Thyroid hormone receptor beta

Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the THRB gene.[5][6]

THRB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BSX, 1N46, 1NAX, 1NQ0, 1NQ1, 1NQ2, 1NUO, 1Q4X, 1R6G, 1XZX, 1Y0X, 2J4A, 2NLL, 2PIN, 3D57, 3GWS, 3IMY, 3JZC, 4ZO1
Identifiers
Aliases	THRB, C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH, THR1, THRB1, THRB2, thyroid hormone receptor beta
External IDs	OMIM: 190160 MGI: 98743 HomoloGene: 36025 GeneCards: THRB
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p24.2 Start 24,117,153 bp[1] End 24,495,756 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 A2 Start 17,660,261 bp[2] End 18,038,090 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • sequence-specific DNA binding • GO:0001106 transcription corepressor activity • zinc ion binding • metal ion binding • steroid hormone receptor activity • GO:0001948 protein binding • enzyme binding • chromatin DNA binding • thyroid hormone binding • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • transcription regulatory region sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • transcription factor binding • ligand-dependent nuclear receptor transcription coactivator activity • signaling receptor activity • GO:0038050, GO:0004886, GO:0038051 nuclear receptor activity Cellular component • nucleoplasm • nuclear chromatin • cell nucleus • nuclear body • RNA polymerase II transcription factor complex Biological process • regulation of transcription, DNA-templated • regulation of heart contraction • female courtship behavior • regulation of transcription from RNA polymerase II promoter • negative regulation of transcription from RNA polymerase II promoter • sensory perception of sound • Type I pneumocyte differentiation • negative regulation of female receptivity • animal organ morphogenesis • transcription initiation from RNA polymerase II promoter • negative regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • steroid hormone mediated signaling pathway • intracellular receptor signaling pathway • transcription, DNA-templated • negative regulation of eye photoreceptor cell development • retinal cone cell development • retinal cone cell apoptotic process • multicellular organism development • hormone-mediated signaling pathway • cell differentiation • thyroid gland development • response to lipid • thyroid hormone mediated signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7068	21834
Ensembl	ENSG00000151090	ENSMUSG00000021779
UniProt	P10828	P37242
RefSeq (mRNA)	NM_000461 NM_001128176 NM_001128177 NM_001252634 NM_001354708 NM_001354709 NM_001354710 NM_001354711 NM_001354712 NM_001354713 NM_001354714 NM_001354715 NM_001374822 NM_001374823 NM_001374824 NM_001374825 NM_001374826 NM_001374827	NM_001113417 NM_009380
RefSeq (protein)	NP_000452 NP_001121648 NP_001121649 NP_001239563 NP_001341637 NP_001341638 NP_001341639 NP_001341640 NP_001341641 NP_001341642 NP_001341643 NP_001341644 NP_001361751 NP_001361752 NP_001361753 NP_001361754 NP_001361755 NP_001361756	NP_001106888 NP_033406
Location (UCSC)	Chr 3: 24.12 – 24.5 Mb	Chr 14: 17.66 – 18.04 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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. Defects in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T₃-T₄), with normal or slightly elevated thyroid stimulating hormone (TSH). Several transcript variants have been observed for this gene, but the full-length nature of only one has been observed so far.[7]

Interactions

Thyroid hormone receptor beta has been shown to interact with:

• BRD8,[8]
• CCND1,[9]
• NCOA1,[10][11]
• NCOA6,[12][13][14][15]
• NCOR2,[10][16][17]
• NR2F6,[18]
• PPARGC1A,[19] and
• RXRA.[8][11]

