Thyroid hormone receptor alpha

THRA

Available structures

Ortholog search: PDBe RCSB

List of PDB id codes
1NAV, 2H77, 2H79, 3HZF, 3ILZ, 3JZB, 4LNW, 4LNX

Identifiers

Aliases

THRA, AR7, CHNG6, EAR7, ERB-T-1, ERBA, ERBA1, NR1A1, THRA1, THRA2, c-ERBA-1, thyroid hormone receptor, alpha

External IDs

MGI: 98742 HomoloGene: 37747 GeneCards: THRA

Gene location (Human)

Chr.	Chromosome 17 (human)^[1]

Band	No data available	Start	40,058,290 bp^[1]
Band	No data available	End	40,093,867 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 11 (mouse)^[2]

Band	No data available	Start	98,740,638 bp^[2]
Band	No data available	End	98,769,006 bp^[2]

RNA expression pattern

More reference expression data

Gene ontology
Molecular function	• protein complex binding • transcription regulatory region sequence-specific DNA binding • protein binding • single-stranded RNA binding • zinc ion binding • chromatin DNA binding • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • steroid receptor RNA activator RNA binding • transcription factor binding • TBP-class protein binding • steroid hormone receptor activity • DNA binding • protein domain specific binding • sequence-specific DNA binding • metal ion binding • transcription regulatory region DNA binding • transcription factor activity, sequence-specific DNA binding • thyroid hormone receptor activity • thyroid hormone binding
Cellular component	• cytoplasm • nucleoplasm • nucleus • cytosol
Biological process	• regulation of transcription from RNA polymerase II promoter • response to cold • cytoplasmic sequestering of transcription factor • hormone-mediated signaling pathway • regulation of thyroid hormone mediated signaling pathway • thyroid gland development • regulation of transcription, DNA-templated • ossification • female courtship behavior • cartilage condensation • negative regulation of RNA polymerase II transcriptional preinitiation complex assembly • Type I pneumocyte differentiation • transcription, DNA-templated • steroid hormone mediated signaling pathway • transcription from RNA polymerase II promoter • regulation of lipid catabolic process • regulation of heart contraction • animal organ morphogenesis • positive regulation of female receptivity • learning or memory • regulation of myeloid cell apoptotic process • positive regulation of transcription from RNA polymerase II promoter • transcription initiation from RNA polymerase II promoter • erythrocyte differentiation • negative regulation of DNA-templated transcription, initiation • positive regulation of myotube differentiation • negative regulation of transcription, DNA-templated • intracellular receptor signaling pathway
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


7067


21833

Ensembl


ENSG00000126351


ENSMUSG00000058756

UniProt


P10827


P63058

RefSeq (mRNA)


NM_199334 NM_001190918 NM_001190919 NM_003250


NM_178060 NM_001313983

RefSeq (protein)


NP_001177847 NP_001177848 NP_003241 NP_955366


NP_001300912 NP_835161

Location (UCSC)

Chr 17: 40.06 – 40.09 Mb

Chr 17: 98.74 – 98.77 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the THRA gene.^[5]^[6]^[7]

Function

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.^[5]

Interactions

THR1 has been shown to interact with:

