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GPR65

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

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 Dual regulatory model of GPR65 in acidic tumor microenvironment and anti-tumor immunity. (OA Literature)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

GPR65 Protein Function: Core Roles in Proton-Sensing GPCR Coupling and Immune Homeostasis

The biological functions of GPR65 are focused on proton-sensing G protein coupling assembly, polarized immune signal propagation and tissue immune balance:

  • GPCR Coupling Modulation: Directly associates with cytoplasmic G protein heterotrimers upon proton binding to stabilize ligand interaction and modulate downstream immune signal activity, the primary molecular mechanism of GPR65-mediated regulation.
  • Immune Polarization Signal Amplification: Recruits cytoplasmic signaling kinases to trigger polarization transcription factor activation, fine-tuning myeloid immune response dynamics under acidic conditions.
  • Acidic Inflammatory Mediation: Supports sustained secretion of immune polarizing mediators to coordinate local mucosal tissue inflammatory reactions.
  • Tissue pH Immune Surveillance: Strengthens proton-triggered GPCR signaling to maintain balanced immune polarization under variable microenvironmental acidity.
  • Disease Relevance: Abnormal GPR65 expression is closely related to skewed immune polarization and chronic acid-driven inflammatory pathologies, making it a key target for proton-sensing GPCR research.

GPR65 Protein Product

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.

GPR65 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

GPR65 Stable Cell Line Product

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.

GPR65 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

GPR65 Recombinant Antibody Product

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.

GPR65 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • Native G Protein Coupling Binding Activity: Retains conformational characteristics and specific heterotrimeric G protein assembly ability, accurately simulating endogenous proton-sensing immune signal transduction and mucosal tissue inflammatory regulation processes.
  • Proton-Sensing GPCR Specificity: Validated for selective binding to GPR65 structural epitopes with no cross-reactivity with other pH-sensitive receptor subunits, supporting specific acidic microenvironment immune signaling research.
  • Inflammatory Tissue Research Compatibility: Optimized for myeloid and mucosal epithelial research systems, providing reliable tools for immune polarization modulator development and mechanism exploration.
  • Comprehensive Customization Support: Enables end-to-end development of tailored GPR65 proteins, antibodies, and stable cell lines to meet diverse acid-sensitive immune and inflammatory disease research needs.

Custom GPR65 Research Services

Beyond catalog products, Creative Biolabs offers specialized custom services for GPR65 research:

  • Custom GPR65 Protein Production: Tailored expression of GPR65 variants, including G protein coupling-defective mutants, tagged proteins, and fusion proteins with other immune signaling mediators.
  • Custom Antibody Development: Generation of GPR65-specific antibodies for localization assays and GPR65-G protein complex analysis, as well as functional blocking assays for GPR65 research.
  • Stable Cell Line Engineering: Custom GPR65-expressing myeloid and mucosal epithelial cell lines and acid-responsive immune signal reporter cell lines, with functional validation of receptor-G protein coupling formation and inflammatory signal output.
  • Functional Assay Development: Design of GPR65-mediated proton sensing binding assays, acid-induced immune signal activity analysis assays, and immune regulatory small molecule screening assays.

Frequently Asked Questions (FAQ)

  1. What is the primary function of GPR65?

    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.

  2. Why is GPR65 a significant research target?

    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.

  3. Are Creative Biolabs' GPR65 products suitable for clinical use?

    No, all GPR65 products and services are strictly for research use only, not intended for clinical diagnosis or treatment.

  4. What types of GPR65 products does Creative Biolabs offer?

    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.

  5. How are GPR65 proteins validated for activity?

    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.

Reference
  1. Grant, Michael, et al. "Low pH, High Stakes: A Narrative Review Exploring the Acid-Sensing GPR65 Pathway as a Novel Approach in Renal Cell Carcinoma." Cancers 17.23 (2025): 3883. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/cancers17233883
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