Thyroid hormone receptor alpha

NameThyroid hormone receptor alpha
Synonyms
  • c-erbA-1
  • c-erbA-alpha
  • EAR-7
  • EAR7
  • ERBA1
  • NR1A1
  • Nuclear receptor subfamily 1 group A member 1
  • THRA1
  • THRA2
  • V-erbA-related protein 7
Gene NameTHRA
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001370|Thyroid hormone receptor alpha
MEQKPSKVECGSDPEENSARSPDGKRKRKNGQCSLKTSMSGYIPSYLDKDEQCVVCGDKA
TGYHYRCITCEGCKGFFRRTIQKNLHPTYSCKYDSCCVIDKITRNQCQLCRFKKCIAVGM
AMDLVLDDSKRVAKRKLIEQNRERRRKEEMIRSLQQRPEPTPEEWDLIHIATEAHRSTNA
QGSHWKQRRKFLPDDIGQSPIVSMPDGDKVDLEAFSEFTKIITPAITRVVDFAKKLPMFS
ELPCEDQIILLKGCCMEIMSLRAAVRYDPESDTLTLSGEMAVKREQLKNGGLGVVSDAIF
ELGKSLSAFNLDDTEVALLQAVLLMSTDRSGLLCVDKIEKSQEAYLLAFEHYVNHRKHNI
PHFWPKLLMKEREVQSSILYKGAAAEGRPGGSLGVHPEGQQLLGMHVVQGPQVRQLEQQL
GEAGSLQGPVLQHQSPKSPQQRLLELLHRSGILHARAVCGEDDSSEADSPSSSEEEPEVC
EDLAGNAASP
Number of residues490
Molecular Weight54815.055
Theoretical pI6.85
GO Classification
Functions
  • thyroid hormone binding
  • steroid hormone receptor activity
  • thyroid hormone receptor activity
  • transcription regulatory region DNA binding
  • transcription factor binding
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
  • chromatin DNA binding
  • protein domain specific binding
  • sequence-specific DNA binding
  • transcription factor activity, sequence-specific DNA binding
  • intronic transcription regulatory region DNA binding
  • steroid receptor RNA activator RNA binding
  • TBP-class protein binding
  • zinc ion binding
Processes
  • negative regulation of RNA polymerase II transcriptional preinitiation complex assembly
  • response to cold
  • brain development
  • regulation of myeloid cell apoptotic process
  • learning or memory
  • adrenal gland development
  • regulation of thyroid hormone mediated signaling pathway
  • digestive tract development
  • embryonic organ development
  • liver development
  • response to drug
  • positive regulation of female receptivity
  • hormone-mediated signaling pathway
  • ossification
  • positive regulation of myotube differentiation
  • transcription from RNA polymerase II promoter
  • cytoplasmic sequestering of transcription factor
  • female courtship behavior
  • gene expression
  • erythrocyte differentiation
  • intracellular receptor signaling pathway
  • transcription initiation from RNA polymerase II promoter
  • thyroid gland development
  • regulation of heart contraction
  • regulation of lipid catabolic process
  • Type I pneumocyte differentiation
  • cartilage condensation
  • positive regulation of transcription from RNA polymerase II promoter
  • regulation of transcription from RNA polymerase II promoter
  • kidney development
  • negative regulation of sequence-specific DNA binding transcription factor activity
  • response to nutrient levels
  • negative regulation of DNA-templated transcription, initiation
  • negative regulation of transcription, DNA-templated
Components
  • mitochondrion
  • nucleus
  • cytosol
  • nucleoplasm
General FunctionZinc ion binding
Specific FunctionIsoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Alpha-2: Does not bind thyroid hormone and functions as a weak dominant negative inhibitor of thyroid hormone action.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID825639
UniProtKB IDP10827
UniProtKB Entry NameTHA_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0016176|Thyroid hormone receptor alpha (THRA)
