KPCT_HUMAN
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 03-AUG-2022, entry version 230.
DE RecName: Full=Protein kinase C theta type;
DE EC=2.7.11.13 {ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:34593629};
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; DOI=10.1016/s0021-9258(19)85228-6;
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; DOI=10.1016/s0021-9258(18)47426-1;
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; DOI=10.1016/s0021-9258(18)53494-3;
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 CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH PRKCH
RP UPSTREAM OPEN READING FRAME 2.
RX PubMed=34593629; DOI=10.1073/pnas.2018899118;
RA Jayaram D.R., Frost S., Argov C., Liju V.B., Anto N.P., Muraleedharan A.,
RA Ben-Ari A., Sinay R., Smoly I., Novoplansky O., Isakov N., Toiber D.,
RA Keasar C., Elkabets M., Yeger-Lotem E., Livneh E.;
RT "Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor
RT of PKCs.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [36]
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 [37]
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 [38]
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, ECO:0000269|PubMed:34593629};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000269|PubMed:34593629};
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. Inhibited
CC by PRKCH upstream open reading frame 2 (PubMed:34593629).
CC {ECO:0000269|PubMed:34593629}.
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). Interacts with PRKCH upstream open reading
CC frame 2; the interaction leads to inhibition of kinase activity
CC (PubMed:34593629). {ECO:0000269|PubMed:10636891,
CC ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:16356855,
CC ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:34593629}.
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.37}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; 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 AlphaFoldDB; Q04759; -.
DR SMR; Q04759; -.
DR BioGRID; 111574; 53.
DR IntAct; Q04759; 23.
DR MINT; Q04759; -.
DR STRING; 9606.ENSP00000263125; -.
DR BindingDB; Q04759; -.
DR ChEMBL; CHEMBL3920; -.
DR DrugBank; DB09096; Benzoyl peroxide.
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; 849 antibodies from 41 providers.
DR DNASU; 5588; -.
DR Ensembl; ENST00000263125.10; ENSP00000263125.5; ENSG00000065675.16. [Q04759-1]
DR Ensembl; ENST00000397176.6; ENSP00000380361.2; ENSG00000065675.16. [Q04759-2]
DR Ensembl; ENST00000539722.5; ENSP00000441752.1; ENSG00000065675.16. [Q04759-3]
DR GeneID; 5588; -.
DR KEGG; hsa:5588; -.
DR MANE-Select; ENST00000263125.10; ENSP00000263125.5; NM_006257.5; NP_006248.1.
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 (lymphoid tissue, skeletal muscle, tongue).
DR MalaCards; PRKCQ; -.
DR MIM; 600448; gene.
DR neXtProt; NX_Q04759; -.
DR OpenTargets; ENSG00000065675; -.
DR PharmGKB; PA33773; -.
DR VEuPathDB; HostDB:ENSG00000065675; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000157638; -.
DR HOGENOM; CLU_000288_54_4_1; -.
DR InParanoid; Q04759; -.
DR OMA; IHLVKCH; -.
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; 10 hits in 1109 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 triceps brachii and 169 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:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
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: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:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
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: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:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
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; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; 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; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; 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 ACT_SITE 504
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 386..394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 409
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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.37,
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.37, 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