References

1. GRCh38: Ensembl release 89: ENSG00000151090 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021779 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian)".
6. Sakurai A, Nakai A, DeGroot LJ (June 1990). "Structural analysis of human thyroid hormone receptor beta gene". Mol. Cell. Endocrinol. 71 (2): 83–91. doi:10.1016/0303-7207(90)90245-4. PMID 1973914. S2CID 54389426.
7. "Entrez Gene: THRB thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian)".
8. Monden T, Wondisford FE, Hollenberg AN (November 1997). "Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein". J. Biol. Chem. 272 (47): 29834–41. doi:10.1074/jbc.272.47.29834. PMID 9368056.
9. Lin HM, Zhao L, Cheng SY (August 2002). "Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors". J. Biol. Chem. 277 (32): 28733–41. doi:10.1074/jbc.M203380200. PMID 12048199.
10. Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM (October 1998). "Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors". Endocrinology. 139 (10): 4197–204. doi:10.1210/endo.139.10.6218. PMID 9751500.
11. Jeyakumar M, Tanen MR, Bagchi MK (June 1997). "Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor". Mol. Endocrinol. 11 (6): 755–67. doi:10.1210/mend.11.6.0003. PMID 9171239.
12. Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW (February 2001). "Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2". Mol. Endocrinol. 15 (2): 241–54. doi:10.1210/me.15.2.241. PMID 11158331.
13. 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.
14. Ko L, Cardona GR, Chin WW (May 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961.
15. Ko L, Cardona GR, Iwasaki T, Bramlett KS, Burris TP, Chin WW (January 2002). "Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs". Mol. Endocrinol. 16 (1): 128–40. doi:10.1210/mend.16.1.0755. PMID 11773444.
16. Tagami T, Lutz WH, Kumar R, Jameson JL (December 1998). "The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators". Biochem. Biophys. Res. Commun. 253 (2): 358–63. doi:10.1006/bbrc.1998.9799. PMID 9878542.
17. Ando S, Sarlis NJ, Krishnan J, Feng X, Refetoff S, Zhang MQ, Oldfield EH, Yen PM (September 2001). "Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance". Mol. Endocrinol. 15 (9): 1529–38. doi:10.1210/me.15.9.1529. PMID 11518802.
18. Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY (April 2000). "The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function". Mol. Cell. Biol. 20 (7): 2604–18. doi:10.1128/MCB.20.7.2604-2618.2000. PMC 85476. PMID 10713182.
19. Wu Y, Delerive P, Chin WW, Burris TP (March 2002). "Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1". J. Biol. Chem. 277 (11): 8898–905. doi:10.1074/jbc.M110761200. PMID 11751919.

