Thyroid hormone receptor alpha

Protein-coding gene in the species Homo sapiens
THRA
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1NAV, 2H77, 2H79, 3HZF, 3ILZ, 3JZB, 4LNW, 4LNX

Identifiers
AliasesTHRA, AR7, CHNG6, EAR7, ERB-T-1, ERBA, ERBA1, NR1A1, THRA1, THRA2, c-ERBA-1, thyroid hormone receptor, alpha, thyroid hormone receptor alpha, TRalpha
External IDsOMIM: 190120 MGI: 98742 HomoloGene: 37747 GeneCards: THRA
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for THRA
Genomic location for THRA
Band17q21.1Start40,058,290 bp[1]
End40,093,867 bp[1]
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)[2]
Chromosome 11 (mouse)
Genomic location for THRA
Genomic location for THRA
Band11 D|11 62.58 cMStart98,631,464 bp[2]
End98,659,832 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • nucleus accumbens

  • middle frontal gyrus

  • amygdala

  • caudate nucleus

  • putamen

  • cingulate gyrus

  • cerebellar hemisphere

  • Brodmann area 9

  • prefrontal cortex

  • sural nerve
Top expressed in
  • entorhinal cortex

  • superior frontal gyrus

  • subiculum

  • hippocampus proper

  • cerebellar cortex

  • olfactory tubercle

  • Region I of hippocampus proper

  • superior colliculus

  • inferior colliculus

  • primary motor cortex
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • transcription cis-regulatory region binding
  • protein binding
  • single-stranded RNA binding
  • zinc ion binding
  • chromatin DNA binding
  • nuclear receptor activity
  • steroid receptor RNA activator RNA binding
  • transcription factor binding
  • TBP-class protein binding
  • steroid hormone receptor activity
  • DNA binding
  • protein domain specific binding
  • sequence-specific DNA binding
  • metal ion binding
  • DNA-binding transcription factor activity
  • thyroid hormone binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • protein-containing complex binding
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding
  • nuclear receptor coactivator activity
  • signaling receptor activity
Cellular component
  • cytoplasm
  • nucleoplasm
  • nucleus
  • cytosol
  • RNA polymerase II transcription regulator complex
Biological process
  • regulation of transcription by RNA polymerase II
  • response to cold
  • cytoplasmic sequestering of transcription factor
  • hormone-mediated signaling pathway
  • regulation of thyroid hormone mediated signaling pathway
  • thyroid gland development
  • regulation of transcription, DNA-templated
  • ossification
  • female courtship behavior
  • cartilage condensation
  • negative regulation of RNA polymerase II transcription preinitiation complex assembly
  • type I pneumocyte differentiation
  • transcription, DNA-templated
  • steroid hormone mediated signaling pathway
  • transcription by RNA polymerase II
  • regulation of lipid catabolic process
  • regulation of heart contraction
  • animal organ morphogenesis
  • positive regulation of female receptivity
  • learning or memory
  • regulation of myeloid cell apoptotic process
  • positive regulation of transcription by RNA polymerase II
  • transcription initiation from RNA polymerase II promoter
  • erythrocyte differentiation
  • negative regulation of DNA-templated transcription, initiation
  • positive regulation of myotube differentiation
  • negative regulation of transcription, DNA-templated
  • intracellular receptor signaling pathway
  • negative regulation of transcription by RNA polymerase II
  • thyroid hormone mediated signaling pathway
  • multicellular organism development
  • brain development
  • cell differentiation
  • response to lipid
  • positive regulation of cold-induced thermogenesis
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

7067

21833

Ensembl

ENSG00000126351

ENSMUSG00000058756

UniProt

P10827

P63058

RefSeq (mRNA)

NM_199334
NM_001190918
NM_001190919
NM_003250

NM_178060
NM_001313983

RefSeq (protein)

NP_001177847
NP_001177848
NP_003241
NP_955366

NP_001300912
NP_835161

Location (UCSC)Chr 17: 40.06 – 40.09 MbChr 11: 98.63 – 98.66 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the THRA gene.[5][6][7]

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. Alternatively spliced transcript variants encoding distinct isoforms have been reported.[5]

Role in pathology

Mutations of the THRA gene may cause nongoitrous congenital hypothyroidism-6, a subtype of congenital hypothyroidism.

