甲状腺激素β受体

甲状腺激素β受体
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1BSX、1N46、1NAX、1NQ0、1NQ1、1NQ2、1NUO、1Q4X、1R6G、1XZX、1Y0X、2J4A、2NLL、2PIN、3D57、3GWS、3IMY、3JZC、4ZO1
识别号
别名	THRB；, C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH, THR1, THRB1, THRB2, thyroid hormone receptor beta, TRbeta
外部ID	OMIM：190160 MGI：98743 HomoloGene：36025 GeneCards：THRB
相关疾病
	selective pituitary resistance to thyroid hormone、generalized resistance to thyroid hormone
为以下药物的标靶
	反三碘甲状腺原氨酸、替拉曲可、三碘甲腺原氨酸、左旋甲状腺素钠
基因位置（人类）
染色体	3号染色体
终止	24,495,756 bp
基因位置（小鼠）
染色体	小鼠14号染色体
终止	4,809,435 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• sequence-specific DNA binding; • transcription corepressor activity; • 锌离子结合; • 金属离子结合; • steroid hormone receptor activity; • 血浆蛋白结合; • 酶结合; • chromatin DNA binding; • thyroid hormone binding; • DNA结合转录因子活性; • DNA结合; • DNA-binding transcription factor activity, RNA polymerase II-specific; • transcription cis-regulatory region binding; • RNA polymerase II transcription regulatory region sequence-specific DNA binding; • 转录因子结合; • nuclear receptor coactivator activity; • signaling receptor activity; • nuclear receptor activity;
细胞组分	• 核质; • 细胞核; • nuclear body; • RNA polymerase II transcription regulator complex;
生物学过程	• regulation of transcription, DNA-templated; • regulation of heart contraction; • female courtship behavior; • regulation of transcription by RNA polymerase II; • negative regulation of transcription by RNA polymerase II; • 听觉; • 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 by RNA polymerase II; • 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; • 细胞分化; • 甲状旁腺的发生; • response to lipid; • thyroid hormone mediated signaling pathway;
	Sources:Amigo / QuickGO
直系同源
	7068
	21834
	ENSG00000151090
	ENSMUSG00000021779
	P10828
	P37242
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
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
	维基数据
查看/编辑人类	查看/编辑小鼠

甲状腺激素β受体（TR-β，或THR-β）也称为核受体亚家族1，A 组，成员2（NR1A2），是一种核受体蛋白，在人类中由THR-β基因编码。^[7]^[8]

功能

该基因编码的蛋白质为三碘甲腺原氨酸的核激素受体。它是甲状腺激素的多种受体之一，已被证明可以调节甲状腺激素的生物活性。小鼠基因敲除研究表明，不同的受体虽然具有一定程度的冗余，但可能介导甲状腺激素的不同功能。已知该基因的缺陷是导致：广泛性甲状腺激素抵抗（GTHR）的成因。该综合症疾病的特征为：甲状腺肿大；循环甲状腺激素（T₃-T₄）水平增加；同时促甲状腺激素（TSH）正常或略微升高。现已发现到该基因的几种转录变体，但迄今为止只观察到一种的全长天然基因。^[9]

