RORB_RAT
ID RORB_RAT Reviewed; 470 AA.
AC P45446;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 171.
DE RecName: Full=Nuclear receptor ROR-beta;
DE AltName: Full=Nuclear receptor RZR-beta;
DE AltName: Full=Nuclear receptor subfamily 1 group F member 2;
DE AltName: Full=Retinoid-related orphan receptor-beta;
GN Name=Rorb; Synonyms=Nr1f2, Rzrb;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION AS TRANSCRIPTION ACTIVATOR
RP (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, DNA-BINDING, AND INDUCTION.
RX PubMed=9729429; DOI=10.1016/s0378-1119(98)00348-5;
RA Andre E., Gawlas K., Becker-Andre M.;
RT "A novel isoform of the orphan nuclear receptor RORbeta is specifically
RT expressed in pineal gland and retina.";
RL Gene 216:277-283(1998).
RN [3]
RP FUNCTION AS TRANSCRIPTION MODULATOR, SUBUNIT, DNA-BINDING, AND DOMAIN.
RX PubMed=8816759; DOI=10.1073/pnas.93.19.10105;
RA Greiner E.F., Kirfel J., Greschik H., Doerflinger U., Becker P., Mercep A.,
RA Schuele R.;
RT "Functional analysis of retinoid Z receptor beta, a brain-specific nuclear
RT orphan receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10105-10110(1996).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=9670004; DOI=10.1093/emboj/17.14.3867;
RA Andre E., Conquet F., Steinmayr M., Stratton S.C., Porciatti V.,
RA Becker-Andre M.;
RT "Disruption of retinoid-related orphan receptor beta changes circadian
RT behavior, causes retinal degeneration and leads to vacillans phenotype in
RT mice.";
RL EMBO J. 17:3867-3877(1998).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 212-463 IN COMPLEX WITH STEARIC
RP ACID AND NCOA1 PEPTIDE, DOMAIN, AND MUTAGENESIS OF ALA-280; TYR-457 AND
RP GLU-459.
RX PubMed=11689423; DOI=10.1093/emboj/20.21.5822;
RA Stehlin C., Wurtz J.-M., Steinmetz A., Greiner E., Schuele R., Moras D.,
RA Renaud J.-P.;
RT "X-ray structure of the orphan nuclear receptor RORbeta ligand-binding
RT domain in the active conformation.";
RL EMBO J. 20:5822-5831(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 219-462 IN COMPLEX WITH RETINOIC
RP ACID AND PEPTIDE SRC-1, FUNCTION AS TRANSCRIPTION ACTIVATOR, AND
RP IDENTIFICATION OF LIGANDS.
RX PubMed=12958591; DOI=10.1038/nsb979;
RA Stehlin-Gaon C., Willmann D., Zeyer D., Sanglier S., van Dorsselaer A.,
RA Renaud J.-P., Moras D., Schule R.;
RT "All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR
RT beta.";
RL Nat. Struct. Biol. 10:820-825(2003).
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. Considered to have intrinsic
CC transcriptional activity, have some natural ligands such as all-trans
CC retinoic acid (ATRA) and other retinoids which act as inverse agonists
CC repressing the transcriptional activity. Required for normal postnatal
CC development of rod and cone photoreceptor cells. Modulates rod
CC photoreceptors differentiation at least by inducing the transcription
CC factor NRL-mediated pathway. In cone photoreceptor cells, regulates
CC transcription of OPN1SW. Involved in the regulation of the period
CC length and stability of the circadian rhythm. May control
CC cytoarchitectural patterning of neocortical neurons during development.
CC May act in a dose-dependent manner to regulate barrel formation upon
CC innervation of layer IV neurons by thalamocortical axons. May play a
CC role in the suppression of osteoblastic differentiation through the
CC inhibition of RUNX2 transcriptional activity.
CC {ECO:0000269|PubMed:12958591, ECO:0000269|PubMed:8816759}.
CC -!- FUNCTION: [Isoform 1]: Critical for hindlimb motor control and for the
CC differentiation of amacrine and horizontal cells in the retina.
CC Regulates the expression of PTF1A synergistically with FOXN4 (By
CC similarity). {ECO:0000250|UniProtKB:Q8R1B8}.
CC -!- SUBUNIT: Monomer. Interacts with CRX. {ECO:0000269|PubMed:11689423,
CC ECO:0000269|PubMed:12958591, ECO:0000269|PubMed:8816759}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q92753}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=2; Synonyms=ROR-beta 2;
CC IsoId=P45446-2; Sequence=Displayed;
CC Name=1; Synonyms=ROR-beta 1;
CC IsoId=P45446-1; Sequence=VSP_022577;
CC -!- TISSUE SPECIFICITY: Isoform 2 expressed with circadian rhythm in eye
CC and pineal gland. Isoform 1 expressed in retina cortex, thalamus, and
CC hypothalamus. {ECO:0000269|PubMed:9670004, ECO:0000269|PubMed:9729429}.
CC -!- INDUCTION: [Isoform 2]: Oscillates diurnally in eye and pineal gland,
CC with highest levels shortly after midnight.
CC {ECO:0000269|PubMed:9729429}.
