TSHR
entrez
7253
canonical
uniprot
P16473
canonical
ensembl
ENSG00000165409
resolver
ensp
ENSP00000298171
resolver
ensp
ENSP00000340113
resolver
ensp
ENSP00000450549
resolver
genesymbol
TSHR
resolver
genesymbol_syn
LGR3
resolver
hgnc
HGNC:12373
resolver
uniprot
A0A0A0MTJ0
resolver
uniprot
A0PJU7
resolver
uniprot
F5GYU5
resolver
uniprot
G3V2A9
resolver
uniprot
Q16503
resolver
uniprot
Q8TB90
resolver
uniprot
Q96GT6
resolver
uniprot
Q9P1V4
resolver
uniprot
Q9ULA3
resolver
uniprot
Q9UPH3
resolver
uniprot_entry
TSHR_HUMAN
resolver
uniprot_sec
A0A0A0MTJ0
resolver
uniprot_sec
A0PJU7
resolver
uniprot_sec
F5GYU5
resolver
uniprot_sec
G3V2A9
resolver
uniprot_sec
Q16503
resolver
uniprot_sec
Q8TB90
resolver
uniprot_sec
Q96GT6
resolver
uniprot_sec
Q9P1V4
resolver
uniprot_sec
Q9ULA3
resolver
uniprot_sec
Q9UPH3
resolver
amino_acid_sequence
MRPADLLQLVLLLDLPRDLGGMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAFSNLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLGIFNTGLKMFPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSVQGYAFNGTKLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKELIARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMCNESSMQSLRQRKSVNALNSPLHQEYEENLGDSIVGYKEKSKFQDTHNNAHYYVFFEEQEDEIIGFGQELKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIVVWFVSLLALLGNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSEYYNHAIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACAIMVGGWVCCFLLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCCYVKIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSKILLVLFYPLNSCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQVQKVTHEMRQGLHNMEDVYELIENSHLTPKKQGQISEEYMQTVL
uniprot
proteins
disease_involvement
DISEASE: Note=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: Note=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: Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) [MIM:275200]: 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. It 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. {ECO:0000269|PubMed:10720030, ECO:0000269|PubMed:11095460, ECO:0000269|PubMed:11442002, ECO:0000269|PubMed:12050212, ECO:0000269|PubMed:14725684, ECO:0000269|PubMed:15531543, ECO:0000269|PubMed:25978107, ECO:0000269|PubMed:7528344, ECO:0000269|PubMed:8954020, ECO:0000269|PubMed:9100579, ECO:0000269|PubMed:9185526, ECO:0000269|PubMed:9329388}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Familial gestational hyperthyroidism (HTFG) [MIM:603373]: A condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy. {ECO:0000269|PubMed:9854118}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Hyperthyroidism, non-autoimmune (HTNA) [MIM:609152]: 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. {ECO:0000269|PubMed:10199795, ECO:0000269|PubMed:10852462, ECO:0000269|PubMed:11081252, ECO:0000269|PubMed:11127522, ECO:0000269|PubMed:11201847, ECO:0000269|PubMed:11517004, ECO:0000269|PubMed:11549687, ECO:0000269|PubMed:15163335, ECO:0000269|PubMed:7800007, ECO:0000269|PubMed:7920658, ECO:0000269|PubMed:8636266, ECO:0000269|PubMed:8964822, ECO:0000269|PubMed:9349581, ECO:0000269|PubMed:9360555, ECO:0000269|PubMed:9398746, ECO:0000269|PubMed:9589634}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P21463, ECO:0000269|PubMed:11847099, ECO:0000269|PubMed:12045258, ECO:0000269|PubMed:27638195, ECO:0000269|PubMed:35940204, ECO:0000269|PubMed:35940205}.
uniprot
proteins
mass_dalton
86844
uniprot
proteins
mutagenesis
MUTAGEN 283; /note="C->S: Abolishes cell surface expression."; /evidence="ECO:0000269|PubMed:11847099"; MUTAGEN 385..387; /note="YDY->EDE: Inhibits intracellular cAMP accumulation."; /evidence="ECO:0000269|PubMed:11847099"; MUTAGEN 385..387; /note="YDY->FDF: Abolishes sulfation. Inhibits intracellular cAMP accumulation."; /evidence="ECO:0000269|PubMed:11847099"; MUTAGEN 385; /note="Y->E: Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation."; /evidence="ECO:0000269|PubMed:11847099, ECO:0000305|PubMed:11847099"; MUTAGEN 385; /note="Y->F: Reduces sulfation. Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation."; /evidence="ECO:0000269|PubMed:11847099, ECO:0000305|PubMed:11847099"; MUTAGEN 387; /note="Y->E: No change in intracellular cAMP accumulation."; /evidence="ECO:0000269|PubMed:11847099"; MUTAGEN 387; /note="Y->F: Reduces sulfation. No change in intracellular cAMP accumulation."; /evidence="ECO:0000269|PubMed:11847099
uniprot
proteins
post_translational_modification
PTM: Glycosylated. {ECO:0000269|PubMed:11847099}.; PTM: Sulfated. Sulfation on Tyr-385 plays a role in thyrotropin receptor binding and activation. {ECO:0000269|PubMed:11847099}.
