RORG_MOUSE
ID RORG_MOUSE Reviewed; 516 AA.
AC P51450; E9Q8I1; Q3U513; Q61027; Q91YT5; Q9QXD9; Q9R177;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Nuclear receptor ROR-gamma;
DE AltName: Full=Nuclear receptor RZR-gamma;
DE AltName: Full=Nuclear receptor subfamily 1 group F member 3;
DE AltName: Full=RAR-related orphan receptor C;
DE AltName: Full=Retinoid-related orphan receptor-gamma;
DE AltName: Full=Thymus orphan receptor;
DE Short=TOR;
GN Name=Rorc; Synonyms=Nr1f3, Rorg, Thor;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=8973331; DOI=10.1016/s0378-1119(96)00504-5;
RA Medvedev A., Yan Z.H., Hirose T., Giguere V., Jetten A.M.;
RT "Cloning of a cDNA encoding the murine orphan receptor RZR/ROR gamma and
RT characterization of its response element.";
RL Gene 181:199-206(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC STRAIN=129;
RX PubMed=9403063; DOI=10.1006/geno.1997.4980;
RA Medvedev A., Chistokhina A., Hirose A., Jetten A.M.;
RT "Genomic structure and chromosomal mapping of the nuclear orphan receptor
RT ROR gamma (RORC) gene.";
RL Genomics 46:93-102(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=CD-1; TISSUE=Thymus;
RX PubMed=8614404; DOI=10.1210/mend.9.12.8614404;
RA Ortiz M.A., Piedrafita F.J., Pfahl M., Maki R.;
RT "TOR: a new orphan receptor expressed in the thymus that can modulate
RT retinoid and thyroid hormone signals.";
RL Mol. Endocrinol. 9:1679-1691(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN T-CELLS (ISOFORM 2),
RP AND TISSUE SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=9881970; DOI=10.1016/s1074-7613(00)80645-7;
RA He Y.-W., Deftos M.L., Ojala E.W., Bevan M.J.;
RT "RORgamma t, a novel isoform of an orphan receptor, negatively regulates
RT Fas ligand expression and IL-2 production in T cells.";
RL Immunity 9:797-806(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN PRE-TCR ACTIVATION
RP (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Thymus;
RX PubMed=10602018;
RX DOI=10.1002/(sici)1521-4141(199912)29:12<4072::aid-immu4072>3.0.co;2-e;
RA Villey I., De Chasseval R., De Villartay J.-P.;
RT "RORgammaT, a thymus-specific isoform of the orphan nuclear receptor
RT RORg/TOR, is up-regulated by signaling through the pre-T cell receptor
RT (TCR) and binds to the TEA promoter.";
RL Eur. J. Immunol. 29:4072-4080(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=NOD {ECO:0000312|EMBL:BAE32267.1};
RC TISSUE=Thymus {ECO:0000312|EMBL:BAE32267.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [9]
RP FUNCTION IN THYMOPOIESIS (ISOFORM 2), DISRUPTION PHENOTYPE (ISOFORM 2),
RP DEVELOPMENTAL STAGE (ISOFORM 2), AND TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=14691482; DOI=10.1038/ni1022;
RA Eberl G., Marmon S., Sunshine M.J., Rennert P.D., Choi Y., Littman D.R.;
RT "An essential function for the nuclear receptor RORgamma(t) in the
RT generation of fetal lymphoid tissue inducer cells.";
RL Nat. Immunol. 5:64-73(2004).
RN [10]
RP FUNCTION IN THYMOCYTE SURVIVAL (ISOFORM 2), INTERACTION WITH NCOA1 AND
RP NCOA2, DISRUPTION PHENOTYPE, DNA-BINDING, MUTAGENESIS OF 56-ARG-ARG-57 AND
RP TYR-500, AND DOMAIN.
RX PubMed=16148126; DOI=10.4049/jimmunol.175.6.3800;
RA Xie H., Sadim M.S., Sun Z.;
RT "RORgammat recruits steroid receptor coactivators to ensure thymocyte
RT survival.";
RL J. Immunol. 175:3800-3809(2005).
RN [11]
RP FUNCTION IN T(H)17 CELLS DIFFERENTIATION (ISOFORM 2), DISRUPTION PHENOTYPE
RP (ISOFORM 2), INDUCTION BY IL6 AND TGFB1 (ISOFORM 2), AND TISSUE SPECIFICITY
RP (ISOFORM 2).
