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RARAA_DANRE
ID   RARAA_DANRE             Reviewed;         444 AA.
AC   Q90271; Q91391;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2006, sequence version 2.
DT   03-AUG-2022, entry version 149.
DE   RecName: Full=Retinoic acid receptor alpha-A;
DE            Short=RAR-alpha-A;
DE   AltName: Full=Nuclear receptor subfamily 1 group B member 1-A;
DE   AltName: Full=Retinoic acid receptor alpha;
DE            Short=zRAR alpha;
DE   AltName: Full=Retinoic acid receptor alpha-2.A;
DE            Short=RAR-alpha-2.A;
GN   Name=raraa {ECO:0000312|ZFIN:ZDB-GENE-980526-284};
GN   Synonyms=nr1b1a, rara2a {ECO:0000312|ZFIN:ZDB-GENE-980526-284};
GN   ORFNames=zgc:109797;
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] {ECO:0000305, ECO:0000312|EMBL:AAB32276.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP   INDUCTION.
RC   TISSUE=Embryo {ECO:0000269|PubMed:7918098};
RX   PubMed=7918098; DOI=10.1016/0925-4773(94)90082-5;
RA   Joore J., van der Lans G.B.L.J., Lanser P.H., Vervaart J.M.A., Zivkovic D.,
RA   Speksnijder J.E., Kruijer W.;
RT   "Effects of retinoic acid on the expression of retinoic acid receptors
RT   during zebrafish embryogenesis.";
RL   Mech. Dev. 46:137-150(1994).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAA50049.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Gastrula {ECO:0000312|EMBL:AAA50049.1};
RA   Stachel S.E., Kushner P.;
RT   "The molecular characterization of three zebrafish retinoic acid receptor
RT   genes suggests the retinoic acid pathway functions in embryonic hindbrain
RT   development.";
RL   Submitted (DEC-1992) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000305, ECO:0000312|EMBL:AAA50049.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain {ECO:0000312|EMBL:AAH92692.1};
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000305}
RP   DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX   PubMed=16455309; DOI=10.1016/j.modgep.2005.10.007;
RA   Hale L.A., Tallafuss A., Yan Y.-L., Dudley L., Eisen J.S.,
RA   Postlethwait J.H.;
RT   "Characterization of the retinoic acid receptor genes raraa, rarab and rarg
RT   during zebrafish development.";
RL   Gene Expr. Patterns 6:546-555(2006).
RN   [5]
RP   DEVELOPMENTAL STAGE, INDUCTION, AND FUNCTION.
RX   PubMed=18929555; DOI=10.1016/j.ydbio.2008.09.022;
RA   Linville A., Radtke K., Waxman J.S., Yelon D., Schilling T.F.;
RT   "Combinatorial roles for zebrafish retinoic acid receptors in the
RT   hindbrain, limbs and pharyngeal arches.";
RL   Dev. Biol. 325:60-70(2009).
CC   -!- FUNCTION: Receptor for retinoic acid. Retinoic acid receptors bind as
CC       heterodimers to their target response elements in response to their
CC       ligands, all-trans or 9-cis retinoic acid, and regulate gene expression
CC       in various biological processes. The rar/rxr heterodimers bind to the
CC       retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3'
CC       sites known as DR1-DR5 (By similarity). Required for hindbrain
CC       patterning. {ECO:0000250, ECO:0000269|PubMed:18929555}.
CC   -!- SUBUNIT: Heterodimer; with an rxr molecule. Binds DNA preferentially as
CC       a rar/rxr heterodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC   -!- TISSUE SPECIFICITY: In the embryo, zygotic expression largely overlaps
CC       that of rarab, with high levels in hindbrain, lateral mesoderm and tail
CC       bud. In the adult, strong expression in brain and muscle, weaker
CC       expression in ovary, liver and digestive tract.
CC       {ECO:0000269|PubMed:16455309, ECO:0000269|PubMed:7918098}.
CC   -!- DEVELOPMENTAL STAGE: Not expressed maternally. First detected at 8
CC       hours post-fertilization (hpf) during gastrulation, with expression
CC       being restricted to the posterior epiblast. Expression then increases,
CC       reaching a peak at 24 hpf and decreasing from 30-48 hpf. At 9 hpf,
CC       expressed throughout the dorsal epiblast except at the dorsal midline,
CC       and ventrally in prospective tail and head regions. At 10-11 hpf,
CC       expressed in presumptive hindbrain, posterior neural plate, lateral
CC       mesoderm and tail bud. At 12 hpf, strongly expressed in the neural
CC       epithelium and tail bud and expressed at low levels elsewhere including
CC       the eye. At 24 hpf, restricted to the hindbrain with an anterior border
CC       at rhombomere 6-7, to anterior spinal cord and to head mesenchyme just
CC       posterior to the otic vesicle. At 48 hpf, hindbrain expression remains
CC       and there is diffuse expression in non-neural tissue in the pharyngeal
CC       region. {ECO:0000269|PubMed:16455309, ECO:0000269|PubMed:18929555,
CC       ECO:0000269|PubMed:7918098}.
