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Protein

Thyroid hormone receptor alpha

Gene

Thra

Organism
Mus musculus (Mouse)
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. Isoform Alpha-deltaE6 does not bind DNA, inhibits the activity of isoform Alpha-1, and stimulates myoblast differentiation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei228Thyroid hormoneBy similarity1
Binding sitei277Thyroid hormone; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi53 – 127Nuclear receptorPROSITE-ProRule annotationAdd BLAST75
Zinc fingeri53 – 73NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri91 – 115NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

  • animal organ morphogenesis Source: MGI
  • cartilage condensation Source: MGI
  • cytoplasmic sequestering of transcription factor Source: MGI
  • erythrocyte differentiation Source: MGI
  • female courtship behavior Source: MGI
  • hormone-mediated signaling pathway Source: MGI
  • learning or memory Source: MGI
  • negative regulation of DNA-templated transcription, initiation Source: MGI
  • negative regulation of RNA polymerase II transcriptional preinitiation complex assembly Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • ossification Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of female receptivity Source: MGI
  • positive regulation of myotube differentiation Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • regulation of heart contraction Source: MGI
  • regulation of lipid catabolic process Source: MGI
  • regulation of myeloid cell apoptotic process Source: MGI
  • regulation of thyroid hormone mediated signaling pathway Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: MGI
  • response to cold Source: MGI
  • thyroid gland development Source: MGI
  • transcription from RNA polymerase II promoter Source: MGI
  • Type I pneumocyte differentiation Source: MGI
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-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98742. Thra.

Subcellular locationi

Isoform Alpha-deltaE6 :

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000534251 – 492Thyroid hormone receptor alphaAdd BLAST492

Proteomic databases

MaxQBiP63058.
PaxDbiP63058.
PRIDEiP63058.

PTM databases

iPTMnetiP63058.
PhosphoSitePlusiP63058.

Expressioni

Tissue specificityi

Ubiquitous (Isoform Alpha-deltaE6).1 Publication

Gene expression databases

BgeeiENSMUSG00000058756.
CleanExiMM_THRA.
ExpressionAtlasiP63058. baseline and differential.
GenevisibleiP63058. MM.

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 AKAP13. Interacts with C1D. Interacts with TP53INP2. Interacts with PER2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Cacnb4D4A0552EBI-6935292,EBI-8028403From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204183. 5 interactors.
DIPiDIP-43752N.
IntActiP63058. 2 interactors.
MINTiMINT-3374329.
STRINGi10090.ENSMUSP00000099428.

Structurei

3D structure databases

ProteinModelPortaliP63058.
SMRiP63058.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 52ModulatingAdd BLAST52
Regioni190 – 370Ligand-bindingAdd BLAST181

Domaini

Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. Isoform Alpha-deltaE6 lacks the hinge region that connects the modulating domain and the DNA binding domain.

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri53 – 73NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri91 – 115NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00850000132242.
HOVERGENiHBG005606.
InParanoidiP63058.
KOiK05547.
OMAiMEHMPKE.
OrthoDBiEOG091G0GC1.
PhylomeDBiP63058.
TreeFamiTF328382.

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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Alpha-2 (identifier: P63058-1) [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 PQVRQLEQQL GEAGSLRGPV LQHQSPKSPQ QRLLELLHRS
460 470 480 490
GILHSRAVCG EDDSSEASSL SSSSDTEDTE VCEDQAGKAA SP
Length:492
Mass (Da):55,023
Last modified:January 19, 2010 - v2
Checksum:i870100FCB5C34A10
GO
Isoform Alpha-1 (identifier: P63058-2) [UniParc] [UniParc]FASTAAdd to basket

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

Show »
Length:410
Mass (Da):46,795
Checksum:iEC0240EF1ECF4111
GO
Isoform Alpha-3 (identifier: P63058-3) [UniParc] [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     371-409: Missing.

Show »
Length:453
Mass (Da):50,954
Checksum:i6DE1FECA97686CAF
GO
Isoform Alpha-deltaE6 (identifier: P63058-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     121-197: AMDLVLDDSK...RRKFLPDDIG → GTSP
     371-492: EREVQSSILY...EDQAGKAASP → VTDLRMIGAC...FLEVFEDQEV

Note: Due to mismatches with the underlying genomic sequence that lie within a microexon, this isoform has been proposed to undergo RNA editing involving both base insertion and deletion.
Show »
Length:337
Mass (Da):37,926
Checksum:i27137623BED67783
GO