RX PubMed=16990136; DOI=10.1016/j.cell.2006.07.035;
RA Ivanov I.I., McKenzie B.S., Zhou L., Tadokoro C.E., Lepelley A.,
RA Lafaille J.J., Cua D.J., Littman D.R.;
RT "The orphan nuclear receptor RORgammat directs the differentiation program
RT of proinflammatory IL-17+ T helper cells.";
RL Cell 126:1121-1133(2006).
RN [12]
RP INTERACTION WITH PPARGC1A.
RX PubMed=17476214; DOI=10.1038/nature05767;
RA Liu C., Li S., Liu T., Borjigin J., Lin J.D.;
RT "Transcriptional coactivator PGC-1alpha integrates the mammalian clock and
RT energy metabolism.";
RL Nature 447:477-481(2007).
RN [13]
RP FUNCTION IN METABOLISM REGULATION, DEVELOPMENTAL STAGE, DISRUPTION
RP PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=17666523; DOI=10.1152/physiolgenomics.00098.2007;
RA Kang H.S., Angers M., Beak J.Y., Wu X., Gimble J.M., Wada T., Xie W.,
RA Collins J.B., Grissom S.F., Jetten A.M.;
RT "Gene expression profiling reveals a regulatory role for ROR alpha and ROR
RT gamma in phase I and phase II metabolism.";
RL Physiol. Genomics 31:281-294(2007).
RN [14]
RP FUNCTION IN T(H)17 CELLS DIFFERENTIATION (ISOFORM 2), INDUCTION BY IL6 AND
RP TGB1 (ISOFORM 2), AND TISSUE SPECIFICITY (ISOFORM 2).
RX PubMed=18164222; DOI=10.1016/j.immuni.2007.11.016;
RA Yang X.O., Pappu B.P., Nurieva R., Akimzhanov A., Kang H.S., Chung Y.,
RA Ma L., Shah B., Panopoulos A.D., Schluns K.S., Watowich S.S., Tian Q.,
RA Jetten A.M., Dong C.;
RT "T helper 17 lineage differentiation is programmed by orphan nuclear
RT receptors ROR alpha and ROR gamma.";
RL Immunity 28:29-39(2008).
RN [15]
RP SUBCELLULAR LOCATION, INTERACTION WITH FOXP3, AND INDUCTION.
RX PubMed=18368049; DOI=10.1038/nature06878;
RA Zhou L., Lopes J.E., Chong M.M., Ivanov I.I., Min R., Victora G.D.,
RA Shen Y., Du J., Rubtsov Y.P., Rudensky A.Y., Ziegler S.F., Littman D.R.;
RT "TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by
RT antagonizing RORgammat function.";
RL Nature 453:236-240(2008).
RN [16]
RP REVIEW ON FUNCTION.
RX PubMed=19381306; DOI=10.1621/nrs.07003;
RA Jetten A.M.;
RT "Retinoid-related orphan receptors (RORs): critical roles in development,
RT immunity, circadian rhythm, and cellular metabolism.";
RL Nucl. Recept. Signal. 7:3-35(2009).
RN [17]
RP FUNCTION IN GLUCOSE METABOLISM REGULATION, AND IDENTIFICATION OF LIGANDS.
RX PubMed=19965867; DOI=10.1074/jbc.m109.080614;
RA Wang Y., Kumar N., Solt L.A., Richardson T.I., Helvering L.M., Crumbley C.,
RA Garcia-Ordonez R.D., Stayrook K.R., Zhang X., Novick S., Chalmers M.J.,
RA Griffin P.R., Burris T.P.;
RT "Modulation of retinoic acid receptor-related orphan receptor alpha and
RT gamma activity by 7-oxygenated sterol ligands.";
RL J. Biol. Chem. 285:5013-5025(2010).
RN [18]
RP FUNCTION IN ADIPOGENESIS, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF CYS-31 AND CYS-48.
RX PubMed=21853531; DOI=10.1002/emmm.201100172;
RA Meissburger B., Ukropec J., Roeder E., Beaton N., Geiger M., Teupser D.,
RA Civan B., Langhans W., Nawroth P.P., Gasperikova D., Rudofsky G.,
RA Wolfrum C.;
RT "Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-
RT related orphan receptor gamma.";
RL EMBO Mol. Med. 3:637-651(2011).
