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 27-MAR-2024, entry version 239. 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; 59. DR IntAct; Q04759; 23. DR MINT; Q04759; -. DR STRING; 9606.ENSP00000263125; -. DR BindingDB; Q04759; -. DR ChEMBL; CHEMBL3920; -. DR DrugBank; DB09096; Benzoyl peroxide. DR DrugBank; DB04209; Dequalinium. 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 GlyGen; Q04759; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q04759; -. DR PhosphoSitePlus; Q04759; -. DR BioMuta; PRKCQ; -. DR DMDM; 20141582; -. DR CPTAC; CPTAC-2825; -. DR CPTAC; non-CPTAC-2890; -. DR EPD; Q04759; -. DR jPOST; Q04759; -. DR MassIVE; Q04759; -. DR MaxQB; Q04759; -. DR PaxDb; 9606-ENSP00000263125; -. DR PeptideAtlas; Q04759; -. DR ProteomicsDB; 4008; -. DR ProteomicsDB; 58279; -. [Q04759-1] DR ProteomicsDB; 58280; -. [Q04759-2] DR Pumba; Q04759; -. DR Antibodypedia; 10940; 938 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 AGR; HGNC:9410; -. 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; GRVMHII; -. DR OrthoDB; 841660at2759; -. 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; 12 hits in 1187 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 170 other cell types or tissues. DR ExpressionAtlas; Q04759; baseline and differential. 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:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; EXP:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. 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: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:0006355; P:regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB. DR CDD; cd20834; C1_nPKC_theta-like_rpt1; 1. DR CDD; cd20837; C1_nPKC_theta-like_rpt2; 1. DR CDD; cd05619; STKc_nPKC_theta; 1. DR Gene3D; 3.30.60.20; -; 2. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24356:SF181; PROTEIN KINASE C THETA TYPE; 1. DR PANTHER; PTHR24356; SERINE/THREONINE-PROTEIN KINASE; 1. DR Pfam; PF00130; C1_1; 2. DR Pfam; PF21494; PKC_C2; 1. 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; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; Q04759; HS. 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 //