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MT000012

UniProt Annotations

Entry Information

Gene Name	ATP citrate lyase
Protein Entry	ACLY_HUMAN
UniProt ID	P53396
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P53396-1; Sequence=Displayed; Name=2; IsoId=P53396-2; Sequence=VSP_042201; Name=3; IsoId=P53396-3; Sequence=VSP_057230, VSP_042201; Note=No experimental confirmation available;
Catalytic Activity	ADP + phosphate + acetyl-CoA + oxaloacetate = ATP + citrate + CoA.
Cofactor	Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation	Phosphorylation results in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal to hyperbolic. Fructose 6-phosphate (F6P) is also a potent activator. {ECO:0000269\|PubMed:10653665}.
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. {ECO:0000269\|PubMed:23932781}.
Ptm	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. {ECO:0000269\|PubMed:19608861, ECO:0000269\|PubMed:23932781}.
Ptm	ISGylated. {ECO:0000269\|PubMed:16139798}.
Ptm	Ubiquitinated at Lys-540, Lys-546 and Lys-554 by UBR4, leading to its degradation. Ubiquitination is probably inhibited by acetylation at same site (Probable). {ECO:0000305\|PubMed:19608861, ECO:0000305\|PubMed:23932781}.
Similarity	Contains 1 ATP-grasp domain. {ECO:0000305}.
Similarity	In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family. {ECO:0000305}.
Similarity	In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family. {ECO:0000305}.
Subcellular Location	Cytoplasm.
Subunit	Homotetramer. {ECO:0000269\|PubMed:20558738, ECO:0000269\|PubMed:22102020}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ACLYID50486ch17q21.html";