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G protein-coupled receptor 65 (GPR65) is a seven-transmembrane glycoprotein encoded by the GPR65 gene, composed of extracellular proton-sensing loops, transmembrane helical bundle and cytoplasmic G protein coupling tail, and acts as a primary proton-sensing receptor subunit for acidic microenvironment GPCR complexes. GPR65 is widely expressed across myeloid, lymphoid and mucosal epithelial cell populations, serving as a core scaffold mediating G protein heterotrimer assembly and downstream inflammatory kinase recruitment upon extracellular acid stimulation.
GPR65 exerts its biological effects through dynamic G protein coupling assembly upon proton binding, a mechanism that modulates proton ligand binding stability and intracellular immune signal cascade activation efficiency. Unlike G protein accessory subunits, GPR65 cannot initiate full immune signal output without proton binding and G protein complex formation; it recruits cytoplasmic signal mediators to assembled receptor-G protein complexes, uncoupling extracellular acidic environment sensing from intracellular immune transcription factor activation and sustaining persistent polarized immune response signals. This dual regulation modulates the intensity of acid-triggered inflammatory responses after microenvironmental pH shift, fine-tuning local immune cell polarization and inflammatory mediator secretion levels, while sustained abnormal GPR65-mediated signal transmission drives skewed immune polarization and chronic inflammatory lesions in acidic tissues. GPR65 participates in key physiological and pathological processes including extracellular proton sensing, myeloid immune polarization, acid-mediated tissue inflammation and chronic inflamed tissue disorders. Dysregulation of GPR65 expression or G protein coupling capacity is closely associated with imbalanced immune polarization and impaired anti-inflammatory tissue defense, making GPR65 a crucial research target for proton-sensing GPCR signaling, innate immune polarization and inflammatory disease research.
Fig. 1 Tumor extracellular acidosis activates GPR65 in innate and adaptive immune cells, triggering immunosuppression, impaired antigen presentation and tumor outgrowth; pharmacological inhibition of GPR65 reverses immune suppression, restores anti-tumor immune function and induces tumor regression.1
The biological functions of GPR65 are focused on proton-sensing G protein coupling assembly, polarized immune signal propagation and tissue immune balance:
Creative Biolabs offers high-purity GPR65 proteins through optimized heterologous expression systems. These products retain native conformational characteristics and G protein heterotrimer binding activity, suitable for proton-sensing GPCR signaling research, receptor-G protein complex interaction detection, and small molecule immune polarizing modulator screening for inflammatory disorder research. All GPR65 proteins undergo strict quality control, including purity analysis and biological activity validation to ensure biological function.
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Creative Biolabs provides custom-engineered GPR65 stable cell lines, including overexpressing and knockdown models in myeloid and mucosal epithelial cell models. These cell lines are optimized for studying GPR65-mediated G protein coupling assembly mechanisms, acid-induced immune signal cascade dynamics, and immune polarization modulator sensitivity. Each cell line undergoes stringent validation, including stable expression detection and functional integrity verification.
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High-specificity recombinant antibodies targeting GPR65 are developed via advanced antibody engineering technologies. These antibodies are validated for multiple applications, including immunofluorescence for GPR65 plasma membrane localization, Western blot for expression analysis, and co-immunoprecipitation for GPR65-G protein complex research, enabling precise analysis of GPR65 expression, subcellular localization and functional regulation.
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Beyond catalog products, Creative Biolabs offers specialized custom services for GPR65 research:
GPR65 is a proton-sensitive G protein-coupled receptor that associates with cytoplasmic G protein trimers upon proton stimulation to modulate acid-induced immune polarization signal amplitude, balance mucosal tissue inflammatory response dynamics, and mediate myeloid cell activation under acidic microenvironment conditions.
GPR65 is a core regulator of pH-dependent GPCR immune signaling and mucosal tissue immune homeostasis, and its dysregulation is associated with skewed immune polarization and chronic acid-triggered inflammatory lesions. It is a critical target for proton-sensing receptor and inflammatory disorder research.
No, all GPR65 products and services are strictly for research use only, not intended for clinical diagnosis or treatment.
Offerings include GPR65 proteins (full-length, extracellular proton-sensing domain variants), specific recombinant antibodies, and custom stable myeloid cell lines, supporting pH-sensitive immune and inflammatory research.
GPR65 proteins are validated by G protein heterotrimer binding assays and acid-triggered immune signal regulation verification to ensure native regulatory function in proton-sensing receptor research.