Interactions

THR1 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126351 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000058756 – 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. ^ a b "Entrez Gene: THRA thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian)".
  6. ^ Spurr NK, Solomon E, Jansson M, Sheer D, Goodfellow PN, Bodmer WF, Vennstrom B (Jan 1984). "Chromosomal localisation of the human homologues to the oncogenes erbA and B". The EMBO Journal. 3 (1): 159–63. doi:10.1002/j.1460-2075.1984.tb01777.x. PMC 557313. PMID 6323162.
  7. ^ Dayton AI, Selden JR, Laws G, Dorney DJ, Finan J, Tripputi P, Emanuel BS, Rovera G, Nowell PC, Croce CM (Jul 1984). "A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 81 (14): 4495–9. Bibcode:1984PNAS...81.4495D. doi:10.1073/pnas.81.14.4495. PMC 345617. PMID 6589608.
  8. ^ Dressel U, Thormeyer D, Altincicek B, Paululat A, Eggert M, Schneider S, Tenbaum SP, Renkawitz R, Baniahmad A (May 1999). "Alien, a highly conserved protein with characteristics of a corepressor for members of the nuclear hormone receptor superfamily". Molecular and Cellular Biology. 19 (5): 3383–94. doi:10.1128/mcb.19.5.3383. PMC 84131. PMID 10207062.
  9. ^ a b De Luca A, Severino A, De Paolis P, Cottone G, De Luca L, De Falco M, Porcellini A, Volpe M, Condorelli G (Feb 2003). "p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor". The Biochemical Journal. 369 (Pt 3): 477–84. doi:10.1042/BJ20020057. PMC 1223100. PMID 12371907.
  10. ^ Li D, Wang F, Samuels HH (Dec 2001). "Domain structure of the NRIF3 family of coregulators suggests potential dual roles in transcriptional regulation". Molecular and Cellular Biology. 21 (24): 8371–84. doi:10.1128/MCB.21.24.8371-8384.2001. PMC 100002. PMID 11713274.
  11. ^ Li D, Desai-Yajnik V, Lo E, Schapira M, Abagyan R, Samuels HH (Oct 1999). "NRIF3 is a novel coactivator mediating functional specificity of nuclear hormone receptors". Molecular and Cellular Biology. 19 (10): 7191–202. doi:10.1128/mcb.19.10.7191. PMC 84712. PMID 10490654.
  12. ^ Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG (Jul 1998). "The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 7939–44. Bibcode:1998PNAS...95.7939Y. doi:10.1073/pnas.95.14.7939. PMC 20908. PMID 9653119.
  13. ^ a b c Ito M, Yuan CX, Malik S, Gu W, Fondell JD, Yamamura S, Fu ZY, Zhang X, Qin J, Roeder RG (Mar 1999). "Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators". Molecular Cell. 3 (3): 361–70. doi:10.1016/S1097-2765(00)80463-3. PMID 10198638.
  14. ^ 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 (Nov 1999). "A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo". The Journal of Biological Chemistry. 274 (48): 34283–93. doi:10.1074/jbc.274.48.34283. PMID 10567404.
  15. ^ Lee SK, Na SY, Jung SY, Choi JE, Jhun BH, Cheong J, Meltzer PS, Lee YC, Lee JW (Jun 2000). "Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2". Molecular Endocrinology. 14 (6): 915–25. doi:10.1210/mend.14.6.0471. PMID 10847592.
  16. ^ Chang KH, Chen Y, Chen TT, Chou WH, Chen PL, Ma YY, Yang-Feng TL, Leng X, Tsai MJ, O'Malley BW, Lee WH (Aug 1997). "A thyroid hormone receptor coactivator negatively regulated by the retinoblastoma protein". Proceedings of the National Academy of Sciences of the United States of America. 94 (17): 9040–5. Bibcode:1997PNAS...94.9040C. doi:10.1073/pnas.94.17.9040. PMC 23019. PMID 9256431.
  17. ^ 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 (Jul 2008). "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell line Chang liver cells". Proteomics. 8 (14): 2885–96. doi:10.1002/pmic.200700887. PMID 18655026. S2CID 25586938.

