ATP-citrate synthase
GeneName
ACLY
Summary
ACLY, also known as ACL or ATP citrate synthase, is a 121 kDa enzyme that catalyses the conversion of citrate to acetyl-CoA and oxaloacetate, playing a pivotal role in cellular metabolism. It is predominantly expressed in the cytosol and is involved in various biosynthetic processes, including fatty acid and cholesterol biosynthesis. ACLY is also implicated in the regulation of ferroptosis, a form of regulated cell death, highlighting its importance in metabolic pathways and cellular homeostasis.
Importance
ACLY is relevant to: - Metabolic reprogramming in cancer, as it provides acetyl-CoA for lipid synthesis and histone acetylation, influencing cell proliferation and survival - Regulation of lipid metabolism, which has implications in obesity and metabolic disorders - The interplay between metabolism and cell death, particularly in the context of ferroptosis, which is being explored for therapeutic strategies in various diseases - The synthesis of key metabolic intermediates, affecting overall cellular energy balance and function
Top Products
For researchers investigating ACLY, we highly recommend the top-selling recombinant antibody, Anti-ATP citrate lyase antibody [EP704Y] (ab40793). This antibody has been validated in knockout models, ensuring its reliability in various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). With 92 citations, it is well-regarded in the research community, making it an excellent choice for those seeking robust and consistent performance in their studies of ACLY.
Abcam Product Citation Summary
The data indicates that ACLY is being studied in various contexts related to cancer, differentiation, and developmental nutrition. The use of Abcam antibody ab40793 in Western blotting across different species highlights its relevance in understanding ACLY's role in these biological processes.
Abcam Product Citation Table
Function
Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism.
Post-translational modifications
Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (PubMed:10653665). Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation state of Ser-455 (By similarity). Phosphorylation on Ser-455 is decreased by prior phosphorylation on the other 2 residues (By similarity). Phosphorylated at Ser-455 by BCKDK and dephosphorylated by protein phosphatase PPM1K.
ISGylated.
Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF (PubMed:23932781). Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites (PubMed:23932781). Acetylation promotes de novo lipid synthesis (PubMed:23932781). Deacetylated by SIRT2.
Benzoylated at Lys-978 (PubMed:39524354). Debenzoylated by SIRT3; inhibiting the ATP-citrate synthase activity (PubMed:39524354).
Ubiquitinated at Lys-540, Lys-546 and Lys-554 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation (PubMed:23932781, PubMed:27664236, PubMed:34491895). Ubiquitination is probably inhibited by acetylation at same site (PubMed:23932781). BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (PubMed:34491895).
Sequence Similarities
In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.
In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.
Cellular localization
- Cytoplasm
- Cytosol
Alternative names
ATP-citrate synthase, ATP-citrate (pro-S-)-lyase, Citrate cleavage enzyme, ACL, ACLY