RORA_MOUSE
ID RORA_MOUSE Reviewed; 523 AA.
AC P51448; P70283; P97741; P97773; Q923G1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Nuclear receptor ROR-alpha;
DE AltName: Full=Nuclear receptor RZR-alpha;
DE AltName: Full=Nuclear receptor subfamily 1 group F member 1;
DE AltName: Full=RAR-related orphan receptor A;
DE AltName: Full=Retinoid-related orphan receptor-alpha;
GN Name=Rora; Synonyms=Nr1f1, Rzra;
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 [MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=8602221; DOI=10.1038/379736a0;
RA Hamilton B.A., Frankel W.N., Kerrebrock A.W., Hawkins T.L., Fitzhugh W.,
RA Kusumi K., Russell L.B., Mueller K.L., Vanberkel V., Birren B.W.,
RA Kruglyak L., Lander E.S.;
RT "Disruption of the nuclear hormone receptor RORalpha in staggerer mice.";
RL Nature 379:736-739(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=7935491; DOI=10.1210/mend.8.6.7935491;
RA Carlberg C., Hooft van Huijsduijnen R., Staple J.K., Delamarter J.F.,
RA Becker-Andre M.;
RT "RZRs, a new family of retinoid-related orphan receptors that function as
RT both monomers and homodimers.";
RL Mol. Endocrinol. 8:757-770(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANT SG 275-HIS--LYS-314
RP DEL.
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=9226375; DOI=10.1006/geno.1997.4757;
RA Matysiak-Scholze U., Nehls M.C.;
RT "The structural integrity of ROR alpha isoforms is mutated in staggerer
RT mice: cerebellar coexpression of ROR alpha1 and ROR alpha4.";
RL Genomics 43:78-84(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=8750880; DOI=10.1016/0169-328x(95)00126-d;
RA Matsui T., Sashihara S., Oh Y., Waxman S.G.;
RT "An orphan nuclear receptor, mROR alpha, and its spatial expression in
RT adult mouse brain.";
RL Brain Res. Mol. Brain Res. 33:217-226(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [6]
RP PROTEIN SEQUENCE OF 39-61, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [7]
RP FUNCTION IN TRIGLYCERIDE METABOLISM, DNA-BINDING, AND CHARACTERIZATION OF
RP VARIANT SG PHENOTYPE.
RX PubMed=11053433; DOI=10.1074/jbc.m004982200;
RA Raspe E., Duez H., Gervois P., Fievet C., Fruchart J.C., Besnard S.,
RA Mariani J., Tedgui A., Staels B.;
RT "Transcriptional regulation of apolipoprotein C-III gene expression by the
RT orphan nuclear receptor RORalpha.";
RL J. Biol. Chem. 276:2865-2871(2001).
RN [8]
RP FUNCTION IN CEREBELLAR DEVELOPMENT, DEVELOPMENTAL STAGE, INTERACTION WITH
RP CTNNB1, AND CHARACTERIZATION OF VARIANT SG PHENOTYPE.
RX PubMed=14687547; DOI=10.1016/s0896-6273(03)00769-4;
RA Gold D.A., Baek S.H., Schork N.J., Rose D.W., Larsen D.D., Sachs B.D.,
RA Rosenfeld M.G., Hamilton B.A.;
RT "RORalpha coordinates reciprocal signaling in cerebellar development
RT through sonic hedgehog and calcium-dependent pathways.";
RL Neuron 40:1119-1131(2003).
RN [9]
RP FUNCTION IN CIRCADIAN RHYTHMS, AND CHARACTERIZATION OF VARIANT SG
RP PHENOTYPE.
RX PubMed=15821743; DOI=10.1038/nsmb925;
RA Akashi M., Takumi T.;
RT "The orphan nuclear receptor RORalpha regulates circadian transcription of
RT the mammalian core-clock Bmal1.";
RL Nat. Struct. Mol. Biol. 12:441-448(2005).
