THRA
Thyroid hormone receptor alpha
Also known as: AR7, EAR-7.1/EAR-7.2, ERBA, ERBA1, NR1A1, THA_HUMAN, THRA1, THRA2, THRA3, TRalpha
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P10827
- Gene
- THRA
- Ensembl
- ENSG00000126351
- Chromosome
- 17
- Canonical length
- 490 aa
- Protein class
- Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Nuclear receptors, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
490 residues, UniProt reviewed canonical sequence.
>P10827|THRA
1 MEQKPSKVEC GSDPEENSAR SPDGKRKRKN GQCSLKTSMS GYIPSYLDKD EQCVVCGDKA
61 TGYHYRCITC EGCKGFFRRT IQKNLHPTYS CKYDSCCVID KITRNQCQLC RFKKCIAVGM
121 AMDLVLDDSK RVAKRKLIEQ NRERRRKEEM IRSLQQRPEP TPEEWDLIHI ATEAHRSTNA
181 QGSHWKQRRK FLPDDIGQSP IVSMPDGDKV DLEAFSEFTK IITPAITRVV DFAKKLPMFS
241 ELPCEDQIIL LKGCCMEIMS LRAAVRYDPE SDTLTLSGEM AVKREQLKNG GLGVVSDAIF
301 ELGKSLSAFN LDDTEVALLQ AVLLMSTDRS GLLCVDKIEK SQEAYLLAFE HYVNHRKHNI
361 PHFWPKLLMK EREVQSSILY KGAAAEGRPG GSLGVHPEGQ QLLGMHVVQG PQVRQLEQQL
421 GEAGSLQGPV LQHQSPKSPQ QRLLELLHRS GILHARAVCG EDDSSEADSP SSSEEEPEVC
481 EDLAGNAASPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against THRA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.37
- Highest tissue expression
- 401 nTPM
Expression across tissuesHPA
Tissue
- basal ganglia: 401 nTPM
- amygdala: 267 nTPM
- cerebral cortex: 254 nTPM
- hippocampal formation: 200 nTPM
- hypothalamus: 176 nTPM
- midbrain: 166 nTPM
Single-cell type
- müller glia: 79 nCPM
- retinal amacrine cells: 77 nCPM
- vascular smooth muscle cells: 75 nCPM
- ovarian stromal cells: 70 nCPM
- retinal bipolar cells: 67 nCPM
- fallopian secretory cells: 65 nCPM
Immune cell
- NK-cell: 2.1 nTPM
- gdT-cell: 2 nTPM
- eosinophil: 1.9 nTPM
- naive CD8 T-cell: 1.7 nTPM
- naive CD4 T-cell: 1.4 nTPM
- memory CD8 T-cell: 1.2 nTPM
Brain region
- basal ganglia: 344 nTPM
- amygdala: 265 nTPM
- cerebral cortex: 246 nTPM
- hippocampal formation: 238 nTPM
- hypothalamus: 235 nTPM
- white matter: 226 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about THRA.
Disease | AllUniProt
Conditions THRA is implicated in, by any mechanism.
- Hypothyroidism, congenital, non-goitrous, 6 (CHNG6) MIM:614450
Disease | GeneticClinVar
19 pathogenic / likely-pathogenic of 102 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Congenital nongoitrous hypothyroidism 6
- Inborn genetic diseases
- Neurodevelopmental disorder
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.45
- gnomAD pLI
- 0.33
- gnomAD missense Z
- 3.47
- DepMap mean gene effect
- -0.09
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cartilage condensation
- cell differentiation
- erythrocyte differentiation
- female courtship behavior
- hormone-mediated signaling pathway
- learning or memory
- mRNA transcription by RNA polymerase II
- negative regulation of DNA-templated transcription
- negative regulation of DNA-templated transcription initiation
- negative regulation of RNA polymerase II transcription preinitiation complex assembly
- negative regulation of transcription by RNA polymerase II
- ossification
- positive regulation of cold-induced thermogenesis
- positive regulation of female receptivity
- positive regulation of thyroid hormone receptor signaling pathway
- positive regulation of transcription by RNA polymerase II
- regulation of heart contraction
- regulation of lipid catabolic process
- regulation of transcription by RNA polymerase II
- response to cold
- retinoic acid receptor signaling pathway
- thyroid gland development
- thyroid hormone receptor signaling pathway
- transcription by RNA polymerase II
- type I pneumocyte differentiation
- regulation of myeloid cell apoptotic process
Molecular functions
- chromatin DNA binding
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- general transcription initiation factor binding
- nuclear receptor activity
- protein domain specific binding
- protein-containing complex binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- TBP-class protein binding
- thyroid hormone binding
- transcription cis-regulatory region binding
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Nuclear hormone receptor, ligand-binding domain
- Zinc finger, nuclear hormone receptor-type
- Nuclear hormone receptor
- Thyroid hormone receptor
- Zinc finger, NHR/GATA-type
- Nuclear hormone receptor-like domain superfamily
- Nuclear hormone receptor family NR1 subfamily
- Ligand-binding domain of nuclear hormone receptor
- Double treble clef zinc finger, C4 type
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of THRA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads THRA as an antibody target. Whether an autoantibody or antibody against THRA could matter depends on whether native THRA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
THRA is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label THRA as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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