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FLASH GENE
Symbol GPR39 contributors: mct/npt/pgu - updated : 07-03-2019
HGNC name G protein-coupled receptor 39
HGNC id 4496
Location 2q21.2      Physical location : 133.174.146 - 133.404.168
Synonym symbol(s) MGC149541, ZNR
DNA
TYPE like-sequence
SPECIAL FEATURE head to head
STRUCTURE 230.62 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   transcription factor
text structure
  • 3' exon overlaps with an antisense gene called LYPD1 (Ly-6/PLAUR domain containing 1)
  • sites for the hepatocyte nuclear factors 1alpha and 4alpha (HNF-1alpha and -4alpha) and specificity protein 1 (SP1) transcription factors as being important for the expression of GPR39
  • MAPPING cloned Y linked N status confirmed
    Map cen - D2S112 - GPR39 - D2S2219 - D2S1508E - qter
    Physical map
    LOC389043 2 hypothetical gene supported by AK125982; BC042817 GNAQP 2q14.3-q21 quanine nucleotide binding protein (G protein), q polypeptide pseudogene LOC344228 2q21.2 similar to Hypothetical UPF0120 protein DKFZp564C186 LOC284988 2q21.2 similar to ARHQ protein H2-ALPHA 2q21.2 alpha-tubulin isotype H2-alpha LOC389045 2 similar to RIKEN cDNA 2610001E06 FLJ41352 2q21.2 FLJ41352 protein LOC90557 2q21.2 hypothetical protein BC016861 LOC389046 2 similar to pote protein; Expressed in prostate, ovary, testis, and placenta LOC389047 2 similar to pote protein; Expressed in prostate, ovary, testis, and placenta LOC129439 2q21.2 similar to FKSG30 LOC391444 2 similar to mKIAA0767 protein LOC389048 2 LOC389048 AF038169 2q21.2 hypothetical protein AF038169 LOC389049 2 similar to Probable mitochondrial import receptor subunit TOM40 homolog (Translocase of outer membrane 40 kDa subunit homolog) (Haymaker protein) (p38.5) LOC389050 2 LOC389050 LOC389051 2 LOC389051 LOC163336 2q21.2 similar to FLJ10101 protein LOC391445 2 similar to PRED65 LOC389052 2 similar to breast cancer antigen NY-BR-1 LOC391446 2 similar to rRNA intron-encoded homing endonuclease LOC391447 2 similar to zinc finger protein 285 GPR39 2q21 G protein-coupled receptor 39 MGC29643 2q21.2 hypothetical protein MGC29643 NAP5 2q21.2 Nck-associated protein 5
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 2821 - 453 . selectively throughout the gastrointestinal tract, including the liver and pancreas as well as in the kidney and adipose tis 2008 18180304
  • variant 1 (GPR39-1a)
  • biologically active seven-transmembrane form
  • down-regulated during adipocyte differentiation of fibroblasts
  • - polyA site 867 - 288 . more broad expression pattern, including the central nervous system but with highest expression in the stomach and small intestine 2007 17488974
  • truncated splice variant five-transmembrane form
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Muscularstriatumskeletal   Mus musculus
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • Zn2+ binds in the extracellular domain to a site involving His17 and His19, located in the N-terminal extension
  • four Cys residues in the extracellular domains
  • two disulfide bridges, the second bridge between a Cys residue located at the extracellular end of transmembrane segment III (TM-III) and one in extracellular loop 2 (ECL-2)
  • seven transmembrane segments (7TM) receptor
  • HOMOLOGY
    interspecies homolog to C.elegans k10b4.4
    intraspecies homolog to growth hormone,secretagogue receptor (GSHR) and neurotensin receptors,highly
    Homologene
    FAMILY
  • orphan member of the ghrelin receptor family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • inhibitor of cell death
  • functions as a Gq-coupled Zn2+-sensing receptor
  • GPR39 is involved in the control of endocrine pancreatic function
  • GHRL/GPR39 system is involved in myogenesis and GHRL is expressed by differentiating myogenic precursors to function in an autocrine manner
  • GPR39 might modulate gut motility via regulating ANO1 function in fibroblast-like cells (FLCs)
  • GPR39 was spatiotemporally expressed during skin wound repair
  • possible role of the GPR39 receptor in monoaminergic and glutamatergic neurotransmission, which plays an important role in the pathophysiology of depressio
  • involvement of the GHRL/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas
  • plays a role in cellular and physiological processes, including insulin secretion, cell death inhibition, wound healing, and obesity
  • GPR39 was shown to regulate the activity of ion transport mechanisms that are essential for the physiological function of epithelial and neuronal cells
  • Zn2+-sensing G-protein coupled receptor, that triggers signaling leading to cell growth
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain
  • a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • receptor of Zn2+ (Zn2+ acts as an agonist for GPR39, not in the classical manner by directly stabilizing an active conformation of the transmembrane domain, but instead by binding to His17 and His19 in the extracellular domain)
  • extracellular Zn(2+), which is either applied or released following injury, activates GPR39 to promote signaling leading to epithelial repair
  • extracellular Zn2+ regulates endothelial cell activity in a GPR39-dependent manner
  • protein
  • receptor for obestatin (GHRL), a peptidic hormone involved in energy homeostasis
  • interact with GHRL
  • GHRL is the ligand for the orphan receptor GPR39, which belongs to the family of the ghrelin and motilin receptors
  • CASR interacts with GPR39 and thereby regulates its activity
  • PLAGL1 interacts likely directly with PAX7, which can regulate GPR39 expression by activating PLAGL1
  • GPR39 phosphorylating CAMK2A, CAMK2B contributes to the distinct roles of PAX3 and PAX7 in myogenic progression
  • exhibits likely an anti-inflammatory activity by enhancing IL10 production from macrophages
  • a novel role of GPR39 in enhancing tight junction assembly in intestinal epithelial cells (IECs) via phospholipase C-CAMKK2-AMPK pathways
  • cell & other
    REGULATION
    activated by zinc ions
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in omental adipose tissue observed in obese patients with T2 Diabetes mellitus
    constitutional       loss of function
    is associated with increased fat accumulation on a high-fat diet, conceivably due to decreased energy expenditure and adipocyte lipolytic activity
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential usefulness of GPR39 as a prognostic marker in gastric cancer
  • Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathy 
    potential role of GHRL/GPR39 for use as a therapeutic agent for the treatment of trauma-induced muscle injuries or skeletal muscle myopathies
    diabetetype 2 
    development of potent and selective GPR39 agonists as a therapeutic approach for diabetes
    cancerreproductivebreast
    GPR39 as a potential therapeutic target for combination treatment in breast cancer, particularly relevant in ER negative tumors
    digestive  
    GPR39 may be a therapeutic target for promoting epithelial function and tight junction barrier integrity during ulcerative colon diseases
    ANIMAL & CELL MODELS
  • Gpr39-deficient mice had weaker bones as a result of altered bone composition