THA_RAT
ID THA_RAT Reviewed; 492 AA.
AC P63059; P10685; P15827; P16416; P37241; Q63107; Q63195; Q63196; Q99146;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Thyroid hormone receptor alpha;
DE AltName: Full=Nuclear receptor subfamily 1 group A member 1;
DE AltName: Full=c-erbA-1;
DE AltName: Full=c-erbA-alpha;
GN Name=Thra; Synonyms=C-erba-alpha, Nr1a1;
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] (ISOFORMS ALPHA-1 AND ALPHA-2).
RX PubMed=2841611; DOI=10.1038/334539a0;
RA Izumo S., Mahdavi V.;
RT "Thyroid hormone receptor alpha isoforms generated by alternative splicing
RT differentially activate myosin HC gene transcription.";
RL Nature 334:539-542(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
RX PubMed=3387247; DOI=10.1093/nar/16.12.5697;
RA Mitsuhashi T., Tennyson G., Nikodem V.;
RT "Nucleotide sequence of novel cDNAs generated by alternative splicing of a
RT rat thyroid hormone receptor gene transcript.";
RL Nucleic Acids Res. 16:5697-5697(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
RX PubMed=2903438; DOI=10.1210/mend-2-10-893;
RA Lazar M.A., Hodin R.A., Darling D.S., Chin W.W.;
RT "Identification of a rat c-erbA alpha-related protein which binds
RT deoxyribonucleic acid but does not bind thyroid hormone.";
RL Mol. Endocrinol. 2:893-901(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
RX PubMed=3629259; DOI=10.1126/science.3629259;
RA Thompson C.C., Weinberger C., Lebo R., Evans R.M.;
RT "Identification of a novel thyroid hormone receptor expressed in the
RT mammalian central nervous system.";
RL Science 237:1610-1614(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-492 (ISOFORM ALPHA-1).
RC TISSUE=Heart;
RA Flink I.L., Bailey T., Bahl J., Morkin E.;
RL Submitted (AUG-1988) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH NCOA6.
RX PubMed=10866662; DOI=10.1128/mcb.20.14.5048-5063.2000;
RA Mahajan M.A., Samuels H.H.;
RT "A new family of nuclear receptor coregulators that integrates nuclear
RT receptor signaling through CBP.";
RL Mol. Cell. Biol. 20:5048-5063(2000).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 152-410 (ISOFORM ALPHA-1).
RX PubMed=7501015; DOI=10.1038/378690a0;
RA Wagner R.L., Apriletti J.W., McGrath M.E., West B.L., Baxter J.D.,
RA Fletterick R.J.;
RT "A structural role for hormone in the thyroid hormone receptor.";
RL Nature 378:690-697(1995).
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 RXRB.
CC Interacts with NCOA3 and NCOA6 coactivators, leading to a strong
CC increase of transcription of target genes. Probably interacts with
CC SFPQ. Interacts with C1D. Interacts with AKAP13. Interacts with
CC TP53INP2. Interacts with PER2 (By similarity). Isoform alpha-2 and
CC isoform alpha-1 interact with TACC1, but the interaction with alpha-1
CC is weaker. The interaction with isoform alpha-1, but not alpha-2, is
CC decreased in the presence of thyroid hormone T3 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P10827}.
CC -!- INTERACTION:
CC P63059-1; O75410-10: TACC1; Xeno; NbExp=2; IntAct=EBI-21350183, EBI-21986506;
CC P63059-2; O75410-10: TACC1; Xeno; NbExp=2; IntAct=EBI-21987107, EBI-21986506;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha-2]: Cytoplasm
CC {ECO:0000250|UniProtKB:P63058}. Nucleus {ECO:0000250|UniProtKB:P63058}.
CC Note=When overexpressed found in the cytoplasm where it colocalizes
CC with TACC1. {ECO:0000250|UniProtKB:P63058}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Alpha-2;
CC IsoId=P63059-1, P15827-1;
CC Sequence=Displayed;
CC Name=Alpha-1;
CC IsoId=P63059-2, P15827-2;
CC Sequence=VSP_011550;
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain.
CC -!- MISCELLANEOUS: [Isoform Alpha-2]: Does not bind thyroid hormone T3.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1
CC subfamily. {ECO:0000305}.
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DR EMBL; M31174; AAA41121.1; -; mRNA.
DR EMBL; M31177; AAA41122.1; -; mRNA.
DR EMBL; M18028; AAA42238.1; -; mRNA.
DR EMBL; X12744; CAA31237.1; -; mRNA.
DR PIR; A36752; TVRTAR.
DR PIR; I57696; I57696.
DR PIR; I67429; I67429.
DR PIR; S06410; S06410.
DR PIR; S06907; S06907.
DR PIR; S09178; S09178.
DR RefSeq; NP_001017960.1; NM_001017960.1. [P63059-2]
DR RefSeq; NP_112396.2; NM_031134.2.
DR AlphaFoldDB; P63059; -.
DR SMR; P63059; -.
DR BioGRID; 249670; 3.
DR IntAct; P63059; 1.
DR STRING; 10116.ENSRNOP00000012340; -.
DR BindingDB; P63059; -.
DR ChEMBL; CHEMBL4823; -.
DR iPTMnet; P63059; -.
DR PhosphoSitePlus; P63059; -.
DR PaxDb; P63059; -.
