Thyrotropin receptor Recombinant Protein | TSHR recombinant protein

Recombinant human Thyrotropin receptor

Cat. Num. AAA1085783

• Gene Names: TSHR; LGR3; CHNG1; hTSHR-I
• Applications: Calibrator or standard
• Purity: 85%±5% by SDS-PAGE
• Synonyms: Thyrotropin receptor; Recombinant human Thyrotropin receptor; Thyroid-stimulating hormone receptor; TSH-R; TSHR recombinant protein

• Host: E.coli
• Purity/Purification: 85%±5% by SDS-PAGE
• Form/Format: Liquid, dissolved in 10 mM Tris-HCl, 1 mM EDTA, pH 8.0,50% glycerol
• Concentration: 1.5 mg/ml (varies by lot)
• Sequence Positions: 21-413aa
• Sequence: GMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLR TIPSHAFSNLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNT RNLTYIDPDALKELPLLKFLGIFNTGLKMFPDLTKVYSTDIFFIL EITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSVQGYAFNGT KLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPS KGLEHLKELIARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFK NQKKIRGILESLMCNESSMQSLRQRKSVNALNSPLHQEYEENL GDSIVGYKEKSKFQDTHNNAHYYVFFEEQEDEIIGFGQELKNP

• Applicable Applications for TSHR recombinant protein: Calibrator or standard
• Tag Info: his-tag
• Expression Region: 21-413aa
• Appearance: Clear Solution
• Preparation and Storage: Aliquot and store at < -20°C. Avoid repeated freeze/thaw cycles.

SDS-Page

(Recombinant human Thyrotropin receptorHis-taggedYeast derived)

