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Protein

Thyroid hormone receptor alpha

Gene

Thra

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei228 – 2281Thyroid hormoneBy similarity
Binding sitei277 – 2771Thyroid hormone; via amide nitrogenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi53 – 12775Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri53 – 7321NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri91 – 11525NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • intronic transcription regulatory region DNA binding Source: RGD
  • protein dimerization activity Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD
  • sequence-specific DNA binding Source: RGD
  • single-stranded RNA binding Source: RGD
  • steroid hormone receptor activity Source: InterPro
  • thyroid hormone binding Source: UniProtKB
  • thyroid hormone receptor activity Source: UniProtKB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • adrenal gland development Source: RGD
  • brain development Source: RGD
  • digestive tract development Source: RGD
  • embryonic organ development Source: RGD
  • kidney development Source: RGD
  • liver development Source: RGD
  • lung development Source: RGD
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: RGD
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • response to drug Source: RGD
  • response to nutrient levels Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-383280. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Thyroid hormone receptor alpha
Alternative name(s):
Nuclear receptor subfamily 1 group A member 1
c-erbA-1
c-erbA-alpha
Gene namesi
Name:Thra
Synonyms:C-erba-alpha, Nr1a1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi3857. Thra.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: RGD
  • cytosol Source: RGD
  • mitochondrion Source: RGD
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 492492Thyroid hormone receptor alphaPRO_0000053427Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki190 – 190Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiP63059.
PRIDEiP63059.

PTM databases

iPTMnetiP63059.
PhosphoSiteiP63059.

Expressioni

Gene expression databases

ExpressionAtlasiP63059. baseline and differential.

Interactioni

Subunit structurei

Binds DNA as a dimer; homodimer and heterodimer with RXRB. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Probably interacts with SFPQ. Interacts with C1D. Interacts with AKAP13. Interacts with TP53INP2. Interacts with PER2 (By similarity).By similarity

GO - Molecular functioni

  • protein dimerization activity Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

BioGridi249670. 2 interactions.
MINTiMINT-1515753.
STRINGi10116.ENSRNOP00000012340.

Structurei

3D structure databases

ProteinModelPortaliP63059.
SMRiP63059. Positions 50-138, 148-403.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5252ModulatingAdd
BLAST
Regioni190 – 370181Ligand-bindingAdd
BLAST

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri53 – 7321NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri91 – 11525NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00840000129681.
HOVERGENiHBG005606.
InParanoidiP63059.
KOiK05547.
PhylomeDBiP63059.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-2 (identifier: P63059-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEQKPSKVEC GSDPEENSAR SPDGKRKRKN GQCPLKSSMS GYIPSYLDKD
60 70 80 90 100
EQCVVCGDKA TGYHYRCITC EGCKGFFRRT IQKNLHPTYS CKYDSCCVID
110 120 130 140 150
KITRNQCQLC RFKKCIAVGM AMDLVLDDSK RVAKRKLIEQ NRERRRKEEM
160 170 180 190 200
IRSLQQRPEP TPEEWDLIHV ATEAHRSTNA QGSHWKQRRK FLPDDIGQSP
210 220 230 240 250
IVSMPDGDKV DLEAFSEFTK IITPAITRVV DFAKKLPMFS ELPCEDQIIL
260 270 280 290 300
LKGCCMEIMS LRAAVRYDPE SDTLTLSGEM AVKREQLKNG GLGVVSDAIF
310 320 330 340 350
ELGKSLSAFN LDDTEVALLQ AVLLMSTDRS GLLCVDKIEK SQEAYLLAFE
360 370 380 390 400
HYVNHRKHNI PHFWPKLLMK EREVQSSILY KGAAAEGRPG GSLGVHPEGQ
410 420 430 440 450
QLLGMHVVQG PQVRQLEQQF GEAGSLRGPV LQHQSPKSPQ QRLLELLHRS
460 470 480 490
GILHSRAVCG EDDSSEASSL SSSSSDEDTE VFEDLAGKAA SP
Length:492
Mass (Da):55,072
Last modified:September 13, 2004 - v1
Checksum:i0B0411F51F614A01
GO
Isoform Alpha-1 (identifier: P63059-2) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     371-492: EREVQSSILY...EDLAGKAASP → VTDLRMIGAC...FLEVFEDQEV