DR ABCD; P63059; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000087346; ENSRNOP00000072739; ENSRNOG00000009066. [P63059-2]
DR GeneID; 81812; -.
DR KEGG; rno:81812; -.
DR CTD; 7067; -.
DR RGD; 3857; Thra.
DR VEuPathDB; HostDB:ENSRNOG00000009066; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000157917; -.
DR InParanoid; P63059; -.
DR OrthoDB; 1112927at2759; -.
DR PhylomeDB; P63059; -.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR PRO; PR:P63059; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000009066; Expressed in frontal cortex and 20 other tissues.
DR ExpressionAtlas; P63059; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:RGD.
DR GO; GO:0140296; F:general transcription initiation factor binding; ISO:RGD.
DR GO; GO:0001161; F:intronic transcription regulatory region sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0003727; F:single-stranded RNA binding; IDA:RGD.
DR GO; GO:0017025; F:TBP-class protein binding; ISO:RGD.
DR GO; GO:0070324; F:thyroid hormone binding; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030325; P:adrenal gland development; IEP:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0001502; P:cartilage condensation; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0048565; P:digestive tract development; IEP:RGD.
DR GO; GO:0048568; P:embryonic organ development; IEP:RGD.
DR GO; GO:0030218; P:erythrocyte differentiation; ISO:RGD.
DR GO; GO:0008050; P:female courtship behavior; ISO:RGD.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; ISO:RGD.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0001889; P:liver development; IEP:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:2000143; P:negative regulation of DNA-templated transcription, initiation; ISO:RGD.
DR GO; GO:0017055; P:negative regulation of RNA polymerase II transcription preinitiation complex assembly; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001503; P:ossification; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045925; P:positive regulation of female receptivity; ISO: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; IDA:RGD.
DR GO; GO:0008016; P:regulation of heart contraction; ISO:RGD.
DR GO; GO:0050994; P:regulation of lipid catabolic process; ISO:RGD.
DR GO; GO:0033032; P:regulation of myeloid cell apoptotic process; ISO:RGD.
DR GO; GO:0002155; P:regulation of thyroid hormone mediated signaling pathway; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0009409; P:response to cold; ISO:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0002154; P:thyroid hormone mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD.
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 Alternative splicing; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
KW Receptor; Reference proteome; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..492
FT /note="Thyroid hormone receptor alpha"
FT /id="PRO_0000053427"
FT DOMAIN 163..407
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 53..127
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 53..73
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 91..115
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..52
FT /note="Modulating"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 457..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..30
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 462..476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 56
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="1"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 73
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 110
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P10828"
FT BINDING 228
FT /ligand="3,3',5-triiodo-L-thyronine"
FT /ligand_id="ChEBI:CHEBI:533015"
FT /evidence="ECO:0000250|UniProtKB:P10827"
FT BINDING 277
FT /ligand="3,3',5-triiodo-L-thyronine"
FT /ligand_id="ChEBI:CHEBI:533015"
FT /evidence="ECO:0000250|UniProtKB:P10827"
FT VAR_SEQ 371..492
FT /note="EREVQSSILYKGAAAEGRPGGSLGVHPEGQQLLGMHVVQGPQVRQLEQQFGE
FT AGSLRGPVLQHQSPKSPQQRLLELLHRSGILHSRAVCGEDDSSEASSLSSSSSDEDTEV
FT FEDLAGKAASP -> VTDLRMIGACHASRFLHMKVECPTELFPPLFLEVFEDQEV (in
FT isoform Alpha-1)"
FT /evidence="ECO:0000303|PubMed:2841611,
FT ECO:0000303|PubMed:3629259, ECO:0000303|Ref.5"
FT /id="VSP_011550"
FT CONFLICT 72
FT /note="G -> C (in Ref. 3; AAA41121)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="A -> T (in Ref. 4; AAA42238)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="E -> K (in Ref. 1 and 4; AAA42238)"
FT /evidence="ECO:0000305"
FT CONFLICT 482
FT /note="F -> C (in Ref. 3; AAA41121/AAA41122)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 55072 MW; 0B0411F51F614A01 CRC64;
MEQKPSKVEC GSDPEENSAR SPDGKRKRKN GQCPLKSSMS GYIPSYLDKD EQCVVCGDKA
TGYHYRCITC EGCKGFFRRT IQKNLHPTYS CKYDSCCVID KITRNQCQLC RFKKCIAVGM
AMDLVLDDSK RVAKRKLIEQ NRERRRKEEM IRSLQQRPEP TPEEWDLIHV ATEAHRSTNA
QGSHWKQRRK FLPDDIGQSP IVSMPDGDKV DLEAFSEFTK IITPAITRVV DFAKKLPMFS
ELPCEDQIIL LKGCCMEIMS LRAAVRYDPE SDTLTLSGEM AVKREQLKNG GLGVVSDAIF
ELGKSLSAFN LDDTEVALLQ AVLLMSTDRS GLLCVDKIEK SQEAYLLAFE HYVNHRKHNI
PHFWPKLLMK EREVQSSILY KGAAAEGRPG GSLGVHPEGQ QLLGMHVVQG PQVRQLEQQF
GEAGSLRGPV LQHQSPKSPQ QRLLELLHRS GILHSRAVCG EDDSSEASSL SSSSSDEDTE
VFEDLAGKAA SP