RN [19]
RP INTERACTION WITH NCOR1 AND NCOA2, AND IDENTIFICATION OF LIGANDS.
RX PubMed=21499262; DOI=10.1038/nature10075;
RA Solt L.A., Kumar N., Nuhant P., Wang Y., Lauer J.L., Liu J., Istrate M.A.,
RA Kamenecka T.M., Roush W.R., Vidovic D., Schuerer S.C., Xu J., Wagoner G.,
RA Drew P.D., Griffin P.R., Burris T.P.;
RT "Suppression of TH17 differentiation and autoimmunity by a synthetic ROR
RT ligand.";
RL Nature 472:491-494(2011).
RN [20]
RP INTERACTION WITH CRY1.
RX PubMed=22170608; DOI=10.1038/nature10700;
RA Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W.,
RA Downes M., Evans R.M.;
RT "Cryptochromes mediate rhythmic repression of the glucocorticoid
RT receptor.";
RL Nature 480:552-556(2011).
RN [21]
RP FUNCTION IN CIRCADIAN RHYTHMS, TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR
RP LOCATION, DNA-BINDING, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-502.
RX PubMed=22753030; DOI=10.1093/nar/gks630;
RA Takeda Y., Jothi R., Birault V., Jetten A.M.;
RT "RORgamma directly regulates the circadian expression of clock genes and
RT downstream targets in vivo.";
RL Nucleic Acids Res. 40:8519-8535(2012).
RN [22]
RP REVIEW ON FUNCTION AND LIGANDS.
RX PubMed=22789990; DOI=10.1016/j.tem.2012.05.012;
RA Solt L.A., Burris T.P.;
RT "Action of RORs and their ligands in (patho)physiology.";
RL Trends Endocrinol. Metab. 23:619-627(2012).
RN [23]
RP TISSUE SPECIFICITY.
RX PubMed=23562159; DOI=10.1016/j.immuni.2013.01.010;
RG Immunological Genome Project Consortium;
RA Malhotra N., Narayan K., Cho O.H., Sylvia K.E., Yin C., Melichar H.,
RA Rashighi M., Lefebvre V., Harris J.E., Berg L.J., Kang J.;
RT "A network of high-mobility group box transcription factors programs innate
RT interleukin-17 production.";
RL Immunity 38:681-693(2013).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PROX1.
RX PubMed=23723244; DOI=10.1093/nar/gkt447;
RA Takeda Y., Jetten A.M.;
RT "Prospero-related homeobox 1 (Prox1) functions as a novel modulator of
RT retinoic acid-related orphan receptors alpha- and gamma-mediated
RT transactivation.";
RL Nucleic Acids Res. 41:6992-7008(2013).
RN [25]
RP FUNCTION (ISOFORM 2).
RX PubMed=26607793; DOI=10.1016/j.cell.2015.10.068;
RA Wang C., Yosef N., Gaublomme J., Wu C., Lee Y., Clish C.B., Kaminski J.,
RA Xiao S., Meyer Zu Horste G., Pawlak M., Kishi Y., Joller N., Karwacz K.,
RA Zhu C., Ordovas-Montanes M., Madi A., Wortman I., Miyazaki T., Sobel R.A.,
RA Park H., Regev A., Kuchroo V.K.;
RT "CD5L/AIM regulates lipid biosynthesis and restrains Th17 cell
RT pathogenicity.";
RL Cell 163:1413-1427(2015).
RN [26]
RP INTERACTION WITH NR0B2.
RX PubMed=25212631; DOI=10.1002/hep.27437;
RA Lee S.M., Zhang Y., Tsuchiya H., Smalling R., Jetten A.M., Wang L.;
RT "Small heterodimer partner/neuronal PAS domain protein 2 axis regulates the
RT oscillation of liver lipid metabolism.";
RL Hepatology 61:497-505(2015).