ATGGAACAGAAGCCAAGCAAGGTGGAGTGTGGGTCAGACCCAGAGGAGAACAGTGCCAGG
TCACCAGATGGAAAGCGAAAAAGAAAGAACGGCCAATGTTCCCTGAAAACCAGCATGTCA
GGGTATATCCCTAGTTACCTGGACAAAGACGAGCAGTGTGTCGTGTGTGGGGACAAGGCA
ACTGGTTATCACTACCGCTGTATCACTTGTGAGGGCTGCAAGGGCTTCTTTCGCCGCACA
ATCCAGAAGAACCTCCATCCCACCTATTCCTGCAAATATGACAGCTGCTGTGTCATTGAC
AAGATCACCCGCAATCAGTGCCAGCTGTGCCGCTTCAAGAAGTGCATCGCCGTGGGCATG
GCCATGGACTTGGTTCTAGATGACTCGAAGCGGGTGGCCAAGCGTAAGCTGATTGAGCAG
AACCGGGAGCGGCGGCGGAAGGAGGAGATGATCCGATCACTGCAGCAGCGACCAGAGCCC
ACTCCTGAAGAGTGGGATCTGATCCACATTGCCACAGAGGCCCATCGCAGCACCAATGCC
CAGGGCAGCCATTGGAAACAGAGGCGGAAATTCCTGCCCGATGACATTGGCCAGTCACCC
ATTGTCTCCATGCCGGACGGAGACAAGGTGGACCTGGAAGCCTTCAGCGAGTTTACCAAG
ATCATCACCCCGGCCATCACCCGTGTGGTGGACTTTGCCAAAAAACTGCCCATGTTCTCC
GAGCTGCCTTGCGAAGACCAGATCATCCTCCTGAAGGGGTGCTGCATGGAGATCATGTCC
CTGCGGGCGGCTGTCCGCTACGACCCTGAGAGCGACACCCTGACGCTGAGTGGGGAGATG
GCTGTCAAGCGGGAGCAGCTCAAGAATGGCGGCCTGGGCGTAGTCTCCGACGCCATCTTT
GAACTGGGCAAGTCACTCTCTGCCTTTAACCTGGATGACACGGAAGTGGCTCTGCTGCAG
GCTGTGCTGCTAATGTCAACAGACCGCTCGGGCCTGCTGTGTGTGGACAAGATCGAGAAG
AGTCAGGAGGCGTACCTGCTGGCGTTCGAGCACTACGTCAACCACCGCAAACACAACATT
CCGCACTTCTGGCCCAAGCTGCTGATGAAGGGTCCGCAGGTCCGGCAGCTTGAGCAGCAG
CTTGGTGAAGCGGGAAGTCTCCAAGGGCCGGTTCTTCAGCACCAGAGCCCGAAGAGCCCG
CAGCAGCGTCTCCTGGAGCTGCTCCACCGAAGCGGAATTCTCCATGCCCGAGCGGTCTGT
GGGGAAGACGACAGCAGTGAGGCGGACTCCCCGAGCTCCTCTGAGGAGGAACCGGAGGTC
TGCGAGGACCTGGCAGGCAATGCAGCCTCTCCCTGA
GenBank Gene IDX55074
GeneCard IDNot Available
GenAtlas IDTHRA
HGNC IDHGNC:11796
Chromosome Location17
Locus17q11.2
References
  1. Laudet V, Begue A, Henry-Duthoit C, Joubel A, Martin P, Stehelin D, Saule S: Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene. Nucleic Acids Res. 1991 Mar 11;19(5):1105-12. 1850510
  2. Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T: Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell. 1989 Apr 7;57(1):31-9. 2539258
  3. Nakai A, Seino S, Sakurai A, Szilak I, Bell GI, DeGroot LJ: Characterization of a thyroid hormone receptor expressed in human kidney and other tissues. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2781-5. 3357890
  4. Pfahl M, Benbrook D: Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor. Nucleic Acids Res. 1987 Nov 25;15(22):9613. 3684612
  5. Nakai A, Sakurai A, Bell GI, DeGroot LJ: Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues. Mol Endocrinol. 1988 Nov;2(11):1087-92. 2464749
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  8. Benbrook D, Pfahl M: A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987 Nov 6;238(4828):788-91. 3672126
  9. Yang YZ, Burgos-Trinidad M, Wu Y, Koenig RJ: Thyroid hormone receptor variant alpha2. Role of the ninth heptad in dna binding, heterodimerization with retinoid X receptors, and dominant negative activity. J Biol Chem. 1996 Nov 8;271(45):28235-42. 8910441
  10. Chen H, Lin RJ, Schiltz RL, Chakravarti D, Nash A, Nagy L, Privalsky ML, Nakatani Y, Evans RM: Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569-80. 9267036
  11. Rubino D, Driggers P, Arbit D, Kemp L, Miller B, Coso O, Pagliai K, Gray K, Gutkind S, Segars J: Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action. Oncogene. 1998 May 14;16(19):2513-26. 9627117
  12. 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. 1999 Nov 26;274(48):34283-93. 10567404
  13. Borngraeber S, Budny MJ, Chiellini G, Cunha-Lima ST, Togashi M, Webb P, Baxter JD, Scanlan TS, Fletterick RJ: Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15358-63. Epub 2003 Dec 12. 14673100
