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]

## Contents

* 1 Function
* 2 Mechanism of action
* 3 Isoforms
* 4 Disease linkage
* 5 References
* 6 External links

## Function

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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

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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

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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

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Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance.[7]

## References

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1. ↑ 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.
2. ↑ 2.0 2.1 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. doi:10.1124/pr.58.4.3. PMID 17132849.
3. ↑ Yen PM (2001). "Physiological and molecular basis of thyroid hormone action". Physiol Rev. 81 (3): 1097–142. PMID 11427693.
4. ↑ Harvey CB, Williams GR (2002). "Mechanism of thyroid hormone action". Thyroid. 12 (6): 441–6. doi:10.1089/105072502760143791. PMID 12165104.
5. ↑ Brent GA (2000). "Tissue-specific actions of thyroid hormone: insights from animal models". Rev Endocr Metab Disord. 1 (1–2): 27–33. doi:10.1023/A:1010056202122. PMID 11704989.
6. ↑ 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. doi:10.1038/355446a0. PMID 1310351.
7. ↑ Olateju TO, Vanderpump MP (2006). "Thyroid hormone resistance". Ann Clin Biochem. 43 (Pt 6): 431–40. doi:10.1258/000456306778904678. PMID 17132274.

## External links

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* Overview at vivo.colostate.edu
* Thyroid+Hormone+Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

Transcription factors and intracellular receptors

(1) Basic domains

| (1.1) Basic leucine zipper (bZIP)|

* Activating transcription factor
* AATF
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* AP-1
* c-Fos
* FOSB
* FOSL1
* FOSL2
* JDP2
* c-Jun
* JUNB
* JunD
* BACH
* 1
* 2
* BATF
* BLZF1
* C/EBP
* α
* β
* γ
* δ
* ε
* ζ
* CREB
* 1
* 3
* L1
* CREM
* DBP
* DDIT3
* GABPA
* GCN4
* HLF
* MAF
* B
* F
* G
* K
* NFE
* 2
* L1
* L2
* L3
* NFIL3
* NRL
* NRF
* 1
* 2
* 3
* XBP1

|

(1.2) Basic helix-loop-helix (bHLH)|

* ATOH1
* AhR
* AHRR
* ARNT
* ASCL1
* BHLH
* 2
* 3
* 9
* ARNTL
* ARNTL
* ARNTL2
* CLOCK
* EPAS1
* FIGLA
* HAND
* 1
* 2
* HES
* 5
* 6
* HEY
* 1
* 2
* L
* HES1
* HIF
* 1A
* 3A
* ID
* 1
* 2
* 3
* 4
* LYL1
* MESP2
* MXD4
* MYCL1
* MYCN
* Myogenic regulatory factors
* MyoD
* Myogenin
* MYF5
* MYF6
* Neurogenins
* 1
* 2
* 3
* NeuroD
* 1
* 2
* NPAS
* 1
* 2
* 3
* OLIG
* 1
* 2
* Pho4
* Scleraxis
* SIM
* 1
* 2
* TAL
* 1
* 2
* Twist
* USF1

(1.3) bHLH-ZIP|

* AP-4
* MAX
* MXD3
* MITF
* MNT
* MLX
* MXI1
* Myc
* SREBP
* 1
* 2

(1.4) NF-1|

* NFI
* A
* B
* C
* X
* SMAD
* R-SMAD
* 1
* 2
* 3
* 5
* 9
* I-SMAD
* 6
* 7
* 4)

(1.5) RF-X|

* RFX
* 1
* 2
* 3
* 4
* 5
* 6
* ANK

(1.6) Basic helix-span-helix (bHSH)|

* AP-2
* α
* β
* γ
* δ
* ε

(2) Zinc finger DNA-binding domains

| (2.1) Nuclear receptor (Cys4)|

| subfamily 1|

* Thyroid hormone
* α
* β
* CAR
* FXR
* LXR
* α
* β
* PPAR
* α
* β/δ
* γ
* PXR
* RAR
* α
* β
* γ
* ROR
* α
* β
* γ
* Rev-ErbA
* α
* β
* VDR

|

subfamily 2|

* COUP-TF
* (I
* II
* Ear-2
* HNF4
* α
* γ
* PNR
* RXR
* α
* β
* γ
* Testicular receptor
* 2
* 4
* TLX

subfamily 3|

* Steroid hormone
* Androgen
* Estrogen
* α
* β
* Glucocorticoid
* Mineralocorticoid
* Progesterone
* Estrogen related
* α
* β
* γ

