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Protein

Thyroid hormone receptor alpha

Gene

THRA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.4 Publications
Isoform Alpha-2: Does not bind thyroid hormone and functions as a weak dominant negative inhibitor of thyroid hormone action.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei228Thyroid hormone1
Binding sitei277Thyroid hormone; via amide nitrogen1

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

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-4090294 SUMOylation of intracellular receptors
SignaLinkiP10827
SIGNORiP10827

Names & Taxonomyi

Protein namesi
Recommended name:
Thyroid hormone receptor alpha
Alternative name(s):
Nuclear receptor subfamily 1 group A member 1
V-erbA-related protein 7
Short name:
EAR-7
c-erbA-1
c-erbA-alpha
Gene namesi
Name:THRA
Synonyms:EAR7, ERBA1, NR1A1, THRA1, THRA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000126351.12
HGNCiHGNC:11796 THRA
MIMi190120 gene
neXtProtiNX_P10827

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hypothyroidism, congenital, non-goitrous, 6 (CHNG6)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance.
See also OMIM:614450
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074559263A → V in CHNG6; no effect on T3 binding; no effect on thyroid hormone-dependent transcriptional activation. 1 Publication1
Natural variantiVAR_074560359N → Y in CHNG6; atypical phenotype; weak reduction in transcriptional activation. 1 Publication1
Isoform Alpha-1 (identifier: P10827-2)
Natural varianti263A → V in CHNG6, reduces T3 binding, impairs thyroid hormone-dependent transcriptional activation, no effect on DNA-binding) (Ref.23. 3 Publications1
Natural varianti359N → Y in CHNG6, decreases transcriptional activity, decreases T3 binding) (Ref.24. 3 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi277S → N: No effect on thyroid hormone binding. 2 Publications1

Keywords - Diseasei

Congenital hypothyroidism, Disease mutation

Organism-specific databases

DisGeNETi7067
MalaCardsiTHRA
MIMi614450 phenotype
OpenTargetsiENSG00000126351
Orphaneti97927 Peripheral resistance to thyroid hormones
PharmGKBiPA36507

Chemistry databases

ChEMBLiCHEMBL1860
DrugBankiDB00509 Dextrothyroxine
DB05035 KB2115
DB00451 Levothyroxine
DB00279 Liothyronine
DB01583 Liotrix
DB05235 NRP409
GuidetoPHARMACOLOGYi588

Polymorphism and mutation databases

BioMutaiTHRA
DMDMi135705

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000534241 – 490Thyroid hormone receptor alphaAdd BLAST490

Proteomic databases

MaxQBiP10827
PaxDbiP10827
PeptideAtlasiP10827
PRIDEiP10827
ProteomicsDBi52657
52658 [P10827-2]
52659 [P10827-3]
52660 [P10827-4]

PTM databases

iPTMnetiP10827
PhosphoSitePlusiP10827

Expressioni

Gene expression databases

BgeeiENSG00000126351 Expressed in 221 organ(s), highest expression level in nucleus accumbens
CleanExiHS_THRA
ExpressionAtlasiP10827 baseline and differential
GenevisibleiP10827 HS

Organism-specific databases

HPAiCAB023349
HPA009654

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 PER2.8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112923, 80 interactors
ComplexPortaliCPX-662 RXRalpha-TRalpha nuclear hormone receptor complex [P10827-2]
CORUMiP10827
DIPiDIP-31452N
IntActiP10827, 27 interactors
MINTiP10827
STRINGi9606.ENSP00000264637

Chemistry databases

BindingDBiP10827

Structurei

Secondary structure

1490
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP10827
SMRiP10827
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10827

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini163 – 407NR LBDPROSITE-ProRule annotationAdd BLAST245

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 52ModulatingAdd BLAST52

Domaini

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

Sequence similaritiesi

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
GeneTreeiENSGT00870000136372
HOGENOMiHOG000010313
HOVERGENiHBG005606
InParanoidiP10827
KOiK05547
OMAiAQGAQWK
OrthoDBiEOG091G0GC1
PhylomeDBiP10827
TreeFamiTF328382

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001728 ThyrH_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
PR00546 THYROIDHORMR
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform Alpha-2 (identifier: P10827-1) [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 GQCSLKTSMS 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 TPEEWDLIHI 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 GEAGSLQGPV LQHQSPKSPQ QRLLELLHRS
460 470 480 490
GILHARAVCG EDDSSEADSP SSSEEEPEVC EDLAGNAASP
Length:490
Mass (Da):54,816
Last modified:July 1, 1989 - v1
Checksum:iC87C7D2F67B1AE49
GO
Isoform Alpha-1 (identifier: P10827-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     371-490: EREVQSSILY...EDLAGNAASP → VTDLRMIGAC...FLEVFEDQEV

Show »
Length:410
Mass (Da):46,813
Checksum:iB9FD7BFAC16D6882
GO
Isoform Alpha-3 (identifier: P10827-3) [UniParc]FASTAAdd to basket

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

Show »
Length:451
Mass (Da):50,747
Checksum:i1495A3F2EE6601DD
GO
Isoform Alpha-4 (identifier: P10827-4) [UniParc]FASTAAdd to basket
Also known as: Alpha3

The sequence of this isoform differs from the canonical sequence as follows:
     371-412: Missing.

