ID KPCT_RAT Reviewed; 707 AA. AC Q9WTQ0; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 09-JAN-2007, sequence version 2. DT 22-FEB-2012, entry version 79. DE RecName: Full=Protein kinase C theta type; DE EC=2.7.11.13; DE AltName: Full=nPKC-theta; GN Name=Prkcq; Synonyms=Pkcq; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., RA Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., RA Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., RA Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., RA Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., RA Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., RA Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., RA Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., RA Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., RA D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., RA Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., RA Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., RA Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., RA Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., RA Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., RA Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., RA Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., RA Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., RA Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., RA Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., RA Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., RA Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., RA Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., RA Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., RA Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., RA Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., RA Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., RA Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., RA Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., RA Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., RA Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., RA Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., RA Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., RA Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., RA Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into RT mammalian evolution."; RL Nature 428:493-521(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 524-667. RC STRAIN=Wistar; TISSUE=Brain; RX PubMed=11220785; DOI=10.1385/JMN:15:2:121; RA Minami H., Owada Y., Suzuki R., Handa Y., Kondo H.; RT "Localization of mRNAs for novel, atypical as well as conventional RT protein kinase C (PKC) isoforms in the brain of developing and mature RT rats."; RL J. Mol. Neurosci. 15:121-135(2000). RN [3] RP FUNCTION IN PHOSPHORYLATION OF MSN. RX PubMed=9516463; DOI=10.1074/jbc.273.13.7594; RA Pietromonaco S.F., Simons P.C., Altman A., Elias L.; RT "Protein kinase C-theta phosphorylation of moesin in the actin-binding RT sequence."; RL J. Biol. Chem. 273:7594-7603(1998). RN [4] RP INTERACTION WITH GLRX3. RX PubMed=18479680; DOI=10.1016/j.cellimm.2008.04.005; RA Kato N., Motohashi S., Okada T., Ozawa T., Mashima K.; RT "PICOT, protein kinase C theta-interacting protein, is a novel RT regulator of FcepsilonRI-mediated mast cell activation."; RL Cell. Immunol. 251:62-67(2008). CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol CC (DAG)-dependent serine/threonine-protein kinase that mediates non- CC redundant functions in T-cell receptor (TCR) signaling, including CC T-cells activation, proliferation, differentiation and survival, CC by mediating activation of multiple transcription factors such as CC NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated CC T-cells, is required for the activation of NF-kappa-B and JUN, CC which in turn are essential for IL2 production, and participates CC to the calcium-dependent NFATC1 and NFATC2 transactivation. CC Mediates the activation of the canonical NF-kappa-B pathway CC (NFKB1) by direct phosphorylation of CARD11 on several serine CC residues, inducing CARD11 association with lipid rafts and CC recruitment of the BCL10-MALT1 complex, which then activates IKK CC complex, resulting in nuclear translocation and activation of CC NFKB1. May also play an indirect role in activation of the non- CC canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway CC leading to JUN activation, acts by phosphorylating the mediator CC STK39/SPAK and may not act through MAP kinases signaling. Plays a CC critical role in TCR/CD28-induced NFATC1 and NFATC2 CC transactivation by participating in the regulation of reduced CC inositol 1,4,5-trisphosphate generation and intracellular calcium CC mobilization. After costimulation of T-cells through CD28 can CC phosphorylate CBLB and is required for the ubiquitination and CC subsequent degradation of CBLB, which is a prerequisite for the CC activation of TCR. During T-cells differentiation, plays an CC important role in the development of T-helper 2 (Th2) cells CC following immune and inflammatory responses, and, in the CC development of inflammatory autoimmune diseases, is necessary for CC the activation of IL17-producing Th17 cells. May play a minor role CC in Th1 response. Upon TCR stimulation, mediates T-cell protective CC survival signal by phosphorylating BAD, thus protecting T-cells CC from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 CC levels through NF-kappa-B and JUN pathways. In platelets, CC regulates signal transduction downstream of the ITGA2B, CD36/GP4, CC F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in CC 'outside-in' signaling and granule secretion signal transduction. CC May relay signals from the activated ITGA2B receptor by regulating CC the uncoupling of WASP and WIPF1, thereby permitting the CC regulation of actin filament nucleation and branching activity of CC the Arp2/3 complex. May mediate inhibitory effects of free fatty CC acids on insulin signaling by phosphorylating IRS1, which in turn CC blocks IRS1 tyrosine phosphorylation and downstream activation of CC the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence CC of phosphatidylglycerol or phosphatidylinositol (By similarity). CC Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively CC regulates its ability to phosphorylate PKB/AKT1 (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Magnesium. CC -!- ENZYME 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 CC of the kinase domain), Ser-676 (turn motif) and Ser-695 CC (hydrophobic region), need to be phosphorylated for its full CC activation (By similarity). CC -!