Adhesion G protein-coupled receptor G5 (ADGRG5 (also commonly referred to as GPR114))

Adhesion G protein-coupled receptor G5 (ADGRG5, also known as GPR114) is an orphan GPCR of the adhesion subfamily distinguished by a large N-terminal extracellular region containing adhesion modules and a conserved GPCR-Autoproteolysis INducing (GAIN) domain. Its main function is transmembrane signal transduction via Gs protein coupling, resulting in adenylate cyclase activation and increased cAMP levels. ADGRG5 is highly expressed in immune cells such as eosinophils and lymphocytes, implicating roles in immune regulation and inflammation. Alternative splicing and unique structural features provide cell-type-specific functional diversity. Drug discovery efforts have identified small molecules (e.g., dihydromunduletone) capable of antagonizing its activation mechanism, and the receptor is a promising but underexplored therapeutic target for inflammatory diseases, cancer, and other disorders.

Other names

G protein-coupled receptor 114 (GPR114)PGR27GP114_HUMAN

Small molecule antagonists can block tethered peptide agonist activation Synthetic peptides can mimic or antagonize the tethered agonist mechanism, activating or inhibiting the receptor