  14. Baumgartner BG, Orpinell M, Duran J, Ribas V, Burghardt HE, Bach D, Villar AV, Paz JC, Gonzalez M, Camps M, Oriola J, Rivera F, Palacin M, Zorzano A: Identification of a novel modulator of thyroid hormone receptor-mediated action. PLoS One. 2007 Nov 21;2(11):e1183. 18030323
  15. 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: Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells. Proteomics. 2008 Jul;8(14):2885-96. doi: 10.1002/pmic.200700887. 18655026
  16. Bochukova E, Schoenmakers N, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, Henning E, Reinemund J, Gevers E, Sarri M, Downes K, Offiah A, Albanese A, Halsall D, Schwabe JW, Bain M, Lindley K, Muntoni F, Vargha-Khadem F, Dattani M, Farooqi IS, Gurnell M, Chatterjee K: A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012 Jan 19;366(3):243-9. doi: 10.1056/NEJMoa1110296. Epub 2011 Dec 14. 22168587
  17. Ye L, Li YL, Mellstrom K, Mellin C, Bladh LG, Koehler K, Garg N, Garcia Collazo AM, Litten C, Husman B, Persson K, Ljunggren J, Grover G, Sleph PG, George R, Malm J: Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. J Med Chem. 2003 Apr 24;46(9):1580-8. 12699376
  18. Nascimento AS, Dias SM, Nunes FM, Aparicio R, Ambrosio AL, Bleicher L, Figueira AC, Santos MA, de Oliveira Neto M, Fischer H, Togashi M, Craievich AF, Garratt RC, Baxter JD, Webb P, Polikarpov I: Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function. J Mol Biol. 2006 Jul 14;360(3):586-98. Epub 2006 May 19. 16781732
  19. Bleicher L, Aparicio R, Nunes FM, Martinez L, Gomes Dias SM, Figueira AC, Santos MA, Venturelli WH, da Silva R, Donate PM, Neves FA, Simeoni LA, Baxter JD, Webb P, Skaf MS, Polikarpov I: Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms. BMC Struct Biol. 2008 Jan 31;8:8. doi: 10.1186/1472-6807-8-8. 18237438
  20. Martinez L, Nascimento AS, Nunes FM, Phillips K, Aparicio R, Dias SM, Figueira AC, Lin JH, Nguyen P, Apriletti JW, Neves FA, Baxter JD, Webb P, Skaf MS, Polikarpov I: Gaining ligand selectivity in thyroid hormone receptors via entropy. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20717-22. doi: 10.1073/pnas.0911024106. Epub 2009 Nov 19. 19926848
  21. Moran C, Agostini M, Visser WE, Schoenmakers E, Schoenmakers N, Offiah AC, Poole K, Rajanayagam O, Lyons G, Halsall D, Gurnell M, Chrysis D, Efthymiadou A, Buchanan C, Aylwin S, Chatterjee KK: Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)alpha1 and TRalpha2: clinical, biochemical, and genetic analyses of three related patients. Lancet Diabetes Endocrinol. 2014 Aug;2(8):619-26. doi: 10.1016/S2213-8587(14)70111-1. Epub 2014 Jun 23. 24969835
  22. Espiard S, Savagner F, Flamant F, Vlaeminck-Guillem V, Guyot R, Munier M, d'Herbomez M, Bourguet W, Pinto G, Rose C, Rodien P, Wemeau JL: A Novel Mutation in THRA Gene Associated With an Atypical Phenotype of Resistance to Thyroid Hormone. J Clin Endocrinol Metab. 2015 Aug;100(8):2841-8. doi: 10.1210/jc.2015-1120. Epub 2015 Jun 2. 26037512
  23. Tylki-Szymanska A, Acuna-Hidalgo R, Krajewska-Walasek M, Lecka-Ambroziak A, Steehouwer M, Gilissen C, Brunner HG, Jurecka A, Rozdzynska-Swiatkowska A, Hoischen A, Chrzanowska KH: Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor alpha gene (THRA). J Med Genet. 2015 May;52(5):312-6. doi: 10.1136/jmedgenet-2014-102936. Epub 2015 Feb 10. 25670821