Adhesion G protein-coupled receptor G6 (ADGRG6)

Adhesion G protein-coupled receptor G6 (ADGRG6) is a member of the adhesion GPCR family characterized by a large extracellular region with five domains and a Stachel sequence that functions as a tethered agonist. ADGRG6 is crucial in various developmental processes, including peripheral nerve myelination, cartilage and skeletal growth plate homeostasis, heart development, angiogenesis, and regulation of the blood-brain barrier. The receptor is widely expressed in tissues subject to mechanical stress, and mutations are associated with diverse human diseases, particularly those affecting the musculoskeletal and nervous systems. ADGRG6 signals primarily via heterotrimeric G proteins (particularly Gi and Gq), with downstream modulation of cAMP-dependent and other intracellular pathways. Although ADGRG6 has clear roles in disease, there are presently no approved therapeutics directly targeting it in the clinic, but its extracellular region is of pharmacological interest for future drug development.

Other names

GPR126Developmentally regulated G-protein-coupled receptorVascular inducible G protein-coupled receptorDREGAPG1PR126PS1TP2VIGRLCCS9FLJ14937HBV PreS1-transactivated protein 2ADGRG6 N-terminal fragmentADGRG6 C-terminal fragment

Ligand binding (including steroid hormones such as progesterone and 17α-hydroxyprogesterone) induces conformational change, triggering signaling via G proteins (including Gi and Gq families), modulating downstream effectors such as adenylate cyclase and affecting cAMP levels.