ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 88,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq]
Function:
ATP citrate-lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. Has a central role in de novo lipid synthesis. In nervous tissue it may be involved in the biosynthesis of acetylcholine.
Subunit:
Homotetramer.
Subcellular Location:
Cytoplasm.
Post-translational modifications:
ISGylated.
Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF. Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites. Acetylation promotes de novo lipid synthesis. Deacetylated by SIRT2.
Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site.
Similarity:
In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.
In the SLCterminal section; belongs to the succinate/malate CoA ligase alpha subunit family.
SWISS:
P53396
Gene ID:
47
Database links:
Entrez Gene: 47 Human
Entrez Gene: 104112 Mouse
Entrez Gene: 24159 Rat
Omim: 108728 Human
SwissProt: P53396 Human
SwissProt: Q91V92 Mouse
SwissProt: P16638 Rat
Unigene: 387567 Human
Unigene: 282039 Mouse
Unigene: 29771 Rat
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