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 27-MAR-2024, entry version 201. 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, BMAL1 and NR1D1 in CC peripheral tissues and in a tissue-selective manner (PubMed:22753030). CC Competes with NR1D1 for binding to their shared DNA response element on CC some clock genes such as BMAL1, CRY1 and NR1D1 itself, resulting in CC NR1D1-mediated repression or RORC-mediated activation of the CC expression, leading to the circadian pattern of clock genes expression. CC Therefore influences the period length and stability of the clock CC (PubMed:22753030). Involved in the regulation of the rhythmic CC expression of genes involved in glucose and lipid metabolism, including CC PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation CC through the regulation of early phase genes expression, such as MMP3. CC Controls adipogenesis as well as adipocyte size and modulates insulin CC sensitivity in obesity. In liver, has specific and redundant functions CC with RORA as positive or negative modulator of expression of genes CC encoding phase I and Phase II proteins involved in the metabolism of CC lipids, steroids and xenobiotics, such as SULT1E1 (PubMed:21853531). CC Also plays also a role in the regulation of hepatocyte glucose CC metabolism through the regulation of G6PC1 and PCK1. Regulates the CC rhythmic expression of PROX1 and promotes its nuclear localization. CC {ECO:0000269|PubMed:17666523, ECO:0000269|PubMed:19381306, CC ECO:0000269|PubMed:19965867, ECO:0000269|PubMed:21853531, CC ECO:0000269|PubMed:22753030, ECO:0000269|PubMed:22789990, CC 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}. 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; 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 PDB; 7XVN; X-ray; 2.30 A; A/B/C/D=24-117. DR PDBsum; 7XVN; -. 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; 10090-ENSMUSP00000029795; -. DR PeptideAtlas; P51450; -. DR ProteomicsDB; 300465; -. [P51450-1] DR ProteomicsDB; 300466; -. [P51450-2] DR ProteomicsDB; 300467; -. [P51450-3] DR Antibodypedia; 20336; 957 antibodies from 43 providers. DR DNASU; 19885; -. DR Ensembl; ENSMUST00000200009.2; ENSMUSP00000143610.2; ENSMUSG00000028150.15. [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 AGR; MGI:104856; -. DR CTD; 6097; -. DR MGI; MGI:104856; Rorc. DR VEuPathDB; HostDB:ENSMUSG00000028150; -. DR eggNOG; KOG4216; Eukaryota. DR GeneTree; ENSGT00940000161521; -. DR InParanoid; P51450; -. DR OrthoDB; 3475284at2759; -. DR PhylomeDB; P51450; -. DR TreeFam; TF319910; -. DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway. DR BioGRID-ORCS; 19885; 2 hits in 80 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 105 other cell types or 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 DNA-templated transcription; IDA:UniProtKB. 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 CDD; cd06939; NR_LBD_ROR_like; 1. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 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 PANTHER; PTHR45805; NUCLEAR HORMONE RECEPTOR HR3-RELATED; 1. DR PANTHER; PTHR45805:SF1; NUCLEAR RECEPTOR ROR-GAMMA; 1. 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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 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 3D-structure; 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 //