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Database: UniProt
Entry: P51448
LinkDB: P51448
Original site: P51448 
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   26-NOV-2014, entry version 146.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; 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.,
RA   Fitzhugh W., Kusumi K., Russell L.B., Mueller K.L., Vanberkel V.,
RA   Birren B.W., Kruglyak L., Lander E.S.;
RT   "Disruption of the nuclear hormone receptor RORalpha in staggerer
RT   mice.";
RL   Nature 379:736-739(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC   STRAIN=C57BL/6; TISSUE=Skin;
RX   PubMed=7935491; DOI=10.1210/me.8.6.757;
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
RT   as both monomers and homodimers.";
RL   Mol. Endocrinol. 8:757-770(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND VARIANT SG
RP   275-HIS--LYS-314 DEL.
RC   STRAIN=C57BL/6; 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
RT   staggerer mice: cerebellar coexpression of ROR alpha1 and ROR
RT   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
RT   project: 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/6; 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
RP   OF 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
RT   the orphan nuclear receptor RORalpha.";
RL   J. Biol. Chem. 276:2865-2871(2001).
RN   [8]
RP   FUNCTION IN CEREBELLAR DEVELOPMENT, DEVELOPMENTAL STAGE, INTERACTION
RP   WITH 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
RT   transcription of 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
RT   and 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
RT   ROR 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
RT   and a functional cross-talk between RORalpha and liver X receptor
RT   (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
RT   LXR 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,
RP   AND 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.,
RA   Muscat G.E.;
RT   "The orphan nuclear receptor, RORalpha, regulates gene expression that
RT   controls lipid metabolism: staggerer (SG/SG) mice are resistant to
RT   diet-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.,
RA   O'Malley B.W.;
RT   "Absence of the SRC-2 coactivator results in a glycogenopathy
RT   resembling 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
RT   subset of cone genes during mouse retinal development.";
RL   J. Neurochem. 108:91-101(2009).
RN   [18]
RP   FUNCTION IN ADIPOGENESIS, INTERACTION WITH CEBPB, AND DEVELOPMENTAL
RP   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
RT   differentiation through a reduction of C/EBPbeta activity and
RT   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
RT   development, 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.,
RA   Gao X., 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 IDENTIFICTION OF
RP   LIGANDS.
RX   PubMed=19965867; DOI=10.1074/jbc.M109.080614;
RA   Wang Y., Kumar N., Solt L.A., Richardson T.I., Helvering L.M.,
RA   Crumbley C., Garcia-Ordonez R.D., Stayrook K.R., Zhang X., Novick S.,
RA   Chalmers M.J., Griffin P.R., Burris T.P.;
RT   "Modulation of retinoic acid receptor-related orphan receptor alpha
RT   and 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
RT   coregulator 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.,
RA   Istrate M.A., Kamenecka T.M., Roush W.R., Vidovic D., Schuerer S.C.,
RA   Xu J., Wagoner G., Drew P.D., Griffin P.R., Burris T.P.;
RT   "Suppression of TH17 differentiation and autoimmunity by a synthetic
RT   ROR 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.,
RA   Jonker J.W., 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
RP   LOCATION, 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
RT   and 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
CC       response elements (RORE) containing a single core motif half-site
CC       5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator
CC       of embryonic development, cellular differentiation, immunity,
CC       circadian rhythm as well as lipid, steroid, xenobiotics and
CC       glucose metabolism. Considered to have intrinsic transcriptional
CC       activity, have some natural ligands like oxysterols that act as
CC       agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated
CC       sterols), enhancing or repressing the transcriptional activity,
CC       respectively. Recruits distinct combinations of cofactors to
CC       target genes regulatory regions to modulate their transcriptional
CC       expression, depending on the tissue, time and promoter contexts.