Show »
Length:448
Mass (Da):50,465
Checksum:i15FD778790B4D26B
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QRA9J3QRA9_HUMAN
Thyroid hormone receptor alpha
THRA
84Annotation score:
J3KTF3J3KTF3_HUMAN
Thyroid hormone receptor alpha
THRA
72Annotation score:
J3QR26J3QR26_HUMAN
Thyroid hormone receptor alpha
THRA
31Annotation score:
J3QRW5J3QRW5_HUMAN
Thyroid hormone receptor alpha
THRA
57Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti37T → S in CAA68539 (PubMed:3684612).Curated1
Sequence conflicti119G → A in CAA68539 (PubMed:3684612).Curated1
Sequence conflicti285E → A in CAB57886 (PubMed:1850510).Curated1
Sequence conflicti285E → A in CAA38899 (PubMed:1850510).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074559263A → V in CHNG6; no effect on T3 binding; no effect on thyroid hormone-dependent transcriptional activation. 1 Publication1
Natural variantiVAR_074560359N → Y in CHNG6; atypical phenotype; weak reduction in transcriptional activation. 1 Publication1
Isoform Alpha-1 (identifier: P10827-2)
Natural varianti263A → V in CHNG6, reduces T3 binding, impairs thyroid hormone-dependent transcriptional activation, no effect on DNA-binding) (Ref.23. 3 Publications1
Natural varianti359N → Y in CHNG6, decreases transcriptional activity, decreases T3 binding) (Ref.24. 3 Publications1
Natural varianti398P → R in CHNG6) (Ref.25. 3 Publications1
Natural varianti403E → Q in CHNG6) (Ref.25. 3 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003621371 – 490EREVQ…NAASP → VTDLRMIGACHASRFLHMKV ECPTELFPPLFLEVFEDQEV in isoform Alpha-1. 2 PublicationsAdd BLAST120
Alternative sequenceiVSP_003623371 – 412Missing in isoform Alpha-4. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_003622371 – 409Missing in isoform Alpha-3. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55074
, X55073, X55070, X55071, X55004, X55069, X55068, X55066 Genomic DNA Translation: CAB57886.1
X55005 mRNA Translation: CAA38749.1
X55074
, X55073, X55070, X55071, X55004, X55069, X55068 Genomic DNA Translation: CAA38899.1
M24899 mRNA Translation: AAA35783.1
M24900 mRNA Translation: AAA52333.1
J03239 mRNA Translation: AAA61176.1
Y00479 mRNA Translation: CAA68539.1
M24748 Genomic DNA Translation: AAA66021.1
AK290530 mRNA Translation: BAF83219.1
CH471152 Genomic DNA Translation: EAW60632.1
BC000261 mRNA Translation: AAH00261.1
BC002728 mRNA Translation: AAH02728.1
BC035137 mRNA Translation: AAH35137.1
AF522368 mRNA Translation: AAM77692.1
CCDSiCCDS11360.1 [P10827-1]
CCDS42316.1 [P10827-2]
CCDS58546.1 [P10827-3]
PIRiA30893
A40917
S06163
RefSeqiNP_001177847.1, NM_001190918.1 [P10827-3]
NP_001177848.1, NM_001190919.1 [P10827-1]
NP_003241.2, NM_003250.5 [P10827-1]
NP_955366.1, NM_199334.3 [P10827-2]
UniGeneiHs.724

