Q99NB1 · ACS2L_MOUSE
- ProteinAcetyl-coenzyme A synthetase 2-like, mitochondrial
- GeneAcss1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids682 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:11150295, PubMed:16790548).
Acetate is the preferred substrate (PubMed:11150295, PubMed:16790548).
Can also utilize propionate with a much lower affinity (PubMed:11150295).
Provides acetyl-CoA that is utilized mainly for oxidation under ketogenic conditions (PubMed:11150295).
Involved in thermogenesis under ketogenic conditions, using acetate as a vital fuel when carbohydrate availability is insufficient (PubMed:19187775).
Acetate is the preferred substrate (PubMed:11150295, PubMed:16790548).
Can also utilize propionate with a much lower affinity (PubMed:11150295).
Provides acetyl-CoA that is utilized mainly for oxidation under ketogenic conditions (PubMed:11150295).
Involved in thermogenesis under ketogenic conditions, using acetate as a vital fuel when carbohydrate availability is insufficient (PubMed:19187775).
Catalytic activity
- acetate + ATP + CoA = acetyl-CoA + AMP + diphosphateThis reaction proceeds in the forward direction.
Activity regulation
Inhibited by acetylation at Lys-635 and activated by deacetylation mediated by the deacetylase SIRT3.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.06 mM | acetate | |||||
4.1 mM | propionate |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 217-220 | CoA (UniProtKB | ChEBI) | ||||
Sequence: RGGR | ||||||
Binding site | 334 | CoA (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 410-412 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GEP | ||||||
Binding site | 434-439 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DTWWQT | ||||||
Binding site | 526 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 541 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 549 | CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 552 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | acetate-CoA ligase activity | |
Molecular Function | AMP binding | |
Molecular Function | ATP binding | |
Molecular Function | propionate-CoA ligase activity | |
Biological Process | acetate biosynthetic process | |
Biological Process | acetyl-CoA biosynthetic process | |
Biological Process | acetyl-CoA biosynthetic process from acetate | |
Biological Process | propionate biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAcetyl-coenzyme A synthetase 2-like, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ99NB1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
No visible phenotype at birth, but exhibit significant growth retardation at the time of weaning. Attain normal size and weight when fed normally. Exhibit hypothermia and hypoglycemia when fed high-fat, low-carbohydrate diet, leading to 50% mortality. Display strongly reduced whole-body acetate oxidation when fasting. Fasting adults exhibit hypothermia, reduced capacity to sustain running and low ATP levels.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 33 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-38 | Mitochondrion | ||||
Sequence: MAARSLGSGVGRLLRGLQGRSGQSGWSLSVSRSTATRL | ||||||
Chain | PRO_0000000597 | 39-682 | Acetyl-coenzyme A synthetase 2-like, mitochondrial | |||
Sequence: PGCVPAAAQPGSYPALSAQAAQEPAAFWGPLARDTLVWDTPYHTVWDCDFRTGKIGWFLGGQLNVSVNCLDQHVQKSPETIALIWERDEPGTEVRITYRELLETTCRLANTLKRHGVHRGDRVAIYMPVSPLAVAAMLACARIGAIHTVVFAGFSAESLAGRINDAKCKAVITFNQGLRGGRVVELKKIVDEAVKSCPTVQHVLVAHRTDTKVPMGSLDIPLEQEMAKEAPVCTPESMSSEDMLFMLYTSGSTGTPKGLVHTQAGYLLYAAMTHKLVFDYQPGDVFGCVADIGWITGHSYVVYGPLCNGATTVLFESTPVYPDAGRYWETVQRLKINQFYGAPTAVRLLLKYGDAWVKKYDRSSLRTLGSVGEPINHEAWEWLHKVVGDGRCTLVDTWWQTETGGICIAPRPSEDGAEILPGMAMRPFFGIVPVLMDEKGNVLEGGDVSGALCISQAWPGMARTIYGDHQRFVDAYFRAYPGYYFTGDGAHRTEGGYYQITGRMDDVINISGHRLGTAEIEDAMADHPAVPETAVIGYPHDIKGEAAFAFIVLKDNISDENMVVNELKLSVATKIAKYAVPDQILVVKRLPKTRSGKVMRRLLRKIITSRGQDLGDTTTLEDPSVITEILSAFQKYEEQRAATN | ||||||
Modified residue | 389 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 635 | N6-acetyllysine | ||||
Sequence: K |
Post-translational modification
Reversibly acetylated at Lys-635 (PubMed:16790548).
The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylase SIRT3
The acetyl-CoA synthase activity is inhibited by acetylation and activated by deacetylation mediated by the deacetylase SIRT3
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in heart, testis, kidney, skeletal muscle, lung and spleen. Detected at low levels in brain.
Induction
By fasting.
Gene expression databases
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length682
- Mass (Da)74,623
- Last updated2001-06-01 v1
- Checksum1B21981D29F9C8E7
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 332 | in Ref. 3; AAH30930 | ||||
Sequence: W → C |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB046742 EMBL· GenBank· DDBJ | BAB21612.1 EMBL· GenBank· DDBJ | mRNA | ||
AK088244 EMBL· GenBank· DDBJ | BAC40232.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030930 EMBL· GenBank· DDBJ | AAH30930.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |