Thyrotropin receptor

TSHR
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2XWT, 3G04
Identifiers
Aliases	TSHR, CHNG1, LGR3, hTSHR-I, thyroid stimulating hormone receptor, Thyrotropin receptor, thyrotropin (TSH) receptor
External IDs	OMIM: 603372; MGI: 98849; HomoloGene: 315; GeneCards: TSHR; OMA:TSHR - orthologs
Gene location (Human)
Chr.	Chromosome 14 (human)
End	81,146,306 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	91,516,582 bp
RNA expression pattern
	Top expressed in
	left lobe of thyroid gland; ; right lobe of thyroid gland; ; testicle; ; thymus; ; bone marrow cells; ; buccal mucosa cell; ; ventricular zone; ; gonad; ; lymph node; ; right lobe of liver;
	Top expressed in
	retinal pigment epithelium; ; white adipose tissue; ; lactiferous gland; ; subcutaneous adipose tissue; ; spermatocyte; ; brown adipose tissue; ; spermatid; ; ventricular zone; ; tunica adventitia of aorta; ; median eminence;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	G protein-coupled peptide receptor activity; protein binding; G protein-coupled receptor activity; protein-hormone receptor activity; signal transducer activity; thyroid-stimulating hormone receptor activity; protein-containing complex binding; signaling receptor activity;
Cellular component	integral component of membrane; receptor complex; integral component of plasma membrane; membrane; cell surface; plasma membrane; basolateral plasma membrane; intracellular anatomical structure;
Biological process	cell-cell signaling; G protein-coupled receptor signaling pathway; G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; adenylate cyclase-activating G protein-coupled receptor signaling pathway; positive regulation of cell population proliferation; activation of adenylate cyclase activity; hormone-mediated signaling pathway; signal transduction; nervous system development; cell surface receptor signaling pathway; positive regulation of adenylate cyclase activity; cellular response to glycoprotein; cellular response to thyrotropin-releasing hormone; thyroid-stimulating hormone signaling pathway; positive regulation of cold-induced thermogenesis;
	Sources:Amigo / QuickGO
Orthologs
	7253
	22095
	ENSG00000165409
	ENSMUSG00000020963
	P16473
	P47750
	NM_000369; NM_001018036; NM_001142626
	NM_001113404; NM_011648
	NP_000360; NP_001018046; NP_001136098
	NP_001106875; NP_035778
	Wikidata
View/Edit Human	View/Edit Mouse

The thyrotropin receptor (or TSH receptor) is a receptor (and associated protein) that 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^[5] and is coupled to the G_s protein.^[6]

It is primarily found on the surface of the thyroid epithelial cells, but also found on adipose tissue and fibroblasts. The latter explains the reason of the myxedema finding during Graves disease. In addition, it has also been found to be expressed in the anterior pituitary gland, hypothalamus and kidneys. Its presence in the anterior pituitary gland may be involved in mediating the paracrine signaling feedback inhibition of thyrotropin along the hypothalamus-pituitary-thyroid axis.^[7]

Function

Upon binding circulating TSH, a G-protein signal cascade activates adenylyl cyclase and intracellular levels of cAMP rise. cAMP activates all functional aspects of the thyroid cell, including iodine pumping; thyroglobulin synthesis, iodination, endocytosis, and proteolysis; thyroid peroxidase activity; and hormone release. TSHR is involved in regulating seasonal reproduction in vertebrates.^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000165409 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020963 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Farid NR, Szkudlinski MW (Sep 2004). "Minireview: structural and functional evolution of the thyrotropin receptor". Endocrinology. 145 (9): 4048–57. doi:10.1210/en.2004-0437. PMID 15231707.
^ Calebiro D, Nikolaev VO, Lohse MJ (Jul 2010). "Imaging of persistent cAMP signaling by internalized G protein-coupled receptors". Journal of Molecular Endocrinology. 45 (1): 1–8. doi:10.1677/JME-10-0014. PMID 20378719.
^ Williams GR (April 2011). "Extrathyroidal expression of TSH receptor". Annales d'Endocrinologie. 54es Journees internationales d'Endocrinologie clinique. 72 (2): 68–73. doi:10.1016/j.ando.2011.03.006. PMID 21511243.
^ Nakane Y, Yoshimura T (February 2019). "Photoperiodic Regulation of Reproduction in Vertebrates". Annual Review of Animal Biosciences. 7 (1): 173–194. doi:10.1146/annurev-animal-020518-115216. PMID 30332291. S2CID 52984435.