基因互作

甲状腺激素β受体已被证明与以下存在基因相互作用：

参考文献

^ 與甲状腺激素β受体相關的疾病；在維基數據上查看/編輯參考.
^ 對Thyroid hormone receptor beta起作用的藥物；在維基數據上查看/編輯參考.
^ ^3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000151090 - Ensembl, May 2017
^ ^4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000021779 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian).
^ Sakurai A, Nakai A, DeGroot LJ. Structural analysis of human thyroid hormone receptor beta gene. Mol. Cell. Endocrinol. June 1990, 71 (2): 83–91. PMID 1973914. S2CID 54389426. doi:10.1016/0303-7207(90)90245-4.
^ Entrez Gene: THRB thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian).
^ ^10.0 ^10.1 Monden T, Wondisford FE, Hollenberg AN. Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J. Biol. Chem. November 1997, 272 (47): 29834–41. PMID 9368056. doi:10.1074/jbc.272.47.29834  .
^ Lin HM, Zhao L, Cheng SY. Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors. J. Biol. Chem. August 2002, 277 (32): 28733–41. PMID 12048199. doi:10.1074/jbc.M203380200  .
^ ^12.0 ^12.1 Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM. Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors. Endocrinology. October 1998, 139 (10): 4197–204. PMID 9751500. doi:10.1210/endo.139.10.6218  .
^ ^13.0 ^13.1 Jeyakumar M, Tanen MR, Bagchi MK. Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor. Mol. Endocrinol. June 1997, 11 (6): 755–67. PMID 9171239. doi:10.1210/mend.11.6.0003  .
^ Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW. Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2. Mol. Endocrinol. February 2001, 15 (2): 241–54. PMID 11158331. doi:10.1210/mend.15.2.0595  .
^ 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. A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J. Biol. Chem. November 1999, 274 (48): 34283–93. PMID 10567404. doi:10.1074/jbc.274.48.34283  .
^ Ko L, Cardona GR, Chin WW. Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator. Proc. Natl. Acad. Sci. U.S.A. May 2000, 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. PMC 18584  . PMID 10823961. doi:10.1073/pnas.97.11.6212  .
^ Ko L, Cardona GR, Iwasaki T, Bramlett KS, Burris TP, Chin WW. Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs. Mol. Endocrinol. January 2002, 16 (1): 128–40. PMID 11773444. doi:10.1210/mend.16.1.0755  .
^ Tagami T, Lutz WH, Kumar R, Jameson JL. The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators. Biochem. Biophys. Res. Commun. December 1998, 253 (2): 358–63. PMID 9878542. doi:10.1006/bbrc.1998.9799.
^ Ando S, Sarlis NJ, Krishnan J, Feng X, Refetoff S, Zhang MQ, Oldfield EH, Yen PM. Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance. Mol. Endocrinol. September 2001, 15 (9): 1529–38. PMID 11518802. doi:10.1210/mend.15.9.0687  .
^ Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY. The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function. Mol. Cell. Biol. April 2000, 20 (7): 2604–18. PMC 85476  . PMID 10713182. doi:10.1128/MCB.20.7.2604-2618.2000.
^ Wu Y, Delerive P, Chin WW, Burris TP. Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1. J. Biol. Chem. March 2002, 277 (11): 8898–905. PMID 11751919. doi:10.1074/jbc.M110761200  .