Product Categories/Family for TSHR recombinant protein

Neuroscience; Raw Materials Assay Development

References

Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor.Nagayama Y., Kaufman K.D., Seto P., Rapoport B.Biochem. Biophys. Res. Commun. 165:1184-1190(1989) Cloning, sequencing and expression of the human thyrotropin (TSH) receptor evidence for binding of autoantibodies.Libert F., Lefort A., Gerard C., Parmentier M., Perret J., Ludgate M., Dumont J.E., Vassart G.Biochem. Biophys. Res. Commun. 165:1250-1255(1989) Cloning, sequencing and expression of human TSH receptor.Misrahi M., Loosfelt H., Atger M., Sar S., Guiochon-Mantel A., Milgrom E.Biochem. Biophys. Res. Commun. 166:394-403(1990) Isolation of TSH and LH/CG receptor cDNAs from human thyroid regulation by tissue specific splicing.Frazier A.L., Robbins L.S., Stork P.J., Sprengel R., Segaloff D.L., Cone R.D.Mol. Endocrinol. 4:1264-1276(1990) Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain.Graves P.N., Tomer Y., Davies T.F.Biochem. Biophys. Res. Commun. 187:1135-1143(1992) Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript.Takeshita A., Nagayama Y., Fujiyama K., Yokoyama N., Namba H., Yamashita S., Izumi M., Nagataki S.Biochem. Biophys. Res. Commun. 188:1214-1219(1992) cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org) .Kopatz S.A., Aronstam R.S., Sharma S.V. The DNA sequence and analysis of human chromosome 14.Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.Nature 421:601-607(2003) Purification and characterization of a soluble bioactive amino-terminal extracellular domain of the human thyrotropin receptor.Cornelis S., Uttenweiler-Joseph S., Panneels V., Vassart G., Costagliola S.Biochemistry 40:9860-9869(2001) Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits, activates the thyroid-stimulating hormone receptor.Nakabayashi K., Matsumi H., Bhalla A., Bae J., Mosselman S., Hsu S.Y., Hsueh A.J.W.J. Clin. Invest. 109:1445-1452(2002) Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway.Lahuna O., Quellari M., Achard C., Nola S., Meduri G., Navarro C., Vitale N., Borg J.-P., Misrahi M.EMBO J. 24:1364-1374(2005) Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions.Jiang X., Dreano M., Buckler D.R., Cheng S., Ythier A., Wu H., Hendrickson W.A., el Tayar N.Structure 3:1341-1353(1995) Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody.Sanders J., Chirgadze D.Y., Sanders P., Baker S., Sullivan A., Bhardwaja A., Bolton J., Reeve M., Nakatake N., Evans M., Richards T., Powell M., Miguel R.N., Blundell T.L., Furmaniak J., Smith B.R.Thyroid 17:395-410(2007) Further studies of genetic susceptibility to Graves' disease in a Russian population.Chistiakov D.A., Savost'anov K.V., Turakulov R.I., Petunina N., Balabolkin M.I., Nosikov V.V.Med. Sci. Monit. 8:CR180-CR184(2002) 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.Ban Y., Greenberg D.A., Concepcion E.S., Tomer Y.Thyroid 12:1079-1083(2002) Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins.Ho S.-C., Goh S.-S., Khoo D.H.Thyroid 13:523-528(2003) The human thyrotropin receptor is highly mutable a review of gain-of-function mutations.Farid N.R., Kascur V., Balazs C.Eur. J. Endocrinol. 143:25-30(2000) A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism.Heldin N.-E., Gustavsson B., Westermark K., Westermark B.J. Clin. Endocrinol. Metab. 73:1374-1376(1991) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas.Parma J., Duprez L., van Sande J., Cochaux P., Gervy C., Mockel J., Dumont J.E., Vassart G.Nature 365:649-651(1993) A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy.Bahn R.S., Dutton C.M., Heufelder A.E., Sarkar G.J. Clin. Endocrinol. Metab. 78:256-260(1994) Novel mutations of thyrotropin receptor gene in thyroid hyperfunctioning adenomas. Rapid identification by fine needle aspiration biopsy.Porcellini A., Ciullo I., Laviola L., Amabile G., Fenzi G., Avvedimento V.E.J. Clin. Endocrinol. Metab. 79:657-661(1994) Identification and functional characterization of two new somatic mutations causing constitutive activation of the thyrotropin receptor in hyperfunctioning autonomous adenomas of the thyroid.Paschke R., Tonacchera M., van Sande J., Parma J., Vassart G.J. Clin. Endocrinol. Metab. 79:1785-1789(1994) Germline mutations in the thyrotropin receptor gene cause non-autoimmune autosomal dominant hyperthyroidism.Duprez L., Parma J., van Sande J., Allgeier A., Leclere J., Schvartz C., Delisle M.-J., Decoulx M., Orgiazzi J., Dumont J.E., Vassart G.Nat. Genet. 7:396-401(1994) Functional analysis of a variant of the thyrotropin receptor gene in a family with Graves' disease.Gustavsson B., Eklof C., Westermark K., Westermark B., Heldin N.