Führer D, Wonerow P, Willgerodt H, Paschke R (Dec 1997). "Identification of a new thyrotropin receptor germline mutation (Leu629Phe) in a family with neonatal onset of autosomal dominant nonautoimmune hyperthyroidism". The Journal of Clinical Endocrinology and Metabolism. 82 (12): 4234–8. doi:10.1210/jcem.82.12.4405. PMID 9398746.
Farid NR, Kascur V, Balazs C (Jul 2000). "The human thyrotropin receptor is highly mutable: a review of gain-of-function mutations". European Journal of Endocrinology. 143 (1): 25–30. doi:10.1530/eje.0.1430025. PMID 10870027.
Szkudlinski MW, Fremont V, Ronin C, Weintraub BD (Apr 2002). "Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships". Physiological Reviews. 82 (2): 473–502. doi:10.1152/physrev.00031.2001. PMID 11917095. S2CID 2919509.
Tonacchera M, Vitti P, De Servi M, Agretti P, De Marco G, Chiovato L, Pinchera A (2004). "Gain of function TSH receptor mutations and iodine deficiency: implications in iodine prophylaxis". Journal of Endocrinological Investigation. 26 (2 Suppl): 2–6. PMID 12762632.
Arturi F, Scarpelli D, Coco A, Sacco R, Bruno R, Filetti S, Russo D (Apr 2003). "Thyrotropin receptor mutations and thyroid hyperfunctioning adenomas ten years after their first discovery: unresolved questions". Thyroid. 13 (4): 341–3. doi:10.1089/105072503321669811. PMID 12804102.
Vaidya B, Campbell V, Tripp JH, Spyer G, Hattersley AT, Ellard S (Jun 2004). "Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation". Clinical Endocrinology. 60 (6): 711–8. doi:10.1111/j.1365-2265.2004.02040.x. PMID 15163335. S2CID 43902851.
Takeshita A, Nagayama Y, Fujiyama K, Yokoyama N, Namba H, Yamashita S, Izumi M, Nagataki S (Nov 1992). "Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript". Biochemical and Biophysical Research Communications. 188 (3): 1214–9. doi:10.1016/0006-291X(92)91360-3. PMID 1445355.
Graves PN, Tomer Y, Davies TF (Sep 1992). "Cloning and sequencing of a 1.3 KB variant of human thyrotropin receptor mRNA lacking the transmembrane domain". Biochemical and Biophysical Research Communications. 187 (2): 1135–43. doi:10.1016/0006-291X(92)91315-H. PMID 1530609.
Loosfelt H, Pichon C, Jolivet A, Misrahi M, Caillou B, Jamous M, Vannier B, Milgrom E (May 1992). "Two-subunit structure of the human thyrotropin receptor". Proceedings of the National Academy of Sciences of the United States of America. 89 (9): 3765–9. Bibcode:1992PNAS...89.3765L. doi:10.1073/pnas.89.9.3765. PMC 525571. PMID 1570295.
Nagayama Y, Russo D, Wadsworth HL, Chazenbalk GD, Rapoport B (Aug 1991). "Eleven amino acids (Lys-201 to Lys-211) and 9 amino acids (Gly-222 to Leu-230) in the human thyrotropin receptor are involved in ligand binding". The Journal of Biological Chemistry. 266 (23): 14926–30. doi:10.1016/S0021-9258(18)98566-2. PMID 1651314.
Murakami M, Mori M (Aug 1990). "Identification of immunogenic regions in human thyrotropin receptor for immunoglobulin G of patients with Graves' disease". Biochemical and Biophysical Research Communications. 171 (1): 512–8. doi:10.1016/0006-291X(90)91423-P. PMID 1697467.
Heldin NE, Gustavsson B, Westermark K, Westermark B (Dec 1991). "A somatic point mutation in a putative ligand binding domain of the TSH receptor in a patient with autoimmune hyperthyroidism". The Journal of Clinical Endocrinology and Metabolism. 73 (6): 1374–6. doi:10.1210/jcem-73-6-1374. PMID 1955520.
Libert F, Passage E, Lefort A, Vassart G, Mattei MG (1991). "Localization of human thyrotropin receptor gene to chromosome region 14q3 by in situ hybridization". Cytogenetics and Cell Genetics. 54 (1–2): 82–3. doi:10.1159/000132964. PMID 2249482.
Frazier AL, Robbins LS, Stork PJ, Sprengel R, Segaloff DL, Cone RD (Aug 1990). "Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing". Molecular Endocrinology. 4 (8): 1264–76. doi:10.1210/mend-4-8-1264. hdl:21.11116/0000-0000-7844-D. PMID 2293030.
Misrahi M, Loosfelt H, Atger M, Sar S, Guiochon-Mantel A, Milgrom E (Jan 1990). "Cloning, sequencing and expression of human TSH receptor". Biochemical and Biophysical Research Communications. 166 (1): 394–403. doi:10.1016/0006-291X(90)91958-U. PMID 2302212.
Nagayama Y, Kaufman KD, Seto P, Rapoport B (Dec 1989). "Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor". Biochemical and Biophysical Research Communications. 165 (3): 1184–90. doi:10.1016/0006-291X(89)92727-7. PMID 2558651.
Libert F, Lefort A, Gerard C, Parmentier M, Perret J, Ludgate M, Dumont JE, Vassart G (Dec 1989). "Cloning, sequencing and expression of the human thyrotropin (TSH) receptor: evidence for binding of autoantibodies". Biochemical and Biophysical Research Communications. 165 (3): 1250–5. doi:10.1016/0006-291X(89)92736-8. PMID 2610690.
Cuddihy RM, Bryant WP, Bahn RS (Aug 1995). "Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor". Thyroid. 5 (4): 255–7. doi:10.1089/thy.1995.5.255. PMID 7488864.
Bahn RS, Dutton CM, Heufelder AE, Sarkar G (Feb 1994). "A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy". The Journal of Clinical Endocrinology and Metabolism. 78 (2): 256–60. doi:10.1210/jcem.78.2.7508946. PMID 7508946.
Sunthornthepvarakui T, Gottschalk ME, Hayashi Y, Refetoff S (Jan 1995). "Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene". The New England Journal of Medicine. 332 (3): 155–60. doi:10.1056/NEJM199501193320305. PMID 7528344.

