Genomes and Genes
Gene Symbol: Thra
Description: thyroid hormone receptor alpha
Alias: ERBA1, Thra1, c-erbA-1, thyroid hormone receptor alpha, c-erbAalpha2, C-erbA-alpha, avian erythroblastic leukemia viral (v-erb-a) oncogene homolog 1, c-erb-A thyroid hormone receptor, c-erbA-alpha2, nuclear receptor subfamily 1 group A member 1, thyroid hormone receptor alpha 1 (avian erythroblastic leukemia viral (v-erb-a) oncogene homolog 1 formerly ERBA1)
- Dellovade T, Chan J, Vennstrom B, Forrest D, Pfaff D. The two thyroid hormone receptor genes have opposite effects on estrogen-stimulated sex behaviors. Nat Neurosci. 2000;3:472-5 pubmed..Instead, they indicate a previously unknown molecular mechanism upon which the two TR genes exert opposite influences. ..
- Winter H, Braig C, Zimmermann U, Geisler H, Fränzer J, Weber T, et al. Thyroid hormone receptors TRalpha1 and TRbeta differentially regulate gene expression of Kcnq4 and prestin during final differentiation of outer hair cells. J Cell Sci. 2006;119:2975-84 pubmed..We show that T3 target genes can differ in their sensitivity to TH receptors having the ligand either bound (holoreceptors) or not bound (aporeceptors) within single cells, and suggest a role for TRalpha1 in final cell differentiation. ..
- Yuan C, Ito M, Fondell J, Fu Z, Roeder R. 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. 1998;95:7939-44 pubmed..for 2 of the 10 thyroid hormone receptor-associated proteins (TRAPs) that are immunopurified with thyroid hormone receptor alpha (TRalpha) from ligand-treated HeLa (alpha-2) cells...
- Gassanov N, Er F, Michels G, Zagidullin N, Brandt M, Hoppe U. Divergent regulation of cardiac KCND3 potassium channel expression by the thyroid hormone receptors alpha1 and beta1. J Physiol. 2009;587:1319-29 pubmed publisher..Thus, I(to) is modulated by diverse T3-dependent regulation of underlying gene transcription. TRalpha1 and TRbeta1 exhibit distinct effects on KCND3 transactivation with TRalpha1 enhancing and TRbeta1 suppressing KCND3 transcription. ..
- De Paul A, Mukdsi J, Pellizas C, Montesinos M, Gutierrez S, Susperreguy S, et al. Thyroid hormone receptor alpha 1-beta 1 expression in epididymal epithelium from euthyroid and hypothyroid rats. Histochem Cell Biol. 2008;129:631-42 pubmed publisher..The differences in expression levels assessed in control and thyroidectomized rats ascertain a specific function of TH on this organ. ..
- Pantos C, Mourouzis I, Galanopoulos G, Gavra M, Perimenis P, Spanou D, et al. Thyroid hormone receptor alpha1 downregulation in postischemic heart failure progression: the potential role of tissue hypothyroidism. Horm Metab Res. 2010;42:718-24 pubmed publisher..In conclusion, progression to congestive heart failure after myocardial infarction is associated with suppressed expression of TR alpha 1 and results in tissue hypothyroidism. This process may, at least in part, be mTOR dependent. ..
- Choi K, Oh S, Kang H, Lee Y, Haam S, Kim H, et al. The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor alpha. Biochem J. 2008;411:19-26 pubmed..Collectively, these results suggest that both SMRT and N-CoR are limited in cells and that knocking down either of them results in co-repressor-free TR and consequently de-repression of TR target genes. ..
- Wang X, Sun Z. Thyroid hormone induces artery smooth muscle cell proliferation: discovery of a new TRalpha1-Nox1 pathway. J Cell Mol Med. 2010;14:368-80 pubmed..e. T3-TRalpha1-NOX1-cell proliferation. TRalpha1 and NOX1 co-localized around the nucleus. T3 induced RASM cell proliferation by up-regulating NOX1 in a TRalpha1-dependent manner. ..
