GPR4

Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions. Activated by an optimal pH of 6.8-7.2. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. GPR4 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity. May also couple with G(i), G(q) and G(12)/G(13) G proteins. Acts as a key regulator of respiratory sensitivity to CO2/H(+) in brain retrotrapezoid nucleus neurons: acts by mediating detection of protons generated by the formation of carbonic acid in the blood, an important mechanism to impulse to breathe (By similarity). Also acts as a regulator of acid secretion in the kidney collecting duct by maintaining acid-base homeostasis in the kidney (By similarity). Acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells, possibly through the G(12)/G(13)/Rho GTPase signaling pathway..

Function from UniProtKB (P46093), read 2026-09-23. CC BY 4.0.