ACSS2
GeneName
ACSS2
Summary
ACSS2, also known as ACS or acetyl CoA synthetase, is a 79 kDa enzyme that plays a pivotal role in the conversion of acetate to acetyl-CoA, a central metabolite in cellular metabolism. It is expressed in various cellular compartments including the cytoplasm, cytosol, mitochondrial matrix, and nucleus. ACSS2 is involved in several biological processes such as acetate and propionate biosynthesis, lipid metabolism, and even has implications in long-term memory through its role in acetyl-CoA production. Its functions are mediated by its enzymatic activities, including acetate-CoA ligase and propionate-CoA ligase activities, as well as its ability to bind AMP and ATP, and interact with chromatin as a transcription coactivator.
Importance
ACSS2 is relevant to: - Metabolic regulation, particularly in the context of acetate utilisation and lipid biosynthesis. - Neurobiology, given its involvement in processes related to long-term memory. - Cancer metabolism, as altered acetate metabolism can influence tumour growth and survival. - Potential therapeutic targets in metabolic disorders, where modulation of acetyl-CoA levels may have beneficial effects.
Top Products
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Abcam Product Citation Summary
The data indicates that ACSS2 is being investigated in the context of mesenchymal stem cell-induced stemness and chemoresistance, highlighting its potential role in cancer biology and treatment resistance.
Abcam Product Citation Table
Function
Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:10843999, PubMed:28003429, PubMed:28552616). Acetate is the preferred substrate (PubMed:10843999, PubMed:28003429). Can also utilize propionate with a much lower affinity (By similarity). Nuclear ACSS2 promotes glucose deprivation-induced lysosomal biogenesis and autophagy, tumor cell survival and brain tumorigenesis (PubMed:28552616). Glucose deprivation results in AMPK-mediated phosphorylation of ACSS2 leading to its translocation to the nucleus where it binds to TFEB and locally produces acetyl-CoA for histone acetylation in the promoter regions of TFEB target genes thereby activating their transcription (PubMed:28552616). The regulation of genes associated with autophagy and lysosomal activity through ACSS2 is important for brain tumorigenesis and tumor survival (PubMed:28552616). Acts as a chromatin-bound transcriptional coactivator that up-regulates histone acetylation and expression of neuronal genes (By similarity). Can be recruited to the loci of memory-related neuronal genes to maintain a local acetyl-CoA pool, providing the substrate for histone acetylation and promoting the expression of specific genes, which is essential for maintaining long-term spatial memory (By similarity).
Post-translational modifications
Reversibly acetylated at Lys-661 (By similarity). The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylases SIRT1 and SIRT3 (By similarity).
Glucose deprivation results in its AMPK-dependent phosphorylation at Ser-659, which leads to exposure of its nuclear localization signal, required for its interaction with KPNA1 and subsequent translocation to the nucleus.
Sequence Similarities
Belongs to the ATP-dependent AMP-binding enzyme family.
Cellular localization
- Cytoplasm
- Cytosol
- Cytoplasm
- Nucleus
- Glucose deprivation results in its AMPK-dependent phosphorylation and subsequent nuclear translocation (PubMed:28552616). Phosphorylation at Ser-659, leads to exposure of its nuclear localization signal which is required for its interaction with KPNA1 and subsequent translocation to the nucleus (PubMed:28552616). Found in the cytoplasm in undifferentiated neurons and upon differentiation, translocates to nucleus (By similarity).
Alternative names
ACAS2, ACSS2, Acetate--CoA ligase, Acetyl-CoA synthetase, Acetyl-CoA synthetase 1, Acyl-CoA synthetase short-chain family member 2, Acyl-activating enzyme, Propionate--CoA ligase, ACS, AceCS, AceCS1