- Pantos C, Mourouzis I, Saranteas T, Brozou V, Galanopoulos G, Kostopanagiotou G, et al. Acute T3 treatment protects the heart against ischemia-reperfusion injury via TR?1 receptor. Mol Cell Biochem. 2011;353:235-41 pubmed publisher..T3 can exert this beneficial effect on ischemic myocardium at a dose that has no effects on non-ischemic myocardium. Acute T3-limiting effect on reperfusion injury is mediated, at least in part, via TR?1 receptor. ..
- Morrish F, Buroker N, Ge M, Ning X, Lopez Guisa J, Hockenbery D, et al. Thyroid hormone receptor isoforms localize to cardiac mitochondrial matrix with potential for binding to receptor elements on mtDNA. Mitochondrion. 2006;6:143-8 pubmed..Thus, TRalpha isoforms may directly regulate T(3) responses at mtDNA in the heart. ..
- Katz D, Lazar M. Dominant negative activity of an endogenous thyroid hormone receptor variant (alpha 2) is due to competition for binding sites on target genes. J Biol Chem. 1993;268:20904-10 pubmed..Furthermore, a TR alpha 2 mutant which binds more avidly to TREs was a more effective inhibitor of T3 action than wild type TR alpha 2. Together these data indicate that TR alpha 2 inhibits T3 action by competing for binding to TREs. ..
- Fraichard A, Chassande O, Plateroti M, Roux J, Trouillas J, Dehay C, et al. The T3R alpha gene encoding a thyroid hormone receptor is essential for post-natal development and thyroid hormone production. EMBO J. 1997;16:4412-20 pubmed..These data define crucial in vivo functions for thyroid hormones through a T3R alpha pathway during post-natal development. ..
- Kinugawa K, Jeong M, Bristow M, Long C. Thyroid hormone induces cardiac myocyte hypertrophy in a thyroid hormone receptor alpha1-specific manner that requires TAK1 and p38 mitogen-activated protein kinase. Mol Endocrinol. 2005;19:1618-28 pubmed
- Compe E, Malerba M, Soler L, Marescaux J, Borrelli E, Egly J. Neurological defects in trichothiodystrophy reveal a coactivator function of TFIIH. Nat Neurosci. 2007;10:1414-22 pubmed..The discovery of an unexpected stabilizing function for TFIIH deepens our understanding of the pathogenesis and neurological manifestations observed in TTD individuals. ..
- Fondell J, Brunel F, Hisatake K, Roeder R. Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression. Mol Cell Biol. 1996;16:281-7 pubmedUnliganded human thyroid hormone receptor alpha (hTR alpha) can repress transcription by inhibiting the formation of a functional preinitiation complex (PIC) on promoters bearing thyroid hormone receptor (TR)-binding elements...
- Izumo S, Mahdavi V. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature. 1988;334:539-42 pubmed..Thus, alternative splicing can produce marked differences in the functional properties of a transcriptional factor. ..
- Pantos C, Xinaris C, Mourouzis I, Perimenis P, Politi E, Spanou D, et al. Thyroid hormone receptor alpha 1: a switch to cardiac cell "metamorphosis"?. J Physiol Pharmacol. 2008;59:253-69 pubmed..Over-expression of TRalpha1 may lead to fetal cardiac phenotype in the absence of thyroid hormone availability. Furthermore, TRalpha1 seems to be critical in cardiac myoblast differentiation. ..
- Mahajan M, Samuels H. A new family of nuclear receptor coregulators that integrate nuclear receptor signaling through CREB-binding protein. Mol Cell Biol. 2000;20:5048-63 pubmed..hNRC binds CREB-binding protein (CBP) with high affinity in vivo, suggesting that hNRC may be an important functional component of a CBP complex involved in mediating the transcriptional effects of nuclear hormone receptors. ..
