TSHB (P01222) Curation Notes

Summary

• Gene: TSHB (UniProtKB:P01222), Thyrotropin subunit beta (Thyroid-stimulating hormone subunit beta).
• PANTHER subfamily: PANTHER:PTHR11515:SF5 (THYROTROPIN SUBUNIT BETA) within PANTHER:PTHR11515 (GLYCOPROTEIN HORMONE BETA CHAIN, root PAINT node PTN000162063).
• Biological role: Secreted cystine-knot beta subunit synthesized in anterior pituitary thyrotrophs. Non-covalently heterodimerizes with the common glycoprotein hormone alpha subunit (CGA, P01215, PANTHER:PTHR11509:SF0) to form biologically active thyroid-stimulating hormone (thyrotropin, TSH) ([Reactome:R-HSA-378952]; PMID:2792087). Secreted heterodimeric TSH binds and activates the thyroid-stimulating hormone receptor (TSHR, P16473) on thyroid follicular cells, coupling to Gs (adenylyl cyclase/cAMP) and Gq/11 (phospholipase C/IP3) to initiate the thyroid-stimulating hormone signaling pathway (GO:0038194) and stimulate thyroid hormone synthesis and secretion (PMID:36001021; [Reactome:R-HSA-391375]).

Ligands in Signaling Pathways Audit (Category A Gap)

• In GOA, GO:0038194 (thyroid-stimulating hormone signaling pathway) is annotated only to the receptor TSHR and the downstream scaffold PDE4DIP, whereas neither subunit of the TSH hormone ligand (TSHB or CGA) is annotated to GO:0038194.
• TSHB carries GO:0005179 (hormone activity, IBA, IEA, TAS PMID:2792087) and GO:0005576 (extracellular region, IBA, IEA, TAS), which are ACCEPTed as core.
• TSHB carries generic signaling BP terms GO:0007186 (G protein-coupled receptor signaling pathway, IBA from PTN000162063 and TAS PMID:2792087), GO:0007267 (cell-cell signaling, TAS PMID:2792087), GO:0007154 (cell communication, IEA), and GO:0023052 (signaling, IEA). All of these are refined via MODIFY to GO:0038194 (thyroid-stimulating hormone signaling pathway), and GO:0038194 is added as a NEW annotation supported by the cryo-EM structure of TSH-bound TSHR (PMID:36001021) and [Reactome:R-HSA-391375].
• GO:0009653 (anatomical structure morphogenesis, TAS PMID:2792087) is MARK_AS_OVER_ANNOTATED: PMID:2792087 characterizes a homozygous G29R mutation in the conserved CAGYC motif of TSHB that prevents heterodimerization with CGA and causes congenital nongoitrous hypothyroidism (growth/mental retardation secondary to thyroid hormone deficiency), not a direct role of TSHB in morphogenesis.