CC       Regulates genes involved in photoreceptor development including
CC       OPN1SW, OPN1SM and ARR3 and skeletal muscle development with
CC       MYOD1. Required for proper cerebellum development, regulates SHH
CC       gene expression, among others, to induce granule cells
CC       proliferation as well as expression of genes involved in calcium-
CC       mediated signal transduction. Regulates the circadian expression
CC       of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and
CC       CRY1. Competes with NR1D1 for binding to their shared DNA response
CC       element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1
CC       itself, resulting in NR1D1-mediated repression or RORA-mediated
CC       activation of clock genes expression, leading to the circadian
CC       pattern of clock genes expression. Therefore influences the period
CC       length and stability of the clock. Regulates genes involved in
CC       lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and
CC       PPARG. In liver, has specific and redundant functions with RORC as
CC       positive or negative modulator of expression of genes encoding
CC       phase I and phase II proteins involved in the metabolism of
CC       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       G6PC and PCK1. In adipose tissue, plays a role as negative
CC       regulator of adipocyte differentiation, probably acting through
CC       dual mechanisms. May suppress CEBPB-dependent adipogenesis through
CC       direct interaction and PPARG-dependent adipogenesis through
CC       competition for DNA-binding. Downstream of IL6 and TGFB and
CC       synergistically with RORC isoform 2, is implicated in the lineage
CC       specification of uncommitted CD4(+) T-helper (T(H)) cells into
CC       T(H)17 cells, antagonizing the T(H)1 program. Probably regulates
CC       IL17 and IL17F expression on T(H) by binding to the essential
CC       enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F
CC       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-
CC       inflammatory role by inducing CHUK expression and inhibiting NF-
CC       kappa-B signaling. {ECO:0000269|PubMed:11053433,
CC       ECO:0000269|PubMed:14687547, ECO:0000269|PubMed:15821743,
CC       ECO:0000269|PubMed:17666523, ECO:0000269|PubMed:18055760,
CC       ECO:0000269|PubMed:18164222, ECO:0000269|PubMed:18441015,
CC       ECO:0000269|PubMed:19014374, ECO:0000269|PubMed:19324970,
CC       ECO:0000269|PubMed:19965867, ECO:0000269|PubMed:21499262,
CC       ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:22753030,
CC       ECO:0000269|PubMed:23172836, ECO:0000269|PubMed:23723244}.
CC   -!- SUBUNIT: Monomer. Interacts (via the DNA-binding domain) with
CC       HIF1A; the interaction enhances HIF1A transcription under hypoxia
CC       through increasing protein stability. Interacts with CEBPB; the
CC       interaction disrupts the interaction CEBPB:EP300. Interacts with
CC       the coactivators NCOA2, PPARGC1A (via LXXLL motif), EP300 and
CC       MED1. Interacts with the corepressor NCOR1. Interacts with MAGED1
CC       and CTNNB1. Interacts with CRY1 and PER2. Interacts (via AF-2
CC       motif) with PROX1. Interacts with NRIP1.
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       P54254:Atxn1; NbExp=3; IntAct=EBI-1169722, EBI-1169713;
CC       Q9QYH6:Maged1; NbExp=5; IntAct=EBI-1169722, EBI-1801274;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
CC       ProRule:PRU00407, ECO:0000269|PubMed:22753030,
CC       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
CC       the 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 E12.5. In
CC       the developing retina, first expressed at E17 in the ganglion cell
CC       layer. At P3, expressed in the inner border of the neuroblasitic
CC       border (presumptive amacrine cells). By P6, levels increase in
CC       developing cones. Expression found in the presumptive bipolar
CC       cells by P9. During adipocyte differentiation, expression
CC       gradually increases. {ECO:0000269|PubMed:14687547,
CC       ECO:0000269|PubMed:19014374, ECO:0000269|PubMed:19324970}.
CC   -!- INDUCTION: In T(H) cells, induced upon antigen receptor ligation
CC       in the presence of IL6 and TGB1 (via STAT3). Oscillates diurnally
CC       in central nervous system. In liver, Isoform 1 oscillates
CC       diurnally but not isoform 4. {ECO:0000269|PubMed:18164222,
CC       ECO:0000269|PubMed:21499262, ECO:0000269|PubMed:22753030,
CC       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
CC       in vitro. {ECO:0000250|UniProtKB:P35398}.
CC   -!- PTM: Sumoylated by SENP1 and SENP2. Sumoylation, promoted by
CC       PIAS2, PIAS3, PIAS4 but not PIAS1, enhances the transcriptional
CC       activity. 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
CC       ubiquitin 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
CC       cell development and immune system functioning. This phenotype
CC       exhibits lower body weight, reduced adiposity, decreased plasma
CC       cholesterol, triglyceride and apolipoprotein CIII levels, and is
CC       resistant to diet-induced obesity. Also has abnormal circadian
CC       rhythms.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC       subfamily. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH03757.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=CAA69930.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; 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   UniGene; Mm.378450; -.
DR   UniGene; Mm.391890; -.
DR   UniGene; Mm.427266; -.
DR   UniGene; Mm.445802; -.
DR   UniGene; Mm.491288; -.
DR   ProteinModelPortal; P51448; -.
DR   SMR; P51448; 73-170, 271-511.
DR   BioGrid; 202956; 1.
DR   DIP; DIP-35351N; -.
DR   IntAct; P51448; 2.
DR   PhosphoSite; P51448; -.
DR   PRIDE; P51448; -.
DR   Ensembl; ENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238. [P51448-1]
DR   Ensembl; ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238. [P51448-2]
DR   GeneID; 19883; -.
DR   KEGG; mmu:19883; -.
DR   UCSC; uc009qmx.1; mouse. [P51448-1]
DR   CTD; 6095; -.
DR   MGI; MGI:104661; Rora.