- Liu C, Li L, Shi F, Zang X, Liu Y, Sun Y, et al. Effects of hyper- and hypothyroid on expression of thyroid hormone receptor mRNA in rat myocardium. J Endocrinol. 2007;195:429-38 pubmed..Taken together, the abnormal expression of TR subtype mRNA may have a close relationship with the pathogenesis of CH and hyperthyroidism heart disease. ..
- Dayton A, Selden J, Laws G, Dorney D, Finan J, Tripputi P, et al. 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. 1984;81:4495-9 pubmed..The apparent close proximity of the c-erbA sequences to the chromosomal breakpoints in these two leukemias suggests a possible role for this oncogene homologue in the development of these neoplasms. ..
- Wikstrom L, Johansson C, Salto C, Barlow C, Campos Barros A, Baas F, et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. EMBO J. 1998;17:455-61 pubmed..The results identify specific and important roles for TR alpha 1 in regulation of tightly controlled physiological functions, such as cardiac pacemaking, ventricular repolarisation and control of body temperature. ..
- Lazar M, Hodin R, Darling D, Chin W. Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. Mol Endocrinol. 1988;2:893-901 pubmed..r-erbA alpha-1 mRNA, unlike r-erbA alpha-2 mRNA, is undetectable in testis. Southern analyses suggest that the r-erbA alpha-1 and r-erbA alpha-2 mRNAs are derived from a single gene transcript. ..
- Kenessey A, Ojamaa K. Ligand-mediated decrease of thyroid hormone receptor-alpha1 in cardiomyocytes by proteosome-dependent degradation and altered mRNA stability. Am J Physiol Heart Circ Physiol. 2005;288:H813-21 pubmed..These data support a role for both the proteosome degradation pathway and altered mRNA stability in T3-induced decrease of nuclear TRalpha1 in the cardiomyocyte and provide novel cellular targets for therapeutic development. ..
- Kenessey A, Sullivan E, Ojamaa K. Nuclear localization of protein kinase C-alpha induces thyroid hormone receptor-alpha1 expression in the cardiomyocyte. Am J Physiol Heart Circ Physiol. 2006;290:H381-9 pubmed..These results implicate PKC alpha as a regulator of TR function and suggest that nuclear localization of PKC alpha may control transcription of the TR alpha gene, and consequently, affect cardiac phenotype. ..
- da ConceiÃ§Ã£o R, Laureano Melo R, Oliveira K, de Carvalho Melo M, Kasamatsu T, de Barros Maciel R, et al. Antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism. Physiol Behav. 2016;157:158-64 pubmed publisher..This effect could be associated to an impaired neuronal activity in acute stress response as it is observed in forced swimming paradigm. ..
- Zandieh Doulabi B, Platvoet Ter Schiphorst M, Kalsbeek A, Fliers E, Bakker O, Wiersinga W. Diurnal variation in rat liver thyroid hormone receptor (TR)-alpha messenger ribonucleic acid (mRNA) is dependent on the biological clock in the suprachiasmatic nucleus, whereas diurnal variation of TR beta 1 mRNA is modified by food intake. Endocrinology. 2004;145:1284-9 pubmed..The findings may have physiological relevance for diurnal variation of T(3)-dependent gene expression, which is supported by a diurnal variation in the expression of the 5'-deiodinase gene. ..
- Gauthier K, Chassande O, Plateroti M, Roux J, Legrand C, Pain B, et al. Different functions for the thyroid hormone receptors TRalpha and TRbeta in the control of thyroid hormone production and post-natal development. EMBO J. 1999;18:623-31 pubmed..We conclude that each of the two families of proteins mediate specific functions of triiodothyronin (T3), and that redundancy is only partial and concerns a limited number of functions. ..
- Kalofoutis C, Mourouzis I, Galanopoulos G, Dimopoulos A, Perimenis P, Spanou D, et al. Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction. Mol Cell Biochem. 2010;345:161-9 pubmed publisher..Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics. ..
