ID   RORB_HUMAN              Reviewed;         470 AA.
AC   Q92753; Q8WX73;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   24-JAN-2024, entry version 198.
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   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Retina;
RA   Becker-Andre M.;
RL   Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Retina;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [4]
RP   INVOLVEMENT IN EIG15, VARIANTS EIG15 77-ARG--LYS-470 DEL; PRO-84 AND
RP   LEU-428 DEL, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT
RP   77-ARG--LYS-470 DEL.
RX   PubMed=27352968; DOI=10.1038/ejhg.2016.80;
RA   Rudolf G., Lesca G., Mehrjouy M.M., Labalme A., Salmi M., Bache I.,
RA   Bruneau N., Pendziwiat M., Fluss J., de Bellescize J., Scholly J.,
RA   Moeller R.S., Craiu D., Tommerup N., Valenti-Hirsch M.P.,
RA   Schluth-Bolard C., Sloan-Bena F., Helbig K.L., Weckhuysen S., Edery P.,
RA   Coulbaut S., Abbas M., Scheffer I.E., Tang S., Myers C.T., Stamberger H.,
RA   Carvill G.L., Shinde D.N., Mefford H.C., Neagu E., Huether R., Lu H.M.,
RA   Dica A., Cohen J.S., Iliescu C., Pomeran C., Rubenstein J., Helbig I.,
RA   Sanlaville D., Hirsch E., Szepetowski P.;
RT   "Loss of function of the retinoid-related nuclear receptor (RORB) gene and
RT   epilepsy.";
RL   Eur. J. Hum. Genet. 24:1761-1770(2016).
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 (By similarity).
CC       {ECO:0000250|UniProtKB:P45446}.
CC   -!- FUNCTION: Isoform 1 is 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:0000250|UniProtKB:P45446}.
CC   -!- INTERACTION:
CC       Q92753; O08785: Clock; Xeno; NbExp=2; IntAct=EBI-6144615, EBI-79859;
CC       Q92753-1; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-18560266, EBI-11954519;
CC       Q92753-1; Q9BSW2: CRACR2A; NbExp=3; IntAct=EBI-18560266, EBI-739773;
CC       Q92753-1; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-18560266, EBI-7960826;
CC       Q92753-1; Q9BYR2: KRTAP4-5; NbExp=3; IntAct=EBI-18560266, EBI-11993254;
CC       Q92753-1; P06239-3: LCK; NbExp=3; IntAct=EBI-18560266, EBI-13287659;
CC       Q92753-1; Q96JN0-2: LCOR; NbExp=3; IntAct=EBI-18560266, EBI-10961483;
CC       Q92753-1; Q71SY5: MED25; NbExp=3; IntAct=EBI-18560266, EBI-394558;
CC       Q92753-1; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-18560266, EBI-10172526;
CC       Q92753-1; P62195: PSMC5; NbExp=3; IntAct=EBI-18560266, EBI-357745;
CC       Q92753-1; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-18560266, EBI-748391;
CC       Q92753-1; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-18560266, EBI-358489;
CC       Q92753-1; O94964-4: SOGA1; NbExp=3; IntAct=EBI-18560266, EBI-14083835;
CC       Q92753-1; Q96M29: TEKT5; NbExp=3; IntAct=EBI-18560266, EBI-10239812;
CC       Q92753-1; Q08117-2: TLE5; NbExp=3; IntAct=EBI-18560266, EBI-11741437;
CC       Q92753-1; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-18560266, EBI-10241197;
CC       Q92753-1; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-18560266, EBI-740727;
CC       Q92753-1; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-18560266, EBI-6427977;
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC       {ECO:0000269|PubMed:27352968}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage; Named isoforms=2;
CC       Name=2;
CC         IsoId=Q92753-2; Sequence=Displayed;
CC       Name=1;
CC         IsoId=Q92753-1; Sequence=VSP_022575;
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. {ECO:0000250|UniProtKB:P45446}.
CC   -!- DISEASE: Epilepsy, idiopathic generalized 15 (EIG15) [MIM:618357]: An
CC       autosomal dominant form of idiopathic generalized epilepsy, a disorder
CC       characterized by recurring generalized seizures in the absence of
CC       detectable brain lesions and/or metabolic abnormalities. Generalized
CC       seizures arise diffusely and simultaneously from both hemispheres of
CC       the brain. Seizure types include juvenile myoclonic seizures, absence
CC       seizures, and generalized tonic-clonic seizures. EIG15 is characterized
CC       by onset of variable types of seizures in the first decade of life.
CC       {ECO:0000269|PubMed:27352968}. Note=Disease susceptibility is
CC       associated with variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC       subfamily. {ECO:0000305}.
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DR   EMBL; Y08639; CAA69929.1; -; mRNA.
DR   EMBL; BX647070; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AL137018; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS6646.1; -. [Q92753-1]
DR   CCDS; CCDS94422.1; -. [Q92753-2]
DR   AlphaFoldDB; Q92753; -.
DR   SMR; Q92753; -.
DR   IntAct; Q92753; 21.
DR   STRING; 9606.ENSP00000366093; -.
DR   BindingDB; Q92753; -.
DR   ChEMBL; CHEMBL3091268; -.
DR   DrugBank; DB01065; Melatonin.
DR   DrugCentral; Q92753; -.
DR   GuidetoPHARMACOLOGY; 599; -.
DR   GlyGen; Q92753; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q92753; -.
DR   PhosphoSitePlus; Q92753; -.
DR   BioMuta; RORB; -.
DR   DMDM; 124028630; -.
DR   MassIVE; Q92753; -.