uniprot
proteins
protein_family
FSH/LSH/TSH subfamily
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
10037070
uniprot
proteins
pubmed
10199795
uniprot
proteins
pubmed
10487707
uniprot
proteins
pubmed
10560955
uniprot
proteins
pubmed
10651846
uniprot
proteins
pubmed
10720030
uniprot
proteins
pubmed
10852462
uniprot
proteins
pubmed
10870027
uniprot
proteins
pubmed
10946859
uniprot
proteins
pubmed
11022192
uniprot
proteins
pubmed
11081252
uniprot
proteins
pubmed
11095460
uniprot
proteins
pubmed
11127522
uniprot
proteins
pubmed
11128715
uniprot
proteins
pubmed
11201847
uniprot
proteins
pubmed
11434721
uniprot
proteins
pubmed
11442002
uniprot
proteins
pubmed
11502179
uniprot
proteins
pubmed
11517004
uniprot
proteins
pubmed
11549687
uniprot
proteins
pubmed
11847099
uniprot
proteins
pubmed
11887032
uniprot
proteins
pubmed
12045258
uniprot
proteins
pubmed
12050212
uniprot
proteins
pubmed
12213664
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
12589819
uniprot
proteins
pubmed
12593721
uniprot
proteins
pubmed
12788902
uniprot
proteins
pubmed
12930595
uniprot
proteins
pubmed
1445355
uniprot
proteins
pubmed
14725684
uniprot
proteins
pubmed
14759073
uniprot
proteins
pubmed
15163335
uniprot
proteins
pubmed
1530609
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15531543
uniprot
proteins
pubmed
15775968
uniprot
proteins
pubmed
17542669
uniprot
proteins
pubmed
1955520
uniprot
proteins
pubmed
2293030
uniprot
proteins
pubmed
2302212
uniprot
proteins
pubmed
2558651
uniprot
proteins
pubmed
25978107
uniprot
proteins
pubmed
2610690
uniprot
proteins
pubmed
27638195
uniprot
proteins
pubmed
35940204
uniprot
proteins
pubmed
35940205
uniprot
proteins
pubmed
7488864
uniprot
proteins
pubmed
7508946
uniprot
proteins
pubmed
7528344
uniprot
proteins
pubmed
7556878
uniprot
proteins
pubmed
7647578
uniprot
proteins
pubmed
7800007
uniprot
proteins
pubmed
7920658
uniprot
proteins
pubmed
7989485
uniprot
proteins
pubmed
8045989
uniprot
proteins
pubmed
8413627
uniprot
proteins
pubmed
8636266
uniprot
proteins
pubmed
8747461
uniprot
proteins
pubmed
8954020
uniprot
proteins
pubmed
8964822
uniprot
proteins
pubmed
9062474
uniprot
proteins
pubmed
9100579
uniprot
proteins
pubmed
9185526
uniprot
proteins
pubmed
9253356
uniprot
proteins
pubmed
9294132
uniprot
proteins
pubmed
9329388
uniprot
proteins
pubmed
9349581
uniprot
proteins
pubmed
9360555
uniprot
proteins
pubmed
9398746
uniprot
proteins
pubmed
9589634
uniprot
proteins
pubmed
9854118
uniprot
proteins
sequence_length
764
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11847099}; Multi-pass membrane protein {ECO:0000305}. Basolateral cell membrane {ECO:0000269|PubMed:11847099}; Multi-pass membrane protein {ECO:0000305}.
uniprot
proteins
transmembrane_region
TRANSMEM 415..440; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:35940205"; TRANSMEM 451..473; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:35940205"; TRANSMEM 493..517; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:35940205"; TRANSMEM 538..558; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:35940205"; TRANSMEM 577..602; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:35940205"; TRANSMEM 626..649; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:35940205"; TRANSMEM 658..681; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:35940205
uniprot
proteins