RORAA_DANRE
ID RORAA_DANRE Reviewed; 468 AA.
AC F1QLY4; A7VL70; F8W254;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 2.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Nuclear receptor ROR-alpha A;
DE AltName: Full=Retinoid-related orphan receptor alpha 2 {ECO:0000303|PubMed:17685489};
DE AltName: Full=Retinoid-related orphan receptor-alpha A;
GN Name=roraa; Synonyms=rora2 {ECO:0000303|PubMed:17685489};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=17685489; DOI=10.1002/dvdy.21275;
RA Katsuyama Y., Oomiya Y., Dekimoto H., Motooka E., Takano A., Kikkawa S.,
RA Hibi M., Terashima T.;
RT "Expression of zebrafish ROR alpha gene in cerebellar-like structures.";
RL Dev. Dyn. 236:2694-2701(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29656859; DOI=10.1016/j.ajhg.2018.02.021;
RA Guissart C., Latypova X., Rollier P., Khan T.N., Stamberger H.,
RA McWalter K., Cho M.T., Kjaergaard S., Weckhuysen S., Lesca G., Besnard T.,
RA Ounap K., Schema L., Chiocchetti A.G., McDonald M., de Bellescize J.,
RA Vincent M., Van Esch H., Sattler S., Forghani I., Thiffault I.,
RA Freitag C.M., Barbouth D.S., Cadieux-Dion M., Willaert R.,
RA Guillen Sacoto M.J., Safina N.P., Dubourg C., Grote L., Carre W.,
RA Saunders C., Pajusalu S., Farrow E., Boland A., Karlowicz D.H.,
RA Deleuze J.F., Wojcik M.H., Pressman R., Isidor B., Vogels A.,
RA Van Paesschen W., Al-Gazali L., Al Shamsi A.M., Claustres M., Pujol A.,
RA Sanders S.J., Rivier F., Leboucq N., Cogne B., Sasorith S., Sanlaville D.,
RA Retterer K., Odent S., Katsanis N., Bezieau S., Koenig M., Davis E.E.,
RA Pasquier L., Kuery S.;
RT "Dual molecular effects of dominant RORA mutations cause two variants of
RT syndromic intellectual disability with either autism or cerebellar
RT ataxia.";
RL Am. J. Hum. Genet. 102:744-759(2018).
CC -!- FUNCTION: Nuclear receptor that binds DNA as a monomer to ROR response
CC elements (RORE) (By similarity). Required for proper cerebellum
CC development (PubMed:29656859). {ECO:0000250|UniProtKB:P35398,
CC ECO:0000269|PubMed:29656859}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P35398,
CC ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, in cerebellar-like
CC structures, including Purkinje cells. {ECO:0000269|PubMed:17685489}.
CC -!- DEVELOPMENTAL STAGE: At 2 dpf, strongly expressed in the developing
CC eyes, as well as midbrain and hindbrain regions. In 3 dpf larvae,
CC expressed in the upper rhombic lip. At 3 dpf, expression in the retina
CC is weak and becomes spatially restricted in the inner nuclear layer.
CC Weakly expressed in the forebrain region.
CC {ECO:0000269|PubMed:17685489}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in a
CC reduced cerebellar area and smaller optic tecta area compared to
CC control larvae. At 3 dpf, transgenic larvae present with a
CC significantly decreased size of Purkinje and granule cell layers
CC compared to controls. {ECO:0000269|PubMed:29656859}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; AB298802; BAF76726.1; -; mRNA.
DR EMBL; CABZ01027882; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01027883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01027884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01027885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU468885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001103637.1; NM_001110167.1.
DR AlphaFoldDB; F1QLY4; -.
DR SMR; F1QLY4; -.
DR STRING; 7955.ENSDARP00000106236; -.
DR PaxDb; F1QLY4; -.
DR Ensembl; ENSDART00000121449; ENSDARP00000106236; ENSDARG00000031768.
DR GeneID; 564951; -.
DR KEGG; dre:564951; -.
DR CTD; 564951; -.
DR ZFIN; ZDB-GENE-060306-2; roraa.
DR eggNOG; KOG4216; Eukaryota.
DR GeneTree; ENSGT00940000157387; -.
DR HOGENOM; CLU_007368_2_0_1; -.
DR InParanoid; F1QLY4; -.
DR OMA; VRKQTCS; -.
DR OrthoDB; 583704at2759; -.
DR TreeFam; TF319910; -.
DR Reactome; R-DRE-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-DRE-4090294; SUMOylation of intracellular receptors.
DR PRO; PR:F1QLY4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 25.
DR Bgee; ENSDARG00000031768; Expressed in layer of retina and 33 other tissues.
DR GO; GO:0005634; C:nucleus; 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:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ZFIN.
DR GO; GO:0010468; P:regulation of gene expression; IGI:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0048511; P:rhythmic process; 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 2: Evidence at transcript level;
KW Activator; Biological rhythms; Developmental protein; DNA-binding;
KW Metal-binding; Nucleus; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..468
FT /note="Nuclear receptor ROR-alpha A"
FT /id="PRO_0000445778"
FT DOMAIN 217..455
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 15..90
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 18..38
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 54..73
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 101..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 142..163
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..455
FT /note="AF-2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT COMPBIAS 115..129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 285
FT /note="R -> H (in Ref. 1; BAF76726)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 468 AA; 53116 MW; 8B6A24ED90C91E3E CRC64;
MMYFVISAMK AQIEIIPCKI CGDKSSGIHY GVITCEGCKG FFRRSQQSNA AYSCPRQKNC
LIDRTSRNRC QHCRLQKCLA VGMSRDAVKF GRMSKKQRDS LYAEVQKHRL QQQQRDHQQQ
PGEAEPLTPT YGLSTNGLTE LHDDLSGYMN GHTPDGTKPD SGVSSFYLDI QPSPDQSGLD
INGIKPEPIC DFTPGSGFFP YCSFTNGETS PTVSMAELEH LAQNISKSHM ETCQYLREEL
QQMTWQAFLQ EEVENYQSKP REVMWQLCAI KITEAIQYVV EFAKRIDGFM ELCQNDQIVL
LKAGSLEVVF VRMCRAFDPQ NNTVYFDGKY AGPDVFKSLG CDDLISSVFE FGKNLCSMHL
SEDEIALFSA FVLMSADRSW LQEKVKVEKL QQKIQLALQH VLQKNHREDG ILTKLICKVS
TLRALCSRHT EKLTAFKAIY PDIVRAHFPP LYKELFGSDF EQSMPVDG
