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Details on Person UniProt:P16473 TSHR
| Class:Id | ReferenceGeneProduct:66509 |
|---|---|
| _chainChangeLog | signal peptide:1-20 added on Fri February 6 2015;chain:21-764 added on Fri February 6 2015 |
| _displayName | UniProt:P16473 TSHR |
| _timestamp | 2026-02-20 21:45:37 |
| chain | signal peptide:1-20 chain:21-764 |
| checksum | 27EE9CEBFD650D45 |
| comment | FUNCTION Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin (PubMed:11847099, PubMed:12045258). Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin (PubMed:12045258). TSHR is coupled to G(s) proteins and mediates the activation of adenylate cyclase (PubMed:11847099, PubMed:35940205, PubMed:35940204). 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) (PubMed:27638195). Additionally, plays a central role in controlling thyroid cell metabolism (By similarity).SUBUNIT Interacts with heterodimer GPHA2:GPHB5; this interaction stimulates cAMP production (PubMed:12045258). Interacts (via the PDZ-binding motif) with SCRIB; regulates TSHR trafficking and function (PubMed:15775968). Interacts with GNAS (PubMed:35940205, PubMed:35940204).INTERACTION Additional isoforms seem to exist.TISSUE SPECIFICITY Expressed in thyroide cells (at protein level) (PubMed:11847099). Expressed in the thyroid (PubMed:2610690).PTM Glycosylated.PTM Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin receptor binding and activation.POLYMORPHISM Polymorphism at position 727 could be associated with Graves disease.DISEASE 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).DISEASE Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.SEQUENCE CAUTION TSH receptor entry |
| description | recommendedName: Thyrotropin receptor alternativeName: Thyroid-stimulating hormone receptor shortName: TSH-R |
| geneName | TSHR LGR3 |
| identifier | P16473 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell membrane Congenital hypothyroidism Direct protein sequencing Disease variant Disulfide bond G-protein coupled receptor Glycoprotein Leucine-rich repeat Membrane Proteomics identification Receptor Reference proteome Repeat Signal Sulfation Transducer Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | TSHR |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8998664] ENSEMBL:ENSG00000165409 TSHR [Homo sapiens] |
| secondaryIdentifier | TSHR_HUMAN A0A0A0MTJ0 A0PJU7 F5GYU5 G3V2A9 Q16503 Q8TB90 Q96GT6 Q9P1V4 Q9ULA3 Q9UPH3 |
| sequenceLength | 764 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:155309] UniProt:P16473-2 TSHR [Homo sapiens] [ReferenceIsoform:403053] UniProt:P16473-1 TSHR [Homo sapiens] [ReferenceIsoform:8971271] UniProt:P16473-3 TSHR [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:391371] TSHR [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P16473 TSHR (66509)