CC -!- FUNCTION: Nuclear receptor that binds DNA as a monomer to ROR response
CC elements (RORE) containing a single core motif half-site 5'-AGGTCA-3'
CC preceded by a short A-T-rich sequence. Key regulator of cellular
CC differentiation, immunity, peripheral circadian rhythm as well as
CC lipid, steroid, xenobiotics and glucose metabolism. Considered to have
CC intrinsic transcriptional activity, have some natural ligands like
CC oxysterols that act as agonists (25-hydroxycholesterol) or inverse
CC agonists (7-oxygenated sterols), enhancing or repressing the
CC transcriptional activity, respectively. Recruits distinct combinations
CC of cofactors to target gene regulatory regions to modulate their
CC transcriptional expression, depending on the tissue, time and promoter
CC contexts (PubMed:17666523, PubMed:19381306, PubMed:19965867,
CC PubMed:21853531, PubMed:22789990, PubMed:23723244). Regulates the
CC circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1
CC in peripheral tissues and in a tissue-selective manner
CC (PubMed:22753030). Competes with NR1D1 for binding to their shared DNA
CC response element on some clock genes such as ARNTL/BMAL1, CRY1 and
CC NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated
CC activation of the expression, leading to the circadian pattern of clock
CC genes expression. Therefore influences the period length and stability
CC of the clock (PubMed:22753030). Involved in the regulation of the
CC rhythmic expression of genes involved in glucose and lipid metabolism,
CC including PLIN2 and AVPR1A. Negative regulator of adipocyte
CC differentiation through the regulation of early phase genes expression,
CC such as MMP3. Controls adipogenesis as well as adipocyte size and
CC modulates insulin sensitivity in obesity. In liver, has specific and
CC redundant functions with RORA as positive or negative modulator of
CC expression of genes encoding phase I and Phase II proteins involved in
CC the metabolism of lipids, steroids and xenobiotics, such as SULT1E1
CC (PubMed:21853531). Also plays also a role in the regulation of
CC hepatocyte glucose metabolism through the regulation of G6PC1 and PCK1.
CC Regulates the rhythmic expression of PROX1 and promotes its nuclear
CC localization. {ECO:0000269|PubMed:17666523,
CC ECO:0000269|PubMed:19381306, ECO:0000269|PubMed:19965867,
CC ECO:0000269|PubMed:21853531, ECO:0000269|PubMed:22753030,
CC ECO:0000269|PubMed:22789990, ECO:0000269|PubMed:23723244}.
CC -!- FUNCTION: [Isoform 2]: Essential for thymopoiesis and the development
CC of several secondary lymphoid tissues, including lymph nodes and
CC Peyer's patches (PubMed:10602018, PubMed:14691482, PubMed:16148126).
CC Required for the generation of LTi (lymphoid tissue inducer) cells.
CC Regulates thymocyte survival through DNA-binding on ROREs of target
CC gene promoter regions and recruitment of coactivaros via the AF-2. Also
CC plays a key role, downstream of IL6 and TGFB and synergistically with
CC RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H))
CC cells into T(H)17 cells, antagonizing the T(H)1 program. Probably
CC regulates IL17 and IL17F expression on T(H) by binding to the essential
CC enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus
CC (PubMed:16990136, PubMed:18164222, PubMed:26607793). May also play a
CC role in the pre-TCR activation cascade leading to the maturation of
CC alpha/beta T-cells and may participate in the regulation of DNA
CC accessibility in the TCR-J(alpha) locus (PubMed:9881970,
CC PubMed:10602018, PubMed:14691482, PubMed:16148126, PubMed:16990136,
CC PubMed:18164222). Plays an indispensable role in the induction of IFN-
CC gamma dependent anti-mycobacterial systemic immunity (By similarity).
CC {ECO:0000250|UniProtKB:P51449, ECO:0000269|PubMed:10602018,
CC ECO:0000269|PubMed:14691482, ECO:0000269|PubMed:16148126,
CC ECO:0000269|PubMed:16990136, ECO:0000269|PubMed:18164222,
CC ECO:0000269|PubMed:26607793, ECO:0000269|PubMed:9881970}.
CC -!- SUBUNIT: Interacts (via AF-2 motif) with the coactivators NCOA1, NCOA2
CC and PPARGC1A (via LXXLL motif) (PubMed:16148126, PubMed:17476214,
CC PubMed:21499262). Interacts with the corepressor NCOR1
CC (PubMed:21499262). Interacts with CRY1 (PubMed:22170608). Interacts
CC (via AF-2 motif) with PROX1 (PubMed:23723244). Interacts with FOXP3
CC (PubMed:18368049). Interacts with NR0B2 (PubMed:25212631).
