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Gene Review

THRA  -  thyroid hormone receptor, alpha

Homo sapiens

Synonyms: AR7, CHNG6, EAR-7, EAR-7.1/EAR-7.2, EAR7, ...
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Disease relevance of THRA


High impact information on THRA


Chemical compound and disease context of THRA


Biological context of THRA


Anatomical context of THRA


Associations of THRA with chemical compounds


Physical interactions of THRA

  • Generalized resistance to thyroid hormones (GRTH) commonly results from mutations in the T3-binding domain of the c-erbA beta thyroid hormone receptor gene [27].
  • Here, we show that v-erbA and c-erbA bind directly to sequences within the promoter of the erythrocyte-specific carbonic anhydrase II (CAII), a gene whose transcription is efficiently suppressed by v-erbA [28].

Enzymatic interactions of THRA


Regulatory relationships of THRA


Other interactions of THRA

  • In addition, TRAP may interact with a certain subset of the nuclear receptor superfamily, since human retinoic acid receptor-beta and vitamin D receptor show increased binding to TREs in the presence of nuclear extract, but c-erbA alpha-2, a variant TR, does not respond to TRAP [33].
  • The phenotypic manifestations of mutated THRB and THRA genes are distinct, indicating isoform-dependent actions of TR mutants in vivo [34].
  • We then used carboxyl-terminal truncations of rat TR alpha-1 and human TR beta in the avidin-biotin complex DNA-binding assay to identify regions that are important for interaction with TRAP [33].
  • Two clinical variants, generalized resistance to thyroid hormone (GRTH) and selective pituitary resistance to thyroid hormone (PRTH), are, in most cases, caused by heterozygous mutations in the ligand-binding domain of the c-erbA beta thyroid hormone receptor gene [35].
  • Four thyroid nuclear receptors have been described in tissues, TR alpha 1, alpha 2, beta 1, and beta 2 [36].

Analytical, diagnostic and therapeutic context of THRA

  • Gel mobility shift assays showed both proximal and distal TREs formed a retarded band with hTR alpha 1 or hTR beta 1 expressed in COS1 cells and reticulocyte lysates [31].
  • To accomplish this, the missing 5'-sequence of a previously isolated partial RC c-erbA alpha cDNA (RC12) was synthesized by polymerase chain reaction (PCR) and spliced to RC12 to yield a 1490-basepair cDNA (RC15) that contained the entire coding sequence of the receptor protein [37].
  • There were no differences in the histologic type, cellular atypism, mitotic index, and other disease parameters between tumors with c-erbB-2 amplification only and those with coamplification of c-erbB-2 and c-erbA-1 [38].
  • All patients after local treatment were randomized into two arms, one without further therapy and the other to receive adjuvant chemotherapy (Adriamycin [Farmitalia-Carlo Erba, Milan, Italy], 450 mg/m2) [39].
  • Despite abundant TR protein expression, Northern blot hybridization of polyadenylated ribonucleic acid (RNA; 10 micrograms) to TR complementary DNAs revealed only a weak signal for c-erbA alpha 2 messenger RNA (mRNA) [40].


  1. Functionally impaired TR mutants are present in thyroid papillary cancer. Puzianowska-Kuznicka, M., Krystyniak, A., Madej, A., Cheng, S.Y., Nauman, J. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  2. Avian erythroleukemia: a model for corepressor function in cancer. Rietveld, L.E., Caldenhoven, E., Stunnenberg, H.G. Oncogene (2001) [Pubmed]
  3. A thyroid hormone receptor beta gene polymorphism associated with Graves' disease. Tassi, V., Scarnecchia, L., Di Cerbo, A., Pirro, M.T., Di Paola, R., Liuzzi, A., Torlontano, M., Zingrillo, M., D'Aloiso, L., De Filippis, V. J. Mol. Endocrinol. (1995) [Pubmed]
  4. Generalized thyroid hormone resistance due to a deletion of the carboxy terminus of the c-erbA beta receptor. Groenhout, E.G., Dorin, R.I. Mol. Cell. Endocrinol. (1994) [Pubmed]
  5. A novel cis element mediating ligand-independent activation by c-ErbA: implications for hormonal regulation. Saatcioglu, F., Deng, T., Karin, M. Cell (1993) [Pubmed]
  6. v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action. Sharif, M., Privalsky, M.L. Cell (1991) [Pubmed]
  7. v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA. Zenke, M., Muñoz, A., Sap, J., Vennström, B., Beug, H. Cell (1990) [Pubmed]
  8. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Koenig, R.J., Lazar, M.A., Hodin, R.A., Brent, G.A., Larsen, P.R., Chin, W.W., Moore, D.D. Nature (1989) [Pubmed]
  9. No benefit of ifosfamide in Ewing's sarcoma: a nonrandomized study of the French Society of Pediatric Oncology. Oberlin, O., Habrand, J.L., Zucker, J.M., Brunat-Mentigny, M., Terrier-Lacombe, M.J., Dubousset, J., Gentet, J.C., Schmitt, C., Ponvert, D., Carrié, C. J. Clin. Oncol. (1992) [Pubmed]
  10. Sequential high-dose methotrexate and fluorouracil combined with doxorubicin--a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. Wils, J.A., Klein, H.O., Wagener, D.J., Bleiberg, H., Reis, H., Korsten, F., Conroy, T., Fickers, M., Leyvraz, S., Buyse, M. J. Clin. Oncol. (1991) [Pubmed]
  11. Phase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety. Catimel, G., Spielmann, M., Dieras, V., Kayitalire, L., Pouillart, P., Guastalla, J.P., Soler-Michel, P., Graffand, N., Garet, F., Dumortier, A., Pellae-Cosset, B., Chazard, M. Semin. Oncol. (1996) [Pubmed]
  12. Reduction in the size of prolactin-producing pituitary tumor after Cabergoline administration. Melis, G.B., Gambacciani, M., Paoletti, A.M., Mais, V., Sghedoni, D., Fioretti, P. Fertil. Steril. (1989) [Pubmed]
  13. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development. Veldhoen, N., Skirrow, R.C., Osachoff, H., Wigmore, H., Clapson, D.J., Gunderson, M.P., Van Aggelen, G., Helbing, C.C. Aquat. Toxicol. (2006) [Pubmed]
  14. Inhibition of c-erbA mRNA splicing by a naturally occurring antisense RNA. Munroe, S.H., Lazar, M.A. J. Biol. Chem. (1991) [Pubmed]
  15. Chromosomal assignment of five cancer-associated rat genes: two thyroid hormone receptor (ERBA) genes, two ERBB genes and the retinoblastoma gene. Szpirer, C., Szpirer, J., Rivière, M., Ingvarsson, S., Vennström, B., Islam, M.Q., Levan, G. Oncogene (1991) [Pubmed]
  16. Myocyte enhancer factor 2 (MEF2). Brand, N.J. Int. J. Biochem. Cell Biol. (1997) [Pubmed]
  17. Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone. Lazar, M.A., Jones, K.E., Chin, W.W. DNA Cell Biol. (1990) [Pubmed]
  18. Characterization of a functional promoter for the human thyroid hormone receptor alpha (c-erbA-1) gene. Laudet, V., Vanacker, J.M., Adelmant, G., Begue, A., Stehelin, D. Oncogene (1993) [Pubmed]
  19. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Fondell, J.D., Ge, H., Roeder, R.G. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  20. Modulation of normal erythroid differentiation by the endogenous thyroid hormone and retinoic acid receptors: a possible target for v-erbA oncogene action. Schroeder, C., Gibson, L., Zenke, M., Beug, H. Oncogene (1992) [Pubmed]
  21. The v-erbA oncogene requires cooperation with tyrosine kinases to arrest erythroid differentiation induced by ligand-activated endogenous c-erbA and retinoic acid receptor. Schroeder, C., Gibson, L., Beug, H. Oncogene (1992) [Pubmed]
  22. Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues. Nakai, A., Sakurai, A., Bell, G.I., DeGroot, L.J. Mol. Endocrinol. (1988) [Pubmed]
  23. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer. Moghal, N., Neel, B.G. Mol. Cell. Biol. (1995) [Pubmed]
  24. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Benbrook, D., Pfahl, M. Science (1987) [Pubmed]
  25. Heterodimerization preferences of thyroid hormone receptor alpha isoforms. Nagaya, T., Nomura, Y., Fujieda, M., Seo, H. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  26. Generalized resistance to thyroid hormone: identification of a novel c-erbA beta thyroid hormone receptor variant (Leu450) in a Japanese family and analysis of its secondary structure by the Chou and Fasman method. Hiramatsu, R., Abe, M., Morita, M., Noguchi, S., Suzuki, T. Jpn. J. Hum. Genet. (1994) [Pubmed]
  27. Homozygosity for a dominant negative thyroid hormone receptor gene responsible for generalized resistance to thyroid hormone. Ono, S., Schwartz, I.D., Mueller, O.T., Root, A.W., Usala, S.J., Bercu, B.B. J. Clin. Endocrinol. Metab. (1991) [Pubmed]
  28. v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII. Disela, C., Glineur, C., Bugge, T., Sap, J., Stengl, G., Dodgson, J., Stunnenberg, H., Beug, H., Zenke, M. Genes Dev. (1991) [Pubmed]
  29. Functional regulation of thyroid hormone receptor variant TR alpha 2 by phosphorylation. Katz, D., Reginato, M.J., Lazar, M.A. Mol. Cell. Biol. (1995) [Pubmed]
  30. A shift in the ligand responsiveness of thyroid hormone receptor alpha induced by heterodimerization with retinoid X receptor alpha. Claret, F.X., Antakly, T., Karin, M., Saatcioglu, F. Mol. Cell. Biol. (1996) [Pubmed]
  31. Two thyroid hormone response elements are present in the promoter of human thyroid hormone receptor beta 1. Suzuki, S., Miyamoto, T., Opsahl, A., Sakurai, A., DeGroot, L.J. Mol. Endocrinol. (1994) [Pubmed]
  32. Overexpression of the alpha-thyroid hormone receptor in avian cell lines. Effects on expression of the malic enzyme gene are selective and cell-specific. Hillgartner, F.B., Chen, W., Goodridge, A.G. J. Biol. Chem. (1992) [Pubmed]
  33. 3,5,3'-triiodothyronine (T3) receptor-auxiliary protein (TRAP) binds DNA and forms heterodimers with the T3 receptor. Darling, D.S., Beebe, J.S., Burnside, J., Winslow, E.R., Chin, W.W. Mol. Endocrinol. (1991) [Pubmed]
  34. Thyroid hormone receptor mutations and disease: beyond thyroid hormone resistance. Cheng, S.Y. Trends Endocrinol. Metab. (2005) [Pubmed]
  35. Resistance to thyroid hormone in children. Usala, S.J. Curr. Opin. Pediatr. (1994) [Pubmed]
  36. Thyroid hormone enhancement of estradiol stimulation of breast carcinoma proliferation. Shao, Z.M., Sheikh, M.S., Rishi, A.K., Dawson, M.I., Li, X.S., Wilber, J.F., Feng, P., Fontana, J.A. Exp. Cell Res. (1995) [Pubmed]
  37. Rana catesbeiana tadpole red blood cells express an alpha, but not a beta, c-erbA gene. Schneider, M.J., Davey, J.C., Galton, V.A. Endocrinology (1993) [Pubmed]
  38. c-erbB-2 and c-erbA-1 (ear-1) gene amplification and c-erbB-2 protein expression in Japanese breast cancers: their relationship to the histology and other disease parameters. Uehara, T., Kaneko, Y., Kanda, N., Yamamoto, T., Higashi, Y., Nomoto, C., Izumo, T., Takayama, S., Sakurai, M. Jpn. J. Cancer Res. (1990) [Pubmed]
  39. A randomized trial for the treatment of high-grade soft-tissue sarcomas of the extremities: preliminary observations. Gherlinzoni, F., Bacci, G., Picci, P., Capanna, R., Calderoni, P., Lorenzi, E.G., Bernini, M., Emiliani, E., Barbieri, E., Normand, A. J. Clin. Oncol. (1986) [Pubmed]
  40. Expression and function of thyroid hormone receptor variants in normal and chronically diseased human liver. Chamba, A., Neuberger, J., Strain, A., Hopkins, J., Sheppard, M.C., Franklyn, J.A. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
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