Adhesion G protein-coupled receptor G3 (ADGRG3)

Adhesion G protein-coupled receptor G3 (ADGRG3, also known as GPR97) is a member of the adhesion GPCR family characterized by a long extracellular N-terminus and a GPCR-Autoproteolysis INducing (GAIN) domain linking it to the seven-transmembrane region. It is primarily expressed in granulocytes (neutrophils, eosinophils, basophils), monocytes, endothelial cells, and certain lymphocytes. The receptor is involved in innate immune signaling, controlling cell adhesion, migration, and antimicrobial activity. Upon binding glucocorticoids, GPR97 activates G protein-dependent signaling cascades, including cAMP regulation, MAPK, and NF-κB pathways, with a demonstrated role in neutrophil effector functions and inflammatory responses. The receptor's expression is upregulated in inflamed and cancerous tissues and is implicated in disease contexts such as inflammation, cancer, kidney injury, and immune cell development. Beclomethasone and endogenous glucocorticoids are known agonists, with structural studies confirming direct ligand binding and activation of downstream Go protein signaling.

Other names

G protein-coupled receptor 97GPR97Probable G-protein coupled receptor 97PB99PGR26Adhesion G-protein coupled receptor G3 N-terminal fragmentAdhesion G-protein coupled receptor G3 C-terminal fragment

Ligand (glucocorticoid) binding induces conformational change and activates G protein signaling (primarily Go, but also can couple to Gi and Gs) Decreases cAMP via Gi coupling after mutation/activation Activates mitogen-activated protein kinases (MAPKs, e.g., ERK, p38) and NF-κB pathways