-E.Mol. Cell. Endocrinol. 111:167-173(1995) Congenital hyperthyroidism caused by a mutation in the thyrotropin-receptor gene.Kopp P., van Sande J., Parma J., Duprez L., Gerber H., Joss E., Jameson J.L., Dumont J.E., Vassart G.N. Engl. J. Med. 332:150-154(1995) Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene.Sunthornthepvarakul T., Gottschalk M.E., Hayashi Y., Refetoff S.N. Engl. J. Med. 332:155-160(1995) Point mutations in the thyrotropin receptor in human thyroid tumors.Ohno M., Endo T., Ohta K., Gunji K., Onaya T.Thyroid 5:97-100(1995) Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor.Cuddihy R.M., Bryant W.P., Bahn R.S.Thyroid 5:255-257(1995) Functional characteristics of three new germline mutations of the thyrotropin receptor gene causing autosomal dominant toxic thyroid hyperplasia.Tonacchera M., van Sande J., Cetani F., Swillens S., Schvartz C., Winiszewski P., Portmann L., Dumont J.E., Vassart G., Parma J.J. Clin. Endocrinol. Metab. 81:547-554(1996) A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism.de Roux N., Polak M., Couet J., Leger J., Czernichow P., Milgrom E., Misrahi M.J. Clin. Endocrinol. Metab. 81:2023-2026(1996) Four families with loss of function mutations of the thyrotropin receptor.de Roux N., Misrahi M., Brauner R., Houang M., Carel J.-C., Granier M., Le Bouc Y., Ghinea N., Boumedienne A., Toublanc J.E., Milgrom E.J. Clin. Endocrinol. Metab. 81:4229-4235(1996) Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma.Russo D., Tumino S., Arturi F., Vigneri P., Grasso G., Pontecorvi A., Filetti S., Belfiore A.J. Clin. Endocrinol. Metab. 82:735-738(1997) Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH.Clifton-Bligh R.J., Gregory J.W., Ludgate M., John R., Persani L., Asteria C., Beck-Peccoz P., Chatterjee V.K.K.J. Clin. Endocrinol. Metab. 82:1094-1100(1997) Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas.Parma J., Duprez L., van Sande J., Hermans J., Rocmans P., van Vliet G., Costagliola S., Rodien P., Dumont J.E., Vassart G.J. Clin. Endocrinol. Metab. 82:2695-2701(1997) Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism.Biebermann H., Schoeneberg T., Krude H., Schultz G., Gudermann T., Grueters A.J. Clin. Endocrinol. Metab. 82:3471-3480(1997) Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene.Holzapfel H.P., Wonerow P., von Petrykowski W., Henschen M., Scherbaum W.A., Paschke R.J. Clin. Endocrinol. Metab. 82:3879-3884(1997) Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism.Fuhrer D., Wonerow P., Willgerodt H., Paschke R.J. Clin. Endocrinol. Metab. 82:4234-4238(1997) Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland.Abramowicz M.J., Duprez L., Parma J., Vassart G., Heinrichs C.J. Clin. Invest. 99:3018-3024(1997) Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281-->isoleucine) in the extracellular domain of the thyrotropin receptor.Kopp P., Muirhead S., Jourdain N., Gu W.X., Jameson J.L., Rodd C.J. Clin. Invest. 100:1634-1639(1997) Congenital nonautoimmune hyperthyroidism in a nonidentical twin caused by a sporadic germline mutation in the thyrotropin receptor gene.Kopp P., Jameson J.L., Roe T.F.Thyroid 7:765-770(1997) Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor.Grueters A., Schoeneberg T., Biebermann H., Krude H., Krohn H.P., Dralle H., Gudermann T.J. Clin. Endocrinol. Metab. 83:1431-1436(1998) Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin.Rodien P., Bremont C., Raffin Sanson M.-L., Parma J., van Sande J., Costagliola S., Luton J.-P., Vassart G., Duprez L.N. Engl. J. Med. 339:1823-1826(1998) A germline mutation of the thyrotropin receptor gene associated with thyrotoxicosis and mitral valve prolapse in a Chinese family.Khoo D.H.C., Parma J., Rajasoorya C., Ho S.C., Vassart G.J. Clin. Endocrinol. Metab. 84:1459-1462(1999) Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter.Gabriel E.M., Bergert E.R., Grant C.S., van Heerden J.A., Thompson G.B., Morris J.C.J. Clin. Endocrinol. Metab. 84:3328-3335(1999) A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell thyroid carcinoma associated with thyrotoxicosis.Russo D., Wong M.G., Costante G., Chiefari E., Treseler P.A., Arturi F., Filetti S., Clark O.H.Thyroid 9:13-17(1999) A novel thyrotropin receptor mutation in an infant with severe thyrotoxicosis.Esapa C.T., Duprez L., Ludgate M., Mustafa M.S., Kendall-Taylor P., Vassart G., Harris P.E.Thyroid 9:1005-1010(1999) A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient.Kosugi S., Hai N., Okamoto H., Sugawa H., Mori T.Eur. J. Endocrinol. 