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FLASH GENE

Symbol

FASN

contributors: mct/npt - updated : 27-05-2017

HGNC name	fatty acid synthase
HGNC id	3594

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004104 43 - 8481 NP_004095 273.3 2511 - 2003 12882974

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     highly   liver         Nervous brain limbic system hippocampus dentate gyrus   Mus musculus Reproductive female system ovary         female system breast mammary gland   highly Skin/Tegument skin       highly Visual eye

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer eye   promising strategy in Retinoblastoma therapy cancer endocrine thyroid FASN and activated AKT1 pathway may be a potential target for therapeutic intervention for the treatment of papillary thyroid cancers immunology infectious   suitable as a therapeutic target in coxsackievirus B3 (CVB3)-induced diseases cancer digestive colon inhibition of FASN upstream of VEGFA and other angiogenic pathways can be a novel therapeutic strategy to prevent or inhibit metastasis in colorectal cancer digestive liver   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