External links

"Glycoprotein Hormone Receptors: TSH". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2013-11-01. Retrieved 2007-10-25.
Thyrotropin+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
SSFA-GPHR: Sequence Structure Function Analysis of Glycoprotein Hormone Receptors
GRIS: Glycoprotein-hormone Receptor Information System
Overview of all the structural information available in the PDB for UniProt: P16473 (Thyrotropin receptor) at the PDBe-KB.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000165409 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020963 – 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.

[pmid15231707-5] Farid NR, Szkudlinski MW (Sep 2004). "Minireview: structural and functional evolution of the thyrotropin receptor". Endocrinology. 145 (9): 4048–57. doi:10.1210/en.2004-0437. PMID 15231707.

[pmid20378719-6] Calebiro D, Nikolaev VO, Lohse MJ (Jul 2010). "Imaging of persistent cAMP signaling by internalized G protein-coupled receptors". Journal of Molecular Endocrinology. 45 (1): 1–8. doi:10.1677/JME-10-0014. PMID 20378719.

[7] Williams GR (April 2011). "Extrathyroidal expression of TSH receptor". Annales d'Endocrinologie. 54es Journees internationales d'Endocrinologie clinique. 72 (2): 68–73. doi:10.1016/j.ando.2011.03.006. PMID 21511243.

[8] Nakane Y, Yoshimura T (February 2019). "Photoperiodic Regulation of Reproduction in Vertebrates". Annual Review of Animal Biosciences. 7 (1): 173–194. doi:10.1146/annurev-animal-020518-115216. PMID 30332291. S2CID 52984435.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

Thyrotropin receptor

Function

See also

References

Further reading

External links