143:471-477(2000) 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.Kaczur V., Takacs M., Szalai C., Falus A., Nagy Z., Berencsi G., Balazs C.Eur. J. Immunogenet. 27:17-23(2000) Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin evidence for a new inactivating mutation of the TSH receptor gene.Tonacchera M., Agretti P., Pinchera A., Rosellini V., Perri A., Collecchi P., Vitti P., Chiovato L.J. Clin. Endocrinol. Metab. 85:1001-1008(2000) Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.Tonacchera M., Agretti P., Chiovato L., Rosellini V., Ceccarini G., Perri A., Viacava P., Naccarato A.G., Miccoli P., Pinchera A., Vitti P.J. Clin. Endocrinol. Metab. 85:2270-2274(2000) 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.Muehlberg T., Herrmann K., Joba W., Kirchberger M., Heberling H.-J., Heufelder A.E.J. Clin. Endocrinol. Metab. 85:2640-2643(2000) 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.Russo D., Betterle C., Arturi F., Chiefari E., Girelli M.E., Filetti S.J. Clin. Endocrinol. Metab. 85:4238-4242(2000) Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood.Biebermann H., Schoeneberg T., Krude H., Gudermann T., Grueters A.Langenbecks Arch. Surg. 385:390-392(2000) Sporadic nonautoimmune congenital hyperthyroidism due to a strong activating mutation of the thyrotropin receptor gene.Tonacchera M., Agretti P., Rosellini V., Ceccarini G., Perri A., Zampolli M., Longhi R., Larizza D., Pinchera A., Vitti P., Chiovato L.Thyroid 10:859-863(2000) A Phe 486 thyrotropin receptor mutation in an autonomously functioning follicular carcinoma that was causing hyperthyroidism.Camacho P., Gordon D., Chiefari E., Yong S., DeJong S., Pitale S., Russo D., Filetti S.Thyroid 10:1009-1012(2000) Novel TSHR germline mutation (Met463Val) masquerading as Graves' disease in a large Welsh kindred with hyperthyroidism.Fuhrer D., Warner J., Sequeira M., Paschke R., Gregory J.W., Ludgate M.Thyroid 10:1035-1041(2000) A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism.Alberti L., Proverbio M.C., Costagliola S., Weber G., Beck-Peccoz P., Chiumello G., Persani L.Eur. J. Endocrinol. 145:249-254(2001) The first activating TSH receptor mutation in transmembrane domain 1 identified in a family with nonautoimmune hyperthyroidism.Biebermann H., Schoeneberg T., Hess C., Germak J., Gudermann T., Grueters A.J. Clin. Endocrinol. Metab. 86:4429-4433(2001) Detection of thyroid-stimulating hormone receptor and G(s) alpha mutations in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.Truelzsch B., Krohn K., Wonerow P., Chey S., Holzapfel H.-P., Ackermann F., Fuehrer D., Paschke R.J. Mol. Med. 78:684-691(2001) Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin.Nagashima T., Murakami M., Onigata K., Morimura T., Nagashima K., Mori M., Morikawa A.Thyroid 11:551-559(2001) Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.Vanvooren V., Uchino S., Duprez L., Costa M.J., Vandekerckhove J., Parma J., Vassart G., Dumont J.E., van Sande J., Noguchi S.Eur. J. Endocrinol. 147:287-291(2002) Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism.Alberti L., Proverbio M.C., Costagliola S., Romoli R., Boldrighini B., Vigone M.C., Weber G., Chiumello G., Beck-Peccoz P., Persani L.J. Clin. Endocrinol. Metab. 87:2549-2555(2002) Functional significance of the thyrotropin receptor germline polymorphism D727E.Sykiotis G.P., Neumann S., Georgopoulos N.A., Sgourou A., Papachatzopoulou A., Markou K.B., Kyriazopoulou V., Paschke R., Vagenakis A.G., Papavassiliou A.G.Biochem. Biophys. Res. Commun. 301:1051-1056(2003) Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects.Peeters R.P., van Toor H., Klootwijk W., de Rijke Y.B., Kuiper G.G.J.M., Uitterlinden A.G., Visser T.J.J. Clin. Endocrinol. Metab. 88:2880-2888(2003) TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism.Tonacchera M., Perri A., De Marco G., Agretti P., Montanelli L., Banco M.E., Corrias A., Bellone J., Tosi M.T., Vitti P., Martino E., Pinchera A., Chiovato L.J. Endocrinol. Invest. 26:997-1000(2003) Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor.Park S.-M., Clifton-Bligh R.J., Betts P., Chatterjee V.K.K.Clin. Endocrinol. (Oxf.) 60:220-227(2004) Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation.Vaidya B., Campbell V., Tripp J.H., Spyer G., Hattersley A.T., Ellard S.Clin. Endocrinol. (Oxf.) 60:711-718(2004) Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism.Tonacchera M., Perri A., De Marco G., Agretti P., Banco M.E., Di Cosmo C., Grasso L., Vitti P., Chiovato L., Pinchera A.J. Clin. Endocrinol. Metab. 89:5787-5793(2004) +Additional computationally mapped references.<p>Provides general information on the entry.

