Adhesion G protein-coupled receptor G4 (ADGRG4)

Adhesion G protein-coupled receptor G4 (ADGRG4, also known as GPR112) is a member of the adhesion GPCR family characterized by large extracellular regions and a signature seven-transmembrane domain. It is an orphan receptor, as its endogenous ligand is unknown. ADGRG4 contains a unique pentraxin-like domain that may form dimers, potentially functioning as a sensor for mechanical shear forces, especially in enterochromaffin and Paneth cells of the small intestine[1][2][4]. The receptor is coupled to G(s) proteins and can activate adenylate cyclase, modulating downstream signaling pathways[4]. ADGRG4 is expressed in normal enterochromaffin cells and gastric neuroendocrine carcinoma cells, and is investigated as a potential marker and therapeutic target for these cancers[2]. ADGRG4 currently lacks well-characterized interacting drugs owing to its status as an orphan receptor, and no established endogenous ligands or antagonist/agonist pharmacology are available. Its role in disease is most recognized in neuroendocrine cancers and as a candidate immunotherapy target[2]. Mechanistically, it is believed to contribute to mechanical force sensing and classical GPCR-mediated adenylate cyclase activation[1][4].

Other names

Adhesion G protein-coupled receptor G4ADGRG4GPR112PGR17RP1-299I16probable G-protein coupled receptor 112ADGRG4 N-terminal fragmentADGRG4 C-terminal fragment

Coupling to G(s) proteins, mediating activation of adenylate cyclase. May act as a sensor for mechanical (shear) forces in intestinal cells.