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FLASH GENE
Symbol HCAR1 contributors: mct - updated : 10-09-2015
HGNC name hydroxycarboxylic acid receptor 1
HGNC id 4532
Location 12q24.31      Physical location : -
Synonym name
  • T cell activation G protein coupled receptor
  • G protein-coupled receptor 104
  • lactate receptor 1
  • putative chemokine receptor
  • G protein-coupled receptor 81
  • Synonym symbol(s) FKSG80, GPR104, TA-GPCR, GPR81, HCA1, LACR1, TA-GPCR, TAGPCR
    DNA
    TYPE functioning gene
    STRUCTURE 2.98 kb     1 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 2977 39.2 346 - 2008 1817460
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  predominantly Mus musculus
    Muscularstriatumskeletal   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificadipocyte Mus musculus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane domains
  • HOMOLOGY
    intraspecies homolog to GPR109A (52p100)
    Homologene
    FAMILY
  • GPCR subfamily
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • cerebral HCAR1 is concentrated on the postsynaptic membranes of excitatory synapses and also is enriched at the blood-brain barrier
  • in synaptic spines and in adipocytes, HCAR1 immunoreactivity is also located on subplasmalemmal vesicular organelles, suggesting trafficking to and from the plasma membrane
  • basic FUNCTION
  • transducing extracellular signals through heterotrimeric G protein
  • may play a role in energy metabolism (Cai 2008)
  • playing a critical role in lactate-mediated suppression of adipose lipolysis (Cai 2008)
  • lactate and its receptor HCAR1 unexpectedly function in an autocrine and paracrine loop to mediate insulin-induced antilipolytic effects
  • 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 important for cancer cell regulation of lactate transport mechanisms, furthermore, lactate transport is important for the survival of cancer cells in the tumor
  • lactate receptor, which promotes lipid storage in adipocytes, and is also active in the mammalian brain
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HCAR1 and ARRB2 physically interacted and were required for these effects
  • lactate negatively regulates TLR induction of the NLRP3 inflammasome and production of IL1B, via ARRB2 and HCAR1
  • endogenous receptor for lactate
  • cell & other
    REGULATION
    activated by lactate, suppressing lipolysis in adipocytes (Liu, 2009)
    hydroxy-carboxylic acid ligands which are intermediates of energy metabolism (Ahmed 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    by high fat diet reducing adipose tissue HCAR2 and HCAR1 gene expression
    tumoral     --over  
    in pancreatic cancer
    constitutional     --low  
    by inflammation decreasing the expression of HCAR1 in adipose tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheromabrain
    HCAR1 antagonism might be a novel therapeutic strategy for the treatment of cerebral ischemia
    metabolismlipid 
    may be an attractive target for the treatment of dyslipidemia and others metabolic disorders
    ANIMAL & CELL MODELS
  • in mice, diet-induced obesity significantly reduced Gpr109a and Gpr81 gene expression in epididymal fat pads
  • ob/ob mice, a mouse model of obesity and type 2 diabetes, demonstrate reduced adipose tissue expression of Gpr81
  • Gpr81 expression was decreased in ob/ob mice, an animal model of type 2 diabetes that is characterized by inflammation