- SUBUNIT: Interacts with GLRX3 (via N-terminus). Interacts with CC ECT2. Part of a membrane raft complex composed at least of BCL10, CC CARD11, MALT1 and IKBKB (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cell membrane (By CC similarity); Peripheral membrane protein. Note=In resting T-cells, CC mostly localized in cytoplasm. In response to TCR stimulation, CC associates with lipid rafts and then localizes in the CC immunological synapse (By similarity). CC -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type CC region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the CC C2 domain is a non-calcium binding domain. CC -!- PTM: Autophosphorylation at Thr-219 is required for targeting to CC the TCR and cellular function of PRKCQ upon antigen receptor CC ligation. Following TCR stimulation, phosphorylated at Tyr-90 and CC Ser-685 (By similarity). CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. PKC subfamily. CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain. CC -!- SIMILARITY: Contains 1 C2 domain. CC -!- SIMILARITY: Contains 2 phorbol-ester/DAG-type zinc fingers. CC -!- SIMILARITY: Contains 1 protein kinase domain. 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; AABR03106275; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03107517; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03106934; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03106283; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03107733; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03106804; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03108584; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR03106764; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB020614; BAA78371.1; -; mRNA. DR IPI; IPI00364921; -. DR UniGene; Rn.225125; -. DR HSSP; Q04759; 1XJD. DR ProteinModelPortal; Q9WTQ0; -. DR SMR; Q9WTQ0; 3-126, 144-213, 227-284, 375-700. DR STRING; Q9WTQ0; -. DR PhosphoSite; Q9WTQ0; -. DR PRIDE; Q9WTQ0; -. DR RGD; 620968; Prkcq. DR eggNOG; COG0515; -. DR HOVERGEN; HBG108317; -. DR InParanoid; Q9WTQ0; -. DR OrthoDB; EOG4J9MZ9; -. DR PhylomeDB; Q9WTQ0; -. DR ArrayExpress; Q9WTQ0; -. DR Genevestigator; Q9WTQ0; -. DR GO; GO:0005737; C:cytoplasm; IDA:RGD. DR GO; GO:0005624; C:membrane fraction; IDA:RGD. DR GO; GO:0031594; C:neuromuscular junction; IDA:RGD. DR GO; GO:0005634; C:nucleus; IDA:RGD. DR GO; GO:0042383; C:sarcolemma; IDA:RGD. DR GO; GO:0005625; C:soluble fraction; IDA:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:RGD. DR GO; GO:0004697; F:protein kinase C activity; IEA:EC. DR GO; GO:0007568; P:aging; IEP:RGD. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0070233; P:negative regulation of T cell apoptosis; ISS:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; IEP:RGD. DR GO; GO:0051491; P:positive regulation of filopodium assembly; IMP:RGD. DR GO; GO:0032740; P:positive regulation of interleukin-17 production; ISS:UniProtKB. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB. DR GO; GO:0042346; P:positive regulation of NF-kappaB import into nucleus; IMP:RGD. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB. DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:RGD. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:RGD. 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:0010389; P:regulation of G2/M transition of mitotic cell cycle; IMP:RGD. DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB. DR GO; GO:0019229; P:regulation of vasoconstriction; IEP:RGD. DR GO; GO:0045730; P:respiratory burst; IEP:RGD. DR GO; GO:0009749; P:response to glucose stimulus; IEP:RGD. DR GO; GO:0009408; P:response to heat; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0032868; P:response to insulin stimulus; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0042246; P:tissue regeneration; IEP:RGD. DR InterPro; IPR000961; AGC-kinase_C. DR InterPro; IPR008973; C2_Ca/lipid-bd_dom_CaLB. DR InterPro; IPR020454; DAG/PE-bd. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR017892; Pkinase_C. DR InterPro; IPR014376; Prot_kin_PKC_delta. DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd. DR InterPro; IPR000719; Prot_kinase_cat_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR017442; Se/Thr_kinase-like_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR002290; Ser/Thr_kinase_dom. DR Pfam; PF00130; C1_1; 2. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR PIRSF; PIRSF000551; PKC_delta; 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_CaLB; 1. DR SUPFAM; SSF56112; Kinase_like; 1. DR PROSITE; PS51285; AGC_KINASE_CTER; 1. DR PROSITE; PS50004; C2; FALSE_NEG. 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 Acetylation; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; KW Immunity; Inflammatory response; Kinase; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Repeat; Serine/threonine-protein kinase; Transferase; Zinc; KW Zinc-finger. FT CHAIN 1 707 Protein kinase C theta type. FT /FTId=PRO_0000270836. FT DOMAIN 8 123 C2. FT DOMAIN 380 634 Protein kinase. FT DOMAIN 635 706 AGC-kinase C-terminal. FT ZN_FING 159 209 Phorbol-ester/DAG-type 1. FT ZN_FING 231 281 Phorbol-ester/DAG-type 2. FT NP_BIND 386 394 ATP (By similarity). FT ACT_SITE 504 504 Proton acceptor (By similarity). FT BINDING 409 409 ATP (By similarity). FT MOD_RES 90 90 Phosphotyrosine; by LCK (By similarity). FT MOD_RES 219 219 Phosphothreonine; by autocatalysis (By FT similarity). FT MOD_RES 348 348 Phosphoserine (By similarity). FT MOD_RES 384 384 N6-acetyllysine (By similarity). FT MOD_RES 536 536 Phosphothreonine (By similarity). FT MOD_RES 538 538 Phosphothreonine; by PDPK1 (By FT similarity). FT MOD_RES 657 657 Phosphoserine (By similarity). FT MOD_RES 676 676 Phosphoserine; by autocatalysis FT (Potential). FT MOD_RES 685 685 Phosphoserine (By similarity). FT MOD_RES 695 695 Phosphoserine; by autocatalysis FT (Potential). SQ SEQUENCE 707 AA; 81750 MW; 7F82E35DE0C09DB9 CRC64; MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GRTEIWLELK PQGRMLMNAR YFLEMSDTKD MSEFENEGFF ALHHRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV WGLNKQGYQC RRCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ ARTLRDSEHI FREGPIEISF PRSIKSETRP PCVPTPGKSE PQGICWESPL DGADKTAQPP EPEVNLQRAS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK RTKQFFAIKA LKKDVVLMDD DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR ATFYAAEVIL GLQFLHSKGI VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPYD CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG METLICS //