subfamily 4|

* NUR
* NGFIB
* NOR1
* NURR1

subfamily 5|

* LRH-1
* SF1

subfamily 6|

* GCNF

subfamily 0|

* DAX1
* SHP

(2.2) Other Cys4|

* GATA
* 1
* 2
* 3
* 4
* 5
* 6
* MTA
* 1
* 2
* 3
* TRPS1

(2.3) Cys2His2|

* General transcription factors
* TFIIA
* TFIIB
* TFIID
* TFIIE
* 1
* 2
* TFIIF
* 1
* 2
* TFIIH
* 1
* 2
* 4
* 2I
* 3A
* 3C1
* 3C2

* ATBF1
* BCL
* 6
* 11A
* 11B
* CTCF
* E4F1
* EGR
* 1
* 2
* 3
* 4
* ERV3
* GFI1
* GLI-Krüppel family
* 1
* 2
* 3
* REST
* S1
* S2
* YY1
* HIC
* 1
* 2
* HIVEP
* 1
* 2
* 3
* IKZF
* 1
* 2
* 3
* ILF
* 2
* 3
* KLF
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10
* 11
* 12
* 13
* 14
* 15
* 17
* MTF1
* MYT1
* OSR1
* PRDM9
* SALL
* 1
* 2
* 3
* 4
* SP
* 1
* 2
* 4
* 7
* 8
* TSHZ3
* WT1
* Zbtb7
* 7A
* 7B
* ZBTB
* 11
* 16
* 17
* 20
* 32
* 33
* 40
* zinc finger
* 3
* 7
* 9
* 10
* 19
* 22
* 24
* 33B
* 34
* 35
* 41
* 43
* 44
* 51
* 74
* 143
* 146
* 148
* 165
* 202
* 217
* 219
* 238
* 239
* 259
* 267
* 268
* 281
* 295
* 300
* 318
* 330
* 346
* 350
* 365
* 366
* 384
* 423
* 451
* 452
* 471
* 593
* 638
* 644
* 649
* 655

(2.4) Cys6|

* HIVEP1

(2.5) Alternating composition|

* AIRE
* DIDO1
* GRLF1
* ING
* 1
* 2
* 4
* JARID
* 1A
* 1B
* 1C
* 1D
* 2
* JMJD1B

(2.6) WRKY|

* WRKY

(3) Helix-turn-helix domains

| (3.1) Homeodomain|

* ARX
* CDX
* 1
* 2
* CRX
* CUTL1
* DBX
* 1
* 2
* DLX
* 1
* 2
* 3
* 4
* 5
* 6
* EMX
* 1
* 2
* EN
* 1
* 2
* FHL
* 1
* 2
* 3
* HESX1
* HHEX
* HLX
* Homeobox
* A1
* A2
* A3
* A4
* A5
* A7
* A9
* A10
* A11
* A13
* B1
* B2
* B3
* B4
* B5
* B6
* B7
* B8
* B9
* B13
* C4
* C5
* C6
* C8
* C9
* C10
* C11
* C12
* C13
* D1
* D3
* D4
* D8
* D9
* D10
* D11
* D12
* D13
* HOPX
* IRX
* 1
* 2
* 3
* 4
* 5
* 6
* MKX
* LMX
* 1A
* 1B
* MEIS
* 1
* 2
* MEOX2
* MNX1
* MSX
* 1
* 2
* NANOG
* NKX
* 2-1
* 2-2
* 2-3
* 2-5
* 3-1
* 3-2
* 6-1
* 6-2
* NOBOX
* PBX
* 1
* 2
* 3
* PHF
* 1
* 3
* 6
* 8
* 10
* 16
* 17
* 20
* 21A
* PHOX
* 2A
* 2B
* PITX
* 1
* 2
* 3
* POU domain
* PIT-1
* BRN-3: A
* B
* C
* Octamer transcription factor: 1
* 2
* 3/4
* 6
* 7
* 11
* OTX
* 1
* 2
* PDX1
* SATB2
* SHOX2
* SIX
* 1
* 2
* 3
* 4
* 5
* VAX1
* ZEB
* 1
* 2

|

(3.2) Paired box|

* PAX
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* PRRX
* 1
* 2
* RAX

(3.3) Fork head / winged helix|

* E2F
* 1
* 2
* 3
* 4
* 5
* FOX proteins
* A1
* A2
* A3
* C1
* C2
* D3
* D4
* E1
* E3
* F1
* G1
* H1
* I1
* J1
* J2
* K1
* K2
* L2
* M1
* N1
* N3
* O1
* O3
* O4
* P1
* P2
* P3
* P4

