Cloned (Comment) | Organism |
---|---|
gene Aacs, recombinant expression of FLAG-tagged enzyme in Lenti-X-293T cells, overexpression of wild-type and mutant enzymes in HEK-293 cells | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
N320Q | site-directed mutagenesis, the mutant is not cleaved by legumain | Mus musculus |
N449Q | site-directed mutagenesis, the mutant is not cleaved by legumain | Mus musculus |
N500Q | site-directed mutagenesis, the mutant is cleaved by legumain | Mus musculus |
N503Q | site-directed mutagenesis, the mutant iscleaved by legumain, but the mutation abolishes the formation of the 56-kDa band through cleavage by legumain | Mus musculus |
N545Q | site-directed mutagenesis, catalytically inactive mutant, that is cleaved by legumain | Mus musculus |
N547Q | site-directed mutagenesis, the mutant iscleaved by legumain, but the mutation abolishes the formation of the 56-kDa band through cleavage by legumain | Mus musculus |
General Stability | Organism |
---|---|
acetoacetyl-CoA synthetase (AACS) is cleaved by legumain, a lysosomal asparaginyl endopeptidase. Asn547 is the specific cleavage site of AACS in mouse livers. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + acetoacetate + CoA | Mus musculus | - |
AMP + diphosphate + acetoacetyl-CoA | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | Q9D2R0 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | site-specific cleavage at residue AACS Asn503 and Asn547 of acetoacetyl-CoA synthetase by recombinant autoactivated legumain, a lysosomal asparaginyl endopeptidase, at pH 5.0 and 30°C. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA. AACS is cleaved by legumain in the liver and the kidney to give two primary bands of approximately 56 kDa and 48 kDa, AACS (1-547) and AACS (1-503) are approximately 56 kDa and 55 kDa, respectively. The cleavage site for the formation of the 56-kDa product is located in the C-terminal side region from amino acid 487, whereas that of the 48-kDa product is located in the N-terminal side region from amino acid 468 | Mus musculus |
Purification (Comment) | Organism |
---|---|
- |
Mus musculus |
recombinant FLAG-tagged enzyme from Lenti-X-293T cells by affinity chromatography and ultrafiltration | Mus musculus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
commercial preparation | - |
Mus musculus | - |
kidney | - |
Mus musculus | - |
liver | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + acetoacetate + CoA | - |
Mus musculus | AMP + diphosphate + acetoacetyl-CoA | - |
? |
Synonyms | Comment | Organism |
---|---|---|
AACS | - |
Mus musculus |
Acetoacetyl-CoA synthetase | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
30 | - |
assay at | Mus musculus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | overexpression of recombinant mutants N500Q, N503Q, or N547Q, as well as of the wild-type enzyme, increases the ketone body-utilizing activity of HEK-293 cells, but that of N545Q does not. Overexpression of wild-type AACS, N500Q, or N503Q has no effect on legumain activity, but mutations N545Q and N547Q significantly reduce the activity compared to wild-type | Mus musculus |
metabolism | acetoacetyl-CoA synthetase (AACS) is responsible for the synthesis of cholesterol and fatty acids. It is cleaved by legumain, a lysosomal asparaginyl endopeptidase. Asn547 is the specific cleavage site of AACS in mouse livers. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA. Overexpression of the cleaved form of AACS (1-547) increases the protein expression of caveolin-1, the principal component of the caveolae. Cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes | Mus musculus |
additional information | site-specific cleavage at residue Asn547 of acetoacetyl-CoA synthetase by legumain, a lysosomal asparaginyl endopeptidase. The cleaved form of AACS (1-547) loses the ability to convert acetoacetate to acetoacetyl-CoA | Mus musculus |
physiological function | acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme and is responsible for the synthesis of cholesterol and fatty acids. Overexpression of wild-type AACS and AACS (1-547) increased the protein expression of caveolin-1, a scaffolding protein and the principal component of the caveolae, in the cytosol of liver cells. Enzyme AACS has a unique role in caveolae/lipid rafts | Mus musculus |
physiological function | hydrodynamics-based gene transduction shows that overexpression of AACS (1547) increases the protein expression of caveolin-1, the principal component of the caveolae. Cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes | Mus musculus |