CC {ECO:0000269|PubMed:16148126, ECO:0000269|PubMed:17476214,
CC ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:21499262,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23723244,
CC ECO:0000269|PubMed:25212631}.
CC -!- INTERACTION:
CC P51450-2; Q9R1E0: Foxo1; NbExp=2; IntAct=EBI-4422078, EBI-1371343;
CC P51450-2; Q61221: Hif1a; NbExp=2; IntAct=EBI-4422078, EBI-298954;
CC P51450-2; Q16665: HIF1A; Xeno; NbExp=2; IntAct=EBI-4422078, EBI-447269;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:21853531,
CC ECO:0000269|PubMed:22753030}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P51450-1; Sequence=Displayed;
CC Name=2; Synonyms=RORgT;
CC IsoId=P51450-2; Sequence=VSP_003659, VSP_003660;
CC Name=3 {ECO:0000305};
CC IsoId=P51450-3; Sequence=VSP_056787, VSP_056788;
CC -!- TISSUE SPECIFICITY: Expressed in immature Vgamma2 gamma-delta T-cells
CC (at protein level) (PubMed:23562159). Expressed in the liver
CC (PubMed:17666523, PubMed:22753030). Expressed in the heart
CC (PubMed:17666523). Expressed in the kidney, jejunum, and brown adipose
CC tissue (PubMed:22753030). {ECO:0000269|PubMed:17666523,
CC ECO:0000269|PubMed:22753030, ECO:0000269|PubMed:23562159}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in muscle and the thymus
CC (PubMed:9881970, PubMed:10602018). Expressed in the brain, heart,
CC kidney, liver, and lung (PubMed:9881970). Expressed in testes
CC (PubMed:10602018). Not expressed in the spleen or bone marrow
CC (PubMed:9881970). {ECO:0000269|PubMed:10602018,
CC ECO:0000269|PubMed:9881970}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the thymus, primarily in
CC immature thymocytes, including Vgamma2 gamma-delta T-cells (at protein
CC levels) (PubMed:9881970, PubMed:10602018). Also expressed in a subset
CC of mature T(H)17 cells (PubMed:18164222). Not expressed in the spleen
CC or bone marrow (PubMed:9881970). {ECO:0000269|PubMed:10602018,
CC ECO:0000269|PubMed:18164222, ECO:0000269|PubMed:9881970}.
CC -!- DEVELOPMENTAL STAGE: In 3T3-L1 cells, sharp decline at mRNA and protein
CC levels upon induction of adipocyte differentiation. Isoform 2 is
CC detected in the immediate vicinity of vessels among small clusters of
CC CD45(+) cells as early as 12.5 dpc. At 16.5 dpc, isoform 2 is expressed
CC exclusively in tight clusters of cells found in lymph node anlagen, in
CC the submucosal region of the intestine and around central vessels in
CC the spleen. {ECO:0000269|PubMed:17666523, ECO:0000269|PubMed:21853531}.
CC -!- INDUCTION: Isoform 1 expression oscillates diurnally in peripheral
CC tissues such as liver, brown adipose tissue (BAT), kidney and small
CC intestines. Isoform 2 is induced upon antigen receptor ligation in the
CC presence of IL6 and TGB1 (via STAT3). Induced by TGFB1 in T-cells.
CC {ECO:0000269|PubMed:18368049, ECO:0000269|PubMed:22753030}.
CC -!- DOMAIN: The AF-2 (activation function-2) motif is required for
CC recruiting coregulators containing LXXLL motifs such as NCOA1 and
CC NCOA2. {ECO:0000269|PubMed:16148126}.
CC -!- DISRUPTION PHENOTYPE: Mice show decreased adipocytes size and highly
CC insulin sensitivity, leading to an improved control of circulating
CC fatty acids. Mutants are protected from hyperglycemia and insulin
CC resistance in the state of obesity. Loss of circadian pattern of some
CC clock genes expression in the peripheral tissues and massive apoptosis
CC of thymocytes. Knockout mice for isoform 2 lack all lymph nodes and
CC Peyer's patches, as well as LTi cells. They also show a reduction of
CC T(H)17 cells in the lamina propria by at least 10-fold to less than 1%
CC of the T(H) cells. Mice are less susceptible to autoimmune inflammatory
CC diseases. {ECO:0000269|PubMed:16148126, ECO:0000269|PubMed:17666523,
CC ECO:0000269|PubMed:21853531, ECO:0000269|PubMed:22753030}.