Further reading

  • Forrest D, Reh TA, Rüsch A (Feb 2002). "Neurodevelopmental control by thyroid hormone receptors". Current Opinion in Neurobiology. 12 (1): 49–56. doi:10.1016/S0959-4388(02)00289-1. PMID 11861164. S2CID 2884828.
  • Sakurai A, Bell GI, DeGroot LJ (Oct 1992). "Dinucleotide repeat polymorphism in the human thyroid hormone receptor alpha gene (THRA1) on chromosome 17". Human Molecular Genetics. 1 (7): 553. doi:10.1093/hmg/1.7.553-a. PMID 1307263.
  • Berrodin TJ, Marks MS, Ozato K, Linney E, Lazar MA (Sep 1992). "Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein". Molecular Endocrinology. 6 (9): 1468–78. doi:10.1210/mend.6.9.1331778. PMID 1331778. S2CID 24291055.
  • Schmidt ED, Schmidt ED, van der Gaag R, Ganpat R, Broersma L, de Boer PA, Moorman AF, Lamers WH, Wiersinga WM, Koornneef L (Apr 1992). "Distribution of the nuclear thyroid-hormone receptor in extraocular and skeletal muscles". The Journal of Endocrinology. 133 (1): 67–74. doi:10.1677/joe.0.1330067. PMID 1517709.
  • Yen PM, Sunday ME, Darling DS, Chin WW (Mar 1992). "Isoform-specific thyroid hormone receptor antibodies detect multiple thyroid hormone receptors in rat and human pituitaries". Endocrinology. 130 (3): 1539–46. doi:10.1210/endo.130.3.1537303. PMID 1537303.
  • Laudet V, Begue A, Henry-Duthoit C, Joubel A, Martin P, Stehelin D, Saule S (Mar 1991). "Genomic organization of the human thyroid hormone receptor alpha (c-erbA-1) gene". Nucleic Acids Research. 19 (5): 1105–12. doi:10.1093/nar/19.5.1105. PMC 333788. PMID 1850510.
  • Nakai A, Sakurai A, Bell GI, DeGroot LJ (Nov 1988). "Characterization of a third human thyroid hormone receptor coexpressed with other thyroid hormone receptors in several tissues". Molecular Endocrinology. 2 (11): 1087–92. doi:10.1210/mend-2-11-1087. PMID 2464749.
  • Miyajima N, Horiuchi R, Shibuya Y, Fukushige S, Matsubara K, Toyoshima K, Yamamoto T (Apr 1989). "Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus". Cell. 57 (1): 31–9. doi:10.1016/0092-8674(89)90169-4. PMID 2539258. S2CID 19135678.
  • Sakurai A, Nakai A, DeGroot LJ (Feb 1989). "Expression of three forms of thyroid hormone receptor in human tissues". Molecular Endocrinology. 3 (2): 392–9. doi:10.1210/mend-3-2-392. PMID 2710139.
  • Sap J, Muñoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H, Vennström B (1987). "The c-erb-A protein is a high-affinity receptor for thyroid hormone". Nature. 324 (6098): 635–40. doi:10.1038/324635a0. PMID 2879242. S2CID 4353175.
  • Nakai A, Seino S, Sakurai A, Szilak I, Bell GI, DeGroot LJ (Apr 1988). "Characterization of a thyroid hormone receptor expressed in human kidney and other tissues". Proceedings of the National Academy of Sciences of the United States of America. 85 (8): 2781–5. Bibcode:1988PNAS...85.2781N. doi:10.1073/pnas.85.8.2781. PMC 280083. PMID 3357890.
  • Mitelman F, Manolov G, Manolova Y, Billström R, Heim S, Kristoffersson U, Mandahl N, Ferro MT, San Roman C (Jun 1986). "High resolution chromosome analysis of constitutional and acquired t(15;17) maps c-erbA to subband 17q11.2". Cancer Genetics and Cytogenetics. 22 (2): 95–8. doi:10.1016/0165-4608(86)90168-8. PMID 3458521.
  • Benbrook D, Pfahl M (Nov 1987). "A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library". Science. 238 (4828): 788–91. Bibcode:1987Sci...238..788B. doi:10.1126/science.3672126. PMID 3672126.
  • Pfahl M, Benbrook D (Nov 1987). "Nucleotide sequence of cDNA encoding a novel human thyroid hormone receptor". Nucleic Acids Research. 15 (22): 9613. doi:10.1093/nar/15.22.9613. PMC 306505. PMID 3684612.
  • Chen JD, Evans RM (Oct 1995). "A transcriptional co-repressor that interacts with nuclear hormone receptors". Nature. 377 (6548): 454–7. Bibcode:1995Natur.377..454C. doi:10.1038/377454a0. PMID 7566127. S2CID 4361329.
  • Desai-Yajnik V, Hadzic E, Modlinger P, Malhotra S, Gechlik G, Samuels HH (Aug 1995). "Interactions of thyroid hormone receptor with the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and the HIV-1 Tat transactivator". Journal of Virology. 69 (8): 5103–12. doi:10.1128/JVI.69.8.5103-5112.1995. PMC 189328. PMID 7609079.
  • Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (Feb 1995). "Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor". Molecular Endocrinology. 9 (2): 243–54. doi:10.1210/mend.9.2.7776974. PMID 7776974.
  • Desai-Yajnik V, Samuels HH (1994). "Regulation of the human immunodeficiency virus type 1 long terminal repeat: interactions of thyroid hormone receptor with retinoid-X receptor, nuclear factor kappa B, Sp1, and Tat". Transactions of the Association of American Physicians. 106: 13–32. PMID 8036737.

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

  • v
  • t
  • e
  • 1nav: Thyroid Receptor Alpha in complex with an agonist selective for Thyroid Receptor Beta1
    1nav: Thyroid Receptor Alpha in complex with an agonist selective for Thyroid Receptor Beta1
  • 2h77: Crystal structure of human TR alpha bound T3 in monoclinic space group
    2h77: Crystal structure of human TR alpha bound T3 in monoclinic space group
  • 2h79: Crystal Structure of human TR alpha bound T3 in orthorhombic space group
    2h79: Crystal Structure of human TR alpha bound T3 in orthorhombic space group
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies
  • v
  • t
  • e
Receptor
(ligands)
THRTooltip Thyroid hormone receptor
Agonists
Thyromimetics
(selective agonists)
Antagonists
  • 1-850
  • NH3
  • Tetraiodothyroacetic acid (Tetrac)
Transporter
(blockers)
NISTooltip Sodium-iodide symporter
 
Enzyme
(inhibitors)
TPOTooltip Thyroid peroxidase
DIOTooltip Iodothyronine deiodinase
Others
  • See also: Receptor/signaling modulators