ID   F1LM10_RAT              Unreviewed;       707 AA.
AC   F1LM10;
DT   03-MAY-2011, integrated into UniProtKB/TrEMBL.
DT   03-MAY-2011, sequence version 1.
DT   27-MAR-2024, entry version 89.
DE   RecName: Full=Protein kinase C theta type {ECO:0000256|PIRNR:PIRNR000551};
DE            EC=2.7.11.13 {ECO:0000256|PIRNR:PIRNR000551};
DE   AltName: Full=nPKC-theta {ECO:0000256|PIRNR:PIRNR000551};
GN   Name=Prkcq {ECO:0000313|Ensembl:ENSRNOP00000025902.4,
GN   ECO:0000313|RGD:620968};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000025902.4, ECO:0000313|Proteomes:UP000002494};
RN   [1] {ECO:0000313|Ensembl:ENSRNOP00000025902.4, ECO:0000313|Proteomes:UP000002494}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000025902.4,
RC   ECO:0000313|Proteomes:UP000002494};
RX   PubMed=15057822; DOI=10.1038/nature02426;
RG   Rat Genome Sequencing Project Consortium;
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., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., 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., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., 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., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2] {ECO:0007829|PubMed:22673903}
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [3] {ECO:0000313|Ensembl:ENSRNOP00000025902.4}
RP   IDENTIFICATION.
RC   STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000025902.4};
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
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 to 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. {ECO:0000256|PIRNR:PIRNR000551}.
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:0000256|ARBA:ARBA00000946};
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:0000256|ARBA:ARBA00000569,
CC         ECO:0000256|PIRNR:PIRNR000551};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000256|PIRNR:PIRNR000551};
CC   -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC       calcium-insensitive, but activated by diacylglycerol (DAG) and
CC       phosphatidylserine. Three specific sites; Thr-538 (activation loop of
CC       the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic
CC       region), need to be phosphorylated for its full activation.
CC       {ECO:0000256|PIRNR:PIRNR000551}.
CC   -!- SUBUNIT: Interacts with GLRX3 (via N-terminus). Interacts with ECT2.
CC       {ECO:0000256|PIRNR:PIRNR000551}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004202,
CC       ECO:0000256|PIRNR:PIRNR000551}; Peripheral membrane protein
CC       {ECO:0000256|ARBA:ARBA00004202, ECO:0000256|PIRNR:PIRNR000551}.
CC       Cytoplasm {ECO:0000256|PIRNR:PIRNR000551}. 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 immunological
CC       synapse. {ECO:0000256|PIRNR:PIRNR000551}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC       protein kinase family. PKC subfamily. {ECO:0000256|ARBA:ARBA00005490,
CC       ECO:0000256|PIRNR:PIRNR000551}.
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DR   RefSeq; NP_001263650.1; NM_001276721.1.
DR   AlphaFoldDB; F1LM10; -.
DR   SMR; F1LM10; -.
DR   Ensembl; ENSRNOT00000025901.7; ENSRNOP00000025902.4; ENSRNOG00000019057.8.
DR   GeneID; 85420; -.
DR   KEGG; rno:85420; -.
DR   CTD; 5588; -.
DR   RGD; 620968; Prkcq.
DR   GeneTree; ENSGT00940000157638; -.
DR   HOGENOM; CLU_000288_54_4_1; -.
DR   OMA; GRVMHII; -.
DR   OrthoDB; 841660at2759; -.
DR   TreeFam; TF102004; -.
DR   Proteomes; UP000002494; Chromosome 17.
DR   Bgee; ENSRNOG00000019057; Expressed in testis and 18 other cell types or tissues.
DR   GO; GO:0016235; C:aggresome; IEA:Ensembl.
DR   GO; GO:0034451; C:centriolar satellite; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IEA:Ensembl.
DR   GO; GO:0060326; P:cell chemotaxis; IEA:Ensembl.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR   GO; GO:0006509; P:membrane protein ectodomain proteolysis; IEA:Ensembl.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0070233; P:negative regulation of T cell apoptotic process; IEA:Ensembl.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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; IEA:Ensembl.
DR   GO; GO:0032743; P:positive regulation of interleukin-2 production; IEA:Ensembl.
DR   GO; GO:0032753; P:positive regulation of interleukin-4 production; IEA:Ensembl.
DR   GO; GO:2000318; P:positive regulation of T-helper 17 type immune response; IEA:Ensembl.
DR   GO; GO:2000570; P:positive regulation of T-helper 2 cell activation; IEA:Ensembl.
DR   GO; GO:1904355; P:positive regulation of telomere capping; IEA:Ensembl.
DR   GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IEA:Ensembl.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:Ensembl.
DR   GO; GO:0090330; P:regulation of platelet aggregation; IEA:Ensembl.
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; 1.
DR   PROSITE; PS50081; ZF_DAG_PE_2; 2.
DR   Genevisible; F1LM10; RN.
PE   1: Evidence at protein level;
KW   ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRNR:PIRNR000551};
KW   Cell membrane {ECO:0000256|PIRNR:PIRNR000551};
KW   Cytoplasm {ECO:0000256|ARBA:ARBA00022490, ECO:0000256|PIRNR:PIRNR000551};
KW   Inflammatory response {ECO:0000256|PIRNR:PIRNR000551};
KW   Kinase {ECO:0000256|ARBA:ARBA00022777, ECO:0000256|PIRNR:PIRNR000551};
KW   Magnesium {ECO:0000256|PIRNR:PIRNR000551};
KW   Membrane {ECO:0000256|PIRNR:PIRNR000551};
KW   Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW   ECO:0000256|PIRNR:PIRNR000551};
KW   Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW   Reference proteome {ECO:0000313|Proteomes:UP000002494};
KW   Repeat {ECO:0000256|ARBA:ARBA00022737};
KW   Serine/threonine-protein kinase {ECO:0000256|ARBA:ARBA00022527,
KW   ECO:0000256|PIRNR:PIRNR000551};
KW   Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000551};
KW   Zinc {ECO:0000256|ARBA:ARBA00022833};
KW   Zinc-finger {ECO:0000256|ARBA:ARBA00022771}.
FT   DOMAIN          1..107
FT                   /note="C2"
FT                   /evidence="ECO:0000259|PROSITE:PS50004"
FT   DOMAIN          159..209
FT                   /note="Phorbol-ester/DAG-type"
FT                   /evidence="ECO:0000259|PROSITE:PS50081"
FT   DOMAIN          231..281
FT                   /note="Phorbol-ester/DAG-type"
FT                   /evidence="ECO:0000259|PROSITE:PS50081"
FT   DOMAIN          380..634
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   DOMAIN          635..706
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000259|PROSITE:PS51285"
FT   ACT_SITE        504
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000551-50"
FT   BINDING         386..394
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000551-51"
FT   BINDING         409
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PIRSR:PIRSR000551-51,
FT                   ECO:0000256|PROSITE-ProRule:PRU10141"
SQ   SEQUENCE   707 AA;  81777 MW;  7F81E6A3371B99A7 CRC64;
     MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF
     DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GRTEIWLELK PQGRMLMNAR
     YFLEMSDTKD MSEFENEGFF ALHHRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV
     WGLNKQGYQC RQCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK
     SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ
     ARTLRDSEHI FREGPIEISF PRSIKSETRP PCVPTPGKKE PQGICWESPL DGADKTAQPP
     EPEVNLQRAS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK RTKQFFAIKA LKKDVVLMDD
     DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR
     ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC
     GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR
     WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPYD
     CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG METLICS
//