Gpr65
entrez
14744
canonical
uniprot
Q61038
canonical
ensembl
ENSMUSG00000021886
resolver
ensp
ENSMUSP00000074581
resolver
enst
ENSMUST00000075072
resolver
genesymbol
Gpr65
resolver
genesymbol_syn
Gpcr25
resolver
genesymbol_syn
Tdag8
resolver
uniprot
A0A0R4J0Y2
resolver
uniprot
Q3UQ35
resolver
uniprot
Q3UZ41
resolver
uniprot
Q921N3
resolver
uniprot_entry
A0A0R4J0Y2_MOUSE
resolver
uniprot_entry
GPR65_MOUSE
resolver
uniprot_entry
Q3UQ35_MOUSE
resolver
uniprot_entry
Q3UZ41_MOUSE
resolver
uniprot_sec
Q921N3
resolver
activity_regulation
ACTIVITY REGULATION: Activated by a network of residues that connects an extracellular-facing cavity to Glu-144, a conserved charged residue buried in the transmembrane core of the receptor (By similarity). 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-144, a residue only conserved in proton-sensing G protein coupled receptors (By similarity). ctivated by the synthetic agonist BTB09089 (PubMed:39661058). {ECO:0000250|UniProtKB:Q8IYL9, ECO:0000269|PubMed:39661058}.
uniprot
proteins
amino_acid_sequence
MAMNSMCIEEQHHLEHYLFPVVYIIVFIVSVPANIGSLCVSFLQAKKENELGIYLFSLSLSDLLYALTLPLWINYTWNKDNWTFSPTLCKGSVFFTYMNFYSSTAFLTCIALDRYLAVVYPLKFSFLRTRRFAFITSLSIWILESFFNSMLLWKDETSVEYCDSDKSNFTLCYDKYPLEKWQINLNLFRTCMGYAIPLITIMICNHKVYRAVRHNQATENSEKRRIIKLLASITLTFVLCFTPFHVMVLIRCVLERDMNVNDKSGWQTFTVYRVTVALTSLNCVADPILYCFVTETGRADMWNILKLCTRKHNRHQGQKRDILSVSTRDAVELEIID
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:39661058). Activated by an optimal pH of 7.4 (By similarity). 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 (By similarity). GPR65 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (By similarity). May also act as a receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (By similarity). Plays a role in immune response by maintaining lysosome function and regulating T-cell metabolism (PubMed:27287411, PubMed:8599842). Acts as a regulator of inflammation by mediating pH-sensing of extracellular acidification which takes place in inflamed tissues: activation regulates endo-lysosomal function of immune cells and T-cell metabolism (PubMed:35668320, PubMed:39661058). Constitutively active in endosomes and stimulates adenylate cyclase production from endosomes independently from extracellular pH changes (By similarity). {ECO:0000250|UniProtKB:Q8IYL9, ECO:0000269|PubMed:27287411, ECO:0000269|PubMed:35668320, ECO:0000269|PubMed:39661058, ECO:0000269|PubMed:8599842}.
uniprot
proteins
mass_dalton
39388
uniprot
proteins
mutagenesis
MUTAGEN 233; /note="I->L: Knockin mice are susceptible to bacterial infection-induced and T cell-driven colitis. Impaired lysosomal proteolysis and endo-lysosomal fusion."; /evidence="ECO:0000269|PubMed:35668320
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
27287411
uniprot
proteins
pubmed
35668320
uniprot
proteins
pubmed
39661058
uniprot
proteins
pubmed
8599842
uniprot
proteins
sequence_length
337
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8IYL9}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8IYL9}. Early endosome membrane {ECO:0000250|UniProtKB:Q8IYL9}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8IYL9}. Late endosome membrane {ECO:0000250|UniProtKB:Q8IYL9}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8IYL9}. Note=Internalizes and localizes to early and late endosomes, from where GPR65 signals at steady state, irrespective of extracellular pH. Changes in extracellular pH may relocalize receptor signaling to the cell membrane. {ECO:0000250|UniProtKB:Q8IYL9}.
uniprot
proteins
transmembrane_region
TRANSMEM 8..44; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:Q8IYL9"; TRANSMEM 49..79; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:Q8IYL9"; TRANSMEM 85..120; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:Q8IYL9"; TRANSMEM 129..155; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:Q8IYL9"; TRANSMEM 177..214; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:Q8IYL9"; TRANSMEM 219..254; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:Q8IYL9"; TRANSMEM 265..293; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:Q8IYL9
uniprot
proteins