NCBI and Uniprot Product Information

• NCBI GI #: 64085121
• NCBI GeneID: 7253
• NCBI Accession #: NP_000360.2
• NCBI GenBank Nucleotide #: NM_000369.2
• UniProt Accession #: P16473; Q16503; Q8TB90; Q96GT6; Q9P1V4; Q9ULA3; Q9UPH3; A0PJU7; F5GYU5; G3V2A9
• NCBI Official Full Name: thyrotropin receptor isoform 1
• NCBI Official Synonym Full Names: thyroid stimulating hormone receptor
• NCBI Official Symbol: TSHR
• NCBI Official Synonym Symbols: LGR3; CHNG1; hTSHR-I
• NCBI Protein Information: thyrotropin receptor
• UniProt Protein Name: Thyrotropin receptor
• Protein Family: Thyrotropin receptor
• UniProt Gene Name: TSHR
• UniProt Synonym Gene Names: LGR3; TSH-R
• UniProt Entry Name: TSHR_HUMAN

NCBI Description

The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Uniprot Description

TSHR: Receptor for thyrothropin. Plays a central role in controlling thyroid cell metabolism. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Also acts as a receptor for thyrostimulin (GPA2+GPB5). Defects in TSHR are found in patients affected by hyperthyroidism with different etiologies. Somatic, constitutively activating TSHR mutations and/or constitutively activating G(s)alpha mutations have been identified in toxic thyroid nodules (TTNs) that are the predominant cause of hyperthyroidism in iodine deficient areas. These mutations lead to TSH independent activation of the cAMP cascade resulting in thyroid growth and hormone production. TSHR mutations are found in autonomously functioning thyroid nodules (AFTN), toxic multinodular goiter (TMNG) and hyperfunctioning thyroid adenomas (HTA). TMNG encompasses a spectrum of different clinical entities, ranging from a single hyperfunctioning nodule within an enlarged thyroid, to multiple hyperfunctioning areas scattered throughout the gland. HTA are discrete encapsulated neoplasms characterized by TSH- independent autonomous growth, hypersecretion of thyroid hormones, and TSH suppression. Defects in TSHR are also a cause of thyroid neoplasms (papillary and follicular cancers). Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation. Defects in TSHR are the cause of congenital hypothyroidism non-goitrous type 1 (CHNG1); also known as congenital hypothyroidism due to TSH resistance. CHNG1 is a non-autoimmune condition characterized by resistance to thyroid- stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. CHNG1 presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. Defects in TSHR are the cause of familial gestational hyperthyroidism (HTFG). HTFG is a condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy. Defects in TSHR are the cause of hyperthyroidism non- autoimmune (HTNA). It is a condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent. Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Receptor, GPCR; GPCR, family 1; Membrane protein, integral; Membrane protein, multi-pass

Chromosomal Location of Human Ortholog: 14q31

Cellular Component: integral to plasma membrane; plasma membrane; receptor complex

Molecular Function: peptide receptor activity, G-protein coupled; protein binding; thyroid-stimulating hormone receptor activity

Biological Process: adenylate cyclase activation; cell-cell signaling; G-protein coupled receptor protein signaling pathway; G-protein signaling, adenylate cyclase activating pathway; G-protein signaling, coupled to cyclic nucleotide second messenger; hormone-mediated signaling; positive regulation of cell proliferation

Disease: Hyperthyroidism, Familial Gestational; Hyperthyroidism, Nonautoimmune; Hypothyroidism, Congenital, Nongoitrous, 1