- Stein E, da Silveira Filho N, Machado D, Hipólide D, Barlow K, Nobrega J. Chronic mild stress induces widespread decreases in thyroid hormone alpha1 receptor mRNA levels in brain--reversal by imipramine. Psychoneuroendocrinology. 2009;34:281-6 pubmed publisher..The reversal of both anhedonic and TR-alpha1 effects of CMS by IMI suggests that TR-alpha1 may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions. ..
- Thompson C, Weinberger C, Lebo R, Evans R. Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system. Science. 1987;237:1610-4 pubmed..Messenger RNA from this gene is expressed in a tissue-specific fashion with highest levels in the central nervous system. ..
- Kim S, Ho S, Hong S, Kim K, So E, Christoffolete M, et al. A novel mechanism of thyroid hormone-dependent negative regulation by thyroid hormone receptor, nuclear receptor corepressor (NCoR), and GAGA-binding factor on the rat cD44 promoter. J Biol Chem. 2005;280:14545-55 pubmed..Therefore, we propose a mechanism by which NCoR, GAF, and TR interact with the CD44 negative T(3)-responsive element to enhance basal transactivation, whereas T(3) induces the remodeling of chromatin structure for repression. ..
- Weinberger C, Thompson C, Ong E, Lebo R, Gruol D, Evans R. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986;324:641-6 pubmed..Binding studies with the protein show it to be a receptor for thyroid hormones. ..
- Lazar M, Chin W. Regulation of two c-erbA messenger ribonucleic acids in rat GH3 cells by thyroid hormone. Mol Endocrinol. 1988;2:479-84 pubmed..These data indicate that these two c-erbA mRNAs are regulated by T3 and suggest that the T3 effect on T3 binding-activity in GH cells may be mediated, in part, by down-regulation of c-erbA mRNA levels. ..
- Liu Y, Kogai T, Schultz J, Mody K, Brent G. Thyroid hormone receptor isoform-specific modification by small ubiquitin-like modifier (SUMO) modulates thyroid hormone-dependent gene regulation. J Biol Chem. 2012;287:36499-508 pubmed publisher..These findings demonstrate that conjugation of SUMO to TR has a TR-isoform preference and is important for T3-dependent gene induction and repression. ..
- Mai W, Janier M, Allioli N, Quignodon L, Chuzel T, Flamant F, et al. Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life. Proc Natl Acad Sci U S A. 2004;101:10332-7 pubmed..These data describe a physiological situation under which conversion of TRalpha from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process. ..
- Mitsuhashi T, Tennyson G, Nikodem V. Nucleotide sequence of novel cDNAs generated by alternative splicing of a rat thyroid hormone receptor gene transcript. Nucleic Acids Res. 1988;16:5697 pubmed
- van Beeren H, Kwakkel J, Ackermans M, Wiersinga W, Fliers E, Boelen A. Action of specific thyroid hormone receptor ?(1) and ?(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat. Thyroid. 2012;22:1275-82 pubmed publisher..Our results suggest an important role for TR?1 in the regulation of hypothalamic TRH mRNA expression, whereas TR? plays a dominant role in pituitary and liver thyroid hormone metabolism. ..
- Eckey M, Tenbaum S, Munoz A, Baniahmad A. Mixed lineage kinase 2 enhances trans-repression of Alien and nuclear receptors. Mol Cell Endocrinol. 2003;213:71-8 pubmed..This novel cross-talk may represent a link between MLK2-mediated signaling and transcriptional repression of target genes during neuronal differentiation processes. ..
- Adan R, Cox J, van Kats J, Burbach J. Thyroid hormone regulates the oxytocin gene. J Biol Chem. 1992;267:3771-7 pubmed..in front of the firefly luciferase gene were co-transfected with an expression vector for the rat thyroid hormone receptor alpha in P19 embryonal carcinoma (EC) cells...