CC -!- MISCELLANEOUS: [Isoform 1]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing of isoform
CC 1. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; U43508; AAB40709.1; -; mRNA.
DR EMBL; AF019660; AAC53501.1; -; Genomic_DNA.
DR EMBL; AF019655; AAC53501.1; JOINED; Genomic_DNA.
DR EMBL; AF019656; AAC53501.1; JOINED; Genomic_DNA.
DR EMBL; AF019657; AAC53501.1; JOINED; Genomic_DNA.
DR EMBL; AF019658; AAC53501.1; JOINED; Genomic_DNA.
DR EMBL; AF019659; AAC53501.1; JOINED; Genomic_DNA.
DR EMBL; U39071; AAB02582.1; -; mRNA.
DR EMBL; AF163668; AAD46913.1; -; mRNA.
DR EMBL; AJ132394; CAA10661.1; -; mRNA.
DR EMBL; AK153941; BAE32267.1; -; mRNA.
DR EMBL; AC164562; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014804; AAH14804.1; -; mRNA.
DR CCDS; CCDS17591.1; -. [P51450-1]
DR CCDS; CCDS79971.1; -. [P51450-2]
DR PIR; JC5375; JC5375.
DR RefSeq; NP_001280663.1; NM_001293734.1.
DR RefSeq; NP_035411.2; NM_011281.3.
DR AlphaFoldDB; P51450; -.
DR BioGRID; 202957; 4.
DR DIP; DIP-59439N; -.
DR IntAct; P51450; 8.
DR STRING; 10090.ENSMUSP00000029795; -.
DR BindingDB; P51450; -.
DR ChEMBL; CHEMBL1293231; -.
DR DrugCentral; P51450; -.
DR iPTMnet; P51450; -.
DR PhosphoSitePlus; P51450; -.
DR jPOST; P51450; -.
DR MaxQB; P51450; -.
DR PaxDb; P51450; -.
DR PeptideAtlas; P51450; -.
DR PRIDE; P51450; -.
DR ProteomicsDB; 300465; -. [P51450-1]
DR ProteomicsDB; 300466; -. [P51450-2]
DR ProteomicsDB; 300467; -. [P51450-3]
DR Antibodypedia; 20336; 818 antibodies from 43 providers.
DR DNASU; 19885; -.
DR Ensembl; ENSMUST00000200009; ENSMUSP00000143610; ENSMUSG00000028150. [P51450-3]
DR GeneID; 19885; -.
DR KEGG; mmu:19885; -.
DR UCSC; uc008qfy.3; mouse. [P51450-1]
DR UCSC; uc008qfz.3; mouse. [P51450-2]
DR UCSC; uc012ctn.2; mouse. [P51450-3]
DR CTD; 6097; -.
DR MGI; MGI:104856; Rorc.
DR VEuPathDB; HostDB:ENSMUSG00000028150; -.
DR eggNOG; KOG4216; Eukaryota.
DR GeneTree; ENSGT00940000161521; -.
DR InParanoid; P51450; -.
DR OrthoDB; 583704at2759; -.
DR PhylomeDB; P51450; -.
DR TreeFam; TF319910; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 19885; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Rorc; mouse.
DR PRO; PR:P51450; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P51450; protein.
DR Bgee; ENSMUSG00000028150; Expressed in hindlimb stylopod muscle and 103 other tissues.
DR ExpressionAtlas; P51450; baseline and differential.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0098531; F:ligand-activated transcription factor activity; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0008142; F:oxysterol binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0060612; P:adipose tissue development; IMP:UniProtKB.
DR GO; GO:0046632; P:alpha-beta T cell differentiation; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IMP:MGI.
DR GO; GO:0036315; P:cellular response to sterol; ISO:MGI.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0048535; P:lymph node development; IMP:UniProtKB.
DR GO; GO:0048537; P:mucosa-associated lymphoid tissue development; IMP:MGI.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0048541; P:Peyer's patch development; IMP:UniProtKB.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0045586; P:regulation of gamma-delta T cell differentiation; IDA:MGI.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR GO; GO:0019218; P:regulation of steroid metabolic process; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:MGI.
