Thyroid hormone receptor alpha
Alternative name(s):
Nuclear receptor subfamily 1 group A member 1
V-erbA-related protein 7
Short name=EAR-7
c-erbA-1
c-erbA-alpha
Gene names
Name: THRA
Synonyms: EAR7, ERBA1, NR1A1, THRA1, THRA2
Function
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Ref.14 Ref.18 Ref.20 Ref.21
Subunit structure
Binds DNA as a dimer; homodimer and heterodimer with RXRB. Interacts with NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Probably interacts with SFPQ. Interacts with C1D By similarity. Interacts with AKAP13. Interacts with TP53INP2. Ref.11 Ref.12 Ref.13 Ref.15 Ref.19
Subcellular location
Nucleus.
Domain
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Involvement in disease
Hypothyroidism, congenital, non-goitrous, 6 (CHNG6) [MIM:614450]: A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17
Sequence similarities
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Contains 1 nuclear receptor DNA-binding domain.
Thyroid hormone receptor beta
Alternative name(s):
Nuclear receptor subfamily 1 group A member 2
c-erbA-2
c-erbA-beta
Gene names
Name: THRB
Synonyms: ERBA2, NR1A2, THR1
Function
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. Ref.14 Ref.16 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24
Subunit structure
Binds DNA as a dimer; homodimer and heterodimer with RXRA. Interacts with the coactivators NCOA1/SRC1, NCOA2/GRIP1, NCOA7 and MED1/TRAP220 in a ligand-inducible manner. Interacts with the corepressor NCOR1 in absence of ligand. Interacts with C1D By similarity. Interacts with NR2F6; the interaction impairs the binding of the THRB homodimer and THRB:RXRB heterodimer to T3 response elements. Interacts with PRMT2 and THRSP. Ref.11 Ref.12 Ref.13 Ref.14 Ref.19 Ref.20 Ref.21 Ref.24
Subcellular location
Nucleus.
Domain
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Involvement in disease
Generalized thyroid hormone resistance (GTHR) [MIM:188570]: A disease characterized by goiter, abnormal mental functions, increased susceptibility to infections, abnormal growth and bone maturation, tachycardia and deafness. Affected individuals may also have attention deficit-hyperactivity disorders (ADHD) and language difficulties. GTHR patients also have high levels of circulating thyroid hormones (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.17 Ref.18 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43
Generalized thyroid hormone resistance autosomal recessive (GTHRAR) [MIM:274300]: An autosomal recessive disorder characterized by goiter, clinical euthyroidism, end-organ unresponsiveness to thyroid hormone, abnormal growth and bone maturation, and deafness. Patients also have high levels of circulating thyroid hormones, with elevated thyroid stimulating hormone.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]: Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.35
Sequence similarities
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Contains 1 nuclear receptor DNA-binding domain.