Sequence cautioni

The sequence CAM46188 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106Q → H in CAA36241 (PubMed:2349106).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038640121 – 197AMDLV…PDDIG → GTSP in isoform Alpha-deltaE6. CuratedAdd BLAST77
Alternative sequenceiVSP_003624371 – 492EREVQ…KAASP → VTDLRMIGACHASRFLHMKV ECPTELFPPLFLEVFEDQEV in isoform Alpha-1 and isoform Alpha-deltaE6. 3 PublicationsAdd BLAST122
Alternative sequenceiVSP_003625371 – 409Missing in isoform Alpha-3. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07750 mRNA. Translation: CAA30575.1.
X07751 mRNA. Translation: CAA30576.1.
X07752 mRNA. Translation: CAA30577.1.
X51983 mRNA. Translation: CAA36241.1.
AK078233 mRNA. Translation: BAC37186.1.
AL590963 Genomic DNA. Translation: CAM46188.1. Sequence problems.
AL590963 Genomic DNA. Translation: CAM46189.1.
AL590963 Genomic DNA. Translation: CAM46190.1.
CH466556 Genomic DNA. Translation: EDL16164.1.
CH466556 Genomic DNA. Translation: EDL16165.1.
BC046795 mRNA. Translation: AAH46795.1.
CCDSiCCDS25362.1. [P63058-2]
PIRiS14416.
S14417.
S14418.
S14690. QRMSA1.
RefSeqiNP_001300912.1. NM_001313983.1. [P63058-1]
NP_835161.1. NM_178060.4. [P63058-2]
UniGeneiMm.265917.
Mm.442648.

Genome annotation databases

EnsembliENSMUST00000064187; ENSMUSP00000068281; ENSMUSG00000058756. [P63058-1]
ENSMUST00000103139; ENSMUSP00000099428; ENSMUSG00000058756. [P63058-2]
GeneIDi21833.
KEGGimmu:21833.
UCSCiuc007lhe.1. mouse. [P63058-2]
uc007lhf.1. mouse.
uc007lhg.1. mouse. [P63058-3]

Keywords - Coding sequence diversityi

Alternative splicing, RNA editing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X07750 mRNA. Translation: CAA30575.1.
X07751 mRNA. Translation: CAA30576.1.
X07752 mRNA. Translation: CAA30577.1.
X51983 mRNA. Translation: CAA36241.1.
AK078233 mRNA. Translation: BAC37186.1.
AL590963 Genomic DNA. Translation: CAM46188.1. Sequence problems.
AL590963 Genomic DNA. Translation: CAM46189.1.
AL590963 Genomic DNA. Translation: CAM46190.1.
CH466556 Genomic DNA. Translation: EDL16164.1.
CH466556 Genomic DNA. Translation: EDL16165.1.
BC046795 mRNA. Translation: AAH46795.1.
CCDSiCCDS25362.1. [P63058-2]
PIRiS14416.
S14417.
S14418.
S14690. QRMSA1.
RefSeqiNP_001300912.1. NM_001313983.1. [P63058-1]
NP_835161.1. NM_178060.4. [P63058-2]
UniGeneiMm.265917.
Mm.442648.

3D structure databases

ProteinModelPortaliP63058.
SMRiP63058.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204183. 5 interactors.
DIPiDIP-43752N.
IntActiP63058. 2 interactors.
MINTiMINT-3374329.
STRINGi10090.ENSMUSP00000099428.

PTM databases

iPTMnetiP63058.
PhosphoSitePlusiP63058.

Proteomic databases

MaxQBiP63058.
PaxDbiP63058.
PRIDEiP63058.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000064187; ENSMUSP00000068281; ENSMUSG00000058756. [P63058-1]
ENSMUST00000103139; ENSMUSP00000099428; ENSMUSG00000058756. [P63058-2]
GeneIDi21833.
KEGGimmu:21833.
UCSCiuc007lhe.1. mouse. [P63058-2]
uc007lhf.1. mouse.
uc007lhg.1. mouse. [P63058-3]

Organism-specific databases

CTDi7067.
MGIiMGI:98742. Thra.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00850000132242.
HOVERGENiHBG005606.
InParanoidiP63058.
KOiK05547.
OMAiMEHMPKE.
OrthoDBiEOG091G0GC1.
PhylomeDBiP63058.
TreeFamiTF328382.

Enzyme and pathway databases

ReactomeiR-MMU-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiP63058.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000058756.
CleanExiMM_THRA.
ExpressionAtlasiP63058. baseline and differential.
GenevisibleiP63058. MM.

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...

Entry informationi

Entry nameiTHA_MOUSE
AccessioniPrimary (citable) accession number: P63058
Secondary accession number(s): A3KFN4
, P10685, P15827, P16416, P37241, Q542U8, Q63107, Q63195, Q63196, Q80Y90, Q99146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: January 19, 2010
Last modified: November 30, 2016
This is version 135 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.