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Details on Person UniProt:Q8IYL9 GPR65
| Class:Id | ReferenceGeneProduct:99191 |
|---|---|
| _chainChangeLog | chain:1-337 added on Sat February 7 2015 |
| _displayName | UniProt:Q8IYL9 GPR65 |
| _timestamp | 2026-02-20 21:30:24 |
| chain | chain:1-337 |
| checksum | CFDBF217291C0FA2 |
| comment | FUNCTION Proton-sensing G-protein coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:15326175, PubMed:15618224, PubMed:20855608, PubMed:33478938, PubMed:37722051, PubMed:39753132, PubMed:40211064). Activated by an optimal pH of 7.4 (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:15326175, PubMed:15618224, PubMed:37722051, PubMed:39753132). GPR65 is mainly coupled to G(s) G proteins and mediates activation of adenylate cyclase activity (PubMed:15618224, PubMed:37722051, PubMed:39753132). May also act as a receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (PubMed:11309421, PubMed:15326175). Plays a role in immune response by maintaining lysosome function and regulating T-cell metabolism (PubMed:27287411). 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 (By similarity). Constitutively active in endosomes and stimulates adenylate cyclase production from endosomes independently from extracellular pH changes (PubMed:39753132).ACTIVITY REGULATION Activated by a network of residues that connects an extracellular-facing cavity to Glu-142, 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-142, a residue only conserved in proton-sensing G-protein coupled receptors (PubMed:39753132). Activated by BTB09089, a positive allosteric modulator (PubMed:26550826).SUBCELLULAR LOCATION Internalizes and localizes to early and late endosomes, from where GPR65 signals at steady state, irrespective of extracellular pH (PubMed:39753132). Changes in extracellular pH may relocalize receptor signaling to the cell membrane (PubMed:39753132).TISSUE SPECIFICITY Predominantly expressed in thymus, spleen, lymph nodes, small intestine, lung, placenta and peripheral blood leukocytes.DOMAIN A multitude of proton-sensing residues, which include extracellular histidine (His-10, His-14 and His-243) residues or triad of buried acidic residues (Asp-60, Glu-142, Asp-286), contribute to activation of the G-protein coupled receptor activity and pH sensitivity.SIMILARITY Belongs to the G-protein coupled receptor 1 family. |
| description | recommendedName: fullName evidence="16"G-protein coupled receptor 65 alternativeName: fullName evidence="15"Psychosine receptor alternativeName: fullName evidence="17"T-cell death-associated gene 8 protein |
| geneName | GPR65 TDAG8 |
| identifier | Q8IYL9 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Apoptosis Cell membrane Disulfide bond Endosome G-protein coupled receptor Glycoprotein Membrane Proteomics identification Receptor Reference proteome Transducer Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | GPR65 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8993843] ENSEMBL:ENSG00000140030 GPR65 [Homo sapiens] |
| secondaryIdentifier | GPR65_HUMAN O75819 |
| sequenceLength | 337 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:444624] GPR65 [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q8IYL9 GPR65 (99191)
