Thyroid hormone receptor
| Thyroid hormone receptor alpha | |
|---|---|
| Identifiers | |
| Symbol | THRA |
| Alt. symbols | THRA1, THRA2, ERBA1 |
| Entrez | 7067 |
| HUGO | 11796 |
| OMIM | 190120 |
| RefSeq | NM_199334 |
| UniProt | P10827 |
| Other data | |
| Locus | Chr. 17 q11.2-17q12 |
| Thyroid hormone receptor beta | |
|---|---|
| Identifiers | |
| Symbol | THRB |
| Alt. symbols | ERBA2 |
| Entrez | 7068 |
| HUGO | 11799 |
| OMIM | 190160 |
| RefSeq | NM_000461 |
| UniProt | P10828 |
| Other data | |
| Locus | Chr. 3 p24.1-p22 |
The thyroid hormone receptor (TR)[1] is a type of nuclear receptor that is activated by binding thyroid hormone.[2]
Function
Among the most important functions of thyroid hormone receptors are regulation of metabolism and heart rate.[3][4] In addition, they play critical roles in the development of organisms.[5]
Mechanism of action
Thyroid hormone receptors regulate gene expression by binding to hormone response elements (HREs) in DNA either as monomers, heterodimers with retinoid X receptor (RXR; which in turn is activated by binding to 9-cis-retinoic acid) or as homodimers. However TR/RXR heterodimers are the most transcriptionally active form of TR.[6]
In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator proteins. The DNA/TR/coactivator complex then recruits RNA polymerase that transcribes downstream DNA into messenger RNA and eventually protein that results in a change in cell function.
Isoforms
There are three forms of the thyroid hormone receptor designated alpha-1, beta-1 and beta-2 that are able to bind thyroid hormone. There are two TR-α receptor splice variants encoded by the THRA gene and two TR-β isoform splice variants encoded by the THRB gene:[2]
- TR-α1 (widely expressed and especially high expression in cardiac and skeletal muscles)
- TR-α2 (homologous with viral oncogene c-erb-A, also widely expressed but unable to bind hormone)
- TR-β1 (predominately expressed in brain, liver and kidney)
- TR-β2 (expression primarily limited to the hypothalamus and pituitary)
Disease linkage
Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance.[7]
References
- ↑ Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B (1984). "Chromosomal localisation of the human homologues to the oncogenes erbA and B". EMBO J. 3 (1): 159–63. PMC 557313
. PMID 6323162. - 1 2 Flamant F, Baxter JD, Forrest D, Refetoff S, Samuels H, Scanlan TS, Vennstrom B, Samarut J (2006). "International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors". Pharmacol Rev. 58 (4): 705–11. PMID 17132849. doi:10.1124/pr.58.4.3.
- ↑ Yen PM (2001). "Physiological and molecular basis of thyroid hormone action". Physiol Rev. 81 (3): 1097–142. PMID 11427693.
- ↑ Harvey CB, Williams GR (2002). "Mechanism of thyroid hormone action". Thyroid (journal). 12 (6): 441–6. PMID 12165104. doi:10.1089/105072502760143791.
- ↑ Brent GA (2000). "Tissue-specific actions of thyroid hormone: insights from animal models". Rev Endocr Metab Disord. 1 (1–2): 27–33. PMID 11704989. doi:10.1023/A:1010056202122.
- ↑ Kliewer SA, Umesono K, Mangelsdorf DJ, Evans RM (January 1992). "Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling". Nature. 355 (6359): 446–9. PMID 1310351. doi:10.1038/355446a0.
- ↑ Olateju TO, Vanderpump MP (2006). "Thyroid hormone resistance". Ann Clin Biochem. 43 (Pt 6): 431–40. PMID 17132274. doi:10.1258/000456306778904678.
External links
- Overview at vivo.colostate.edu
- Thyroid Hormone Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)