- Silva J, Dominguez G, González Sancho J, Garcia J, Silva J, García Andrade C, et al. Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer. Oncogene. 2002;21:4307-16 pubmed
- Casas F, Busson M, Grandemange S, Seyer P, Carazo A, Pessemesse L, et al. Characterization of a novel thyroid hormone receptor alpha variant involved in the regulation of myoblast differentiation. Mol Endocrinol. 2006;20:749-63 pubmed..We suggest that this novel TRalpha variant may act as down regulator of overall T3 receptor activity, including its ability to repress MyoD transcriptional activity during myoblast proliferation. ..
- Fondell J, Ge H, Roeder R. Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc Natl Acad Sci U S A. 1996;93:8329-33 pubmed..Here we show that human thyroid hormone receptor alpha purified from HeLa cells grown in the presence of thyroid hormone (T3) is associated with a group of ..
- Kamiya Y, Puzianowska Kuznicka M, McPhie P, Nauman J, Cheng S, Nauman A. Expression of mutant thyroid hormone nuclear receptors is associated with human renal clear cell carcinoma. Carcinogenesis. 2002;23:25-33 pubmed..These results indicate that the normal functions of TRs in RCCC tissues were impaired. Together with the aberrant expression patterns, these mutated TRs could contribute to the carcinogenesis of RCCC. ..
- Zheng K, Sulieman F, Li J, Wei Q, Xu M, Shi F. Nitric oxide and thyroid hormone receptor alpha 1 contribute to ovarian follicular development in immature hyper- and hypo-thyroid rats. Reprod Biol. 2015;15:27-33 pubmed publisher..In the current study, we examined the roles of nitric oxide synthase (NOS) and thyroid hormone receptor alpha 1 (TRÎ±1) in these disorders using immature hyper-thyroid (hyper-T) and hypo-thyroid (hypo-T) rats...
- Sandler B, Webb P, Apriletti J, Huber B, Togashi M, Cunha Lima S, et al. Thyroxine-thyroid hormone receptor interactions. J Biol Chem. 2004;279:55801-8 pubmed..While T(3) is the major active TH, our results suggest that T(4) could activate nuclear TRs at appropriate concentrations. The ability of TR to adapt to the 5' extension should be considered in TR ligand design. ..
- Xu B, Koenig R. An RNA-binding domain in the thyroid hormone receptor enhances transcriptional activation. J Biol Chem. 2004;279:33051-6 pubmed..We conclude that thyroid hormone receptors bind RNA through a novel domain and that the interaction of this domain with SRA, and perhaps other RNAs, enhances thyroid hormone receptor function. ..
- Wilcoxon J, Nadolski G, Samarut J, Chassande O, Redei E. Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha. Behav Brain Res. 2007;177:109-16 pubmed..To determine the contribution of thyroid hormone receptor alpha (TRalpha) in these behaviors, we examined the behavior of euthyroid as well as hypo- and hyperthyroid ..
- Keijzer R, Blommaart P, Labruyere W, Vermeulen J, Doulabi B, Bakker O, et al. Expression of thyroid hormone receptors A and B in developing rat tissues; evidence for extensive posttranscriptional regulation. J Mol Endocrinol. 2007;38:523-35 pubmed..The data indicate that the TR-dependent regulatory cascades are controlled differently in organs with a complementary tissue expression pattern and in those with cellular co-expression of the TRalpha and TRbeta genes. ..
- Sugizaki M, Leopoldo A, Okoshi M, Bruno A, Conde S, Lima Leopoldo A, et al. Severe food restriction induces myocardial dysfunction related to SERCA2 activity. Can J Physiol Pharmacol. 2009;87:666-73 pubmed publisher..These results suggest that food restriction promotes myocardial dysfunction related to impairment of sarcoplasmic reticulum Ca2+ uptake as a result of a hypothyroid state. ..
