Thyroid hormone receptor alpha

Thyroid hormone receptor, alpha
PDB rendering based on 1nav.
Available structures PDB 1NAV, 2H77, 2H79, 3ILZ, 3JZB
Identifiers
Symbols	THRA; AR7; EAR7; ERB-T-1; ERBA; ERBA1; MGC000261; MGC43240; NR1A1; THRA1; THRA2; c-ERBA-1
External IDs	OMIM: 190120 MGI: 98742 HomoloGene: 37747 IUPHAR: NR1A1 GeneCards: THRA Gene
Gene Ontology Molecular function • sequence-specific DNA binding transcription factor activity • steroid hormone receptor activity • thyroid hormone receptor activity • protein binding • transcription factor binding • zinc ion binding • TBP-class protein binding • protein domain specific binding • sequence-specific DNA binding • transcription regulatory region DNA binding • metal ion binding • thyroid hormone binding • thyroid hormone binding Cellular component • nucleus • nucleoplasm • cytosol Biological process • regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • hormone-mediated signaling pathway • gene expression • negative regulation of RNA polymerase II transcriptional preinitiation complex assembly • regulation of transcription from RNA polymerase II promoter by nuclear hormone receptor • negative regulation of transcription, DNA-dependent • negative regulation of transcription initiation, DNA-dependent Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7067	21833
Ensembl	ENSG00000126351	ENSMUSG00000058756
UniProt	P10827	Q80Y90
RefSeq (mRNA)	NM_001190918.1	NM_178060.3
RefSeq (protein)	NP_001177847.1	NP_835161.1
Location (UCSC)	Chr 17: 38.22 – 38.25 Mb	Chr 11: 98.6 – 98.63 Mb
PubMed search	[1]	[2]

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.^[1][2][3]

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.^[1]

Interactions

THR1 has been shown to interact with:

• COPS2,^[4]
• EP300,^[5]
• ITGB3BP,^[6][7]
• MED1,^[8]
• MED6,^[9]
• MED12,^[9]
• MED16,^[9]
• MEF2A,^[5]
• NCOA6,^[10][11]
• TRIP11,^[12] and
• UBC.^[13]

References

1. ^ ^{a b} "Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7067. 
2. ^ Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B (January 1984). "Chromosomal localisation of the human homologues to the oncogenes erbA and B". EMBO J. 3 (1): 159–63. PMC 557313. PMID 6323162. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=557313. 
3. ^ Dayton AI, Selden JR, Laws G, Dorney DJ, Finan J, Tripputi P, Emanuel BS, Rovera G, Nowell PC, Croce CM (July 1984). "A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia". Proc. Natl. Acad. Sci. U.S.A. 81 (14): 4495–9. doi:10.1073/pnas.81.14.4495. PMC 345617. PMID 6589608. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=345617. 
4. ^ 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". Mol. Cell. Biol. 19 (5): 3383–94. PMC 84131. PMID 10207062. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84131. 
5. ^ ^{a b} De Luca A, Severino A, De Paolis P, Cottone G, De Luca L, De Falco M, Porcellini A, Volpe M, Condorelli G (February 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". Biochem. J. 369 (Pt 3): 477–84. doi:10.1042/BJ20020057. PMC 1223100. PMID 12371907. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1223100. 
6. ^ Li D, Wang F, Samuels HH (December 2001). "Domain structure of the NRIF3 family of coregulators suggests potential dual roles in transcriptional regulation". Mol. Cell. Biol. 21 (24): 8371–84. doi:10.1128/MCB.21.24.8371-8384.2001. PMC 100002. PMID 11713274. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=100002. 
7. ^ Li D, Desai-Yajnik V, Lo E, Schapira M, Abagyan R, Samuels HH (October 1999). "NRIF3 is a novel coactivator mediating functional specificity of nuclear hormone receptors". Mol. Cell. Biol. 19 (10): 7191–202. PMC 84712. PMID 10490654. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84712. 
8. ^ Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG (July 1998). "The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion". Proc. Natl. Acad. Sci. U.S.A. 95 (14): 7939–44. doi:10.1073/pnas.95.14.7939. PMC 20908. PMID 9653119. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=20908. 
9. ^ ^{a b c} Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (March 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Mol. Cell 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638. 
10. ^ 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 (November 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". J. Biol. Chem. 274 (48): 34283–93. doi:10.1074/jbc.274.48.34283. PMID 10567404. 
11. ^ Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (June 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Mol. Endocrinol. 14 (6): 915–25. doi:10.1210/me.14.6.915. PMID 10847592. 
12. ^ Chang KH, Chen Y, Chen TT, Chou WH, Chen PL, Ma YY, Yang-Feng TL, Leng X, Tsai MJ, O'Malley BW, Lee WH (August 1997). "A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9040–5. doi:10.1073/pnas.94.17.9040. PMC 23019. PMID 9256431. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=23019. 
13. ^ 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 (July 2008). "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells". Proteomics 8 (14): 2885–96. doi:10.1002/pmic.200700887. PMID 18655026. 

