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FLASH GENE
Symbol FFAR1 contributors: mct - updated : 11-02-2011
HGNC name free fatty acid receptor 1
HGNC id 4498
Location 19q13.12      Physical location : 35.842.444 - 35.843.367
Synonym name G protein-coupled receptor 40
Synonym symbol(s) GPR40, GPCR40, FFA1R
DNA
TYPE functioning gene
STRUCTURE 0.92 kb     1 Exon(s)
regulatory sequence Promoter
text structure
  • FFAR3 is transcribed from the promoter of the FFAR1 gene
  • MAPPING cloned Y linked N status provisional
    regionally located tightly linked to CD22
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 923 - 300 - 2007 17525159
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   predominantly Homo sapiens
    Gustatory (taste)      Homo sapiens
    Reproductivefemale systemuterus  lowly
    Respiratoryrespiratory tractbronchus    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmooth    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Endocrineislet cell (alpha,beta...) Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven transmembrane segments (7TM) receptor
  • two Glu residues (Glu-145 and Glu-172) in the second extracellular loop that form putative interactions individually with two transmembrane Arg residues (Arg-183(5.39) and Arg-258(7.35)) to create two ionic locks
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Ffar1 (82.7 pc)
    homolog to rattus Ffar1 (81.7 pc)
    Homologene
    FAMILY
  • G-protein coupled receptor 1 family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • acting as a receptor for medium and long chain saturated and unsaturated fatty acids
  • binding of the ligand increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion
  • acting as a rhodopsin-like receptor
  • playing a dual role in the regulation of glucose homeostasis in diet-related type II diabetes
  • playing an important role for the beta-cell function
  • its acute activation potentiates insulin secretion from beta cells, whereas prolonged binding might contribute to the deleterious effects of chronic exposure to long-chain fatty acids
  • correlation with insulin secretion, raises the possibility of an involvement of FFAR1 in diabetes beta-cell dysfunction
  • implicated in mediating both physiological and pathological effects of fatty acids on beta-cells
  • plays a role not only in fatty acid modulation of insulin secretion, but also in glucose-induced insulin secretion after high-fat feeding
  • partially required for insulin secretion following activation of beta3-adrenergic receptors
  • FFAR1 and FFAR4 mediate the taste of fatty acids
  • is involved in both the acute and chronic effects of palmitate on insulin secretion
  • hypothalamic FFAR1 activated by free long chain fatty acids might have an important role in this pain control system
  • FFAR1, FFAR4 are two GPCRs activated by saturated and unsaturated longer-chain free fatty acids
  • is the functionally dominant free fatty acid receptor in airway smooth muscle
  • is a free fatty acid receptor that has been recently shown to impact bone remodeling
  • differentially impacts osteoblast behavior depending on differentiation stage and environment
  • mediating enhancement of glucose-stimulated insulin secretion
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • acting as the target receptor for FFAs (free fatty acids), which play the role of extracellular signaling molecules that regulate neural functions such as the lipid-sensing mechanism in the hypothalamus and the control of energy balance
  • activation of the hypothalamic FFAR1 signaling pathway may regulate beta-endorphin release via PCSK2, and regulate the endogenous pain control system
  • FFAR4 enhanced and FFAR1 inhibited the cell motile activity of highly migratory osteosarcoma cells
  • cell & other
  • binding to lipid
  • REGULATION
    activated by medium and long chain fatty acids
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to type 2 diabetes
    Variant & Polymorphism repeat rare variant that causes a loss of function associated with impaired insulin secretion in response to oral glucose and lipid load, resulting in a loss of function that prevents the beta-cell ability to adequately sense lipids as an insulin secretory stimulus because of impaired intracellular Ca2+ concentration increase
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    drug target because of its role in FFA-mediated enhancement of glucose-stimulated insulin release, in type 2 diabetes
    diabetetype 2 
    potentially attractive target to best meet the need for novel treatments for Type II diabetes
    osteoarticularbone 
    is a relevant target for the design of new nutritional and therapeutic strategies to counter bone complications
    ANIMAL & CELL MODELS
  • Gpr40/Ffar1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior
  • in the retinas of Vldlr(-/-) mice with low fatty acid uptake but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1
  • Gpr40(-/-) mice exhibit osteoporotic features suggesting a positive role of Gpr40 on bone density