ID THAA_DANRE Reviewed; 427 AA.
AC Q98867; A0ST47; Q4V9Q5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 27-MAR-2024, entry version 175.
DE RecName: Full=Thyroid hormone receptor alpha-A;
DE Short=zTRalpha-A;
DE AltName: Full=Nuclear receptor subfamily 1 group A member 1-A;
DE AltName: Full=Thyroid hormone receptor alpha-1;
DE Short=TRalpha-1;
GN Name=thraa; Synonyms=nr1a1a, thra, thraa1, tra1;
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Blastula;
RX PubMed=9447705; DOI=10.1046/j.1432-0436.1997.6230107.x;
RA Essner J.J., Breuer J.J., Essner R.D., Fahrenkrug S.C., Hackett P.B. Jr.;
RT "The zebrafish thyroid hormone receptor alpha 1 is expressed during early
RT embryogenesis and can function in transcriptional repression.";
RL Differentiation 62:107-117(1997).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 224-427 (ISOFORM 2), FUNCTION, INTERACTION
RP WITH NCOA2, DEVELOPMENTAL STAGE, DOMAIN, AND ALTERNATIVE SPLICING.
RC TISSUE=Heart;
RX PubMed=17583703; DOI=10.1016/j.ygcen.2007.04.012;
RA Takayama S., Hostick U., Haendel M., Eisen J., Darimont B.;
RT "An F-domain introduced by alternative splicing regulates activity of the
RT zebrafish thyroid hormone receptor alpha.";
RL Gen. Comp. Endocrinol. 155:176-189(2008).
CC -!- FUNCTION: High affinity receptor for triiodothyronine (By similarity).
CC In the absence of thyroid hormone during late blastula stage
CC development, acts as a transcriptional repressor. Whereas in the
CC presence of thyroid hormone, can act as an activator of transcription.
CC In addition, represses retinoic acid (RA)-signaling during blastula and
CC gastrula stages of development. {ECO:0000250,
CC ECO:0000269|PubMed:17583703, ECO:0000269|PubMed:9447705}.
CC -!- SUBUNIT: Interacts with ncoa2. {ECO:0000269|PubMed:17583703}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:9447705}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=TRalphaA1;
CC IsoId=Q98867-1; Sequence=Displayed;
CC Name=2; Synonyms=TRalphaA1-2;
CC IsoId=Q98867-2; Sequence=VSP_036323;
CC -!- TISSUE SPECIFICITY: After the mid-blastula transition (MBT), expressed
CC throughout the deep cells, which give rise to the embryo proper. In
CC adults, isoform 2 shows highest expression in the eye and liver.
CC Expressed in adult gonads. {ECO:0000269|PubMed:9447705}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Most
CC abundant during early oogenesis during stages I and II, and expression
CC levels drop by oocyte maturation. Expressed at the 1-cell stage and
CC then again after the MBT from the blastula to early gastrula (shield)
CC stages, during which expression levels decrease. Not detected after
CC gastrulation until adults. {ECO:0000269|PubMed:17583703,
CC ECO:0000269|PubMed:9447705}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC {ECO:0000269|PubMed:17583703}.
CC -!- DOMAIN: The C-terminal extension present in isoform 1 and absent in
CC isoform 2 (the F-domain) regulates transcriptional activity by altering
CC the selectivity of binding to cofactors. {ECO:0000269|PubMed:17583703}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; U54796; AAA99811.1; -; mRNA.
DR EMBL; AL590145; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096778; AAH96778.1; -; mRNA.
DR EMBL; DQ991961; ABK64188.1; -; mRNA.
DR RefSeq; NP_571471.1; NM_131396.1. [Q98867-1]
DR RefSeq; XP_005164043.1; XM_005163986.3. [Q98867-2]
DR RefSeq; XP_009297789.1; XM_009299514.2.
DR AlphaFoldDB; Q98867; -.
DR SMR; Q98867; -.
DR STRING; 7955.ENSDARP00000000160; -.
DR PaxDb; 7955-ENSDARP00000000160; -.
DR GeneID; 30670; -.
DR KEGG; dre:30670; -.
DR AGR; ZFIN:ZDB-GENE-990415-263; -.
DR CTD; 30670; -.
DR ZFIN; ZDB-GENE-990415-263; thraa.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q98867; -.
DR OMA; CISCSCV; -.
DR OrthoDB; 5390715at2759; -.
DR PhylomeDB; Q98867; -.
DR TreeFam; TF328382; -.
DR PRO; PR:Q98867; -.
DR Proteomes; UP000000437; Chromosome 3.
DR Bgee; ENSDARG00000000151; Expressed in spleen and 43 other cell types or tissues.
DR ExpressionAtlas; Q98867; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IDA:ZFIN.
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:0007507; P:heart development; IMP:ZFIN.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0014032; P:neural crest cell development; IMP:ZFIN.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; IMP:ZFIN.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ZFIN.
DR GO; GO:0009725; P:response to hormone; IDA:ZFIN.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0002154; P:thyroid hormone mediated signaling pathway; IMP:ZFIN.
DR GO; GO:0021591; P:ventricular system development; IMP:ZFIN.
DR CDD; cd06961; NR_DBD_TR; 1.
DR CDD; cd06935; NR_LBD_TR; 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; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001728; ThyrH_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR24082; NUCLEAR HORMONE RECEPTOR; 1.
DR PANTHER; PTHR24082:SF42; THYROID HORMONE RECEPTOR ALPHA; 1.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR PRINTS; PR00546; THYROIDHORMR.
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 Activator; Alternative splicing; Developmental protein; DNA-binding;
KW Metal-binding; Nucleus; Receptor; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..427
FT /note="Thyroid hormone receptor alpha-A"
FT /id="PRO_0000053433"
FT DOMAIN 167..410
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 57..131
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 57..77
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 95..119
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..56
FT /note="Modulating"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..22
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 23..40
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 413..427
FT /note="GSTGVAAQEDGSCLR -> V (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17583703"
FT /id="VSP_036323"
SQ SEQUENCE 427 AA; 48728 MW; 75E234071F43A616 CRC64;
MENTEQEHNL PEGDETQWPN GVKRKRKNSQ CSMNSTSDKS ISVPGYVPSY LEKDEPCVVC
GDKATGYHYR CITCEGCKGF FRRTIQKNLH PSYSCKYDSC CIIDKITRNQ CQLCRFRKCI
SVGMAMDLVL DDSKRVAKRR LIEENREKRK KEEIVKTLHN RPEPTVSEWE LIRMVTEAHR
HTNAQGPHWK QKRKFLPEDI GQSPAPTSDN DKVDLEAFSE FTKIITPAIT RVVDFAKKLP
MFSELPCEDQ IILLKGCCME IMSLRAAVRY DPESETLTLS GEMAVSREQL KNGGLGVVSD
AIFDLGKSLS QFNLDDSEVA LLQAVLLMSS DRSGLTCVEK IEKCQEMYLL AFEHYINHRK
HNISHFWPKL LMKVTNLRMI GACHASRFLH MKVECPTELF PPLFLEVFED QEGSTGVAAQ
EDGSCLR
//