RN [10]
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 [11]
RP FUNCTION IN METABOLISM REGULATION, CHARACTERIZATION OF VARIANT SG
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 [12]
RP FUNCTION IN METABOLISM REGULATION, CHARACTERIZATION OF VARIANT SG
RP PHENOTYPE, AND DNA-BINDING.
RX PubMed=18055760; DOI=10.1124/mol.107.040741;
RA Wada T., Kang H.S., Angers M., Gong H., Bhatia S., Khadem S., Ren S.,
RA Ellis E., Strom S.C., Jetten A.M., Xie W.;
RT "Identification of oxysterol 7alpha-hydroxylase (Cyp7b1) as a novel
RT retinoid-related orphan receptor alpha (RORalpha) (NR1F1) target gene and a
RT functional cross-talk between RORalpha and liver X receptor (NR1H3).";
RL Mol. Pharmacol. 73:891-899(2008).
RN [13]
RP REVIEW OF FUNCTION IN METABOLISM REGULATION.
RX PubMed=18535165; DOI=10.3181/0802-mr-50;
RA Wada T., Kang H.S., Jetten A.M., Xie W.;
RT "The emerging role of nuclear receptor RORalpha and its crosstalk with LXR
RT in xeno- and endobiotic gene regulation.";
RL Exp. Biol. Med. 233:1191-1201(2008).
RN [14]
RP FUNCTION IN T(H)17 CELLS DIFFERENTIATION, INDUCTION BY IL6 AND TGFB1, AND
RP TISSUE SPECIFICITY.
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 FUNCTION IN LIPID METABOLISM REGULATION, TISSUE SPECIFICITY, AND
RP CHARACTERIZATION OF VARIANT SG PHENOTYPE.
RX PubMed=18441015; DOI=10.1074/jbc.m710526200;
RA Lau P., Fitzsimmons R.L., Raichur S., Wang S.C., Lechtken A., Muscat G.E.;
RT "The orphan nuclear receptor, RORalpha, regulates gene expression that
RT controls lipid metabolism: staggerer (SG/SG) mice are resistant to diet-
RT induced obesity.";
RL J. Biol. Chem. 283:18411-18421(2008).
RN [16]
RP INTERACTION WITH NCOA2.
RX PubMed=19039140; DOI=10.1126/science.1164847;
RA Chopra A.R., Louet J.F., Saha P., An J., Demayo F., Xu J., York B.,
RA Karpen S., Finegold M., Moore D., Chan L., Newgard C.B., O'Malley B.W.;
RT "Absence of the SRC-2 coactivator results in a glycogenopathy resembling
RT Von Gierke's disease.";
RL Science 322:1395-1399(2008).
RN [17]
RP FUNCTION, DEVELOPMENTAL STAGE, AND CHARACTERIZATION OF VARIANT SG.
RX PubMed=19014374; DOI=10.1111/j.1471-4159.2008.05739.x;
RA Fujieda H., Bremner R., Mears A.J., Sasaki H.;
RT "Retinoic acid receptor-related orphan receptor alpha regulates a subset of
RT cone genes during mouse retinal development.";
RL J. Neurochem. 108:91-101(2009).
RN [18]
RP FUNCTION IN ADIPOGENESIS, INTERACTION WITH CEBPB, AND DEVELOPMENTAL STAGE.
RX PubMed=19324970; DOI=10.1210/me.2008-0277;
RA Ohoka N., Kato S., Takahashi Y., Hayashi H., Sato R.;
RT "The orphan nuclear receptor RORalpha restrains adipocyte differentiation
RT through a reduction of C/EBPbeta activity and perilipin gene expression.";
RL Mol. Endocrinol. 23:759-771(2009).
RN [19]
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 [20]
RP INTERACTION WITH MAGED1.
RX PubMed=20300063; DOI=10.1038/emboj.2010.34;
RA Wang X., Tang J., Xing L., Shi G., Ruan H., Gu X., Liu Z., Wu X., Gao X.,
RA Xu Y.;
RT "Interaction of MAGED1 with nuclear receptors affects circadian clock
RT function.";
RL EMBO J. 29:1389-1400(2010).
RN [21]
RP INTERACTION WITH PER2.