DR GO; GO:0072539; P:T-helper 17 cell differentiation; IDA:MGI.
DR GO; GO:0042093; P:T-helper cell differentiation; IMP:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IMP:UniProtKB.
DR CDD; cd06968; NR_DBD_ROR; 1.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR044101; NR_DBD_ROR.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR003079; ROR_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01293; RORNUCRECPTR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative promoter usage; Alternative splicing;
KW Biological rhythms; Developmental protein; DNA-binding; Metal-binding;
KW Nucleus; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..516
FT /note="Nuclear receptor ROR-gamma"
FT /id="PRO_0000053518"
FT DOMAIN 267..506
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 31..96
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 31..51
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 67..91
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..30
FT /note="Modulating"
FT /evidence="ECO:0000255"
FT REGION 104..145
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 499..504
FT /note="AF-2"
FT COMPBIAS 117..134
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..24
FT /note="MDRAPQRHHRTSRELLAAKKTHTS -> MAGSYLHCA (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_056787"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10602018,
FT ECO:0000303|PubMed:9881970"
FT /id="VSP_003659"
FT VAR_SEQ 22..24
FT /note="HTS -> MRT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10602018,
FT ECO:0000303|PubMed:9881970"
FT /id="VSP_003660"
FT VAR_SEQ 310..463
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_056788"
FT MUTAGEN 31
FT /note="C->A: Loss of adipogenesis inhibition, when
FT associated with A-48."
FT /evidence="ECO:0000269|PubMed:21853531"
FT MUTAGEN 48
FT /note="C->A: Loss of adipogenesis inhibition, when
FT associated with A-31."
FT /evidence="ECO:0000269|PubMed:21853531"
FT MUTAGEN 56..57
FT /note="RR->AG: Abolishes DNA-binding. No effect neither on
FT interaction with NCOA1 and NCOA2 nor on inhibition of
FT NFATC1 expression."
FT /evidence="ECO:0000269|PubMed:16148126"
FT MUTAGEN 500
FT /note="Y->F: Abolishes interaction with NCOA1 and NCOA2."
FT /evidence="ECO:0000269|PubMed:16148126"
FT MUTAGEN 502
FT /note="E->Q: Loss of transactivation function."
FT /evidence="ECO:0000269|PubMed:22753030"
FT CONFLICT 70..71
FT /note="QQ -> HR (in Ref. 6; BAE32267)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="A -> R (in Ref. 6; BAE32267)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="G -> A (in Ref. 6; BAE32267)"
FT /evidence="ECO:0000305"
FT CONFLICT 181
FT /note="G -> D (in Ref. 3; AAB02582)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="N -> H (in Ref. 6; BAE32267)"
FT /evidence="ECO:0000305"
FT CONFLICT 207
FT /note="G -> C (in Ref. 6; BAE32267)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="T -> K (in Ref. 3; AAB02582, 4; AAD46913 and 8;
FT AAH14804)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 516 AA; 58117 MW; 218068AF4598A93B CRC64;
MDRAPQRHHR TSRELLAAKK THTSQIEVIP CKICGDKSSG IHYGVITCEG CKGFFRRSQQ
CNVAYSCTRQ QNCPIDRTSR NRCQHCRLQK CLALGMSRDA VKFGRMSKKQ RDSLHAEVQK
QLQQQQQQEQ VAKTPPAGSR GADTLTYTLG LSDGQLPLGA SPDLPEASAC PPGLLRASGS
GPPYSNTLAK TEVQGASCHL EYSPERGKAE GRDSIYSTDG QLTLGRCGLR FEETRHPELG
EPEQGPDSHC IPSFCSAPEV PYASLTDIEY LVQNVCKSFR ETCQLRLEDL LRQRTNLFSR
EEVTSYQRKS MWEMWERCAH HLTEAIQYVV EFAKRLSGFM ELCQNDQIIL LTAGAMEVVL
VRMCRAYNAN NHTVFFEGKY GGVELFRALG CSELISSIFD FSHFLSALCF SEDEIALYTA
LVLINANRPG LQEKRRVEHL QYNLELAFHH HLCKTHRQGL LAKLPPKGKL RSLCSQHVEK
LQIFQHLHPI VVQAAFPPLY KELFSTDVES PEGLSK