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000126351 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000058756 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
1 2 "Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian)".
↑ Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B (Jan 1984). "Chromosomal localisation of the human homologues to the oncogenes erbA and B". The EMBO Journal. 3 (1): 159–63. PMC 557313 . PMID 6323162.
↑ Dayton AI, Selden JR, Laws G, Dorney DJ, Finan J, Tripputi P, Emanuel BS, Rovera G, Nowell PC, Croce CM (Jul 1984). "A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 81 (14): 4495–9. PMC 345617 . PMID 6589608. doi:10.1073/pnas.81.14.4495.
↑ Dressel U, Thormeyer D, Altincicek B, Paululat A, Eggert M, Schneider S, Tenbaum SP, Renkawitz R, Baniahmad A (May 1999). "Alien, a highly conserved protein with characteristics of a corepressor for members of the nuclear hormone receptor superfamily". Molecular and Cellular Biology. 19 (5): 3383–94. PMC 84131 . PMID 10207062. doi:10.1128/mcb.19.5.3383.
1 2 De Luca A, Severino A, De Paolis P, Cottone G, De Luca L, De Falco M, Porcellini A, Volpe M, Condorelli G (Feb 2003). "p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor". The Biochemical Journal. 369 (Pt 3): 477–84. PMC 1223100 . PMID 12371907. doi:10.1042/BJ20020057.
↑ Li D, Wang F, Samuels HH (Dec 2001). "Domain structure of the NRIF3 family of coregulators suggests potential dual roles in transcriptional regulation". Molecular and Cellular Biology. 21 (24): 8371–84. PMC 100002 . PMID 11713274. doi:10.1128/MCB.21.24.8371-8384.2001.
↑ Li D, Desai-Yajnik V, Lo E, Schapira M, Abagyan R, Samuels HH (Oct 1999). "NRIF3 is a novel coactivator mediating functional specificity of nuclear hormone receptors". Molecular and Cellular Biology. 19 (10): 7191–202. PMC 84712 . PMID 10490654. doi:10.1128/mcb.19.10.7191.
↑ Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG (Jul 1998). "The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 7939–44. PMC 20908 . PMID 9653119. doi:10.1073/pnas.95.14.7939.
1 2 3 Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Molecular Cell. 3 (3): 361–70. PMID 10198638. doi:10.1016/S1097-2765(00)80463-3.
↑ Lee SK, Anzick SL, Choi JE, Bubendorf L, Guan XY, Jung YK, Kallioniemi OP, Kononen J, Trent JM, Azorsa D, Jhun BH, Cheong JH, Lee YC, Meltzer PS, Lee JW (Nov 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". The Journal of Biological Chemistry. 274 (48): 34283–93. PMID 10567404. doi:10.1074/jbc.274.48.34283.
↑ Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (Jun 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Molecular Endocrinology. 14 (6): 915–25. PMID 10847592. doi:10.1210/mend.14.6.0471.
↑ Chang KH, Chen Y, Chen TT, Chou WH, Chen PL, Ma YY, Yang-Feng TL, Leng X, Tsai MJ, O'Malley BW, Lee WH (Aug 1997). "A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein". Proceedings of the National Academy of Sciences of the United States of America. 94 (17): 9040–5. PMC 23019 . PMID 9256431. doi:10.1073/pnas.94.17.9040.
↑ Tan F, Lu L, Cai Y, Wang J, Xie Y, Wang L, Gong Y, Xu BE, Wu J, Luo Y, Qiang B, Yuan J, Sun X, Peng X (Jul 2008). "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells". Proteomics. 8 (14): 2885–96. PMID 18655026. doi:10.1002/pmic.200700887.

