ID THB_RAT Reviewed; 461 AA. AC P18113; P37826; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 2. DT 24-JAN-2024, entry version 182. DE RecName: Full=Thyroid hormone receptor beta; DE AltName: Full=Nuclear receptor subfamily 1 group A member 2; DE AltName: Full=c-erbA-2; DE AltName: Full=c-erbA-beta; GN Name=Thrb; Synonyms=Erba2, Nr1a2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1). RC TISSUE=Liver; RX PubMed=2457590; DOI=10.1016/s0021-9258(18)37820-7; RA Murray M.B., Zilz N.D., McCreary N.L., Macdonald M.J., Towle H.C.; RT "Isolation and characterization of rat cDNA clones for two distinct thyroid RT hormone receptors."; RL J. Biol. Chem. 263:12770-12777(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-1). RC TISSUE=Pituitary; RX PubMed=2899322; DOI=10.1073/pnas.85.14.5031; RA Koenig R.J., Warne R.L., Brent G.A., Harney J.W., Larsen P.R., Moore D.D.; RT "Isolation of a cDNA clone encoding a biologically active thyroid hormone RT receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 85:5031-5035(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-121 (ISOFORM BETA-2). RC TISSUE=Pituitary; RX PubMed=2539642; DOI=10.1126/science.2539642; RA Hodin R.A., Lazar M.A., Wintman B.I., Darling D.S., Koenig R.J., RA Larsen P.R., Moore D.D., Chin W.W.; RT "Identification of a thyroid hormone receptor that is pituitary-specific."; RL Science 244:76-78(1989). RN [4] RP INTERACTION WITH TACC1. RX PubMed=20078863; DOI=10.1186/1471-2199-11-3; RA Guyot R., Vincent S., Bertin J., Samarut J., Ravel-Chapuis P.; RT "The transforming acidic coiled coil (TACC1) protein modulates the RT transcriptional activity of the nuclear receptors TR and RAR."; RL BMC Mol. Biol. 11:3-3(2010). RN [5] RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 104-206, AND SUBUNIT. RX PubMed=20610536; DOI=10.1210/me.2010-0129; RA Chen Y., Young M.A.; RT "Structure of a thyroid hormone receptor DNA-binding domain homodimer bound RT to an inverted palindrome DNA response element."; RL Mol. Endocrinol. 24:1650-1664(2010). CC -!- FUNCTION: Nuclear hormone receptor that can act as a repressor or CC activator of transcription. High affinity receptor for thyroid CC hormones, including triiodothyronine and thyroxine. CC -!- SUBUNIT: Binds DNA as a dimer; homodimer and heterodimer with RXRA (By CC similarity). Interacts with the coactivators NCOA1/SRC1, NCOA2/GRIP1, CC NCOA7 and MED1/TRAP220 in a ligand-inducible manner (By similarity). CC Interacts with the corepressor NCOR1 in absence of ligand. Interacts CC with C1D (By similarity). Interacts with NR2F6; the interaction impairs CC the binding of the THRB homodimer and THRB:RXRB heterodimer to T3 CC response elements (By similarity). Interacts with PRMT2 and THRSP (By CC similarity). Interacts with TACC1; this interaction is decreased in the CC presence of thyroid hormone T3 (PubMed:20078863). {ECO:0000250, CC ECO:0000269|PubMed:20078863}. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta-1; CC IsoId=P18113-1; Sequence=Displayed; CC Name=Beta-2; CC IsoId=P18113-2, P37826-1; Sequence=VSP_031079; 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 -!- SEQUENCE CAUTION: CC Sequence=AAA40916.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA42200.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; J03933; AAA40916.1; ALT_INIT; mRNA. DR EMBL; J03819; AAA60743.1; -; mRNA. DR EMBL; M25071; AAA42200.1; ALT_INIT; mRNA. DR PIR; A31820; A31820. DR PIR; A41355; A41355. DR PDB; 3M9E; X-ray; 2.41 A; A/B/E/F=104-206. DR PDBsum; 3M9E; -. DR AlphaFoldDB; P18113; -. DR SMR; P18113; -. DR DIP; DIP-61264N; -. DR IntAct; P18113; 2. DR STRING; 10116.ENSRNOP00000073083; -. DR BindingDB; P18113; -. DR ChEMBL; CHEMBL3917; -. DR DrugCentral; P18113; -. DR PhosphoSitePlus; P18113; -. DR PaxDb; 10116-ENSRNOP00000008752; -. DR ABCD; P18113; 3 sequenced antibodies. DR UCSC; RGD:3858; rat. [P18113-1] DR AGR; RGD:3858; -. DR RGD; 3858; Thrb. DR eggNOG; KOG3575; Eukaryota. DR InParanoid; P18113; -. DR PhylomeDB; P18113; -. DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway. DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors. DR EvolutionaryTrace; P18113; -. DR PRO; PR:P18113; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD. DR GO; GO:0003682; F:chromatin binding; ISO:RGD. DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD. DR GO; GO:0019899; F:enzyme binding; ISO:RGD. DR GO; GO:0042802; F:identical protein binding; IPI:RGD. DR GO; GO:0004879; F:nuclear receptor activity; IDA:RGD. 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; ISO:RGD. DR GO; GO:0070324; F:thyroid hormone binding; ISS:UniProtKB. DR GO; GO:0001223; F:transcription coactivator binding; ISO:RGD. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; ISO:RGD. DR GO; GO:0048568; P:embryonic organ development; IEP:RGD. DR GO; GO:0008050; P:female courtship behavior; ISO:RGD. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0007621; P:negative regulation of female receptivity; ISO:RGD. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IDA:RGD. DR GO; GO:0045778; P:positive regulation of ossification; IDA:RGD. DR GO; GO:0002157; P:positive regulation of thyroid hormone mediated signaling pathway; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0090181; P:regulation of cholesterol metabolic process; IMP:RGD. DR GO; GO:0008016; P:regulation of heart contraction; ISO:RGD. DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:RGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0090207; P:regulation of triglyceride metabolic process; IMP:RGD. DR GO; GO:0097474; P:retinal cone cell apoptotic process; ISO:RGD. DR GO; GO:0046549; P:retinal cone cell development; ISO:RGD. DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IBA:GO_Central. DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD. DR GO; GO:0002154; P:thyroid hormone mediated signaling pathway; IBA:GO_Central. DR GO; GO:0060509; P:type I pneumocyte differentiation; ISO:RGD. 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 3D-structure; Alternative splicing; DNA-binding; Metal-binding; Nucleus; KW Receptor; Reference proteome; Transcription; Transcription regulation; KW Zinc; Zinc-finger. FT CHAIN 1..461 FT /note="Thyroid hormone receptor beta" FT /id="PRO_0000053450" FT DOMAIN 217..461 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 107..181 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 107..127 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 145..169 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..106 FT /note="Modulating" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 244..461 FT /note="Interaction with NR2F6" FT /evidence="ECO:0000250" FT BINDING 107 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 110 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 124 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 127 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 145 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 151 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 161 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 164 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 282 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 282 FT /ligand="L-thyroxine" FT /ligand_id="ChEBI:CHEBI:58448" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 331 FT /ligand="3,3',5-triiodo-L-thyronine" FT /ligand_id="ChEBI:CHEBI:533015" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 331 FT /ligand="L-thyroxine" FT /ligand_id="ChEBI:CHEBI:58448" FT /evidence="ECO:0000250|UniProtKB:P10828" FT BINDING 435 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 BINDING 435 FT /ligand="L-thyroxine" FT /ligand_id="ChEBI:CHEBI:58448" FT /evidence="ECO:0000250|UniProtKB:P10828" FT VAR_SEQ 1..93 FT /note="MTPNSMTENRLPAWDKQKPHPDRGQDWKLVGMSEACLHRKSHVERRGALKNE FT QTSSHLIQATWASSIFHLDPDDVNDQSVSSAQTFQTEEKKC -> MNYCVPEVHEVCPA FT AGSNRYMQVTDYLAYLEDSPAYSGCDVQAVPGSSIYLEQAWTLNQPYTCSYPGNLFKSK FT DSDLDMALSQYSQPAHLPEEKPFPQVRSPPHSHK (in isoform Beta-2)" FT /evidence="ECO:0000303|PubMed:2539642" FT /id="VSP_031079" FT CONFLICT 9..10 FT /note="NR -> KC (in Ref. 2; AAA60743)" FT /evidence="ECO:0000305" FT CONFLICT 263 FT /note="Q -> K (in Ref. 2; AAA60743)" FT /evidence="ECO:0000305" FT TURN 108..110 FT /evidence="ECO:0007829|PDB:3M9E" FT STRAND 116..122 FT /evidence="ECO:0007829|PDB:3M9E" FT HELIX 125..136 FT /evidence="ECO:0007829|PDB:3M9E" FT HELIX 140..142 FT /evidence="ECO:0007829|PDB:3M9E" FT TURN 155..159 FT /evidence="ECO:0007829|PDB:3M9E" FT HELIX 162..171 FT /evidence="ECO:0007829|PDB:3M9E" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:3M9E" FT HELIX 182..202 FT /evidence="ECO:0007829|PDB:3M9E" SQ SEQUENCE 461 AA; 52656 MW; 16705C200E02995B CRC64; MTPNSMTENR LPAWDKQKPH PDRGQDWKLV GMSEACLHRK SHVERRGALK NEQTSSHLIQ ATWASSIFHL DPDDVNDQSV SSAQTFQTEE KKCKGYIPSY LDKDELCVVC GDKATGYHYR CITCEGCKGF FRRTIQKSLH PSYSCKYEGK CIIDKVTRNQ CQECRFKKCI YVGMATDLVL DDSKRLAKRK LIEENREKRR REELQKSIGH KPEPTDEEWE LIKTVTEAHV ATNAQGSHWK QKRKFLPEDI GQAPIVNAPE GGQVDLEAFS HFTKIITPAI TRVVDFAKKL PMFCELPCED QIILLKGCCM EIMSLRAAVR YDPDSETLTL NGEMAVTRGQ LKNGGLGVVS DAIFDLGMSL SSFNLDDTEV ALLQAVLLMS SDRPGLACVE RIEKYQDSFL LAFEHYINYR KHHVTHFWPK LLMKVTDLRM IGACHASRFL HMKVECPTEL FPPLFLEVFE D //