扩展阅读

Lazar MA, Chin WW. Nuclear thyroid hormone receptors. J. Clin. Invest. 1990, 86 (6): 1777–82. PMC 329808  . PMID 2254444. doi:10.1172/JCI114906.
Forrest D, Reh TA, Rüsch A. Neurodevelopmental control by thyroid hormone receptors. Curr. Opin. Neurobiol. 2002, 12 (1): 49–56. PMID 11861164. S2CID 2884828. doi:10.1016/S0959-4388(02)00289-1.
González-Sancho JM, García V, Bonilla F, Muñoz A. Thyroid hormone receptors/THR genes in human cancer. Cancer Lett. 2003, 192 (2): 121–32. PMID 12668276. doi:10.1016/S0304-3835(02)00614-6.
Cugini CD, Leidy JW, Chertow BS, Bérard J, Bradley WE, Menke JB, Hao EH, Usala SJ. 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. 1992, 74 (5): 1164–70. PMID 1314846. doi:10.1210/jcem.74.5.1314846.
Behr M, Loos U. 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. 1992, 6 (7): 1119–26. PMID 1324420. doi:10.1210/mend.6.7.1324420  .
Falcone M, Miyamoto T, Fierro-Renoy F, Macchia E, DeGroot LJ. Antipeptide polyclonal antibodies specifically recognize each human thyroid hormone receptor isoform. Endocrinology. 1992, 131 (5): 2419–29. PMID 1425440. doi:10.1210/endo.131.5.1425440.
Schmidt ED, Schmidt ED, van der Gaag R, Ganpat R, Broersma L, de Boer PA, Moorman AF, Lamers WH, Wiersinga WM, Koornneef L. Distribution of the nuclear thyroid-hormone receptor in extraocular and skeletal muscles. J. Endocrinol. 1992, 133 (1): 67–74. PMID 1517709. doi:10.1677/joe.0.1330067.
Adams M, Nagaya T, Tone Y, Jameson JL, Chatterjee VK. Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome. Clin. Endocrinol. 1992, 36 (3): 281–9. PMID 1563081. S2CID 25897422. doi:10.1111/j.1365-2265.1992.tb01444.x.
Sasaki S, Nakamura H, Tagami T, Miyoshi Y, Tanaka K, Imura H. A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone. Mol. Cell. Endocrinol. 1992, 84 (3): 159–66. PMID 1587388. S2CID 24853283. doi:10.1016/0303-7207(92)90026-3.
Nagaya T, Madison LD, Jameson JL. Thyroid hormone receptor mutants that cause resistance to thyroid hormone. Evidence for receptor competition for DNA sequences in target genes. J. Biol. Chem. 1992, 267 (18): 13014–9. PMID 1618799. doi:10.1016/S0021-9258(18)42375-7  .
Shuto Y, Wakabayashi I, Amuro N, Minami S, Okazaki T. 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. 1992, 75 (1): 213–7. PMID 1619012. doi:10.1210/jcem.75.1.1619012.
Näär AM, Boutin JM, Lipkin SM, Yu VC, Holloway JM, Glass CK, Rosenfeld MG. The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. Cell. 1991, 65 (7): 1267–79. PMID 1648451. S2CID 22572347. doi:10.1016/0092-8674(91)90021-P.
Usala SJ, Menke JB, Watson TL, Wondisford FE, Weintraub BD, Bérard J, Bradley WE, Ono S, Mueller OT, Bercu BB. 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. 1991, 5 (3): 327–35. PMID 1653889. doi:10.1210/mend-5-3-327  .
Bodenner DL, Mroczynski MA, Weintraub BD, Radovick S, Wondisford FE. A detailed functional and structural analysis of a major thyroid hormone inhibitory element in the human thyrotropin beta-subunit gene. J. Biol. Chem. 1991, 266 (32): 21666–73. PMID 1657975. doi:10.1016/S0021-9258(18)54688-3  .
Parrilla R, Mixson AJ, McPherson JA, McClaskey JH, Weintraub BD. 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. 1991, 88 (6): 2123–30. PMC 295818  . PMID 1661299. doi:10.1172/JCI115542.
Usala SJ, Menke JB, Watson TL, Bérard WE, Bradley C, Bale AE, Lash RW, Weintraub BD. 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. 1991, 72 (1): 32–8. PMID 1846005. doi:10.1210/jcem-72-1-32.
Usala SJ, Tennyson GE, Bale AE, Lash RW, Gesundheit N, Wondisford FE, Accili D, Hauser P, Weintraub BD. 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. 1990, 85 (1): 93–100. PMC 296391  . PMID 2153155. doi:10.1172/JCI114438.
Sakurai A, Takeda K, Ain K, Ceccarelli P, Nakai A, Seino S, Bell GI, Refetoff S, DeGroot LJ. 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. 1989, 86 (22): 8977–81. Bibcode:1989PNAS...86.8977S. PMC 298414  . PMID 2510172. doi:10.1073/pnas.86.22.8977  .

甲状腺激素β受体引用了美国国家医学图书馆提供的数据，这些数据属于公共领域。

[1] 與甲状腺激素β受体相關的疾病；在維基數據上查看/編輯參考.

[2] 對Thyroid hormone receptor beta起作用的藥物；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-3] 3.0 ^3.1 ^3.2 GRCh38: Ensembl release 89: ENSG00000151090 - Ensembl, May 2017

[refGRCm38Ensembl-4] 4.0 ^4.1 ^4.2 GRCm38: Ensembl release 89: ENSMUSG00000021779 - Ensembl, May 2017

[5] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[6] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrezA-7] Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian).