RX PubMed=20159955; DOI=10.1101/gad.564110;
RA Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.;
RT "The mammalian clock component PERIOD2 coordinates circadian output by
RT interaction with nuclear receptors.";
RL Genes Dev. 24:345-357(2010).
RN [22]
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 [23]
RP FUNCTION, AND INTERACTION WITH NRIP1.
RX PubMed=21628546; DOI=10.1177/0748730411401579;
RA Poliandri A.H., Gamsby J.J., Christian M., Spinella M.J., Loros J.J.,
RA Dunlap J.C., Parker M.G.;
RT "Modulation of clock gene expression by the transcriptional coregulator
RT receptor interacting protein 140 (RIP140).";
RL J. Biol. Rhythms 26:187-199(2011).
RN [24]
RP FUNCTION IN T(H)17 CELLS DIFFERENTIATION, INDUCTION BY IL6 AND TGFB1,
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 [25]
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 [26]
RP FUNCTION IN CIRCADIAN RHYTHMS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP DNA-BINDING, AND INDUCTION.
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 [27]
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 [28]
RP FUNCTION, AND INDUCTION.
RX PubMed=23172836; DOI=10.1161/circulationaha.112.135608;
RA Saito T., Hirano M., Ide T., Ichiki T., Koibuchi N., Sunagawa K.,
RA Hirano K.;
RT "Pivotal role of Rho-associated kinase 2 in generating the intrinsic
RT circadian rhythm of vascular contractility.";
RL Circulation 127:104-114(2013).
RN [29]
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).
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 embryonic
CC development, cellular differentiation, immunity, circadian rhythm as
CC well as lipid, steroid, xenobiotics and glucose metabolism. Considered
CC to have intrinsic transcriptional activity, have some natural ligands
CC like 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 genes regulatory regions to modulate their
CC transcriptional expression, depending on the tissue, time and promoter
CC contexts. Regulates genes involved in photoreceptor development
CC including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with
CC MYOD1. Required for proper cerebellum development, regulates SHH gene
CC expression, among others, to induce granule cells proliferation as well
CC as expression of genes involved in calcium-mediated signal
CC transduction. Regulates the circadian expression of several clock
CC genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with
CC NR1D1 for binding to their shared DNA response element on some clock
CC genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-
CC mediated repression or RORA-mediated activation of clock genes
CC expression, leading to the circadian pattern of clock genes expression.
CC Therefore influences the period length and stability of the clock.
CC Regulates genes involved in lipid metabolism such as apolipoproteins
CC APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant
CC functions with RORC as positive or negative modulator of expression of
CC genes encoding phase I and phase II proteins involved in the metabolism
CC of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1.
CC Induces a rhythmic expression of some of these genes. In addition,
CC interplays functionally with NR1H2 and NR1H3 for the regulation of
CC genes involved in cholesterol metabolism. Also involved in the
CC regulation of hepatic glucose metabolism through the modulation of
CC G6PC1 and PCK1. In adipose tissue, plays a role as negative regulator
CC of adipocyte differentiation, probably acting through dual mechanisms.
CC May suppress CEBPB-dependent adipogenesis through direct interaction
CC and PPARG-dependent adipogenesis through competition for DNA-binding.
CC Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is
CC implicated in the lineage specification of uncommitted CD4(+) T-helper
CC (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program.
CC Probably regulates IL17 and IL17F expression on T(H) by binding to the
CC essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-
CC IL17F locus. Involved in hypoxia signaling by interacting with and
CC activating the transcriptional activity of HIF1A. May inhibit cell
CC growth in response to cellular stress. May exert an anti-inflammatory
CC role by inducing CHUK expression and inhibiting NF-kappa-B signaling.
CC {ECO:0000269|PubMed:11053433, ECO:0000269|PubMed:14687547,
CC ECO:0000269|PubMed:15821743, ECO:0000269|PubMed:17666523,
CC ECO:0000269|PubMed:18055760, ECO:0000269|PubMed:18164222,
CC ECO:0000269|PubMed:18441015, ECO:0000269|PubMed:19014374,
CC ECO:0000269|PubMed:19324970, ECO:0000269|PubMed:19965867,
CC ECO:0000269|PubMed:21499262, ECO:0000269|PubMed:21628546,
CC ECO:0000269|PubMed:22753030, ECO:0000269|PubMed:23172836,
CC ECO:0000269|PubMed:23723244}.
CC -!- SUBUNIT: Monomer. Interacts (via the DNA-binding domain) with HIF1A;
CC the interaction enhances HIF1A transcription under hypoxia through
CC increasing protein stability. Interacts with CEBPB; the interaction
CC disrupts the interaction CEBPB:EP300. Interacts with the coactivators
CC NCOA2, PPARGC1A (via LXXLL motif), EP300 and MED1. Interacts with the
CC corepressor NCOR1. Interacts with MAGED1 and CTNNB1. Interacts with
CC CRY1 and PER2. Interacts (via AF-2 motif) with PROX1. Interacts with
CC NRIP1. Isoform 4 interacts (via AF-2 motif) with isoform 1 of FOXP3
CC (via LXXLL motif) (By similarity). {ECO:0000250|UniProtKB:P35398,
CC ECO:0000269|PubMed:14687547, ECO:0000269|PubMed:17476214,
CC ECO:0000269|PubMed:19039140, ECO:0000269|PubMed:19324970,
CC ECO:0000269|PubMed:20159955, ECO:0000269|PubMed:20300063,
CC ECO:0000269|PubMed:21499262, ECO:0000269|PubMed:21628546,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23723244}.
CC -!- INTERACTION:
CC P51448; P54254: Atxn1; NbExp=3; IntAct=EBI-1169722, EBI-1169713;
CC P51448; Q9QYH6: Maged1; NbExp=5; IntAct=EBI-1169722, EBI-1801274;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:22753030, ECO:0000269|PubMed:23723244}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=4;
CC Name=1; Synonyms=Alpha-1;
CC IsoId=P51448-1; Sequence=Displayed;
CC Name=2; Synonyms=Alpha-2;
CC IsoId=P51448-3; Sequence=Not described;
CC Name=3; Synonyms=Alpha-3;
CC IsoId=P51448-4; Sequence=Not described;
CC Name=4; Synonyms=Alpha-4;
CC IsoId=P51448-2; Sequence=VSP_003658;
CC -!- TISSUE SPECIFICITY: Expressed in cerebellum, heart, liver, lung,
CC kidney, retina and brown and white adipose tissues. Expressed in the
CC subset of mature Th17 cells. {ECO:0000269|PubMed:17666523,
CC ECO:0000269|PubMed:18164222, ECO:0000269|PubMed:18441015,
CC ECO:0000269|PubMed:22753030}.
CC -!- DEVELOPMENTAL STAGE: In cerebellum, expression begins at 12.5 dpc. In
CC the developing retina, first expressed at 17 dpc in the ganglion cell
CC layer. At P3, expressed in the inner border of the neuroblasitic border
CC (presumptive amacrine cells). By P6, levels increase in developing
CC cones. Expression found in the presumptive bipolar cells by P9. During
CC adipocyte differentiation, expression gradually increases.
CC {ECO:0000269|PubMed:14687547, ECO:0000269|PubMed:19014374,
CC ECO:0000269|PubMed:19324970}.
CC -!- INDUCTION: In T(H) cells, induced upon antigen receptor ligation in the
CC presence of IL6 and TGB1 (via STAT3). Oscillates diurnally in central
CC nervous system. In liver, Isoform 1 oscillates diurnally but not
CC isoform 4. {ECO:0000269|PubMed:18164222, ECO:0000269|PubMed:21499262,
CC ECO:0000269|PubMed:22753030, ECO:0000269|PubMed:23172836}.
CC -!- DOMAIN: The AF-2 (activation function-2) motif is required for
CC recruiting coregulators containing LXXLL motifs.
CC {ECO:0000250|UniProtKB:P35398}.
CC -!- PTM: Phosphorylation by conventional PKCs in neurons inhibits
CC transcriptional activity. Phosphorylated on Thr-183 by MAPK1/ERK1 in
CC vitro. {ECO:0000250|UniProtKB:P35398}.
