ID THB_DANRE Reviewed; 395 AA. AC Q9PVE4; A3QJW1; B3DIF2; O42560; Q90Y31; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 176. DE RecName: Full=Thyroid hormone receptor beta; DE Short=TR-beta; DE Short=TRb; DE AltName: Full=Nuclear receptor subfamily 1 group A member 2; DE AltName: Full=Thyroid hormone receptor beta-1; DE Short=TRbeta1; GN Name=thrb; Synonyms=nr1a2, trb; ORFNames=si:ch211-264a6.2; 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 2), FUNCTION, TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, AND INDUCTION. RX PubMed=10687864; DOI=10.1016/s0303-7207(99)00193-8; RA Liu Y.-W., Lo L.-J., Chan W.-K.; RT "Temporal expression and T3 induction of thyroid hormone receptors alpha1 RT and beta1 during early embryonic and larval development in zebrafish, Danio RT rerio."; RL Mol. Cell. Endocrinol. 159:187-195(2000). 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 2). RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-97. RX PubMed=9192646; DOI=10.1073/pnas.94.13.6803; RA Escriva H., Safi R., Haenni C., Langlois M.-C., Saumitou-Laprade P., RA Stehelin D., Capron A., Pierce R., Laudet V.; RT "Ligand binding was acquired during evolution of nuclear receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 94:6803-6808(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 70-347 (ISOFORM 1). RX PubMed=11174854; DOI=10.1677/jme.0.0260051; RA Marchand O., Safi R., Escriva H., Van Rompaey E., Prunet P., Laudet V.; RT "Molecular cloning and characterization of thyroid hormone receptors in RT teleost fish."; RL J. Mol. Endocrinol. 26:51-65(2001). RN [6] RP REVIEW. RX PubMed=11738632; DOI=10.1016/s1532-0456(01)00271-x; RA Power D.M., Llewellyn L., Faustino M., Nowell M.A., Bjoernsson B.T., RA Einarsdottir I.E., Canario A.V.M., Sweeney G.E.; RT "Thyroid hormones in growth and development of fish."; RL Comp. Biochem. Physiol. 130C:447-459(2001). RN [7] RP DEVELOPMENTAL STAGE, AND INDUCTION. RX PubMed=11963654; DOI=10.1046/j.1432-0436.2002.700104.x; RA Liu Y.-W., Chan W.-K.; RT "Thyroid hormones are important for embryonic to larval transitory phase in RT zebrafish."; RL Differentiation 70:36-45(2002). RN [8] RP INTERACTION WITH NCOA2. RX PubMed=18248177; DOI=10.1089/zeb.2005.2.33; RA Tan J.-H., Quek S.-I., Chan W.-K.; RT "Cloning, genomic organization, and expression analysis of zebrafish RT nuclear receptor coactivator, TIF2."; RL Zebrafish 2:33-46(2005). RN [9] RP DEVELOPMENTAL STAGE. RX PubMed=17418841; DOI=10.1016/j.ygcen.2007.02.020; RA Walpita C.N., Van der Geyten S., Rurangwa E., Darras V.M.; RT "The effect of 3,5,3'-triiodothyronine supplementation on zebrafish (Danio RT rerio) embryonic development and expression of iodothyronine deiodinases RT and thyroid hormone receptors."; RL Gen. Comp. Endocrinol. 152:206-214(2007). RN [10] RP TISSUE SPECIFICITY. RX PubMed=17997606; DOI=10.1371/journal.pgen.0030188; RA Bertrand S., Thisse B., Tavares R., Sachs L., Chaumot A., Bardet P.-L., RA Escriva H., Duffraisse M., Marchand O., Safi R., Thisse C., Laudet V.; RT "Unexpected novel relational links uncovered by extensive developmental RT profiling of nuclear receptor expression."; RL PLoS Genet. 3:E188-E188(2007). CC -!- FUNCTION: Nuclear hormone receptor that can act as a repressor or CC activator of transcription. High affinity receptor for the thyroid CC gland hormone triiodothyronine (T3). Transactivating activity is CC ligand-dependent, and is repressed in the absence of T3. CC {ECO:0000269|PubMed:10687864}. CC -!- SUBUNIT: Interacts (via the ligand-binding domain) with ncoa2. CC {ECO:0000269|PubMed:18248177}. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9PVE4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9PVE4-2; Sequence=VSP_035801; CC -!- TISSUE SPECIFICITY: Widely expressed in a range of adult tissues CC including the brain, eye, fin, gill, intestine, liver, swim bladder and CC ovary. In the eye, expressed in the outer nuclear layer of the retina. CC {ECO:0000269|PubMed:10687864, ECO:0000269|PubMed:17997606}. CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC Expressed at the 1 cell stage (0 hpf) but disappears by the 2 cell CC stage. Expressed again from the 16 cell stage onwards. Embryonic CC expression increases dramatically around the hatching period. High CC expression then continues until 6 dpf, before declining. CC {ECO:0000269|PubMed:10687864, ECO:0000269|PubMed:11963654, CC ECO:0000269|PubMed:17418841}. CC -!