Show »
Length:410
Mass (Da):46,795
Checksum:iEC0240EF1ECF4111
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti72 – 721G → C in AAA41121 (PubMed:2903438).Curated
Sequence conflicti281 – 2811A → T in AAA42238 (PubMed:3629259).Curated
Sequence conflicti285 – 2851E → K (PubMed:2841611).Curated
Sequence conflicti285 – 2851E → K in AAA42238 (PubMed:3629259).Curated
Sequence conflicti482 – 4821F → C in AAA41121 (PubMed:2903438).Curated
Sequence conflicti482 – 4821F → C in AAA41122 (PubMed:2903438).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei371 – 492122EREVQ…KAASP → VTDLRMIGACHASRFLHMKV ECPTELFPPLFLEVFEDQEV in isoform Alpha-1. 3 PublicationsVSP_011550Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31174 mRNA. Translation: AAA41121.1.
M31177 mRNA. Translation: AAA41122.1.
M18028 mRNA. Translation: AAA42238.1.
X12744 mRNA. Translation: CAA31237.1.
PIRiA36752. TVRTAR.
I57696.
I67429.
S06410.
S06907.
S09178.
RefSeqiNP_001017960.1. NM_001017960.1. [P63059-2]
NP_112396.2. NM_031134.2.
UniGeneiRn.11307.

Genome annotation databases

EnsembliENSRNOT00000087346; ENSRNOP00000072739; ENSRNOG00000009066. [P63059-2]
GeneIDi81812.
KEGGirno:81812.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31174 mRNA. Translation: AAA41121.1.
M31177 mRNA. Translation: AAA41122.1.
M18028 mRNA. Translation: AAA42238.1.
X12744 mRNA. Translation: CAA31237.1.
PIRiA36752. TVRTAR.
I57696.
I67429.
S06410.
S06907.
S09178.
RefSeqiNP_001017960.1. NM_001017960.1. [P63059-2]
NP_112396.2. NM_031134.2.
UniGeneiRn.11307.

3D structure databases

ProteinModelPortaliP63059.
SMRiP63059. Positions 50-138, 148-403.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249670. 2 interactions.
MINTiMINT-1515753.
STRINGi10116.ENSRNOP00000012340.

PTM databases

iPTMnetiP63059.
PhosphoSiteiP63059.

Proteomic databases

PaxDbiP63059.
PRIDEiP63059.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000087346; ENSRNOP00000072739; ENSRNOG00000009066. [P63059-2]
GeneIDi81812.
KEGGirno:81812.

Organism-specific databases

CTDi7067.
RGDi3857. Thra.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00840000129681.
HOVERGENiHBG005606.
InParanoidiP63059.
KOiK05547.
PhylomeDBiP63059.

Enzyme and pathway databases

ReactomeiR-RNO-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiP63059.

Gene expression databases

ExpressionAtlasiP63059. baseline and differential.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001728. ThyrH_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
PR00546. THYROIDHORMR.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription."
    Izumo S., Mahdavi V.
    Nature 334:539-542(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA-1 AND ALPHA-2).
  2. "Nucleotide sequence of novel cDNAs generated by alternative splicing of a rat thyroid hormone receptor gene transcript."
    Mitsuhashi T., Tennyson G., Nikodem V.
    Nucleic Acids Res. 16:5697-5697(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
  3. "Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone."
    Lazar M.A., Hodin R.A., Darling D.S., Chin W.W.
    Mol. Endocrinol. 2:893-901(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2).
  4. "Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system."
    Thompson C.C., Weinberger C., Lebo R., Evans R.M.
    Science 237:1610-1614(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-1).
  5. Flink I.L., Bailey T., Bahl J., Morkin E.
    Submitted (AUG-1988) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-492 (ISOFORM ALPHA-1).
    Tissue: Heart.
  6. "A new family of nuclear receptor coregulators that integrates nuclear receptor signaling through CBP."
    Mahajan M.A., Samuels H.H.
    Mol. Cell. Biol. 20:5048-5063(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NCOA6.
  7. "A structural role for hormone in the thyroid hormone receptor."
    Wagner R.L., Apriletti J.W., McGrath M.E., West B.L., Baxter J.D., Fletterick R.J.
    Nature 378:690-697(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 152-410 (ISOFORM ALPHA-1).

Entry informationi

Entry nameiTHA_RAT
AccessioniPrimary (citable) accession number: P63059
Secondary accession number(s): P10685
, P15827, P16416, P37241, Q63107, Q63195, Q63196, Q99146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: September 13, 2004
Last modified: July 6, 2016
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.