CC -!- PTM: Sumoylated by SENP1 and SENP2. Sumoylation, promoted by PIAS2,
CC PIAS3, PIAS4 but not PIAS1, enhances the transcriptional activity.
CC Desumoylated by SENP1. {ECO:0000250|UniProtKB:P35398}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Proteasomal degradation is required for efficient transcriptional
CC activity and is prevented by HR. {ECO:0000250|UniProtKB:P35398}.
CC -!- PTM: [Isoform 1]: Monomethylated at Lys-38 by EZH2, this creates a
CC degron recognized by a DCX (DDB1-DCAF1/VPRBP-CUL4A-RBX1) E3 ubiquitin
CC ligase complex. {ECO:0000250|UniProtKB:P35398}.
CC -!- DISEASE: Note=Defects in Rora are the cause of the staggerer (SG)
CC mutant phenotype which is characterized by disturbance of Purkinje cell
CC development and immune system functioning. This phenotype exhibits
CC lower body weight, reduced adiposity, decreased plasma cholesterol,
CC triglyceride and apolipoprotein CIII levels, and is resistant to diet-
CC induced obesity. Also has abnormal circadian rhythms.
CC {ECO:0000269|PubMed:11053433, ECO:0000269|PubMed:14687547,
CC ECO:0000269|PubMed:15821743, ECO:0000269|PubMed:17666523,
CC ECO:0000269|PubMed:18055760, ECO:0000269|PubMed:18441015,
CC ECO:0000269|PubMed:19014374, ECO:0000269|PubMed:9226375}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03757.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA69930.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U53228; AAC52513.1; -; mRNA.
DR EMBL; Y08640; CAA69930.1; ALT_INIT; mRNA.
DR EMBL; Z82994; CAB05396.1; -; mRNA.
DR EMBL; S82720; AAB46801.2; -; mRNA.
DR EMBL; D45910; BAA22970.1; -; mRNA.
DR EMBL; BC003757; AAH03757.2; ALT_INIT; mRNA.
DR CCDS; CCDS23314.1; -. [P51448-1]
DR CCDS; CCDS72268.1; -. [P51448-2]
DR PIR; S68517; S68517.
DR RefSeq; NP_001276845.1; NM_001289916.1. [P51448-2]
DR RefSeq; NP_038674.1; NM_013646.2. [P51448-1]
DR AlphaFoldDB; P51448; -.
DR SMR; P51448; -.
DR BioGRID; 202956; 1.
DR CORUM; P51448; -.
DR DIP; DIP-35351N; -.
DR IntAct; P51448; 4.
DR MINT; P51448; -.
DR STRING; 10090.ENSMUSP00000034766; -.
DR ChEMBL; CHEMBL3217403; -.
DR iPTMnet; P51448; -.
DR PhosphoSitePlus; P51448; -.
DR PaxDb; P51448; -.
DR PeptideAtlas; P51448; -.
DR PRIDE; P51448; -.
DR ProteomicsDB; 260916; -. [P51448-1]
DR ProteomicsDB; 260917; -. [P51448-2]
DR Antibodypedia; 4080; 583 antibodies from 37 providers.
DR DNASU; 19883; -.
DR Ensembl; ENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238. [P51448-1]
DR Ensembl; ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238. [P51448-2]
DR GeneID; 19883; -.
DR KEGG; mmu:19883; -.
DR UCSC; uc009qmx.2; mouse. [P51448-1]
DR CTD; 6095; -.
DR MGI; MGI:104661; Rora.
DR VEuPathDB; HostDB:ENSMUSG00000032238; -.
DR eggNOG; KOG4216; Eukaryota.
DR GeneTree; ENSGT00940000157387; -.
DR HOGENOM; CLU_007368_2_0_1; -.
DR InParanoid; P51448; -.
DR OMA; VRKQTCS; -.
DR PhylomeDB; P51448; -.
DR TreeFam; TF319910; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR BioGRID-ORCS; 19883; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Rora; mouse.
