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FLASH GENE

Symbol

ACLY

contributors: mct - updated : 17-07-2017

HGNC name	ATP citrate lyase
HGNC id	115

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001303275 28 - 4339 NP_001290204 - 1145 - 2015 26452058 NM_001303274 29 - 4369 NP_001290203 - 1155 - 2015 26452058 NM_198830 28 - 4420 NP_942127 - 1091 - 2015 26452058 NM_001096 29 - 4450 NP_001087 - 1101 - 2015 26452058

EXPRESSION

Type	ubiquitous

constitutive of

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 Reproductive female system uterus cervix   highly Urinary bladder       highly Visual eye       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
	CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cardiovascular     is a major new target in cardiovascular medicine cancer lung   negative regulation of ACLY and lipid synthesis is a novel and critical mechanism for CUL3 in tumor suppression

ANIMAL & CELL MODELS