Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit.
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Identifies a homozygous G29R (GGT to AGT) mutation in the conserved CAGYC region of TSHB that prevents heterodimerization with the alpha subunit and causes congenital isolated TSH deficiency.
"Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the beta-subunit."
Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia.
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Demonstrates that TSH is a heterodimer of a common alpha subunit (CGA) and the subtype-specific beta subunit (TSHB) that determines receptor specificity, and that biallelic pathogenic TSHB mutations cause severe isolated TSH deficiency.
"TSH is a member of the glycoprotein hormone family, which includes luteinising hormone, follicle-stimulating hormone, and human chorionic gonadotropin. All are heterodimers of a common α subunit and subtype-specific β subunit, which determines the biologic specificity."
Thyrotropin is a heterodimer
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Describes the non-covalent heterodimerization of CGA and TSHB to form active thyrotropin (TSH).
"Thyroid-stimulating hormone (TSH, thyrotropin) is a glycopeptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland. Like other glycoprotein hormones, TSH consists of a common alpha subunit and a beta subunit unique to TSH which determines its specificty."
Liganded Gs-activating GPCR acts as a GEF for Gs
TSHR binds TSH/Thyrostimulin
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Describes binding of heterodimeric TSH (CGA:TSHB) to TSHR on thyroid follicular cells and downstream activation of Gs signaling.
"Thyroid-stimulating hormone (TSH, thyrotropin) binds thyrotropin receptor (TSHR) on the basolateral membrane of thyroid cells (Nagayama Y et al., 1989)."
The Ligand:GPCR:Gs complex dissociates
Liganded Gs-activating GPCRs bind inactive heterotrimeric Gs