Forrest D, Reh TA, Rüsch A (Feb 2002). "Neurodevelopmental control by thyroid hormone receptors". Current Opinion in Neurobiology. 12 (1): 49–56. PMID 11861164. doi:10.1016/S0959-4388(02)00289-1.
Sakurai A, Bell GI, DeGroot LJ (Oct 1992). "Dinucleotide repeat polymorphism in the human thyroid hormone receptor alpha gene (THRA1) on chromosome 17". Human Molecular Genetics. 1 (7): 553. PMID 1307263. doi:10.1093/hmg/1.7.553-a.
Berrodin TJ, Marks MS, Ozato K, Linney E, Lazar MA (Sep 1992). "Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein". Molecular Endocrinology. 6 (9): 1468–78. PMID 1331778. doi:10.1210/me.6.9.1468.
Schmidt ED, Schmidt ED, van der Gaag R, Ganpat R, Broersma L, de Boer PA, Moorman AF, Lamers WH, Wiersinga WM, Koornneef L (Apr 1992). "Distribution of the nuclear thyroid-hormone receptor in extraocular and skeletal muscles". The Journal of Endocrinology. 133 (1): 67–74. PMID 1517709. doi:10.1677/joe.0.1330067.
Yen PM, Sunday ME, Darling DS, Chin WW (Mar 1992). "Isoform-specific thyroid hormone receptor antibodies detect multiple thyroid hormone receptors in rat and human pituitaries". Endocrinology. 130 (3): 1539–46. PMID 1537303. doi:10.1210/en.130.3.1539.
Laudet V, Begue A, Henry-Duthoit C, Joubel A, Martin P, Stehelin D, Saule S (Mar 1991). "Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene". Nucleic Acids Research. 19 (5): 1105–12. PMC 333788 . PMID 1850510. doi:10.1093/nar/19.5.1105.
Nakai A, Sakurai A, Bell GI, DeGroot LJ (Nov 1988). "Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues". Molecular Endocrinology. 2 (11): 1087–92. PMID 2464749. doi:10.1210/mend-2-11-1087.
Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T (Apr 1989). "Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus". Cell. 57 (1): 31–9. PMID 2539258. doi:10.1016/0092-8674(89)90169-4.
Sakurai A, Nakai A, DeGroot LJ (Feb 1989). "Expression of three forms of thyroid hormone receptor in human tissues". Molecular Endocrinology. 3 (2): 392–9. PMID 2710139. doi:10.1210/mend-3-2-392.
Sap J, Muñoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H, Vennström B (1987). "The c-erb-A protein is a high-affinity receptor for thyroid hormone". Nature. 324 (6098): 635–40. PMID 2879242. doi:10.1038/324635a0.
Nakai A, Seino S, Sakurai A, Szilak I, Bell GI, DeGroot LJ (Apr 1988). "Characterization of a thyroid hormone receptor expressed in human kidney and other tissues". Proceedings of the National Academy of Sciences of the United States of America. 85 (8): 2781–5. PMC 280083 . PMID 3357890. doi:10.1073/pnas.85.8.2781.
Mitelman F, Manolov G, Manolova Y, Billström R, Heim S, Kristoffersson U, Mandahl N, Ferro MT, San Roman C (Jun 1986). "High resolution chromosome analysis of constitutional and acquired t(15;17) maps c-erbA to subband 17q11.2". Cancer Genetics and Cytogenetics. 22 (2): 95–8. PMID 3458521. doi:10.1016/0165-4608(86)90168-8.
Benbrook D, Pfahl M (Nov 1987). "A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library". Science. 238 (4828): 788–91. PMID 3672126. doi:10.1126/science.3672126.
Pfahl M, Benbrook D (Nov 1987). "Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor". Nucleic Acids Research. 15 (22): 9613. PMC 306505 . PMID 3684612. doi:10.1093/nar/15.22.9613.
Chen JD, Evans RM (Oct 1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature. 377 (6548): 454–7. PMID 7566127. doi:10.1038/377454a0.
Desai-Yajnik V, Hadzic E, Modlinger P, Malhotra S, Gechlik G, Samuels HH (Aug 1995). "Interactions of thyroid hormone receptor with the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and the HIV-1 Tat transactivator". Journal of Virology. 69 (8): 5103–12. PMC 189328 . PMID 7609079.
Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (Feb 1995). "Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor". Molecular Endocrinology. 9 (2): 243–54. PMID 7776974. doi:10.1210/me.9.2.243.
Desai-Yajnik V, Samuels HH (1994). "Regulation of the human immunodeficiency virus type 1 long terminal repeat: interactions of thyroid hormone receptor with retinoid-X receptor, nuclear factor kappa B, Sp1, and Tat". Transactions of the Association of American Physicians. 106: 13–32. PMID 8036737.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery

1nav: Thyroid Receptor Alpha in complex with an agonist selective for Thyroid Receptor Beta1

2h77: Crystal structure of human TR alpha bound T3 in monoclinic space group

2h79: Crystal Structure of human TR alpha bound T3 in orthorhombic space group

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 3 4 5 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

Thyroid hormone receptor modulators

THR
(ligands)

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
(inhibitors)

NIS	Cyanogenic glycosides Perchlorates (e.g., potassium perchlorate) Pertechnetates (e.g., sodium pertechnetate) Thiocyanates

Enzyme
(inhibitors)

TPO	Benzylthiouracil Carbimazole Genistein Methimazole Methylthiouracil Propylthiouracil Thiouracil Thiourea
DIO	Dexpropranolol Iopanoic acid Ipodate sodium (sodium iopodate) Propranolol Propylthiouracil

Others

See also: Receptor/signaling modulators
Nuclear receptor modulators

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Thyroid hormone receptor alpha

Function

Interactions

References

Further reading