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FLASH GENE
Symbol FNDC5 contributors: mct - updated : 04-03-2014
HGNC name fibronectin type III domain containing 5
HGNC id 20240
Location 1p35.1      Physical location : 33.327.869 - 33.338.082
Genatlas name irisin
Synonym symbol(s) FRCP2, irisin, PEP
DNA
TYPE functioning gene
STRUCTURE 10.22 kb     6 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 3046 - 153 - 2012 22237023
6 - 2099 - 181 - 2012 22237023
6 - 2748 - 212 - 2012 22237023
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Nervousbrain    
Reproductivemale systemprostate   
Respiratorylung    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticplasma    Homo sapiensAdult
Connectiveadipose    Homo sapiens
Connectiveadiposewhite   Homo sapiens
Muscularstriatum    Homo sapiens
cell lineage
cell lines
fluid/secretion present in mouse and human plasma
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a fibronectin, type III motif
  • a signal peptide,
  • two fibronectin domains
  • one hydrophobic domain that is likely to be membrane inserted
  • isoforms Precursor irisin is a cleaved and secreted fragment of FNDC5
    HOMOLOGY
    interspecies homolog to rattus LOC260327
    homolog to murine irisin (100p100)
    Homologene
    FAMILY FNIII repeat containing gene family
    CATEGORY
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text type I membrane protein
    basic FUNCTION
  • type I membrane protein that is processed proteolytically to form a newly identified hormone secreted into the blood, termed irisin
  • Irisin is induced in exercise and activates profound changes in the subcutaneous adipose tissue
  • its action recapitulates some of the most important benefits of exercise and muscle activity
  • activation of browning and thermogenic genes by FNDC5 is a major part of the action of this polypeptide on these cells
  • induces browning of white adipose tissues and protects against diet-induced obesity and diabetes
  • is not only a myokine but also an adipokine
  • determines insulin sensitivity in humans
  • may play a major role in affecting high-density lipoprotein cholesterol levels and abnormal energy expenditure in chronic kidney disease patients
  • positively linked to muscle mass, strength and metabolism, pointing to common regulatory factors and/or the potential for irisin to modify muscle phenotype
  • muscle-derived hormone stimulating thermogenesis
  • exercise-induced irisin secretion could have evolved from shivering-related muscle contraction, serving to augment brown fat thermogenesis in concert with FGF21
  • is a novel myokine produced by skeletal muscle
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PPARGC1A stimulates the expression of several muscle gene products that are potentially secreted, including FNDC5
  • stimulating browning and UCP1 expression
  • acts to induce UCP1 gene expression, at least in part, via PPARA
  • FNDC5 activated MAPK14 in an PRKAA1-dependent manner
  • FNDC5 plays an important role in glucose metabolism via the ROS-mediated PRKAA1 pathway in skeletal muscle cells
  • cell & other
    REGULATION
    Other neuronal FNDC5 gene expression is regulated by PPARGC1A
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    increased with exercise
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    metabolismlipid 
    could be therapeutic for human metabolic disease and other disorders that are improved with exercise
    obesity  
    attractive therapeutic potential of irisin in obesity
    ANIMAL & CELL MODELS