Further reading

• Lazar MA, Chin WW (1990). "Nuclear thyroid hormone receptors". J. Clin. Invest. 86 (6): 1777–82. doi:10.1172/JCI114906. PMC 329808. PMID 2254444.
• 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. S2CID 2884828.
• González-Sancho JM, García V, Bonilla F, Muñoz A (2003). "Thyroid hormone receptors/THR genes in human cancer". Cancer Lett. 192 (2): 121–32. doi:10.1016/S0304-3835(02)00614-6. PMID 12668276.
• Cugini CD, Leidy JW, Chertow BS, Bérard J, Bradley WE, Menke JB, Hao EH, Usala SJ (1992). "An arginine to histidine mutation in codon 315 of the c-erbA beta thyroid hormone receptor in a kindred with generalized resistance to thyroid hormones results in a receptor with significant 3,5,3'-triiodothyronine binding activity". J. Clin. Endocrinol. Metab. 74 (5): 1164–70. doi:10.1210/jc.74.5.1164. PMID 1314846.
• Behr M, Loos U (1992). "A point mutation (Ala229 to Thr) in the hinge domain of the c-erbA beta thyroid hormone receptor gene in a family with generalized thyroid hormone resistance". Mol. Endocrinol. 6 (7): 1119–26. doi:10.1210/me.6.7.1119. PMID 1324420.
• Falcone M, Miyamoto T, Fierro-Renoy F, Macchia E, DeGroot LJ (1992). "Antipeptide polyclonal antibodies specifically recognize each human thyroid hormone receptor isoform". Endocrinology. 131 (5): 2419–29. doi:10.1210/en.131.5.2419. PMID 1425440.
• Schmidt ED, Schmidt ED, van der Gaag R, Ganpat R, Broersma L, de Boer PA, Moorman AF, Lamers WH, Wiersinga WM, Koornneef L (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.
• Adams M, Nagaya T, Tone Y, Jameson JL, Chatterjee VK (1992). "Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome". Clin. Endocrinol. 36 (3): 281–9. doi:10.1111/j.1365-2265.1992.tb01444.x. PMID 1563081. S2CID 25897422.
• Sasaki S, Nakamura H, Tagami T, Miyoshi Y, Tanaka K, Imura H (1992). "A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone". Mol. Cell. Endocrinol. 84 (3): 159–66. doi:10.1016/0303-7207(92)90026-3. PMID 1587388. S2CID 24853283.
• Nagaya T, Madison LD, Jameson JL (1992). "Thyroid hormone receptor mutants that cause resistance to thyroid hormone. Evidence for receptor competition for DNA sequences in target genes". J. Biol. Chem. 267 (18): 13014–9. PMID 1618799.
• Shuto Y, Wakabayashi I, Amuro N, Minami S, Okazaki T (1992). "A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid hormone receptor-beta associated with a family with generalized resistance to thyroid hormone". J. Clin. Endocrinol. Metab. 75 (1): 213–7. doi:10.1210/jc.75.1.213. PMID 1619012.
• Näär AM, Boutin JM, Lipkin SM, Yu VC, Holloway JM, Glass CK, Rosenfeld MG (1991). "The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors". Cell. 65 (7): 1267–79. doi:10.1016/0092-8674(91)90021-P. PMID 1648451. S2CID 22572347.
• Usala SJ, Menke JB, Watson TL, Wondisford FE, Weintraub BD, Bérard J, Bradley WE, Ono S, Mueller OT, Bercu BB (1991). "A homozygous deletion in the c-erbA beta thyroid hormone receptor gene in a patient with generalized thyroid hormone resistance: isolation and characterization of the mutant receptor". Mol. Endocrinol. 5 (3): 327–35. doi:10.1210/mend-5-3-327. PMID 1653889.
• Bodenner DL, Mroczynski MA, Weintraub BD, Radovick S, Wondisford FE (1991). "A detailed functional and structural analysis of a major thyroid hormone inhibitory element in the human thyrotropin beta-subunit gene". J. Biol. Chem. 266 (32): 21666–73. PMID 1657975.
• Parrilla R, Mixson AJ, McPherson JA, McClaskey JH, Weintraub BD (1991). "Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two "hot spot" regions of the ligand binding domain". J. Clin. Invest. 88 (6): 2123–30. doi:10.1172/JCI115542. PMC 295818. PMID 1661299.
• Usala SJ, Menke JB, Watson TL, Bérard WE, Bradley C, Bale AE, Lash RW, Weintraub BD (1991). "A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance". J. Clin. Endocrinol. Metab. 72 (1): 32–8. doi:10.1210/jcem-72-1-32. PMID 1846005.
• Usala SJ, Tennyson GE, Bale AE, Lash RW, Gesundheit N, Wondisford FE, Accili D, Hauser P, Weintraub BD (1990). "A base mutation of the C-erbA beta thyroid hormone receptor in a kindred with generalized thyroid hormone resistance. Molecular heterogeneity in two other kindreds". J. Clin. Invest. 85 (1): 93–100. doi:10.1172/JCI114438. PMC 296391. PMID 2153155.
• Sakurai A, Takeda K, Ain K, Ceccarelli P, Nakai A, Seino S, Bell GI, Refetoff S, DeGroot LJ (1989). "Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid hormone receptor beta". Proc. Natl. Acad. Sci. U.S.A. 86 (22): 8977–81. Bibcode:1989PNAS...86.8977S. doi:10.1073/pnas.86.22.8977. PMC 298414. PMID 2510172.

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