Further reading

• Forrest D, Reh TA, Rüsch A (2002). "Neurodevelopmental control by thyroid hormone receptors.". Curr. Opin. Neurobiol. 12 (1): 49–56. doi:10.1016/S0959-4388(02)00289-1. PMID 11861164. 
• Sakurai A, Bell GI, DeGroot LJ (1993). "Dinucleotide repeat polymorphism in the human thyroid hormone receptor alpha gene (THRA1) on chromosome 17.". Hum. Mol. Genet. 1 (7): 553. doi:10.1093/hmg/1.7.553-a. PMID 1307263. 
• Berrodin TJ, Marks MS, Ozato K, et al. (1992). "Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein.". Mol. Endocrinol. 6 (9): 1468–78. doi:10.1210/me.6.9.1468. PMID 1331778. 
• Schmidt ED, Schmidt ED, van der Gaag R, et al. (1992). "Distribution of the nuclear thyroid-hormone receptor in extraocular and skeletal muscles.". J. Endocrinol. 133 (1): 67–74. doi:10.1677/joe.0.1330067. PMID 1517709. 
• Yen PM, Sunday ME, Darling DS, Chin WW (1992). "Isoform-specific thyroid hormone receptor antibodies detect multiple thyroid hormone receptors in rat and human pituitaries.". Endocrinology 130 (3): 1539–46. doi:10.1210/en.130.3.1539. PMID 1537303. 
• Laudet V, Begue A, Henry-Duthoit C, et al. (1991). "Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene.". Nucleic Acids Res. 19 (5): 1105–12. doi:10.1093/nar/19.5.1105. PMC 333788. PMID 1850510. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=333788. 
• Nakai A, Sakurai A, Bell GI, DeGroot LJ (1989). "Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues.". Mol. Endocrinol. 2 (11): 1087–92. doi:10.1210/mend-2-11-1087. PMID 2464749. 
• Miyajima N, Horiuchi R, Shibuya Y, et al. (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. doi:10.1016/0092-8674(89)90169-4. PMID 2539258. 
• Sakurai A, Nakai A, DeGroot LJ (1989). "Expression of three forms of thyroid hormone receptor in human tissues.". Mol. Endocrinol. 3 (2): 392–9. doi:10.1210/mend-3-2-392. PMID 2710139. 
• Sap J, Muñoz A, Damm K, et al. (1987). "The c-erb-A protein is a high-affinity receptor for thyroid hormone.". Nature 324 (6098): 635–40. doi:10.1038/324635a0. PMID 2879242. 
• Nakai A, Seino S, Sakurai A, et al. (1988). "Characterization of a thyroid hormone receptor expressed in human kidney and other tissues.". Proc. Natl. Acad. Sci. U.S.A. 85 (8): 2781–5. doi:10.1073/pnas.85.8.2781. PMC 280083. PMID 3357890. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=280083. 
• Mitelman F, Manolov G, Manolova Y, et al. (1986). "High resolution chromosome analysis of constitutional and acquired t(15;17) maps c-erbA to subband 17q11.2.". Cancer Genet. Cytogenet. 22 (2): 95–8. doi:10.1016/0165-4608(86)90168-8. PMID 3458521. 
• Benbrook D, Pfahl M (1987). "A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library.". Science 238 (4828): 788–91. doi:10.1126/science.3672126. PMID 3672126. 
• Pfahl M, Benbrook D (1988). "Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor.". Nucleic Acids Res. 15 (22): 9613. doi:10.1093/nar/15.22.9613. PMC 306505. PMID 3684612. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=306505. 
• Chen JD, Evans RM (1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors.". Nature 377 (6548): 454–7. doi:10.1038/377454a0. PMID 7566127. 
• Desai-Yajnik V, Hadzic E, Modlinger P, et al. (1995). "Interactions of thyroid hormone receptor with the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and the HIV-1 Tat transactivator.". J. Virol. 69 (8): 5103–12. PMC 189328. PMID 7609079. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=189328. 
• Lee JW, Choi HS, Gyuris J, et al. (1995). "Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.". Mol. Endocrinol. 9 (2): 243–54. doi:10.1210/me.9.2.243. PMID 7776974. 
• 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.". Trans. Assoc. Am. Physicians 106: 13–32. PMID 8036737. 

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