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FLASH GENE
Symbol FASN contributors: mct/npt - updated : 27-05-2017
HGNC name fatty acid synthase
HGNC id 3594
Location 17q25.3      Physical location : 80.036.214 - 80.056.106
Synonym name short chain dehydrogenase/reductase family 27X, member 1
Synonym symbol(s) FAEES1, OA-519, FAS, SDR27X1, MGC14367, MGC15706
EC.number 2.3.1.85, 1.1.1.100, 2.3.1.38, 4.2.1.61
DNA
TYPE functioning gene
STRUCTURE 19.95 kb     43 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
43 - 8481 273.3 2511 - 2003 12882974
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinesmall intestine  highly
 liver    
Nervousbrainlimbic systemhippocampusdentate gyrus  Mus musculus
Reproductivefemale systemovary   
 female systembreastmammary gland highly
Skin/Tegumentskin   highly
Visualeye    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • three separate domains
  • DI (beta ketoacyl synthase, acetyl/malonyl transacyclase, beta-hydroxydehydratase)
  • DII required for dimerization, DII (enoyl reductase, beta-ketoacid reductase, acyl carrier protein ACP)
  • DIII thioesterase
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • fatty acid ethyl ester synthase 1, NADPH dependent
  • multifunctional protein, catalyzing the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty
  • plays an important role very early in colorectal tumorigenesis and may be a target for chemoprevention (Kearney 2009)
  • can act as a prostate cancer oncogene in the presence of AR and exerts its oncogenic effect by inhibiting the intrinsic pathway of apoptosis (Migita 2009)
  • promotes energy storage through de novo lipogenesis and participates in signaling by the nuclear receptor PPARA in noncardiac tissues
  • modulates homeostatic responses to myocardial stress
  • key enzyme of de novo lipogenesis
  • FASN activity is potentially required for neural stem and progenitor cells (NSPCs) maintenance
  • plays an important role in exercise-mediated cognitive enhancement, which might be associated to its role in modulating exercise-induced stimulation of neurogenesis
  • cancer cell-associated FASN regulates tumor vasculature through alteration of the profile of secreted angiogenic factors and regulation of their bioavailability
  • is essential for the development, functional competence, and maintenance of the lactating mammary gland
  • FASN, ERBB2-mediated glycolysis is required for breast cancer cell migration
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • two lipogenic genes encoding DGAT2 and FABP4 were induced in ELOVL2-overexpressing cells, whereas no such effect was seen on the fatty acid synthase (FASN) gene
  • within adipocytes, CD5L associates with cytosolic fatty acid synthase (FASN), thereby decreasing FASN activity
  • hypoxic cell death is promoted by the reduced expression of FASN through SREBF1 down-regulation
  • THRSP seems to act as a molecular brake on FASN-dependent lipogenesis, potentially also integrating other signals, such as thyroid hormone-regulated pathways
  • THRSP stimulated fatty acid synthase (FASN) activity in vitro, and increased the synthesis of fatty acids in mammary epithelial cells in vivo
  • positive feedback regulation between FASN and ERBB2 expression and phosphorylation in osteosarcoma (OS) cells
  • FASN gene silencing indeed mediated apoptosis in RB1 cells through the PI3K/AKT pathway
  • RNA N6-methyladenosine methylase METTL3 inhibits hepatic insulin sensitivity via N6-methylation of FASN mRNA and promoting fatty acid metabolism
  • cell & other
    REGULATION
    activated by SREBF1 in lipogenesis (activating number of enzyme genes, such as FASN or ACACA, that are involved in this pathway at the transcriptional level
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in adipose tissue is linked to visceral fat accumulation, impaired insulin sensitivity, increased circulating fasting insulin, and leading to the development of obesity and type 2 diabetes (Berndt 2007)
    tumoral     --over  
    in several neoplasms including colorectal adenomas and carcinomas (Kearney 2009)
    tumoral     --over  
    in prostate carcinoma (Migita 2009)
    tumoral     --over  
    in uterine leiomyomata
    constitutional   deletion    
    hindered the development and induced the premature involution of the lactating mammary gland and significantly decreased medium- and long-chain fatty acids and total fatty acid contents in the milk
    constitutional     --over  
    in the hearts of humans with end stage cardiomyopathy
    Susceptibility
  • to severe epileptic encephalopathies
  • Variant & Polymorphism other
  • causative role of FASN mutations in severe epileptic encephalopathies
  • Candidate gene
    Marker
  • may serve as a new diagnostic marker of NAFLD (nonalcoholic fatty liver disease)
  • circulating FASN is a biomarker of overnutrition-induced insulin resistance that could provide diagnostic and prognostic advantages by providing insights on the individualized metabolic stress
  • Therapy target
    SystemTypeDisorderPubmed
    cancereye 
    promising strategy in Retinoblastoma therapy
    cancerendocrinethyroid
    FASN and activated AKT1 pathway may be a potential target for therapeutic intervention for the treatment of papillary thyroid cancers
    immunologyinfectious 
    suitable as a therapeutic target in coxsackievirus B3 (CVB3)-induced diseases
    cancerdigestivecolon
    inhibition of FASN upstream of VEGFA and other angiogenic pathways can be a novel therapeutic strategy to prevent or inhibit metastasis in colorectal cancer
    digestiveliver 
    therapeutic target for the progression of NAFLD (nonalcoholic fatty liver disease)
    ANIMAL & CELL MODELS
  • conditional deletion of Fasn in mouse neural stem and progenitor cells (NSPCs) impairs adult neurogenesis