(3.4) Heat shock factors|

* HSF
* 1
* 2
* 4

(3.5) Tryptophan clusters|

* ELF
* 2
* 4
* 5
* EGF
* ELK
* 1
* 3
* 4
* ERF
* ETS
* 1
* 2
* ERG
* SPIB
* ETV
* 1
* 4
* 5
* 6
* FLI1
* Interferon regulatory factors
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* MYB
* MYBL2

(3.6) TEA domain|

* transcriptional enhancer factor
* 1
* 2
* 3
* 4

(4) β-Scaffold factors with minor groove contacts

| (4.1) Rel homology region|

* NF-κB
* NFKB1
* NFKB2
* REL
* RELA
* RELB
* NFAT
* C1
* C2
* C3
* C4
* 5

|

(4.2) STAT|

* STAT
* 1
* 2
* 3
* 4
* 5
* 6

(4.3) p53|

* p53
* TBX
* 1
* 2
* 3
* 5
* 19
* 21
* 22
* TBR1
* TBR2
* TFT
* MYRF
* TP63

(4.4) MADS box|

* Mef2
* A
* B
* C
* D
* SRF

(4.6) TATA-binding proteins|

* TBP
* TBPL1

(4.7) High-mobility group|

* BBX
* HMGB
* 1
* 2
* 3
* 4
* HMGN
* 1
* 2
* 3
* 4
* HNF
* 1A
* 1B
* LEF1
* SOX
* 1
* 2
* 3
* 4
* 5
* 6
* 8
* 9
* 10
* 11
* 12
* 13
* 14
* 15
* 18
* 21
* SRY
* SSRP1
* TCF
* 3
* 4
* TOX
* 1
* 2
* 3
* 4

(4.9) Grainyhead|

* TFCP2

(4.10) Cold-shock domain|

* CSDA
* YBX1

(4.11) Runt|

* CBF
* CBFA2T2
* CBFA2T3
* RUNX1
* RUNX2
* RUNX3
* RUNX1T1

(0) Other transcription factors

| (0.2) HMGI(Y)|

* HMGA
* 1
* 2
* HBP1

|

(0.3) Pocket domain|

* Rb
* RBL1
* RBL2

(0.5) AP-2/EREBP-related factors|

* Apetala 2
* EREBP
* B3

(0.6) Miscellaneous|

* ARID
* 1A
* 1B
* 2
* 3A
* 3B
* 4A
* CAP
* IFI
* 16
* 35
* MLL
* 2
* 3
* T1
* MNDA
* NFY
* A
* B
* C
* Rho/Sigma

see also transcription factor/coregulator deficiencies

* v
* t
* e

Thyroid hormone receptor modulators

Receptor
(ligands)|

| THR|

* Agonists: Dextrothyroxine
* DIMIT
* DITPA
* Eprotirome (KB-2115)
* KB-141
* KB-2611
* KB-130015
* Levothyroxine
* Liothyronine
* Liotrix
* MB-07344
* MB-07811
* MGL-3196 (VIA-3196)
* Sobetirome (GC-1, GRX-431)
* Thyroxine
* Tiratricol (TRIAC)
* Triiodothyronine
* Thyroid extract
* VK-0214
* VK-2809
* ZYT1

* Antagonists: 1-850
* NH3
* Tetraiodothyroacetic acid (Tetrac)

|

Transporter
(blockers)|

| NIS

* Inhibitors: Cyanogenic glycosides
* Perchlorates (e.g., potassium perchlorate)
* Pertechnetates (e.g., sodium pertechnetate)
* Thiocyanates

|

Enzyme
(inhibitors)|

| TPO|

* Inhibitors: Benzylthiouracil
* Carbimazole
* Genistein
* Methimazole
* Methylthiouracil
* Propylthiouracil
* Thiouracil
* Thiourea

|

DIO|

* Inhibitors: Dexpropranolol
* Iopanoic acid
* Ipodate sodium (sodium iopodate)
* Propranolol
* Propylthiouracil

Others|

* Iodine
* Iodine-131
* Selenium
* Thyroglobulin
* Tyrosine

* See also: Receptor/signaling modulators
* Nuclear receptor modulators

*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[THR]: Thyroid hormone receptor
*[NIS]: Sodium-iodide symporter
*[TPO]: Thyroid peroxidase
*[DIO]: Iodothyronine deiodinase