Search
thyrotropin receptor; thyroid-stimulating hormone receptor; TSH-R (TSHR LGR3)
Function:
- receptor for thyrotropin (TSH)
- role in controlling thyroid cell metabolism
- activity is mediated by G proteins which activate adenylate cyclase
- also acts as a receptor for thyrostimulin (GPA2+GPB5)
Structure:
- belongs to the G-protein coupled receptor 1 family FSH/LSH/TSH subfamily
- contains 6 LRR repeats (leucine-rich repeats)
Compartment: cell membrane
Alternative splicing: named isoforms=2
Additional isoforms seem to exist
Polymorphism:
- the Asp727Glu polymorphism is associated with Graves disease in a Russian population. Th
- the Glu727 allele & the heterozygous Asp727Glu genotype are related to higher risk of Graves disease
- the Asp727Glu polymorphism significantly ameliorates Gs-alpha activation in the presence of the gain-of-function mutation Ala593Asn although it is functionally inert in the context of the wild-type TSHR
Pathology:
1) defects in TSHR are the cause of
a) congenital hypothyroidism non-goitrous type 1
b) hyperthyroidism
1] autosomal dominant non-autoimmune hyperthyroidism
2] sporadic congenital hyperthyroidism
3] hyperthyroidism associated with autonomously functioning thyroid nodules
4] toxic multinodular goiter
5] hyperfunctioning thyroid adenomas
6] familial gestational hyperthyroidism
7] thyroid neoplasms
a] papillary thyroid carcinoma
b] follicular thyroid carcinoma)
2) autoantibodies directed against the TSH receptor result in hyperthyroidism of Graves disease
Related
thyroid-stimulating hormone (TSH) or thyrotropin
General
glycoprotein
G-protein coupled receptor; serpentine receptor
Properties
SIZE: entity length = 764 aa
MW = 87 kD
COMPARTMENT: plasma membrane
CELL: follicular cell
WITHIN: thyroid
MOTIF: exoplasmic domain {1-413}
MOTIF: signal sequence {1-20}
leucine-rich repeat
SITE: 51-74
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N77}
N-glycosylation site {N99}
N-glycosylation site {N113}
leucine-rich repeat
SITE: 125-150
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 152-174
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 176-199
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N177}
N-glycosylation site {N198}
leucine-rich repeat
SITE: 200-223
MOTIF: leucine residue (SEVERAL)
leucine-rich repeat
SITE: 227-248
MOTIF: leucine residue (SEVERAL)
N-glycosylation site {N302}
transmembrane domain {414-441}
cytoplasmic loop {442-450}
transmembrane domain {451-473}
exoplasmic loop {474-494}
MOTIF: cysteine residue {C494}
MODIFICATION: cysteine residue {C569}
transmembrane domain {495-517}
cytoplasmic loop {518-537}
transmembrane domain {538-560}
exoplasmic loop {561-580}
MOTIF: cysteine residue {C569}
MODIFICATION: cysteine residue {C494}
transmembrane domain {581-602}
cytoplasmic loop {603-625}
transmembrane domain {626-649}
exoplasmic loop {650-660}
transmembrane domain {661-682}
cytoplasmic domain {683-764}
Database Correlations
OMIM correlations
MORBIDMAP 603372
UniProt P16473
PFAM correlations
Entrez Gene 7253
Kegg hsa:7253
References
- UniProt :accession P16473
- TSH receptor database
http://innere.uniklinikum-leipzig.de/tsh/
- GRIS; Note: glycoprotein-hormone receptors information system
http://gris.ulb.ac.be/
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=TSHR
- SHMPD; The Singapore human mutation and polymorphism database
http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TSHR
- Wikipedia; Note: TSH receptor entry
http://en.wikipedia.org/wiki/TSH_receptor