECO:0000269|PubMed:16252004,
FT                   ECO:0000269|Ref.36, ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT   VAR_SEQ         2..126
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054550"
FT   VAR_SEQ         550..612
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.4"
FT                   /id="VSP_017294"
FT   VARIANT         240
FT                   /note="K -> N (in a colorectal adenocarcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042319"
FT   VARIANT         306
FT                   /note="D -> V (in dbSNP:rs45590231)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042320"
FT   VARIANT         330
FT                   /note="P -> L (in dbSNP:rs2236379)"
FT                   /evidence="ECO:0000269|PubMed:17344846,
FT                   ECO:0000269|PubMed:7686153, ECO:0000269|Ref.4"
FT                   /id="VAR_020401"
FT   VARIANT         354
FT                   /note="D -> N (in dbSNP:rs34524148)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_042321"
FT   MUTAGEN         90
FT                   /note="Y->F: Loss of function in T-cells proliferation. No
FT                   effect on kinase activity."
FT                   /evidence="ECO:0000269|PubMed:10652356"
FT   MUTAGEN         148
FT                   /note="A->E: Constitutively active form."
FT                   /evidence="ECO:0000269|PubMed:10652356"
FT   MUTAGEN         219
FT                   /note="T->A: Loss of transactivation of the IL2 promoter
FT                   and translocation to the plasma membrane. No effect on
FT                   kinase activity."
FT                   /evidence="ECO:0000269|PubMed:16252004"
FT   MUTAGEN         409
FT                   /note="K->A,E: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:10652356"
FT   MUTAGEN         538
FT                   /note="T->A: Loss of kinase activity."
FT                   /evidence="ECO:0000269|PubMed:11772397,
FT                   ECO:0000269|PubMed:16252004"
FT   MUTAGEN         676
FT                   /note="S->A: Reduction in kinase activity."
FT                   /evidence="ECO:0000269|PubMed:16252004"
FT   MUTAGEN         695
FT                   /note="S->A: Reduction in kinase activity."
FT                   /evidence="ECO:0000269|PubMed:11772397,
FT                   ECO:0000269|PubMed:16252004"
FT   CONFLICT        700
FT                   /note="G -> R (in Ref. 1; AAA75571 and 4; AAU29340)"
FT                   /evidence="ECO:0000305"
FT   STRAND          5..13
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          28..39
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          42..52
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          56..62
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          69..75
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          83..89
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   HELIX           90..98
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   TURN            99..101
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          103..108
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          110..112
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          114..121
FT                   /evidence="ECO:0007829|PDB:2ENJ"
FT   STRAND          155..159
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   STRAND          161..165
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   STRAND          174..176
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   STRAND          187..189
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   STRAND          191..193
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   STRAND          196..199
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   HELIX           200..202
FT                   /evidence="ECO:0007829|PDB:2ENN"
FT   STRAND          234..236
FT                   /evidence="ECO:0007829|PDB:2ENZ"
FT   STRAND          246..248
FT                   /evidence="ECO:0007829|PDB:2ENZ"
FT   STRAND          255..257
FT                   /evidence="ECO:0007829|PDB:2ENZ"
FT   STRAND          259..265
FT                   /evidence="ECO:0007829|PDB:2ENZ"
FT   TURN            271..276
FT                   /evidence="ECO:0007829|PDB:2ENZ"
FT   TURN            281..283
FT                   /evidence="ECO:0007829|PDB:2ENZ"
FT   HELIX           377..379
FT                   /evidence="ECO:0007829|PDB:5F9E"
FT   STRAND          380..388
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          390..399
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   TURN            400..402
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          405..412
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           413..418
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           422..435
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          444..449
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          451..459
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          463..465
FT                   /evidence="ECO:0007829|PDB:5F9E"
FT   HELIX           466..473
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           478..497
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           507..509
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          510..512
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   STRAND          518..520
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           543..545
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           548..551
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           559..574
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           584..593
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           604..613
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           618..620
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           628..630
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           632..634
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           639..643
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           666..669
FT                   /evidence="ECO:0007829|PDB:5F9E"
FT   HELIX           680..685
FT                   /evidence="ECO:0007829|PDB:5F9E"
FT   TURN            690..693
FT                   /evidence="ECO:0007829|PDB:1XJD"
FT   HELIX           699..706
FT                   /evidence="ECO:0007829|PDB:5F9E"
SQ   SEQUENCE   706 AA;  81865 MW;  B3C53AB892D5210A CRC64;
     MSPFLRIGLS NFDCGSCQSC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF
     DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GKTEIWLELK PQGRMLMNAR
     YFLEMSDTKD MNEFETEGFF ALHQRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV
     WGLNKQGYQC RQCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK
     SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ
     ARCLRDTEQI FREGPVEIGL PCSIKNEARP PCLPTPGKRE PQGISWESPL DEVDKMCHLP
     EPELNKERPS LQIKLKIEDF ILHKMLGKGS FGKVFLAEFK KTNQFFAIKA LKKDVVLMDD
     DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR
     ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI LLDKDGHIKI ADFGMCKENM LGDAKTNTFC
     GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR
     WLEKEAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPFD
     CSNFDKEFLN EKPRLSFADR ALINSMDQNM FRNFSFMNPG MERLIS
//
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