DR   eggNOG; NOG324222; -.
DR   GeneTree; ENSGT00760000119049; -.
DR   HOGENOM; HOG000010200; -.
DR   HOVERGEN; HBG106848; -.
DR   InParanoid; P51448; -.
DR   KO; K08532; -.
DR   OMA; GHCLTGQ; -.
DR   OrthoDB; EOG79PJNW; -.
DR   PhylomeDB; P51448; -.
DR   TreeFam; TF319910; -.
DR   Reactome; REACT_118837; Rora activates circadian gene expression.
DR   Reactome; REACT_198351; RORA activates circadian gene expression.
DR   Reactome; REACT_198352; REV-ERBA represses gene expression.
DR   Reactome; REACT_198602; PPARA activates gene expression.
DR   Reactome; REACT_234105; Nuclear Receptor transcription pathway.
DR   Reactome; REACT_241925; Circadian Clock.
DR   Reactome; REACT_24972; Circadian Clock.
DR   ChiTaRS; Rora; mouse.
DR   NextBio; 297388; -.
DR   PRO; PR:P51448; -.
DR   Bgee; P51448; -.
DR   CleanEx; MM_RORA; -.
DR   ExpressionAtlas; P51448; baseline and differential.
DR   Genevestigator; P51448; -.
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:0098531; F:direct ligand regulated sequence-specific DNA binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0004879; F:ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; IEA:InterPro.
DR   GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:UniProtKB.
DR   GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
DR   GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
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:0036315; P:cellular response to sterol; ISS:UniProtKB.
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: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:UniProtKB.
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 from RNA polymerase II promoter; IDA:MGI.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0010575; P:positive regulation vascular endothelial growth factor production; ISS:UniProtKB.
DR   GO; GO:2000188; P:regulation of cholesterol homeostasis; IMP: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:0060850; P:regulation of transcription involved in cell fate commitment; IDA:UniProtKB.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0072539; P:T-helper 17 cell differentiation; IMP:UniProtKB.
DR   GO; GO:0070328; P:triglyceride homeostasis; IMP:UniProtKB.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IMP:UniProtKB.
DR   Gene3D; 1.10.565.10; -; 2.
DR   Gene3D; 3.30.50.10; -; 1.
DR   InterPro; IPR008946; Nucl_hormone_rcpt_ligand-bd.
DR   InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd_core.
DR   InterPro; IPR003079; ROR_rcpt.
DR   InterPro; IPR001723; Str_hrmn_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; 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   Complete proteome; Direct protein sequencing; Disease mutation;
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       Nuclear receptor ROR-alpha.
FT                                /FTId=PRO_0000053513.
FT   DNA_BIND     73    138       Nuclear receptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00407}.
FT   ZN_FING      73     93       NR C4-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00407}.
FT   ZN_FING     109    133       NR C4-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00407}.
FT   REGION      139    271       Hinge.
FT   REGION      272    523       Ligand-binding.
FT   MOTIF       506    511       AF-2.
FT   COMPBIAS    101    175       Gln-rich.
FT   MOD_RES      38     38       N6-methyllysine. {ECO:0000250}.
FT   MOD_RES     183    183       Phosphothreonine; by MAPK1.
FT                                {ECO:0000250}.
FT   CROSSLNK    240    240       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000250}.
FT   VAR_SEQ       1     66       MESAPAAPDPAASEPGSSGSEAAAGSRETPLTQDTGRKSEA
FT                                PGAGRRQSYASSSRGISVTKKTHTS -> MYFVIAAMKA
FT                                (in isoform 4).
FT                                {ECO:0000303|PubMed:15489334,
FT                                ECO:0000303|PubMed:7935491,
FT                                ECO:0000303|PubMed:8750880,
FT                                ECO:0000303|PubMed:9226375}.
FT                                /FTId=VSP_003658.
FT   VARIANT     275    314       Missing (in SG; disturbance of Purkinje
FT                                cell and muscle development, lipid
FT                                metabolism, circadian behavior and immune
FT                                system functioning).
FT                                {ECO:0000269|PubMed:9226375}.
FT   CONFLICT    163    163       H -> R (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    180    181       EP -> T (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    182    182       L -> I (in Ref. 4; AAB46801/BAA22970).
FT                                {ECO:0000305}.
FT   CONFLICT    193    194       LT -> SA (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    304    304       L -> W (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    315    315       Missing (in Ref. 4; AAB46801/BAA22970).
FT                                {ECO:0000305}.
FT   CONFLICT    362    362       E -> G (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    433    433       R -> P (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    450    451       QL -> HM (in Ref. 2; CAA69930).
FT                                {ECO:0000305}.
FT   CONFLICT    487    487       K -> N (in Ref. 4; AAB46801/BAA22970).
FT                                {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
//
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