Thyroid Stimulating Hormone Receptor (TSHR)

LGR3; HTSHR-I; Thyrotropin Receptor; TSH Receptor

SPN	U032
HGNC	12373
MGI	98849
PubMed	16106256
RGD	3911
UniProt	P16473
Wiki	TSHR

The thyrotropin receptor is a protein responds to thyroid-stimulating hormone (also known as "thyrotropin", and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH receptor is a member of the G-protein coupled receptor superfamily of integral membrane proteins.It is primarily found on the surface of the thyroid epithelial cells.It should not be confused with "thyrotropin-releasing hormone" (TRH) or "thyrotropin-releasing hormone receptor" (TRHR).The deduced 764-amino acid protein has a molecular mass of 86.8 kD and contains a signal peptide, 7 transmembrane regions, 5 potential glycosylation sites, and a short intracytoplasmic region. The TSHR cDNA encoded a functional receptor that activated adenylate cyclase in response to TSH.

Reference

"Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor."
Biochem. Biophys. Res. Commun. 165:1184-1190(1989) [PubMed] [Europe PMC] [Abstract]

"Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies."
Biochem. Biophys. Res. Commun. 165:1250-1255(1989) [PubMed] [Europe PMC] [Abstract]

"Cloning, sequencing and expression of human TSH receptor."
Biochem. Biophys. Res. Commun. 166:394-403(1990) [PubMed] [Europe PMC] [Abstract]

"Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing."
Mol. Endocrinol. 4:1264-1276(1990) [PubMed] [Europe PMC] [Abstract]

"Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain."
Biochem. Biophys. Res. Commun. 187:1135-1143(1992) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript."
Biochem. Biophys. Res. Commun. 188:1214-1219(1992) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and analysis of human chromosome 14."
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor."
Biochemistry 40:9860-9869(2001) [PubMed] [Europe PMC] [Abstract]

"Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor."
J. Clin. Invest. 109:1445-1452(2002) [PubMed] [Europe PMC] [Abstract]

"Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway."
EMBO J. 24:1364-1374(2005) [PubMed] [Europe PMC] [Abstract]

"Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions."
Structure 3:1341-1353(1995) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody."
Thyroid 17:395-410(2007) [PubMed] [Europe PMC] [Abstract]

"Further studies of genetic susceptibility to Graves' disease in a Russian population."
Med. Sci. Monit. 8:CR180-CR184(2002) [PubMed] [Europe PMC] [Abstract]

"A germline single nucleotide polymorphism at the intracellular domain of the human thyrotropin receptor does not have a major effect on the development of Graves' disease."
Thyroid 12:1079-1083(2002) [PubMed] [Europe PMC] [Abstract]

"Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins."
Thyroid 13:523-528(2003) [PubMed] [Europe PMC] [Abstract]

"The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations."
Eur. J. Endocrinol. 143:25-30(2000) [PubMed] [Europe PMC] [Abstract]

"A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism."
J. Clin. Endocrinol. Metab. 73:1374-1376(1991) [PubMed] [Europe PMC] [Abstract]

"Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas."
Nature 365:649-651(1993) [PubMed] [Europe PMC] [Abstract]

"A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy."
J. Clin. Endocrinol. Metab. 78:256-260(1994) [PubMed] [Europe PMC] [Abstract]

"Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. Rapid identification by fine needle aspiration biopsy."
J. Clin. Endocrinol. Metab. 79:657-661(1994) [PubMed] [Europe PMC] [Abstract]

"Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid."
J. Clin. Endocrinol. Metab. 79:1785-1789(1994) [PubMed] [Europe PMC] [Abstract]

"Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism."
Nat. Genet. 7:396-401(1994) [PubMed] [Europe PMC] [Abstract]

"Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease."
Mol. Cell. Endocrinol. 111:167-173(1995) [PubMed] [Europe PMC] [Abstract]

"Congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene."
N. Engl. J. Med. 332:150-154(1995) [PubMed] [Europe PMC] [Abstract]

"Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene."
N. Engl. J. Med. 332:155-160(1995) [PubMed] [Europe PMC] [Abstract]

"Point mutations in the thyrotropin receptor in human thyroid tumors."
Thyroid 5:97-100(1995) [PubMed] [Europe PMC] [Abstract]

"Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor."
Thyroid 5:255-257(1995) [PubMed] [Europe PMC] [Abstract]

"Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia."
J. Clin. Endocrinol. Metab. 81:547-554(1996) [PubMed] [Europe PMC] [Abstract]

"A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism."
J. Clin. Endocrinol. Metab. 81:2023-2026(1996) [PubMed] [Europe PMC] [Abstract]

"Four families with loss of function mutations of the thyrotropin receptor."
J. Clin. Endocrinol. Metab. 81:4229-4235(1996) [PubMed] [Europe PMC] [Abstract]

"Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma."
J. Clin. Endocrinol. Metab. 82:735-738(1997) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH."
J. Clin. Endocrinol. Metab. 82:1094-1100(1997) [PubMed] [Europe PMC] [Abstract]

"Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas."
J. Clin. Endocrinol. Metab. 82:2695-2701(1997) [PubMed] [Europe PMC] [Abstract]

"Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism."
J. Clin. Endocrinol. Metab. 82:3471-3480(1997) [PubMed] [Europe PMC] [Abstract]

"Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene."
J. Clin. Endocrinol. Metab. 82:3879-3884(1997) [PubMed] [Europe PMC] [Abstract]

"Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism."
J. Clin. Endocrinol. Metab. 82:4234-4238(1997) [PubMed] [Europe PMC] [Abstract]

"Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland."
J. Clin. Invest. 99:3018-3024(1997) [PubMed] [Europe PMC] [Abstract]

"Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor."
J. Clin. Invest. 100:1634-1639(1997) [PubMed] [Europe PMC] [Abstract]

"Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene."
Thyroid 7:765-770(1997) [PubMed] [Europe PMC] [Abstract]

"Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor."
J. Clin. Endocrinol. Metab. 83:1431-1436(1998) [PubMed] [Europe PMC] [Abstract]

"Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin."
N. Engl. J. Med. 339:1823-1826(1998) [PubMed] [Europe PMC] [Abstract]

"A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family."
J. Clin. Endocrinol. Metab. 84:1459-1462(1999) [PubMed] [Europe PMC] [Abstract]

"Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter."
J. Clin. Endocrinol. Metab. 84:3328-3335(1999) [PubMed] [Europe PMC] [Abstract]

"A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell thyroid carcinoma associated with thyrotoxicosis."
Thyroid 9:13-17(1999) [PubMed] [Europe PMC] [Abstract]

"A novel thyrotropin receptor mutation in an infant with severe thyrotoxicosis."
Thyroid 9:1005-1010(1999) [PubMed] [Europe PMC] [Abstract]

"A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient."
Eur. J. Endocrinol. 143:471-477(2000) [PubMed] [Europe PMC] [Abstract]

"Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012-1704) of the TSH receptor gene in Graves' disease."
Eur. J. Immunogenet. 27:17-23(2000) [PubMed] [Europe PMC] [Abstract]

"Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene."
J. Clin. Endocrinol. Metab. 85:1001-1008(2000) [PubMed] [Europe PMC] [Abstract]

"Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter."
J. Clin. Endocrinol. Metab. 85:2270-2274(2000) [PubMed] [Europe PMC] [Abstract]

"Lack of association of nonautoimmune hyperfunctioning thyroid disorders and a germline polymorphism of codon 727 of the human thyrotropin receptor in a European Caucasian population."
J. Clin. Endocrinol. Metab. 85:2640-2643(2000) [PubMed] [Europe PMC] [Abstract]

"A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH."
J. Clin. Endocrinol. Metab. 85:4238-4242(2000) [PubMed] [Europe PMC] [Abstract]

"Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood."
Langenbecks Arch. Surg. 385:390-392(2000) [PubMed] [Europe PMC] [Abstract]

"Sporadic nonautoimmune congenital hyperthyroidism due to a strong activating mutation of the thyrotropin receptor gene."
Thyroid 10:859-863(2000) [PubMed] [Europe PMC] [Abstract]

"A Phe 486 thyrotropin receptor mutation in an autonomously functioning follicular carcinoma that was causing hyperthyroidism."
Thyroid 10:1009-1012(2000) [PubMed] [Europe PMC] [Abstract]

"Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease in a large Welsh kindred with hyperthyroidism."
Thyroid 10:1035-1041(2000) [PubMed] [Europe PMC] [Abstract]

"A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism."
Eur. J. Endocrinol. 145:249-254(2001) [PubMed] [Europe PMC] [Abstract]

"The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism."
J. Clin. Endocrinol. Metab. 86:4429-4433(2001) [PubMed] [Europe PMC] [Abstract]

"Detection of thyroid-stimulating hormone receptor and G(s)alpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis."
J. Mol. Med. 78:684-691(2001) [PubMed] [Europe PMC] [Abstract]

"Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin."
Thyroid 11:551-559(2001) [PubMed] [Europe PMC] [Abstract]

"Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population."
Eur. J. Endocrinol. 147:287-291(2002) [PubMed] [Europe PMC] [Abstract]

"Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism."
J. Clin. Endocrinol. Metab. 87:2549-2555(2002) [PubMed] [Europe PMC] [Abstract]

"Functional significance of the thyrotropin receptor germline polymorphism D727E."
Biochem. Biophys. Res. Commun. 301:1051-1056(2003) [PubMed] [Europe PMC] [Abstract]

"Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects."
J. Clin. Endocrinol. Metab. 88:2880-2888(2003) [PubMed] [Europe PMC] [Abstract]

"TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism."
J. Endocrinol. Invest. 26:997-1000(2003) [PubMed] [Europe PMC] [Abstract]

"Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor."
Clin. Endocrinol. (Oxf.) 60:220-227(2004) [PubMed] [Europe PMC] [Abstract]

"Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation."
Clin. Endocrinol. (Oxf.) 60:711-718(2004) [PubMed] [Europe PMC] [Abstract]

"Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism."
J. Clin. Endocrinol. Metab. 89:5787-5793(2004) [PubMed] [Europe PMC] [Abstract]