RORB_HUMAN
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 03-AUG-2022, entry version 190.
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 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; Q92753; -.
DR PeptideAtlas; Q92753; -.
DR PRIDE; Q92753; -.
DR ProteomicsDB; 75444; -. [Q92753-2]
DR ProteomicsDB; 75445; -. [Q92753-1]
DR Antibodypedia; 1699; 413 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 GeneCards; RORB; -.
DR HGNC; HGNC:10259; RORB.
DR HPA; ENSG00000198963; Tissue enhanced (brain, 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; TIACKIC; -.
DR OrthoDB; 1412946at2759; -.
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 147 other tissues.
DR ExpressionAtlas; Q92753; baseline and differential.
DR Genevisible; Q92753; HS.
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:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS: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:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc.
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 Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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 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; unknown pathological
FT significance; 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
