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FLASH GENE
Symbol ACLY contributors: mct - updated : 17-07-2017
HGNC name ATP citrate lyase
HGNC id 115
Location 17q21.2      Physical location : 40.023.180 - 40.075.272
Synonym symbol(s) ATPCL, CLATP, ACL
EC.number 2.3.3.8
DNA
TYPE functioning gene
STRUCTURE 63.62 kb     29 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Map cen - ERBB2 - RARA RARA - TOP2A - GAST - ACLY - D17S856 - D17S855 - PPY - qter
Authors Couch (94)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
28 - 4339 - 1145 - 2015 26452058
29 - 4369 - 1155 - 2015 26452058
28 - 4420 - 1091 - 2015 26452058
29 - 4450 - 1101 - 2015 26452058
EXPRESSION
Type ubiquitous
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinesmall intestine  highly
Reproductivefemale systemuteruscervix highly
Urinarybladder   highly
Visualeye   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , tetramer
HOMOLOGY
Homologene
FAMILY
CATEGORY enzyme
SUBCELLULAR LOCALIZATION     intracellular
intracellular,cytoplasm
basic FUNCTION
  • ATP-citrate lyase, used as a substrate for synthesis of the cytosolic acetyl-CoA
  • having a central role in lipid synthesis
  • in nervous tissue it may be involved in the biosynthesis of acetylcholine
  • ACL activity is required to link growth factor-induced increases in nutrient metabolism to the regulation of histone acetylation and gene
  • ACLY expression and activity can be suppressed by exogenous lipids, demonstrating a critical role for ACLY in pancreatic beta cell survival
  • is likely important for the pyruvate citrate shuttle and lipid synthesis in insulin secretion
  • direct role for ACLY in macrophage inflammatory metabolism
  • potential function of ACLY in cellular senescence and tumorigenesis
  • cytosolic enzyme that catalyzes mitochondria-derived citrate into oxaloacetate and acetyl-CoA
  • ACACA and ACLY regulate the levels of ETV4 under hypoxia via increased alpha-ketoglutarate
  • controls a glucose-to-acetate metabolic switch
  • critical enzyme linking glucose catabolism to lipogenesis by providing acetyl-CoA from mitochondrial citrate for fatty acid and cholesterol biosynthesis
  • key enzyme linking aerobic glycolysis and fatty acid synthesis that is of high biological and prognostic significance in breast cancer
  • facilitates histone acetylation at double-strand break (DSB) sites, impairing TP53BP1 localization and enabling BRCA1 recruitment and DNA repair by homologous recombination
  • the spatial and temporal control of acetyl-CoA production by ACLY participates in the mechanism of DNA repair pathway choice
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text lipogenic cholesterologenesis
    PATHWAY
    metabolism energetic , lipid/lipoprotein
    signaling
  • tricarboxylic cycle
  • activation of the IGF1/ACLy/cardiolipin pathway combines anabolic signaling with induction of mechanisms needed to provide required ATP
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction between MORC2 and adenosine triphosphate (ATP)-citrate lyase (ACLY), an enzyme that catalyzes the formation of acetyl-coA and plays a central role in lipogenesis, cholesterogenesis, and histone acetylation
  • ACLY physically interacted with the catalytic subunit of AMP-activated protein kinase (AMPK) and inhibited AMPK activity
  • ACLY phosphorylation and nuclear localization are necessary for its role in promoting BRCA1 recruitment
  • cell & other
    REGULATION
    induced by IGF1 inducing activation of ACLY in an AKT1-dependent fashion
    Phosphorylated by nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia telangiectasia mutated (ATM) and AKT following DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer tissue compared with normal tissue
    tumoral        
    resulted in elevated expression of acyl-CoA synthetase short-chain family member 2 (ACSS2), an enzyme that also produces acetyl-CoA using acetate as a substrate, suggesting its role in cancer cell growth
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    is a major new target in cardiovascular medicine
    ANIMAL & CELL MODELS