CC -!- DOMAIN: AF-2 (activation function-2) motif is required for recruiting
CC coregulators containing the LXXLL motif, such as NCOA1, and control the
CC transactivational activity (PubMed:8816759 and PubMed:11689423).
CC {ECO:0000269|PubMed:11689423, ECO:0000269|PubMed:8816759}.
CC -!- MISCELLANEOUS: [Isoform 2]: Shows a 4-fold higher transcriptional
CC activation of an optimal promoter compared to isoform 1.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA42095.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L14610; AAA42095.1; ALT_INIT; Genomic_DNA.
DR PIR; I65219; I65219.
DR PDB; 1K4W; X-ray; 1.90 A; A=212-463.
DR PDB; 1N4H; X-ray; 2.10 A; A=212-470.
DR PDB; 1NQ7; X-ray; 1.50 A; A=219-462.
DR PDBsum; 1K4W; -.
DR PDBsum; 1N4H; -.
DR PDBsum; 1NQ7; -.
DR AlphaFoldDB; P45446; -.
DR SMR; P45446; -.
DR STRING; 10116.ENSRNOP00000018137; -.
DR BindingDB; P45446; -.
DR ChEMBL; CHEMBL4105721; -.
DR PhosphoSitePlus; P45446; -.
DR PaxDb; P45446; -.
DR UCSC; RGD:1306778; rat. [P45446-2]
DR RGD; 1306778; Rorb.
DR eggNOG; KOG4216; Eukaryota.
DR InParanoid; P45446; -.
DR PhylomeDB; P45446; -.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR EvolutionaryTrace; P45446; -.
DR PRO; PR:P45446; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0008502; F:melatonin receptor activity; IDA:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035881; P:amacrine cell differentiation; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:RGD.
DR GO; GO:0042462; P:eye photoreceptor cell development; ISS:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0060041; P:retina development in camera-type eye; ISS:UniProtKB.
DR GO; GO:0046549; P:retinal cone cell development; ISS:UniProtKB.
DR GO; GO:0046548; P:retinal rod cell development; ISS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd06968; NR_DBD_ROR; 1.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR IDEAL; IID50142; -.
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 3D-structure; Activator; Alternative promoter usage; Biological rhythms;
KW Developmental protein; DNA-binding; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Sensory transduction; Transcription;
KW Transcription regulation; Vision; Zinc; Zinc-finger.
FT CHAIN 1..470
FT /note="Nuclear receptor ROR-beta"
FT /id="PRO_0000053516"
FT DOMAIN 222..460
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 18..93
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 21..41
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 57..81
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 104..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 456..461
FT /note="AF-2"
FT VAR_SEQ 1..13
FT /note="MCENQLKTKADGT -> MR (in isoform 1)"
FT /evidence="ECO:0000305"
FT /id="VSP_022577"
FT MUTAGEN 280
FT /note="A->F,V,S: Inhibits transactivation activity."
FT /evidence="ECO:0000269|PubMed:11689423"
FT MUTAGEN 280
FT /note="A->G: No effect on transactivation activity."
FT /evidence="ECO:0000269|PubMed:11689423"
FT MUTAGEN 457
FT /note="Y->A: Inhibits transactivation activity."
FT /evidence="ECO:0000269|PubMed:11689423"
FT MUTAGEN 459
FT /note="E->A: Inhibits transactivation activity."
FT /evidence="ECO:0000269|PubMed:11689423"
FT HELIX 220..237
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 242..248
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 255..263
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 266..289
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 299..318
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:1NQ7"
FT TURN 324..327
FT /evidence="ECO:0007829|PDB:1NQ7"
FT STRAND 328..331
FT /evidence="ECO:0007829|PDB:1NQ7"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 338..344
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 347..361
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 367..378
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 389..410
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 416..422
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 424..444
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 446..451
FT /evidence="ECO:0007829|PDB:1NQ7"
FT HELIX 455..461
FT /evidence="ECO:0007829|PDB:1NQ7"
SQ SEQUENCE 470 AA; 53201 MW; FC31D327410FF310 CRC64;
MCENQLKTKA DGTAQIEVIP CKICGDKSSG IHYGVITCEG CKGFFRRSQQ NNASYSCPRQ
RNCLIDRTNR NRCQHCRLQK CLALGMSRDA VKFGRMSKKQ RDSLYAEVQK HQQRLQEQRQ
QQSGEAEALA RVYSSSISNG LSNLNTETGG TYANGHVIDL PKSEGYYNID SGQPSPDQSG
LDMTGIKQIK QEPIYDLTSV HNLFTYSSFN NGQLAPGITM SEIDRIAQNI IKSHLETCQY
TMEELHQLAW QTHTYEEIKA YQSKSREALW QQCAIQITHA IQYVVEFAKR ITGFMELCQN
DQILLLKSGC LEVVLVRMCR AFNPLNNTVL FEGKYGGMQM FKALGSDDLV NEAFDFAKNL
CSLQLTEEEI ALFSSAVLIS PDRAWLLEPR KVQKLQEKIY FALQHVIQKN HLDDETLAKL
IAKIPTITAV CNLHGEKLQV FKQSHPDIVN TLFPPLYKEL FNPDCAAVCK