- INDUCTION: By triiodothyronine (T3) and L-thyroxine (T4). CC {ECO:0000269|PubMed:10687864, ECO:0000269|PubMed:11963654}. CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a CC DNA-binding domain and a C-terminal ligand-binding domain. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 CC subfamily. {ECO:0000305}. CC -!- CAUTION: In contrast to PubMed:10687864 and PubMed:11963654, CC PubMed:17418841 found that triiodothyronine (T3) did not induce CC expression in the embryo. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF109732; AAF14239.1; -; mRNA. DR EMBL; BX927163; CAN87984.1; -; Genomic_DNA. DR EMBL; CR382334; CAN87984.1; JOINED; Genomic_DNA. DR EMBL; CR382334; CAM56478.2; -; Genomic_DNA. DR EMBL; BX927163; CAM56478.2; JOINED; Genomic_DNA. DR EMBL; BC163106; AAI63106.1; -; mRNA. DR EMBL; BC163114; AAI63114.1; -; mRNA. DR EMBL; U93487; AAB68764.1; -; Genomic_DNA. DR EMBL; AF302242; AAL06722.1; -; mRNA. DR RefSeq; NP_571415.1; NM_131340.1. [Q9PVE4-2] DR RefSeq; XP_017207667.1; XM_017352178.1. DR AlphaFoldDB; Q9PVE4; -. DR SMR; Q9PVE4; -. DR STRING; 7955.ENSDARP00000152808; -. DR PaxDb; 7955-ENSDARP00000126275; -. DR GeneID; 30607; -. DR KEGG; dre:30607; -. DR AGR; ZFIN:ZDB-GENE-990415-268; -. DR CTD; 7068; -. DR ZFIN; ZDB-GENE-990415-268; thrb. DR eggNOG; KOG3575; Eukaryota. DR HOGENOM; CLU_007368_18_0_1; -. DR InParanoid; Q9PVE4; -. DR OrthoDB; 5390715at2759; -. DR PhylomeDB; Q9PVE4; -. DR Reactome; R-DRE-383280; Nuclear Receptor transcription pathway. DR Reactome; R-DRE-4090294; SUMOylation of intracellular receptors. DR PRO; PR:Q9PVE4; -. DR Proteomes; UP000000437; Chromosome 19. DR Bgee; ENSDARG00000021163; Expressed in photoreceptor layer of retina and 28 other cell types or tissues. DR ExpressionAtlas; Q9PVE4; baseline and differential. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. 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:0070324; F:thyroid hormone binding; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0043010; P:camera-type eye development; IMP:ZFIN. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0048839; P:inner ear 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:0006355; P:regulation of DNA-templated transcription; IDA:ZFIN. DR GO; GO:0046549; P:retinal cone cell development; IMP:ZFIN. DR GO; GO:0042670; P:retinal cone cell differentiation; IMP:ZFIN. DR GO; GO:0042671; P:retinal cone cell fate determination; IMP: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 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:SF210; THYROID HORMONE RECEPTOR BETA; 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 Alternative splicing; DNA-binding; Metal-binding; Nucleus; Receptor; KW Reference proteome; Transcription; Transcription regulation; Zinc; KW Zinc-finger. FT CHAIN 1..395 FT /note="Thyroid hormone receptor beta" FT /id="PRO_0000053455" FT DOMAIN 142..395 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 29..106 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 32..52 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 70..89 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..31 FT /note="Modulating" FT /evidence="ECO:0000255" FT BINDING 32 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 35 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 49 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 52 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 70 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 76 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 86 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 89 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 216 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 265 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 369 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT VAR_SEQ 172..180 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10687864, ECO:0000303|Ref.3" FT /id="VSP_035801" FT CONFLICT 95..96 FT /note="IA -> NP (in Ref. 4; AAB68764)" FT /evidence="ECO:0000305" FT CONFLICT 347 FT /note="K -> Q (in Ref. 5; AAL06722)" FT /evidence="ECO:0000305" SQ SEQUENCE 395 AA; 45155 MW; 1E18666BCCACFE8A CRC64; MSEQADKCNS RWKDEAMQNG YIPSYLDKDE LCVVCGDKAT GYHYRCITCE GCKGFFRRTI QKNLNPTYAC KYEGKCVIDK VTRNQCQECR FKKCIAVGMA TDLVLDDSKR LAKRKLIEEN RERRRREELQ KTVWDRPEPT QEEWEMIRVV TEAHMATNAQ GNHWKQKRKF LSAVGVKEAK PEDIGSAPIV NAPEGNKVDI EAFSQFTKII TPAITRVVDF AKKLPMFCEL PCEDQIILLK GCCMEIMSLR AAVRYDPESD TLTLNGEMAV TRGQLKNGGL GVVSDAIFDL GVSLSSFNLD DSEVALLQAV ILLSSDRPGL TSVERIERCQ EEFLLAFEHY INYRKHKVAH FWPKLLMKVT DLRMIGACHA SRFLHMKVEC PTELFPPLFL EVFED //