GPR65

GPR65

Target · Proton-sensing GPCR

GPR65 G protein-coupled receptor 65 · T-cell death-associated gene 8 protein

GPR65 (G protein-coupled receptor 65, also known as TDAG8 and hTDAG8) is a proton-sensing G protein-coupled receptor activated by extracellular pH. It couples mainly to G(s) proteins and stimulates adenylate cyclase, linking pH changes to immune cell responses. Browse Assay Genie's current range of GPR65 research reagents below, or read on for the biology behind the target.

Plasma and endosomal membranesProton-sensing GPCRConstitutively active in endosomes
337 aa
Protein length
~39 kDa
Molecular weight
14q31.3
Gene locus
Class A GPCR
Receptor class
Target information

What is GPR65 (g protein-coupled receptor 65)?

GPR65 is a proton-sensing G protein-coupled receptor that monitors extracellular pH and helps cells generate adaptive reactions to changes in it. It is activated at an optimal pH of 7.4. Ligand binding causes a conformational change that triggers signalling through guanine nucleotide-binding proteins (G proteins) and modulates downstream effectors such as adenylate cyclase. GPR65 is mainly coupled to G(s) proteins and mediates activation of adenylate cyclase activity. It may also act as a receptor for the glycosphingolipid psychosine and several related glycosphingolipids.

In immune cells, GPR65 plays a role in the immune response by maintaining lysosome function and regulating T-cell metabolism. It acts as a regulator of inflammation by mediating pH-sensing of the extracellular acidification that occurs in inflamed tissues. Activation regulates endo-lysosomal function of immune cells as well as T-cell metabolism. The receptor is also constitutively active in endosomes, where it stimulates adenylate cyclase production independently of extracellular pH changes.

The protein is found at the cell membrane and on early and late endosome membranes. NCBI Gene annotates the GPR65 gene with G protein-coupled receptor activity, adenylate cyclase-activating G protein-coupled receptor signalling, cellular response to acidic pH and positive regulation of stress fibre assembly. It belongs to the G protein-coupled receptor 1 family and is classed by HGNC among the Class A orphan receptors. The mouse ortholog is Gpr65. The aliases TDAG8 and hTDAG8 are still widely used in the literature.

Proton sensing and pH biology

GPR65 detects extracellular pH and drives adaptive cellular reactions, making it a model for studying how cells respond to acidic environments.

Inflammation research

The receptor mediates pH-sensing of extracellular acidification in inflamed tissues and regulates inflammatory responses.

T-cell metabolism and immunity

GPR65 regulates T-cell metabolism and maintains lysosome function, supporting studies of immune cell regulation.

GPCR and cAMP signalling

Coupling mainly to G(s) and adenylate cyclase, including from endosomes, makes GPR65 useful for studying compartmentalised GPCR signalling.

Background

GPR65 frequently asked questions

What does GPR65 do?

GPR65 is a proton-sensing G protein-coupled receptor activated by extracellular pH, with an optimal pH of 7.4. It couples mainly to G(s) proteins to activate adenylate cyclase, and it regulates lysosome function, T-cell metabolism and inflammation-related pH responses in immune cells.

Why is GPR65 also called TDAG8?

TDAG8 and hTDAG8 are alternative names for the gene and protein officially named G protein-coupled receptor 65 (GPR65) by HGNC. The source data do not give the history of these names, so use the approved symbol alongside the aliases when searching the literature.

Is GPR65 conserved in other species?

A mouse ortholog, Gpr65, is recorded for the human gene. The human protein belongs to the G protein-coupled receptor 1 family. Check the datasheet of any product for its validated reactivity before using it with a particular species.

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Related targets

Other G protein-coupled receptors, including orphan and proton-sensing family members, with products at Assay Genie.

Gene and protein annotations from HGNC, NCBI Gene and UniProt Q8IYL9; product specifications from Assay Genie datasheets.

GPR65 Product listing