THA_PIG
ID THA_PIG Reviewed; 506 AA.
AC O97716; O97715;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 149.
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=NR1A1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
RC STRAIN=Large white; TISSUE=Heart;
RA White P., Dauncey M.J.;
RT "Differential expression of alpha 1 and alpha 2 thyroid hormone receptor
RT isoforms in porcine cardiac and skeletal muscles postnatally.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
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). Interacts with PER2.
CC Isoform alpha-2 and isoform alpha-1 interact with TACC1, but the
CC interaction with alpha-1 is weaker. The interaction with isoform alpha-
CC 1, but not alpha-2, is decreased in the presence of thyroid hormone T3
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P10827}.
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=O97716-1; Sequence=Displayed;
CC Name=Alpha-1;
CC IsoId=O97716-2; Sequence=VSP_003626;
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; AJ005798; CAA06702.1; -; mRNA.
DR EMBL; AJ005797; CAA06701.1; -; mRNA.
DR RefSeq; NP_999355.1; NM_214190.1. [O97716-2]
DR AlphaFoldDB; O97716; -.
DR SMR; O97716; -.
DR PRIDE; O97716; -.
DR Ensembl; ENSSSCT00000047067; ENSSSCP00000036874; ENSSSCG00000035969. [O97716-2]
DR Ensembl; ENSSSCT00000060832; ENSSSCP00000032431; ENSSSCG00000035969. [O97716-1]
DR Ensembl; ENSSSCT00015025497; ENSSSCP00015009958; ENSSSCG00015019223. [O97716-1]
DR Ensembl; ENSSSCT00015025551; ENSSSCP00015009979; ENSSSCG00015019223. [O97716-1]
DR Ensembl; ENSSSCT00025091091; ENSSSCP00025039926; ENSSSCG00025066098. [O97716-1]
DR Ensembl; ENSSSCT00025091278; ENSSSCP00025040035; ENSSSCG00025066098. [O97716-2]
DR Ensembl; ENSSSCT00030049889; ENSSSCP00030022664; ENSSSCG00030035812. [O97716-1]
DR Ensembl; ENSSSCT00030049909; ENSSSCP00030022679; ENSSSCG00030035812. [O97716-1]
DR Ensembl; ENSSSCT00030049980; ENSSSCP00030022726; ENSSSCG00030035812. [O97716-1]
DR Ensembl; ENSSSCT00035066516; ENSSSCP00035026974; ENSSSCG00035049912. [O97716-1]
DR Ensembl; ENSSSCT00035066570; ENSSSCP00035027002; ENSSSCG00035049912. [O97716-2]
DR Ensembl; ENSSSCT00040005431; ENSSSCP00040001975; ENSSSCG00040004192. [O97716-1]
DR Ensembl; ENSSSCT00040005437; ENSSSCP00040001979; ENSSSCG00040004192. [O97716-2]
DR Ensembl; ENSSSCT00045060844; ENSSSCP00045042736; ENSSSCG00045035402. [O97716-1]
DR Ensembl; ENSSSCT00045061283; ENSSSCP00045043050; ENSSSCG00045035402. [O97716-2]
DR Ensembl; ENSSSCT00050101087; ENSSSCP00050043926; ENSSSCG00050073891. [O97716-2]
DR Ensembl; ENSSSCT00050101093; ENSSSCP00050043930; ENSSSCG00050073891. [O97716-1]
DR Ensembl; ENSSSCT00055004638; ENSSSCP00055003578; ENSSSCG00055002444. [O97716-1]
DR Ensembl; ENSSSCT00055004765; ENSSSCP00055003687; ENSSSCG00055002444. [O97716-2]
DR Ensembl; ENSSSCT00060102103; ENSSSCP00060044427; ENSSSCG00060074529. [O97716-1]
DR Ensembl; ENSSSCT00060102164; ENSSSCP00060044461; ENSSSCG00060074529. [O97716-2]
DR Ensembl; ENSSSCT00065005721; ENSSSCP00065002539; ENSSSCG00065004151. [O97716-1]
DR Ensembl; ENSSSCT00065005724; ENSSSCP00065002540; ENSSSCG00065004151. [O97716-1]
DR Ensembl; ENSSSCT00065005735; ENSSSCP00065002544; ENSSSCG00065004151. [O97716-1]
DR Ensembl; ENSSSCT00070031832; ENSSSCP00070026538; ENSSSCG00070016193. [O97716-1]
DR GeneID; 397387; -.
DR KEGG; ssc:397387; -.
DR CTD; 7067; -.
DR GeneTree; ENSGT00940000157917; -.
DR InParanoid; O97716; -.
DR OMA; IMCLRIA; -.
DR OrthoDB; 1112927at2759; -.
DR Reactome; R-SSC-383280; Nuclear Receptor transcription pathway.
DR Proteomes; UP000008227; Chromosome 12.
DR Proteomes; UP000314985; Chromosome 12.
DR Bgee; ENSSSCG00000035969; Expressed in prefrontal cortex and 44 other tissues.
DR ExpressionAtlas; O97716; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
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:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
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:0002154; P:thyroid hormone mediated signaling pathway; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Alternative splicing; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
KW Receptor; Reference proteome; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..506
FT /note="Thyroid hormone receptor alpha"
FT /id="PRO_0000053426"
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..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 460..506
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 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..506
FT /note="EREVQSSILYKGAAAEGRPGGSLGVHPEGQQLLGMHVVQGPQVRQLEQQLGE
FT AGSLRGPVLQHQSPKSPQQRLLELLHRSGILHARAVCGEDDSSEAGSLTSSDEDPEVCE
FT DAAQATQPLPEAPPRADGEGGGGGS -> VTDLRMIGACHASRFLHMKVECPTELFPPL
FT FLEVFEDQEV (in isoform Alpha-1)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_003626"
SQ SEQUENCE 506 AA; 56265 MW; FA8D1643FFD4FBA1 CRC64;
MEQKPSKVEC GSDPEENSAR SPDGKRKRKN GQCSLKTSMS 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 PQVRQLEQQL
GEAGSLRGPV LQHQSPKSPQ QRLLELLHRS GILHARAVCG EDDSSEAGSL TSSDEDPEVC
EDAAQATQPL PEAPPRADGE GGGGGS
