| Function |
Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:12955148, PubMed:17462861, PubMed:33478938, PubMed:39753132, PubMed:39799123, PubMed:40211064, PubMed:40215959, PubMed:40215960). Activated by an optimal pH of 6.8-7.2 (PubMed:12955148, PubMed:17462861, PubMed:39753132). 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 (PubMed:39753132, PubMed:40211064, PubMed:40215960). GPR4 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (PubMed:12955148, PubMed:17462861, PubMed:20211729, PubMed:22110680, PubMed:39753132, PubMed:40211064, PubMed:40215960). May also couple with G(i), G(q) and G(12)/G(13) G proteins (PubMed:12955148, PubMed:17462861, PubMed:20211729, PubMed:22110680). 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 (PubMed:32058960). {ECO:0000250|UniProtKB:Q8BUD0, ECO:0000269|PubMed:12955148, ECO:0000269|PubMed:17462861, ECO:0000269|PubMed:20211729, ECO:0000269|PubMed:22110680, ECO:0000269|PubMed:32058960, ECO:0000269|PubMed:33478938, ECO:0000269|PubMed:39753132, ECO:0000269|PubMed:39799123, ECO:0000269|PubMed:40211064, ECO:0000269|PubMed:40215959, ECO:0000269|PubMed:40215960}. |
4.0
GPR4
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binding