- Gassanov N, Er F, Endres Becker J, Wolny M, Schramm C, Hoppe U. Distinct regulation of cardiac I(f) current via thyroid receptors alpha1 and beta1. Pflugers Arch. 2009;458:1061-8 pubmed publisher..TH-induced positive chronotropic effects are likely to be mediated by TR alpha 1 through enhanced expression of I(f) pacemaker current and its underlying genes. ..
- Puzianowska Kuznicka M, Krystyniak A, Madej A, Cheng S, Nauman J. Functionally impaired TR mutants are present in thyroid papillary cancer. J Clin Endocrinol Metab. 2002;87:1120-8 pubmed..These findings suggest a possible role for mutated thyroid hormone receptors in the tumorigenesis of human papillary thyroid carcinoma. ..
- Lin H, Sun M, Tang H, Lin C, Luidens M, Mousa S, et al. L-Thyroxine vs. 3,5,3'-triiodo-L-thyronine and cell proliferation: activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase. Am J Physiol Cell Physiol. 2009;296:C980-91 pubmed publisher..T(3) action here is inhibited by tetrac alone, but the effect of T(4) is blocked by both tetrac and the RGD peptide. ..
- Kenessey A, Ojamaa K. Thyroid hormone stimulates protein synthesis in the cardiomyocyte by activating the Akt-mTOR and p70S6K pathways. J Biol Chem. 2006;281:20666-72 pubmed..Thus, rapid T3-mediated activation of PI3K by cytosolic TRalpha1 and subsequent activation of the Akt-mTOR-S6K signaling pathway may underlie one of the mechanisms by which thyroid hormone regulates physiological cardiac growth. ..
- Khetchoumian K, Teletin M, Mark M, Lerouge T, Cerviño M, Oulad Abdelghani M, et al. TIF1delta, a novel HP1-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids. J Biol Chem. 2004;279:48329-41 pubmed..Collectively, these data are consistent with specific, nonredundant functions for the TIF1 family members in vivo and suggest a role for TIF1delta in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. ..
- Koenig R, Lazar M, Hodin R, Brent G, Larsen P, Chin W, et al. Inhibition of thyroid hormone action by a non-hormone binding c-erbA protein generated by alternative mRNA splicing. Nature. 1989;337:659-61 pubmed..Alternative splicing of the erbA alpha transcript thus generates products with opposing biological activities, suggesting a novel mechanism for the modulation of hormonal responsiveness. ..
- Liu Y, Schultz J, Brent G. A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice. J Biol Chem. 2003;278:38913-20 pubmed..We generated mice with a point mutation in the thyroid hormone receptor alpha (TRalpha) gene producing a dominant-negative TRalpha mutant receptor with a proline to histidine ..
- Lazar J, Desvergne B, Zimmerman E, Zimmer D, Magnuson M, Nikodem V. A role for intronic sequences on expression of thyroid hormone receptor alpha gene. J Biol Chem. 1994;269:20352-9 pubmedWe have cloned and characterized the organization of the rat thyroid hormone receptor alpha (THR) gene. Multiple transcription start sites were mapped by RNA primer extension analyses...
- Li X, Misik A, Rieder C, Solaro R, Lowen A, Fliegel L. Thyroid hormone receptor alpha 1 regulates expression of the Na+/H+ exchanger (NHE1). J Biol Chem. 2002;277:28656-62 pubmed..Our results are the first demonstration that thyroid hormone and the thyroid hormone receptor TRalpha(1) regulate expression of the Na+/H+ exchanger. ..
- Flamant F, Poguet A, Plateroti M, Chassande O, Gauthier K, Streichenberger N, et al. Congenital hypothyroid Pax8(-/-) mutant mice can be rescued by inactivating the TRalpha gene. Mol Endocrinol. 2002;16:24-32 pubmed..Pax8/TRalpha compound mutants can survive to adulthood, and the expression of target genes is partially restored. This demonstrates the importance of TRalpha aporeceptor activity in several aspects of postnatal development. ..