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FLASH GENE
Symbol GPR65 contributors: mct - updated : 13-12-2016
HGNC name G protein-coupled receptor 65
HGNC id 4517
Location 14q31.3      Physical location : 88.471.467 - 88.481.154
Synonym name
  • T cell death-associated gene 8
  • psychosine receptor
  • Synonym symbol(s) TDAG8, HTDAG8
    DNA
    TYPE functioning gene
    STRUCTURE 9.69 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D14S67 - GPR65 - D14S68 - D14S1066 - qter
    Authors Gene Map (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 4522 - 337 - 2005 15618224
    - - 1800 - - . spleen and peripheral blood leukocytes highly, lymph node, thymus, lung and small intestine . appendix,bone marrow . fetal liver lowly 1998 9655242
    EXPRESSION
    Rna function
  • TDAG8 mRNA has a relatively limited gene expression profile but is highly expressed in the immune system
  • Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinethyroid    
    Lymphoid/Immunespleen    
     thymus    
    Urinarybladder    
     kidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticeosinophil Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM)
  • three potential N-linked glycosylation sites
  • HOMOLOGY
    interspecies homolog to murine Tdag8
    Homologene
    FAMILY G protein coupled receptor superfamily
    CATEGORY protooncogene , receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • proton-sensing GPCRs coupling to adenylyl cyclase and psychosine, proton-sensing and psychosine-sensitive G-protein-coupled receptor
  • expression of GPR65 by immune cells may regulate responses in acidic microenvironments
  • proton-sensing GPCRs which could have some roles in nociception or in compensation of loss of ACCN3 gene
  • functions as an extracellular pH sensor which enhances cAMP production in response to an acidified extracellular environment
  • involved in the establishment of immunological autotolerance
  • orphan G protein-coupled receptor (GPCR) in apoptotic thymocytes
  • may play biological roles in immune response and cellular transformation under conditions accompanying tissue acidosis
  • extracellular pH-sensing G protein-coupled receptor that is overexpressed in various tumors and tumor cell lines
  • enhances tumor development by promoting adaptation to the acidic environment to enhance cell survival/proliferation
  • candidate molecule that contributes to acid resistance and tumor proliferation
  • is likely to trigger adaptations that allow the tumor cells to survive in an acidic environment and promote further tumor development
  • acts likely as a negative regulator of inflammation
  • proton sensor, inhibits the production of pro-inflammatory cytokines induced by extracellular acidification
  • GPR65 is vital regulatory genes upstream of MMP3
  • potential involvement of GPR65 in behavioral response relevant to depression
  • GPR4, GPR65 and GPR68 are G protein-coupled receptors that aid cells to sense and survive conditions of acidic pH
  • GPR65 may be involved in a mechanism that supports survival of photoreceptors in the degenerating retina
  • is a negative regulator for lung neutrophilic inflammation and injury, in part, through the inhibition of chemokine production
  • GPR4, GPR68, GPR65, GPR132 are regulators of cell proliferation and migration during tumor growth and wound healing
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS development , immunity/defense
    text cell fate specification
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction of psychosine with GPR65, but GPR65 is dispensable for psychosine-induced formation of multinucleated cells
  • correlation of GPR65 with BCL2 suggesting a novel cytoprotective mechanism that enables chronic lymphocytic leukemia (CLL) cell adaptation to acidic extracellular conditions
  • cell & other
    REGULATION
    activated by psychosine (1-beta-d-galactosylsphingosine)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in cancer tissues
    tumoral     --over  
    in tumor cells promotes cell survival under acidic conditions and enhances tumor development
    constitutional       gain of function
    attenuates immune-mediated inflammation by regulating the cytokine production of T cells and macrophages
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    antagonists of GPR65 or anti-GPR65 antibody drugs may be promising therapeutic candidates for the treatment of GPR65-expressing tumors
    osteoarticularboneostéoporosis
    enhancement of GPR65 function represents a new strategy for preventing bone resorption diseases, such as osteoporosis
    ANIMAL & CELL MODELS
  • GPR65(-/-) mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease
  • Tdag8-deficient mice showed significant exacerbation of anti-type II collagen antibody-induced arthritis and delayed-type hypersensitivity, and showed a slight exacerbation of collagen-induced arthritis