Thyrotropin receptor

Function

Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. TSHR is coupled to G(s) proteins and mediates the activation of adenylate cyclase. This leads to the generation of cyclic adenosine monophosphate (cAMP), which in turn activates protein kinase A (PKA). PKA subsequently phosphorylates downstream targets involved in thyroid hormone biosynthesis and secretion, including thyroid peroxidase (TPO) and the sodium/iodide symporter (NIS). Additionally, plays a central role in controlling thyroid cell metabolism (By similarity).

Classification

Family (Pfam)

PF00001 7tm_1, PF13306 LRR_5

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, Gphrmn_rcpt_fam, LRR_5, LRR_dom_sf, TSH_rcpt

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 9

• 2XWT X-ray 1.90A
• 3G04 X-ray 2.55A
• 7T9I EM 2.90A
• 7T9M EM 3.10A
• 7T9N EM 2.90A
• 7UTZ EM 2.40A
• 7XW5 EM 2.96A
• 7XW6 EM 2.78A
• 7XW7 EM 5.50A

A predicted model is available from AlphaFold.

Gene Ontology · 20

• GO:0016323 basolateral plasma membrane
• GO:0009986 cell surface
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0008528 G protein-coupled peptide receptor activity
• GO:0004930 G protein-coupled receptor activity
• GO:0044877 protein-containing complex binding
• GO:0038023 signaling receptor activity
• GO:0004996 thyroid-stimulating hormone receptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0007166 cell surface receptor signaling pathway
• GO:0007267 cell-cell signaling
• GO:1904588 cellular response to glycoprotein
• GO:1905229 cellular response to thyrotropin-releasing hormone
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007187 G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• GO:0009755 hormone-mediated signaling pathway
• GO:0008284 positive regulation of cell population proliferation
• GO:0120162 positive regulation of cold-induced thermogenesis
• GO:0038194 thyroid-stimulating hormone signaling pathway

Disease associations

• hypothyroidism due to TSH receptor mutations MONDO:0010142
• OMIM:603372 RAW:OMIM_603372
• familial gestational hyperthyroidism MONDO:0011309
• familial hyperthyroidism due to mutations in TSH receptor MONDO:0012203

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Thyrotropin receptor 0.99
• Thyrotropin receptor 0.98
• Thyrotropin receptor 0.98
• Thyrotropin receptor 0.98
• Thyrotropin receptor 0.98
• Thyrotropin receptor 0.98
• Thyrotropin receptor 0.98
• Follicle-stimulating hormone receptor 0.93
• Follicle-stimulating hormone receptor 0.93
• Follicle-stimulating hormone receptor 0.93
• Follicle-stimulating hormone receptor 0.93
• Thyrotropin receptor 0.93

Co-cited proteins · studied together in the literature

• Lutropin-choriogonadotropic hormone receptor 3 shared papers
• Follicle-stimulating hormone receptor 2 shared papers
• Thyrotropin receptor 1 shared papers
• Thyrotropin receptor 1 shared papers
• Glycoprotein hormone alpha-2 1 shared papers
• Protein scribble homolog 1 shared papers
• Glycoprotein hormone beta-5 1 shared papers

Literature · 73 cited papers

• Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature · 2022
• Hormone- and antibody-mediated activation of the thyrotropin receptor. Nature · 2022
• Thyrotropin and Insulin-Like Growth Factor 1 Receptor Crosstalk Upregulates Sodium-Iodide Symporter Expression in Primary Cultures of Human Thyrocytes. Thyroid · 2016
• Loss-of-function variants in a Hungarian cohort reveal structural insights on TSH receptor maturation and signaling. J. Clin. Endocrinol. Metab. · 2015
• Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody. Thyroid · 2007
• Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway. EMBO J. · 2005
• Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism. J. Clin. Endocrinol. Metab. · 2004
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation. Clin. Endocrinol. (Oxf.) · 2004
• TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism. J. Endocrinol. Invest. · 2003
• Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor. Clin. Endocrinol. (Oxf.) · 2004
• Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins. Thyroid · 2003
• … and 61 more in the literature graph