CC   -!- INDUCTION: By retinoic acid in embryos. {ECO:0000269|PubMed:18929555,
CC       ECO:0000269|PubMed:7918098}.
CC   -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC       DNA-binding domain and a C-terminal ligand-binding domain.
CC   -!- DOMAIN: The 9aaTAD motif is a transactivation domain present in a large
CC       number of yeast and animal transcription factors.
CC       {ECO:0000250|UniProtKB:P10276}.
CC   -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC       subfamily. {ECO:0000255}.
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DR   EMBL; S74155; AAB32276.1; -; mRNA.
DR   EMBL; L03398; AAA50049.1; -; mRNA.
DR   EMBL; BC092692; AAH92692.1; -; mRNA.
DR   PIR; I51256; I51256.
DR   RefSeq; NP_571481.2; NM_131406.2.
DR   AlphaFoldDB; Q90271; -.
DR   SMR; Q90271; -.
DR   STRING; 7955.ENSDARP00000073792; -.
DR   PaxDb; Q90271; -.
DR   Ensembl; ENSDART00000079336; ENSDARP00000073792; ENSDARG00000056783.
DR   GeneID; 30680; -.
DR   KEGG; dre:30680; -.
DR   CTD; 30680; -.
DR   ZFIN; ZDB-GENE-980526-284; raraa.
DR   eggNOG; KOG3575; Eukaryota.
DR   GeneTree; ENSGT00940000165576; -.
DR   InParanoid; Q90271; -.
DR   PhylomeDB; Q90271; -.
DR   TreeFam; TF328382; -.
DR   Reactome; R-DRE-383280; Nuclear Receptor transcription pathway.
DR   Reactome; R-DRE-4090294; SUMOylation of intracellular receptors.
DR   Reactome; R-DRE-5362517; Signaling by Retinoic Acid.
DR   Reactome; R-DRE-9616222; Transcriptional regulation of granulopoiesis.
DR   SignaLink; Q90271; -.
DR   PRO; PR:Q90271; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 12.
DR   Bgee; ENSDARG00000056783; Expressed in retinal neural layer and 55 other tissues.
DR   ExpressionAtlas; Q90271; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB.
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:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0021575; P:hindbrain morphogenesis; IDA:UniProtKB.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0001889; P:liver development; IMP:ZFIN.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0032526; P:response to retinoic acid; IDA:UniProtKB.
DR   GO; GO:0048384; P:retinoic acid receptor signaling pathway; IBA:GO_Central.
DR   Gene3D; 1.10.565.10; -; 1.
DR   Gene3D; 3.30.50.10; -; 1.
DR   InterPro; IPR035500; NHR-like_dom_sf.
DR   InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR   InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR   InterPro; IPR003078; Retinoic_acid_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; PR01292; RETNOICACIDR.
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   DNA-binding; Metal-binding; Nucleus; Receptor; Reference proteome;
KW   Transcription; Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..444
FT                   /note="Retinoic acid receptor alpha-A"
FT                   /id="PRO_0000262962"
FT   DOMAIN          170..404
FT                   /note="NR LBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT   DNA_BIND        72..147
FT                   /note="Nuclear receptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         75..95
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   ZN_FING         111..130
FT                   /note="NR C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT   REGION          1..71
FT                   /note="Modulating"
FT                   /evidence="ECO:0000255"
FT   REGION          35..67
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          148..169
FT                   /note="Hinge"
FT                   /evidence="ECO:0000255"
FT   REGION          402..444
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           395..403
FT                   /note="9aaTAD"
FT                   /evidence="ECO:0000250|UniProtKB:P10276"
FT   COMPBIAS        35..58
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        403..444
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        381..382
FT                   /note="RV -> LL (in Ref. 2; AAA50049)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   444 AA;  49924 MW;  7B0DED7B660D5E7F CRC64;
     MYESVDVNPF LMMDYYNQSR GCLIPDKMPH PFSSSIRHQH WSGSNHSIET QSTSSEEIVP
     SPPSPPPPPR IYKPCFVCQD KSSGYHYGVS ACEGCKGFFR RSIQKNMVYT CHREKNCIIN
     KVTRNRCQYC RLQKCLEVGM SKESVRNDRN KKKKEEKKPE CTENYTLSPD TEQMIDRVRK
     AHQETFPSLC QLGKYTTSNS SERRVALDVD LWDKFSELST KCIIKTVEFA KQLPGFTTLT
     IADQITLLKA ACLDILILRI CTRYTPEQDT MTFSDGLTLN RTQMHNAGFG PLTDLVFAFA
     NQLLPLEMDD AETGLLSAIC LLCGDRQDLE QADKVDVLQE PLLEALKIYV RNRRPHKPHM
     FPKMLMKITD LRSISAKGAE RVITLKMEIP GSMPPLIQEM LENSEGLESS SGAQGSRASA
     TTPGSCSPSL SPNSAQSSPP TQSP
 
 
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