[pmid1973914-8] Sakurai A, Nakai A, DeGroot LJ. Structural analysis of human thyroid hormone receptor beta gene. Mol. Cell. Endocrinol. June 1990, 71 (2): 83–91. PMID 1973914. S2CID 54389426. doi:10.1016/0303-7207(90)90245-4.

[entrezB-9] Entrez Gene: THRB thyroid hormone receptor, beta (erythroblastic leukemia viral (v-erb-a) oncogene homolog 2, avian).

[pmid9368056-10] 10.0 ^10.1 Monden T, Wondisford FE, Hollenberg AN. Isolation and characterization of a novel ligand-dependent thyroid hormone receptor-coactivating protein. J. Biol. Chem. November 1997, 272 (47): 29834–41. PMID 9368056. doi:10.1074/jbc.272.47.29834  .

[pmid12048199-11] Lin HM, Zhao L, Cheng SY. Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors. J. Biol. Chem. August 2002, 277 (32): 28733–41. PMID 12048199. doi:10.1074/jbc.M203380200  .

[pmid9751500-12] 12.0 ^12.1 Liu Y, Takeshita A, Misiti S, Chin WW, Yen PM. Lack of coactivator interaction can be a mechanism for dominant negative activity by mutant thyroid hormone receptors. Endocrinology. October 1998, 139 (10): 4197–204. PMID 9751500. doi:10.1210/endo.139.10.6218  .

[pmid9171239-13] 13.0 ^13.1 Jeyakumar M, Tanen MR, Bagchi MK. Analysis of the functional role of steroid receptor coactivator-1 in ligand-induced transactivation by thyroid hormone receptor. Mol. Endocrinol. June 1997, 11 (6): 755–67. PMID 9171239. doi:10.1210/mend.11.6.0003  .

[pmid11158331-14] Lee SK, Jung SY, Kim YS, Na SY, Lee YC, Lee JW. Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2. Mol. Endocrinol. February 2001, 15 (2): 241–54. PMID 11158331. doi:10.1210/mend.15.2.0595  .

[pmid10567404-15] 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. A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo. J. Biol. Chem. November 1999, 274 (48): 34283–93. PMID 10567404. doi:10.1074/jbc.274.48.34283  .

[pmid10823961-16] Ko L, Cardona GR, Chin WW. Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator. Proc. Natl. Acad. Sci. U.S.A. May 2000, 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. PMC 18584  . PMID 10823961. doi:10.1073/pnas.97.11.6212  .

[pmid11773444-17] Ko L, Cardona GR, Iwasaki T, Bramlett KS, Burris TP, Chin WW. Ser-884 adjacent to the LXXLL motif of coactivator TRBP defines selectivity for ERs and TRs. Mol. Endocrinol. January 2002, 16 (1): 128–40. PMID 11773444. doi:10.1210/mend.16.1.0755  .

[pmid9878542-18] Tagami T, Lutz WH, Kumar R, Jameson JL. The interaction of the vitamin D receptor with nuclear receptor corepressors and coactivators. Biochem. Biophys. Res. Commun. December 1998, 253 (2): 358–63. PMID 9878542. doi:10.1006/bbrc.1998.9799.

[pmid11518802-19] Ando S, Sarlis NJ, Krishnan J, Feng X, Refetoff S, Zhang MQ, Oldfield EH, Yen PM. Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance. Mol. Endocrinol. September 2001, 15 (9): 1529–38. PMID 11518802. doi:10.1210/mend.15.9.0687  .

[pmid10713182-20] Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, Cheng SY. The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function. Mol. Cell. Biol. April 2000, 20 (7): 2604–18. PMC 85476  . PMID 10713182. doi:10.1128/MCB.20.7.2604-2618.2000.

[pmid11751919-21] Wu Y, Delerive P, Chin WW, Burris TP. Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1. J. Biol. Chem. March 2002, 277 (11): 8898–905. PMID 11751919. doi:10.1074/jbc.M110761200  .

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