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FLASH GENE
Symbol HCAR2 contributors: mct/npt - updated : 10-09-2015
HGNC name hydroxycarboxylic acid receptor 2
HGNC id 24827
Location 12q24.31      Physical location : -
Synonym name
  • G-protein coupled receptor HM74A
  • nicotinic acid receptor 1
  • niacin receptor
  • G protein-coupled receptor 109A
  • G-protein-coupled receptor HM74A
  • Synonym symbol(s) HM74a, HM74b, PUMAG, Puma-g, NIACR1, GPR109A
    DNA
    TYPE functioning gene
    STRUCTURE 2.06 kb     1 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 2082 - 363 - 2009 19276343
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    Respiratorylung   highly
    Skin/Tegumentskin     Homo sapiens
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  predominantly Mus musculus
    Epithelialbarrier liningretinal pigment epithelium (RPE) highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Mus musculus
    Blood/Hematopoieticneutrophil Mus musculus
    Lymphoid/Immunedendritic cell Mus musculus
    Lymphoid/Immunemacrophage Mus musculus
    not specificadipocyte Mus musculus
    Skin/Tegumentkeratinocyte Homo sapiens
    Skin/Tegumentkeratinocyte Mus musculus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a sequence from AAs 329 to 343 in the C-terminal tail of HCAR2 plays a crucial role in keeping HCAR2 in an inactive conformation
  • HOMOLOGY
    intraspecies homolog to GPR109B
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • GPCR subfamily
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • acting as a high affinity receptor for nicotinic acid and other compounds with related pharmacology
  • being sufficient to mediate anti-lipolytic effect of niacin in adipose tissue
  • may play a role in defense mechanisms against pathogens, at least within the innate immune system
  • might be involved in the regulation of neutrophil numbers (Kostylina 2008)
  • mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in colon (Thangaraju 2009)
  • playing a role in in diabetic retinopathy (Martin 2009)
  • HCAR2, HCAR3 play an essential role in the regulation of metabolic processes and immune reactions
  • possible specific role(s) of HCAR2, HCAR3 in human skin homeostasis
  • for the AAs important for HCAR1 function, the corresponding AAs or motifs in HCAR2 are also critical for HCAR2 function
  • HCAR1, HCAR2 are G protein-coupled receptors located predominantly on adipocytes that mediate anti-lipolytic effects
  • HCAR1, HCAR2 are positively correlated with PPARG gene expression in fat
  • is a tumor suppressor in mammary gland and pharmacologic induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • nicotinic acid-HCAR2 axis is a novel negative regulator of macrophage activation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • niacin receptor (receptor for nicotinic acid, used to modify lipoprotein profiles, resulting in a beneficial modification of multiple cardiovascular risk factors due to its direct activation of GPR109A on the surface of adipocytes)
  • receptor for the bacterial fermentation product butyrate (Thangaraju 2009)
  • receptor for beta-HB, the predominate ketone body in circulation, an important energy source for neurons, including retinal neurons, under various physiologic and pathologic conditions (Martin 2009)
  • upon niacin activation, HCAR2 couples to a G(i) protein and inhibits adenylate cyclase activity, leading to inhibition of liberation of free fatty acid
  • cell & other
    REGULATION
    activated by nicotinic acid (NA), a lipid-lowering drug (Kostylina 2008)
    hydroxy-carboxylic acid ligands which are intermediates of energy metabolism (Ahmed 2009)
    by niacin and butyrate
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    silenced in colon cancer (Thangaraju 2009)
    constitutional     --low  
    by high fat diet reducing adipose tissue HCAR2 and HCAR1 gene expression
    constitutional     --over  
    in the blood as well as in the substantia nigra (SN) in the Parkinson disease group compared to age-matched controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in mice, diet-induced obesity significantly reduced Gpr109a and Gpr81 gene expression in epididymal fat pads