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 01-MAY-2013, entry version 129.
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=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 ALPHA-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 ALPHA-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 ALPHA-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 ALPHA-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 ALPHA-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 MASS SPECTROMETRY.
RC STRAIN=C57BL/6; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [7]
RP FUNCTION, AND CHARACTERIZATION 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, AND CHARACTERIZATION OF VARIANT SG 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 [9]
RP FUNCTION.
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 [10]
RP FUNCTION, TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT SG
RP 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 [11]
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).
CC -!- FUNCTION: Orphan nuclear receptor. Binds DNA as a monomer to
CC hormone response elements (HRE) containing a single core motif
CC half-site preceded by a short A-T-rich sequence. This isomer binds
CC to the consensus sequence 5'-[AT][TA]A[AT][CGT]TAGGTCA-3'.
CC Regulates a number of genes involved in lipid metabolism such as
CC apolipoproteins AI, APOA5, CIII, CYP71 and PPARgamma, in
CC cerebellum and photoreceptor development including PCP2, OPN1SW,
CC OPN1SM AND ARR3, in circadian rhythm with BMAL1, and skeletal
CC muscle development with MYOD1. Possible receptor for cholesterol
CC or one of its derivatives (By similarity).
CC -!- ENZYME REGULATION: Activated by CaMK4 (By similarity).
CC -!- SUBUNIT: Monomer. Interacts (via the DNA-binding domain) with
CC HIF1; the interaction enhances HIF1A transcription under hypoxia
CC through increasing protein stability (By similarity).
CC -!- INTERACTION:
CC P54254:Atxn1; NbExp=3; IntAct=EBI-1169722, EBI-1169713;
CC -!- SUBCELLULAR LOCATION: Nucleus (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Alpha-1;
CC IsoId=P51448-1; Sequence=Displayed;
CC Name=Alpha-2;
CC IsoId=P51448-3; Sequence=Not described;
CC Name=Alpha-3;
CC IsoId=P51448-4; Sequence=Not described;
CC Name=Alpha-4;
CC IsoId=P51448-2; Sequence=VSP_003658;
CC -!- TISSUE SPECIFICITY: Expressed in cerebellum, liver, lung, kidney
CC and retina.
CC -!- DEVELOPMENTAL STAGE: In the developing retina, first expressed at
CC E17 in the ganglion cell layer. At P3, expressed in the inner
CC border of the neuroblasitic border (presumptive amacrine cells).
CC By P6, levels increase in developing cones. Expression found in
CC the presumptive bipolar cells by P9.
CC -!- PTM: Phosphorylation by PKC in neurons inhibits transcriptional
CC activity. Phosphorylated on Thr-183 by ERK2 in vitro (By
CC similarity).
CC -!- PTM: Sumoylated by SENP1 and SENP2. Sumoylation, promoted by
CC PIAS2, PIAS3, PIASy but not PIAS1, enhances the transcriptional
CC activity. Desumoylated by SENP1 (By similarity).
CC -!- PTM: Ubiquitinated. Ubiquitination is required for efficient
CC transcriptional activity and is prevented by Hairless (By
CC similarity).
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.
CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03757.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAA69930.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 IPI; IPI00122512; -.
DR IPI; IPI00395039; -.
DR PIR; S68517; S68517.
DR RefSeq; NP_038674.1; NM_013646.1.
DR UniGene; Mm.378450; -.
DR UniGene; Mm.391890; -.
DR UniGene; Mm.427266; -.
DR UniGene; Mm.490614; -.
DR ProteinModelPortal; P51448; -.
DR SMR; P51448; 73-147, 271-511.
DR DIP; DIP-35351N; -.
DR IntAct; P51448; 2.
DR PhosphoSite; P51448; -.
DR PRIDE; P51448; -.
DR Ensembl; ENSMUST00000034766; ENSMUSP00000034766; ENSMUSG00000032238.
DR Ensembl; ENSMUST00000113624; ENSMUSP00000109254; ENSMUSG00000032238.
DR GeneID; 19883; -.
DR KEGG; mmu:19883; -.
DR CTD; 6095; -.
DR MGI; MGI:104661; Rora.
DR eggNOG; NOG324222; -.
DR GeneTree; ENSGT00700000104109; -.
DR HOGENOM; HOG000010200; -.
DR HOVERGEN; HBG106848; -.
DR InParanoid; P51448; -.
DR KO; K08532; -.
DR OMA; VAAQIEI; -.
DR OrthoDB; EOG4GHZP3; -.
DR Reactome; REACT_109335; Circadian Clock.
DR Reactome; REACT_24972; Circadian Clock (mouse).
DR ChiTaRS; RORA; mouse.
DR NextBio; 297388; -.
DR ArrayExpress; P51448; -.
DR Bgee; P51448; -.
DR CleanEx; MM_RORA; -.
DR Genevestigator; P51448; -.
DR GermOnline; ENSMUSG00000032238; Mus musculus.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0004879; F:ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:MGI.
DR GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IMP:MGI.
DR GO; GO:0046068; P:cGMP metabolic process; IMP:MGI.
DR GO; GO:0030522; P:intracellular receptor mediated signaling pathway; IEA:GOC.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:MGI.
DR GO; GO:0043030; P:regulation of macrophage activation; IMP:MGI.
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; Str_ncl_receptor; 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 splicing; Complete proteome;
KW Direct protein sequencing; Disease mutation; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1 523 Nuclear receptor ROR-alpha.
FT /FTId=PRO_0000053513.
FT DNA_BIND 73 138 Nuclear receptor.
FT ZN_FING 73 93 NR C4-type.
FT ZN_FING 109 133 NR C4-type.
FT REGION 1 72 Modulating.
FT REGION 139 271 Hinge.
FT REGION 272 523 Ligand-binding.
FT COMPBIAS 101 175 Gln-rich.
FT CROSSLNK 240 240 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT VAR_SEQ 1 66 MESAPAAPDPAASEPGSSGSEAAAGSRETPLTQDTGRKSEA
FT PGAGRRQSYASSSRGISVTKKTHTS -> MYFVIAAMKA
FT (in isoform Alpha-4).
FT /FTId=VSP_003658.
FT VARIANT 275 314 Missing (in SG; disturbance of Purkinje
FT cell development and immune system
FT functioning).
FT CONFLICT 163 163 H -> R (in Ref. 2; CAA69930).
FT CONFLICT 180 181 EP -> T (in Ref. 2; CAA69930).
FT CONFLICT 182 182 L -> I (in Ref. 4; AAB46801/BAA22970).
FT CONFLICT 193 194 LT -> SA (in Ref. 2; CAA69930).
FT CONFLICT 304 304 L -> W (in Ref. 2; CAA69930).
FT CONFLICT 315 315 Missing (in Ref. 4; AAB46801/BAA22970).
FT CONFLICT 362 362 E -> G (in Ref. 2; CAA69930).
FT CONFLICT 433 433 R -> P (in Ref. 2; CAA69930).
FT CONFLICT 450 451 QL -> HM (in Ref. 2; CAA69930).
FT CONFLICT 487 487 K -> N (in Ref. 4; AAB46801/BAA22970).
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
//
