Gpr68
entrez
238377
canonical
uniprot
Q8BFQ3
canonical
ensembl
ENSMUSG00000047415
resolver
ensp
ENSMUSP00000057510
resolver
ensp
ENSMUSP00000105692
resolver
ensp
ENSMUSP00000105693
resolver
enst
ENSMUST00000053668
resolver
enst
ENSMUST00000110065
resolver
enst
ENSMUST00000110066
resolver
genesymbol
Gpr68
resolver
genesymbol_syn
Ogr1
resolver
uniprot
Q148P7
resolver
uniprot
Q3U1L3
resolver
uniprot
Q80T34
resolver
uniprot_entry
GPR68_MOUSE
resolver
uniprot_sec
Q148P7
resolver
uniprot_sec
Q3U1L3
resolver
uniprot_sec
Q80T34
resolver
activity_regulation
ACTIVITY REGULATION: Activated by a network of residues that connects an extracellular-facing cavity to Glu-149, 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-149, a residue only conserved in proton-sensing G protein coupled receptors (By similarity). Activated in an allosteric manner by divalent metal ions at the extracellular surface following the order: Cd(2+) > Co(2+) > Ni(2+) > Zn(2+) > Fe(2+) > Ca(2+) > Mg(2+) (By similarity). Activated by ogerin (ZINC67740571), a selective GPR68 positive allosteric modulator (PubMed:26550826). Inhibited by small molecule GPR68-I, decreasing inflammation in models of colitis (PubMed:34722644). {ECO:0000250|UniProtKB:Q15743, ECO:0000269|PubMed:26550826, ECO:0000269|PubMed:34722644}.
uniprot
proteins
amino_acid_sequence
MGNITTENSSLSCPIDHTIHQTLAPVVYVTVLVVGFPANCLSLYFGYLQIKARNELGVYLCNLTIADLFYICSLPFWLQYVLQHDDWSHGDLSCQVCGILLYENIYISVGFLCCISIDRYLAVAHPFRFHQFRTLKAAVGVSVLIWAKELLTSIYFLNHKEVIEDEDQHRVCFEHYPIQAWQRSINYYRFLVGFLFPICLLLASYQGILRAVRRSHGTQKSRKDQIQRLVLSTVVIFLACFLPYHVLLLVRSLWERNCEFAKSIFNVYHFSLLLTSFNCVADPVLYCFVSETTHRDLARLRGACLAVLTCSRTSRAREAYPLGAPEASGKSGAQGEEPELLTKLHSAFQTPSSLGVGGPSTVGLA
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 (By similarity). The receptor is almost silent at pH 7.8 but fully activated at pH 6.8 (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 phospholipase C (By similarity). GPR68 is mainly coupled to G(q) G proteins and mediates production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (By similarity). Acts as a key mechanosensor of fluid shear stress and membrane stretch (PubMed:29677517). Expressed in endothelial cells of small-diameter resistance arteries, where it mediates flow-induced dilation in response to shear stress (PubMed:29677517). May represents an osteoblastic pH sensor regulating cell-mediated responses to acidosis in bone (PubMed:18847331). Acts as a regulator of calcium-sensing receptor CASR in a seesaw manner: GPR68-mediated signaling inhibits CASR signaling in response to protons, while CASR inhibits GPR68 in presence of extracellular calcium (PubMed:26261299). Also functions as a metastasis suppressor gene in prostate cancer (PubMed:17728215). {ECO:0000250|UniProtKB:Q15743, ECO:0000269|PubMed:17728215, ECO:0000269|PubMed:18847331, ECO:0000269|PubMed:26261299, ECO:0000269|PubMed:29677517}.
uniprot
proteins
mass_dalton
41209
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
12679517
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17728215
uniprot
proteins
pubmed
18847331
uniprot
proteins
pubmed
19479052
uniprot
proteins
pubmed
26261299
uniprot
proteins
pubmed
26550826
uniprot
proteins
pubmed
29677517
uniprot
proteins
pubmed
34722644
uniprot
proteins
sequence_length
365
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q15743}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 13..49; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:Q15743"; TRANSMEM 54..84; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:Q15743"; TRANSMEM 90..125; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:Q15743"; TRANSMEM 134..160; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:Q15743"; TRANSMEM 177..214; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:Q15743"; TRANSMEM 219..254; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:Q15743"; TRANSMEM 261..289; /note="Helical; Name=7"; /evidence="ECO:0000250|UniProtKB:Q15743
uniprot
proteins