Thyroid hormone receptor alpha

Function

Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.

Classification

Family (Pfam)

PF00104 Hormone_recep, PF00105 zf-C4

InterPro

NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR1, Nuclear_hrmn_rcpt, ThyrH_rcpt, Znf_hrmn_rcpt, Znf_NHR/GATA

Functional cluster

Zinc-Finger & Chromatin Regulatory Proteins

Experimental structures · PDB · 10

• 1NAV X-ray 2.50A
• 2H77 X-ray 2.33A
• 2H79 X-ray 1.87A
• 3HZF X-ray 2.50A
• 3ILZ X-ray 1.85A
• 3JZB X-ray 2.01A
• 4LNW X-ray 1.90A
• 4LNX X-ray 2.05A
• 7QDT X-ray 3.00A
• 8RQO X-ray 2.74A

A predicted model is available from AlphaFold.

Gene Ontology · 31

• GO:0000785 chromatin
• GO:0005829 cytosol
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0090575 RNA polymerase II transcription regulator complex
• GO:0031490 chromatin DNA binding
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0140296 general transcription initiation factor binding
• GO:0004879 nuclear receptor activity
• GO:0019904 protein domain specific binding
• GO:0044877 protein-containing complex binding
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0017025 TBP-class protein binding
• GO:0070324 thyroid hormone binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0008270 zinc ion binding
• GO:0030154 cell differentiation
• GO:0009755 hormone-mediated signaling pathway
• GO:0042789 mRNA transcription by RNA polymerase II
• GO:0045892 negative regulation of DNA-templated transcription
• GO:2000143 negative regulation of DNA-templated transcription initiation
• GO:0017055 negative regulation of RNA polymerase II transcription preinitiation complex assembly
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0120162 positive regulation of cold-induced thermogenesis
• GO:0002157 positive regulation of thyroid hormone receptor signaling pathway
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0048384 retinoic acid receptor signaling pathway
• GO:0002154 thyroid hormone receptor signaling pathway
• GO:0006366 transcription by RNA polymerase II

Disease associations

• congenital nongoitrous hypothyroidism 6 MONDO:0013757

Drugs targeting this protein · 6

• LIOTHYRONINE SODIUM agonist
• LIOTHYRONINE agonist
• LEVOTHYROXINE SODIUM agonist
• DEXTROTHYROXINE SODIUM agonist
• TIRATRICOL agonist
• DEXTROTHYROXINE agonist

Related proteins · sequence + function similarity

• Thyroid hormone receptor alpha 1.00
• Thyroid hormone receptor alpha 0.99
• Thyroid hormone receptor alpha 0.99
• Thyroid hormone receptor beta 0.90
• Thyroid hormone receptor beta 0.89
• Thyroid hormone receptor beta 0.89
• Gag polyprotein 0.87
• Thyroid hormone receptor alpha-A 0.86
• Thyroid hormone receptor beta-B 0.86
• Thyroid hormone receptor alpha 0.86
• Thyroid hormone receptor alpha 0.86
• Thyroid hormone receptor beta 0.86

Co-cited proteins · studied together in the literature

• Thyroid hormone receptor beta 6 shared papers
• Nuclear receptor subfamily 1 group D member 1 2 shared papers
• Tumor protein p53-inducible nuclear protein 2 1 shared papers
• Tumor protein p53-inducible nuclear protein 2 1 shared papers
• Tumor protein p53-inducible nuclear protein 2 1 shared papers
• Peroxisome proliferator-activated receptor alpha 1 shared papers
• A-kinase anchor protein 13 1 shared papers
• Retinoic acid receptor alpha 3 shared papers
• Thyroid hormone receptor beta 1 shared papers
• Retinoic acid receptor RXR-alpha 3 shared papers
• Estrogen receptor 3 shared papers
• Transcription initiation factor IIA subunit 2 1 shared papers

Literature · 23 cited papers

• A novel mutation in THRA gene associated with an atypical phenotype of resistance to thyroid hormone. J. Clin. Endocrinol. Metab. · 2015
• Thyroid hormone resistance syndrome due to mutations in the thyroid hormone receptor alpha gene (THRA). J. Med. Genet. · 2015
• 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
• A mutation in the thyroid hormone receptor alpha gene. N. Engl. J. Med. · 2012
• The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR. BMC Mol. Biol. · 2010
• Gaining ligand selectivity in thyroid hormone receptors via entropy. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms. BMC Struct. Biol. · 2008
• Identification of a novel modulator of thyroid hormone receptor-mediated action. PLoS ONE · 2007
• Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function. J. Mol. Biol. · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor. Proc. Natl. Acad. Sci. U.S.A. · 2003
• … and 11 more in the literature graph