THB_RAT
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 03-AUG-2022, entry version 175.
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;
CC 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};
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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.ENSRNOP00000008752; -.
DR BindingDB; P18113; -.
DR ChEMBL; CHEMBL3917; -.
DR DrugCentral; P18113; -.
DR PhosphoSitePlus; P18113; -.
DR ABCD; P18113; 3 sequenced antibodies.
DR UCSC; RGD:3858; rat. [P18113-1]
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:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; 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:0045892; P:negative regulation of transcription, DNA-templated; 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: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 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; IPR001728; ThyrH_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; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR PRINTS; PR00546; THYROIDHORMR.
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 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