DR   PaxDb; 9606-ENSP00000366093; -.
DR   PeptideAtlas; Q92753; -.
DR   ProteomicsDB; 75444; -. [Q92753-2]
DR   ProteomicsDB; 75445; -. [Q92753-1]
DR   Antibodypedia; 1699; 464 antibodies from 31 providers.
DR   DNASU; 6096; -.
DR   Ensembl; ENST00000376896.8; ENSP00000366093.2; ENSG00000198963.11. [Q92753-1]
DR   Ensembl; ENST00000396204.2; ENSP00000379507.2; ENSG00000198963.11. [Q92753-2]
DR   MANE-Select; ENST00000376896.8; ENSP00000366093.2; NM_006914.4; NP_008845.2. [Q92753-1]
DR   UCSC; uc004ajh.4; human. [Q92753-2]
DR   AGR; HGNC:10259; -.
DR   GeneCards; RORB; -.
DR   HGNC; HGNC:10259; RORB.
DR   HPA; ENSG00000198963; Tissue enriched (retina).
DR   MalaCards; RORB; -.
DR   MIM; 601972; gene.
DR   MIM; 618357; phenotype.
DR   neXtProt; NX_Q92753; -.
DR   OpenTargets; ENSG00000198963; -.
DR   PharmGKB; PA34631; -.
DR   VEuPathDB; HostDB:ENSG00000198963; -.
DR   eggNOG; KOG4216; Eukaryota.
DR   GeneTree; ENSGT00940000157708; -.
DR   HOGENOM; CLU_007368_2_0_1; -.
DR   InParanoid; Q92753; -.
DR   OMA; WEQLHDY; -.
DR   OrthoDB; 3475284at2759; -.
DR   PhylomeDB; Q92753; -.
DR   TreeFam; TF319910; -.
DR   PathwayCommons; Q92753; -.
DR   Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR   SignaLink; Q92753; -.
DR   SIGNOR; Q92753; -.
DR   ChiTaRS; RORB; human.
DR   Pharos; Q92753; Tchem.
DR   PRO; PR:Q92753; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; Q92753; Protein.
DR   Bgee; ENSG00000198963; Expressed in endothelial cell and 149 other cell types or tissues.
DR   ExpressionAtlas; Q92753; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR   GO; GO:0008502; F:melatonin receptor activity; IBA:GO_Central.
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; IBA:GO_Central.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
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; ISS:UniProtKB.
DR   GO; GO:0042462; P:eye photoreceptor cell development; ISS:UniProtKB.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:ProtInc.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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:0048511; P:rhythmic process; IEA:UniProtKB-KW.
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   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.
DR   Genevisible; Q92753; HS.
PE   1: Evidence at protein level;
KW   Activator; Alternative promoter usage; Biological rhythms;
KW   Developmental protein; Disease variant; DNA-binding; Epilepsy;
KW   Metal-binding; Nucleus; Receptor; Reference proteome; Sensory transduction;
KW   Transcription; Transcription regulation; Vision; Zinc; Zinc-finger.
FT   CHAIN           1..470
FT                   /note="Nuclear receptor ROR-beta"
FT                   /id="PRO_0000053514"
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="MCENQLKTKADAT -> MR (in isoform 1)"
FT                   /evidence="ECO:0000303|Ref.1"
FT                   /id="VSP_022575"
FT   VARIANT         77..470
FT                   /note="Missing (in EIG15; loss of subcellular location in
FT                   the nucleoplasm)"
FT                   /evidence="ECO:0000269|PubMed:27352968"
FT                   /id="VAR_082061"
FT   VARIANT         84
FT                   /note="L -> P (in EIG15; dbSNP:rs869312971)"
FT                   /evidence="ECO:0000269|PubMed:27352968"
FT                   /id="VAR_082062"
FT   VARIANT         428
FT                   /note="Missing (in EIG15; uncertain significance;
FT                   dbSNP:rs869312972)"
FT                   /evidence="ECO:0000269|PubMed:27352968"
FT                   /id="VAR_082063"
FT   CONFLICT        121
FT                   /note="Q -> E (in Ref. 1; CAA69929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128
FT                   /note="A -> R (in Ref. 1; CAA69929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        156
FT                   /note="H -> S (in Ref. 1; CAA69929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        170
FT                   /note="D -> V (in Ref. 1; CAA69929)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        468
FT                   /note="G -> A (in Ref. 1; CAA69929)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   470 AA;  53220 MW;  F41FAF95FA5E7100 CRC64;
     MCENQLKTKA DATAQIEVIP CKICGDKSSG IHYGVITCEG CKGFFRRSQQ NNASYSCPRQ
     RNCLIDRTNR NRCQHCRLQK CLALGMSRDA VKFGRMSKKQ RDSLYAEVQK HQQRLQEQRQ
     QQSGEAEALA RVYSSSISNG LSNLNNETSG TYANGHVIDL PKSEGYYNVD SGQPSPDQSG
     LDMTGIKQIK QEPIYDLTSV PNLFTYSSFN NGQLAPGITM TEIDRIAQNI IKSHLETCQY
     TMEELHQLAW QTHTYEEIKA YQSKSREALW QQCAIQITHA IQYVVEFAKR ITGFMELCQN
     DQILLLKSGC LEVVLVRMCR AFNPLNNTVL FEGKYGGMQM FKALGSDDLV NEAFDFAKNL
     CSLQLTEEEI ALFSSAVLIS PDRAWLIEPR KVQKLQEKIY FALQHVIQKN HLDDETLAKL
     IAKIPTITAV CNLHGEKLQV FKQSHPEIVN TLFPPLYKEL FNPDCATGCK
//