Genome annotation databases

EnsembliENST00000264637; ENSP00000264637; ENSG00000126351 [P10827-1]
ENST00000394121; ENSP00000377679; ENSG00000126351 [P10827-1]
ENST00000450525; ENSP00000395641; ENSG00000126351 [P10827-2]
ENST00000546243; ENSP00000443972; ENSG00000126351 [P10827-2]
ENST00000584985; ENSP00000463466; ENSG00000126351 [P10827-3]
GeneIDi7067
KEGGihsa:7067
UCSCiuc002htw.4 human [P10827-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X55074
, X55073, X55070, X55071, X55004, X55069, X55068, X55066 Genomic DNA Translation: CAB57886.1
X55005 mRNA Translation: CAA38749.1
X55074
, X55073, X55070, X55071, X55004, X55069, X55068 Genomic DNA Translation: CAA38899.1
M24899 mRNA Translation: AAA35783.1
M24900 mRNA Translation: AAA52333.1
J03239 mRNA Translation: AAA61176.1
Y00479 mRNA Translation: CAA68539.1
M24748 Genomic DNA Translation: AAA66021.1
AK290530 mRNA Translation: BAF83219.1
CH471152 Genomic DNA Translation: EAW60632.1
BC000261 mRNA Translation: AAH00261.1
BC002728 mRNA Translation: AAH02728.1
BC035137 mRNA Translation: AAH35137.1
AF522368 mRNA Translation: AAM77692.1
CCDSiCCDS11360.1 [P10827-1]
CCDS42316.1 [P10827-2]
CCDS58546.1 [P10827-3]
PIRiA30893
A40917
S06163
RefSeqiNP_001177847.1, NM_001190918.1 [P10827-3]
NP_001177848.1, NM_001190919.1 [P10827-1]
NP_003241.2, NM_003250.5 [P10827-1]
NP_955366.1, NM_199334.3 [P10827-2]
UniGeneiHs.724

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NAVX-ray2.50A148-370[»]
2H77X-ray2.33A148-370[»]
2H79X-ray1.87A148-370[»]
3HZFX-ray2.50A148-370[»]
3ILZX-ray1.85A148-370[»]
3JZBX-ray2.01A148-370[»]
4LNWX-ray1.90A148-370[»]
4LNXX-ray2.05A148-370[»]
ProteinModelPortaliP10827
SMRiP10827
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112923, 80 interactors
ComplexPortaliCPX-662 RXRalpha-TRalpha nuclear hormone receptor complex [P10827-2]
CORUMiP10827
DIPiDIP-31452N
IntActiP10827, 27 interactors
MINTiP10827
STRINGi9606.ENSP00000264637

Chemistry databases

BindingDBiP10827
ChEMBLiCHEMBL1860
DrugBankiDB00509 Dextrothyroxine
DB05035 KB2115
DB00451 Levothyroxine
DB00279 Liothyronine
DB01583 Liotrix
DB05235 NRP409
GuidetoPHARMACOLOGYi588

PTM databases

iPTMnetiP10827
PhosphoSitePlusiP10827

Polymorphism and mutation databases

BioMutaiTHRA
DMDMi135705

Proteomic databases

MaxQBiP10827
PaxDbiP10827
PeptideAtlasiP10827
PRIDEiP10827
ProteomicsDBi52657
52658 [P10827-2]
52659 [P10827-3]
52660 [P10827-4]

Protocols and materials databases

DNASUi7067
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264637; ENSP00000264637; ENSG00000126351 [P10827-1]
ENST00000394121; ENSP00000377679; ENSG00000126351 [P10827-1]
ENST00000450525; ENSP00000395641; ENSG00000126351 [P10827-2]
ENST00000546243; ENSP00000443972; ENSG00000126351 [P10827-2]
ENST00000584985; ENSP00000463466; ENSG00000126351 [P10827-3]
GeneIDi7067
KEGGihsa:7067
UCSCiuc002htw.4 human [P10827-1]

Organism-specific databases

CTDi7067
DisGeNETi7067
EuPathDBiHostDB:ENSG00000126351.12
GeneCardsiTHRA
HGNCiHGNC:11796 THRA
HPAiCAB023349
HPA009654
MalaCardsiTHRA
MIMi190120 gene
614450 phenotype
neXtProtiNX_P10827
OpenTargetsiENSG00000126351
Orphaneti97927 Peripheral resistance to thyroid hormones
PharmGKBiPA36507
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00870000136372
HOGENOMiHOG000010313
HOVERGENiHBG005606
InParanoidiP10827
KOiK05547
OMAiAQGAQWK
OrthoDBiEOG091G0GC1
PhylomeDBiP10827
TreeFamiTF328382

Enzyme and pathway databases

ReactomeiR-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-4090294 SUMOylation of intracellular receptors
SignaLinkiP10827
SIGNORiP10827

Miscellaneous databases

ChiTaRSiTHRA human
EvolutionaryTraceiP10827
GeneWikiiThyroid_hormone_receptor_alpha
GenomeRNAii7067
PROiPR:P10827
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000126351 Expressed in 221 organ(s), highest expression level in nucleus accumbens
CleanExiHS_THRA
ExpressionAtlasiP10827 baseline and differential
GenevisibleiP10827 HS

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001728 ThyrH_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
PR00546 THYROIDHORMR
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTHA_HUMAN
AccessioniPrimary (citable) accession number: P10827
Secondary accession number(s): A8K3B5
, P21205, Q8N6A1, Q96H73
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 7, 2018
This is version 224 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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