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Details on Person UniProt:P46093 GPR4
| Class:Id | ReferenceGeneProduct:55888 |
|---|---|
| _chainChangeLog | chain:1-362 added on Sat February 7 2015 |
| _displayName | UniProt:P46093 GPR4 |
| _timestamp | 2026-02-20 23:05:58 |
| chain | chain:1-362 |
| checksum | 6C75D97C36204541 |
| comment | 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).ACTIVITY REGULATION Activated by a network of residues that connects an extracellular-facing cavity to Glu-145, a conserved charged residue buried in the transmembrane core of the receptor (PubMed:39753132). Protonation likely drives conformational changes in extracellular loop 2 (ECL2), which stabilizes movement of transmembrane 3 (TM3) and a series of rearrangements that connect the extracellular-facing cavity to Glu-145, a residue only conserved in proton-sensing G-protein coupled receptors (PubMed:39753132). Inhibited by the antagonist NE52-QQ57, which prevents activation by protons (PubMed:40211064, PubMed:40215960).SUBCELLULAR LOCATION A multitude of proton-sensing residues, which include extracellular histidine residues (His-155, His-165 and His-269) or triad of buried acidic residues (Asp-63, Glu-145 and Asp-282), contribute to activation of the G-protein coupled receptor activity and pH sensitivity.SIMILARITY Belongs to the G-protein coupled receptor 1 family.CAUTION Was originally thought to be a receptor for sphingosylphosphorylcholine and lysophosphatidylcholine (PubMed:11535583). However, this work has been retracted (PubMed:16498716). |
| description | recommendedName: fullName evidence="19"G-protein coupled receptor 4 shortName evidence="17"hGPR4 alternativeName: fullName evidence="18"G-protein coupled receptor 6C.l shortName evidence="18"GPR6C.l |
| geneName | GPR4 |
| identifier | P46093 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cell membrane Disulfide bond G-protein coupled receptor Glycoprotein Membrane Receptor Reference proteome Transducer Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | GPR4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9002372] ENSEMBL:ENSG00000177464 GPR4 [Homo sapiens] |
| secondaryIdentifier | GPR4_HUMAN A8K3T3 B0M0K1 Q6NWM4 |
| sequenceLength | 362 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:444708] GPR4 [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P46093 GPR4 (55888)