DR PRO; PR:P51448; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P51448; protein.
DR Bgee; ENSMUSG00000032238; Expressed in medial geniculate body and 288 other tissues.
DR ExpressionAtlas; P51448; baseline and differential.
DR Genevisible; P51448; MM.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
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:0098531; F:ligand-activated transcription factor activity; ISS:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:MGI.
DR GO; GO:0036315; P:cellular response to sterol; ISS:UniProtKB.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:MGI.
DR GO; GO:0021930; P:cerebellar granule cell precursor proliferation; IMP:UniProtKB.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IMP:MGI.
DR GO; GO:0046068; P:cGMP metabolic process; IMP:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0030522; P:intracellular receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0042692; P:muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:GO_Central.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IMP:MGI.
DR GO; GO:0042753; P:positive regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR GO; GO:0043030; P:regulation of macrophage activation; IMP:MGI.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; 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:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0072539; P:T-helper 17 cell differentiation; IMP:GO_Central.
DR GO; GO:0070328; P:triglyceride homeostasis; 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; Biological rhythms;
KW Developmental protein; Direct protein sequencing; Disease variant;
KW DNA-binding; Isopeptide bond; Metal-binding; Methylation; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..523
FT /note="Nuclear receptor ROR-alpha"
FT /id="PRO_0000053513"
FT DOMAIN 272..510
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 73..138
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 73..93
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 109..133
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 506..511
FT /note="AF-2"
FT COMPBIAS 19..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 38
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:P35398"
FT MOD_RES 183
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P35398"
FT CROSSLNK 240
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..66
FT /note="MESAPAAPDPAASEPGSSGSEAAAGSRETPLTQDTGRKSEAPGAGRRQSYAS
FT SSRGISVTKKTHTS -> MYFVIAAMKA (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:7935491, ECO:0000303|PubMed:8750880,
FT ECO:0000303|PubMed:9226375"
FT /id="VSP_003658"
FT VARIANT 275..314
FT /note="Missing (in SG; disturbance of Purkinje cell and
FT muscle development, lipid metabolism, circadian behavior
FT and immune system functioning)"
FT /evidence="ECO:0000269|PubMed:9226375"
FT CONFLICT 163
FT /note="H -> R (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 180..181
FT /note="EP -> T (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="L -> I (in Ref. 4; AAB46801/BAA22970)"
FT /evidence="ECO:0000305"
FT CONFLICT 193..194
FT /note="LT -> SA (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="L -> W (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 315
FT /note="Missing (in Ref. 4; AAB46801/BAA22970)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="E -> G (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="R -> P (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 450..451
FT /note="QL -> HM (in Ref. 2; CAA69930)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="K -> N (in Ref. 4; AAB46801/BAA22970)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 58845 MW; A194E02E4D9D177E CRC64;
MESAPAAPDP AASEPGSSGS EAAAGSRETP LTQDTGRKSE APGAGRRQSY ASSSRGISVT
KKTHTSQIEI IPCKICGDKS SGIHYGVITC EGCKGFFRRS QQSNATYSCP RQKNCLIDRT
SRNRCQHCRL QKCLAVGMSR DAVKFGRMSK KQRDSLYAEV QKHRMQQQQR DHQQQPGEAE
PLTPTYNISA NGLTELHDDL STYMDGHTPE GSKADSAVSS FYLDIQPSPD QSGLDINGIK
PEPICDYTPA SGFFPYCSFT NGETSPTVSM AELEHLAQNI SKSHLETCQY LREELQQITW
QTFLQEEIEN YQNKQREVMW QLCAIKITEA IQYVVEFAKR IDGFMELCQN DQIVLLKAGS
LEVVFIRMCR AFDSQNNTVY FDGKYASPDV FKSLGCEDFI SFVFEFGKSL CSMHLTEDEI
ALFSAFVLMS ADRSWLQEKV KIEKLQQKIQ LALQHVLQKN HREDGILTKL ICKVSTLRAL
CGRHTEKLMA FKAIYPDIVR LHFPPLYKEL FTSEFEPAMQ IDG
