Gpr4
entrez
319197
canonical
uniprot
Q8BUD0
canonical
ensembl
ENSMUSG00000044317
resolver
ensp
ENSMUSP00000061243
resolver
enst
ENSMUST00000060225
resolver
genesymbol
Gpr4
resolver
uniprot_entry
GPR4_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Activated by a network of residues that connects an extracellular-facing cavity to Glu-147, a conserved charged residue buried in the transmembrane core of the receptor (PubMed:39753131). 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-147, a residue only conserved in proton-sensing G protein coupled receptors (By similarity). {ECO:0000250|UniProtKB:P46093, ECO:0000269|PubMed:39753131}.
uniprot
proteins
amino_acid_sequence
MDNSTGTGEGCHVDSRVDHLFPPSLYIFVIGVGLPTNCLALWAAYRQVRQHNELGVYLMNLSIADLLYICTLPLWVDYFLHHDNWIHGPGSCKLFGFIFYSNIYISIAFLCCISVDRYLAVAHPLRFARLRRVKTAVAVSSVVWATELGANSAPLFHDELFRDRYNHTFCFEKFPMERWVAWMNLYRVFVGFLFPWALMLLCYRGILRAVQSSVSTERQEKVKIKRLALSLIAIVLVCFAPYHALLLSRSAVYLGRPWDCGFEERVFSAYHSSLAFTSLNCVADPILYCLVNEGARSDVAKALHNLLRFLASNKPQEMANASLTLETPLTSKRSTTGKSSGAVWAVPPTAQGDQVPLKVLLPPAQ
uniprot
proteins
function
FUNCTION: Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:17145776, PubMed:20798260, PubMed:26068853, PubMed:39753131). Activated by an optimal pH of 6.8-7.2 (PubMed:39753131). 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:20798260, PubMed:39753131). GPR4 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (PubMed:20798260, PubMed:39753131). May also couple with G(i), G(q) and G(12)/G(13) G proteins (PubMed:17145776, PubMed:39753131). 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 (PubMed:26068853, PubMed:31896584). Also acts as a regulator of acid secretion in the kidney collecting duct by maintaining acid-base homeostasis in the kidney (PubMed:20798260). 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:0000269|PubMed:17145776, ECO:0000269|PubMed:20798260, ECO:0000269|PubMed:26068853, ECO:0000269|PubMed:31896584, ECO:0000269|PubMed:32058960, ECO:0000269|PubMed:39753131}.
uniprot
proteins
mass_dalton
41105
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="E->K: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 121; /note="V->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 124; /note="P->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 125; /note="L->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 157; /note="H->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 163; /note="D->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 167; /note="H->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 172; /note="E->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 213; /note="S->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131"; MUTAGEN 271; /note="H->A: Decreased proton-induced G protein-coupled receptor activity."; /evidence="ECO:0000269|PubMed:39753131
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17145776
uniprot
proteins
pubmed
20798260
uniprot
proteins
pubmed
26068853
uniprot
proteins
pubmed
31896584
uniprot
proteins
pubmed
32058960
uniprot
proteins
pubmed
39753131
uniprot
proteins
sequence_length
365
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P46093}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 11..47; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:39753131"; TRANSMEM 52..82; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:39753131"; TRANSMEM 88..123; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:39753131"; TRANSMEM 132..158; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:39753131"; TRANSMEM 175..212; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:39753131"; TRANSMEM 217..252; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:39753131"; TRANSMEM 263..291; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:39753131
uniprot
proteins