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 08-NOV-2023, entry version 176. 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, 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}; 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; 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; 10116-ENSRNOP00000018137; -. DR UCSC; RGD:1306778; rat. [P45446-2] DR AGR; RGD:1306778; -. 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: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:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. 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:0060221; P:retinal rod cell differentiation; ISO:RGD. DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW. 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 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 PANTHER; PTHR45805; NUCLEAR HORMONE RECEPTOR HR3-RELATED; 1. DR PANTHER; PTHR45805:SF6; NUCLEAR RECEPTOR ROR-BETA; 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; 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 //