ACS1 encodes the "aerobic" isozyme of acetyl-coenzyme A synthetase (EC 6.2.1.1), an AMP-forming acyl-CoA synthetase that converts acetate, ATP and CoA to acetyl-CoA, AMP and diphosphate. Compared with Acs2p it has a ~30-fold lower Km for acetate and can also activate propionate. ACS1 is subject to glucose (and ethanol) repression and is induced on non-fermentable carbon sources and in stationary phase; acs1 mutants cannot grow on acetate but still grow on ethanol because Acs2p compensates. Acs1p functions in the nucleocytosolic compartment as part of the pyruvate dehydrogenase bypass (pyruvate -> acetaldehyde -> acetate -> acetyl-CoA) and can supply acetyl-CoA for histone acetylation when cells grow on glycerol/ethanol; a fraction has also been detected in mitochondrial proteomes. The protein is inactivated and degraded upon glucose addition. During meiosis Acs1p polymerises into filaments in the nucleoplasm and cytoplasm; this polymerisation helps chronologically aged spores recover and starved cells re-enter the cell cycle.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003987 acetyl-CoA synthetase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PANTHER node PTN000644161 (acetyl-CoA synthetase clade; donors include both yeast ACS genes, mouse/rat ACSS1/ACSS2 and E. coli Acs). ACS1 lies inside this clade and retains every catalytic motif of the AMP-forming acetyl-CoA synthetases; its own activity is shown experimentally (IDA, PMID:8910545). The appearance of ACS1 among the donors reflects that experimental grounding, not circularity. Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate; PMID:8910545 Saccharomyces cerevisiae contains two structural genes, ACS1 and ACS2, each encoding an active acetyl-coenzyme A synthetase. |
| GO:0003987 acetyl-CoA synthetase activity | IDA PMID:8910545 The two acetyl-coenzyme A synthetases of Saccharomyces cerev... | ACCEPT | Summary: IDA: van den Berg et al. characterised acetyl-CoA synthetase activity in extracts of strains expressing only ACS1 (or only ACS2) and measured kinetic constants; this is the defining activity of the gene product (EC 6.2.1.1). Supporting Evidence: PMID:8910545 Saccharomyces cerevisiae contains two structural genes, ACS1 and ACS2, each encoding an active acetyl-coenzyme A synthetase. PMID:8910545 The Km for acetate of Acs1p was about 30-fold lower than that of Acs2p and Acs1p, but not Acs2p, could use propionate as a substrate. |
| GO:0003987 acetyl-CoA synthetase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (GO_REF:0000120) combining InterPro IPR011904 (acetate-CoA ligase), RHEA:23176 and EC 6.2.1.1. The mapping is correct for ACS1; redundant with the IDA row. Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate; |
| GO:0003987 acetyl-CoA synthetase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from acetate utilization (ACETATEUTIL2-PWY), assigning the acetate + ATP + CoA -> acetyl-CoA + AMP + PPi step to ACS1. Correct activity, supported by IDA for ACS1. Supporting Evidence: PMID:8910545 Saccharomyces cerevisiae contains two structural genes, ACS1 and ACS2, each encoding an active acetyl-coenzyme A synthetase. |
| GO:0003987 acetyl-CoA synthetase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from ethanol degradation (PWY3O-4300), whose last step activates acetate to acetyl-CoA. The activity is correct for ACS1; whether the gene is physiologically important for ethanol catabolism is assessed on the BP row. Supporting Evidence: PMID:8910545 Saccharomyces cerevisiae contains two structural genes, ACS1 and ACS2, each encoding an active acetyl-coenzyme A synthetase. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular-location mapping (SL-0191 Nucleus). Takahashi et al. showed that Acs1p, like Acs2p, supplies nucleocytosolic acetyl-CoA used by histone acetyltransferases when cells grow on non-fermentable carbon, consistent with a nuclear pool of the enzyme. Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt Mitochondrion. Nucleus. PMID:16857587 In glycerol with ethanol, Acs1p is an alternate acetyl-CoA source for HATs. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0086 Cytoplasm). Correct but general; the more specific cytosol annotation is supported by IDA (PMID:9711835). Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt SUBCELLULAR LOCATION: Microsome {ECO:0000305}. Cytoplasm. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | KEEP AS NON CORE | Summary: HDA: Acs1p was detected in the high-purity mitochondrial proteome of Sickmann et al. Acs1p has an alternative upstream start codon and has been reported in several compartments (UniProt lists microsome, cytoplasm, mitochondrion, nucleus). A mitochondrial pool is plausible but Takahashi et al. found mitochondrial and nucleocytosolic acetyl-CoA pools to be biochemically isolated, and the physiologically important Acs1p activity is extramitochondrial. Retained as a non-core location. Supporting Evidence: PMID:14576278 From >20 million MS spectra, 750 different proteins were identified file:yeast/ACS1/ACS1-uniprot.txt Mitochondrion. Nucleus. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | KEEP AS NON CORE | Summary: HDA: Acs1p identified in the expanded PROMITO mitochondrial proteome. Same considerations as the other mitochondrial proteomics row: plausible minor pool, not the compartment of its main metabolic role. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: IEA from UniProt subcellular location (SL-0173 Mitochondrion), itself based on the proteomics data. Kept as non-core for the same reasons. Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt Mitochondrion. Nucleus. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN001185784, a node seeded by both yeast ACS genes) placing activity in the cytosol. Acs1p acts in the nucleocytosolic compartment to provide acetyl-CoA; consistent with IDA for cytosol. Supporting Evidence: PMID:16857587 Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. |
| GO:0005829 cytosol | IDA PMID:9711835 Overproduction of acetyl-coenzyme A synthetase isoenzymes in... | ACCEPT | Summary: IDA from de Jong-Gubbels et al. (abstract-only in cache; the localization data are presumably in the full text, which the curator read). Cytosolic Acs1p is consistent with its role in the PDH bypass and with the nucleocytosolic acetyl-CoA pool described by Takahashi et al. Supporting Evidence: PMID:9711835 the ACS1 and ACS2 genes were introduced on multi-copy plasmids PMID:16857587 Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA model ARBA00029243 (cytosol for acetyl-CoA synthetases). Correct for Acs1p. Supporting Evidence: PMID:16857587 Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA placing the acetate utilization acetyl-CoA synthetase step in the cytosol; consistent with IDA. Supporting Evidence: PMID:16857587 Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA placing the ethanol-degradation acetyl-CoA synthetase step in the cytosol; consistent with IDA. Supporting Evidence: PMID:16857587 Yeast mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated. |
| GO:0006068 ethanol catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA from ethanol degradation (PWY3O-4300: ethanol -> acetaldehyde -> acetate -> acetyl-CoA). Acs1p does catalyse the terminal step of this route, so the assignment is mechanistically sound, but acs1 null mutants still grow on ethanol because Acs2p provides the activity; the gene is better described by acetyl-CoA biosynthesis from acetate. Supporting Evidence: PMID:1363452 disruption of the ACS1 gene did not affect growth on media containing ethanol as the sole carbon source |
| GO:0006085 acetyl-CoA biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the acetyl-CoA synthetase clade (PTN000644161). Acetyl-CoA formation from acetate is the direct product of the enzyme; ACS1 has its own experimental support. Supporting Evidence: PMID:8910545 Saccharomyces cerevisiae contains two structural genes, ACS1 and ACS2, each encoding an active acetyl-coenzyme A synthetase. |
| GO:0006085 acetyl-CoA biosynthetic process | IDA PMID:8910545 The two acetyl-coenzyme A synthetases of Saccharomyces cerev... | ACCEPT | Summary: IDA: enzymatic acetyl-CoA formation by Acs1p in cell-free extracts. Core process for this enzyme (nucleocytosolic acetyl-CoA supply via the PDH bypass and acetate assimilation). Supporting Evidence: PMID:8910545 The Km for acetate of Acs1p was about 30-fold lower than that of Acs2p and Acs1p, but not Acs2p, could use propionate as a substrate. |
| GO:0006085 acetyl-CoA biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (ARBA00027592 and InterPro IPR011904 acetate-CoA ligase). Correct for ACS1; redundant with IDA. Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate; |
| GO:0006085 acetyl-CoA biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA from acetate utilization (ACETATEUTIL2-PWY). Correct and core. Supporting Evidence: PMID:1363452 As expected, the mutant was unable to grow on acetate as sole carbon source. |
| GO:0016208 AMP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: IEA from InterPro2GO (IPR011904). AMP-forming acetyl-CoA synthetases proceed via an acetyl-AMP intermediate and release AMP, so AMP binding is a mechanistic consequence of the catalytic activity rather than an independent function. Not wrong, but not informative beyond GO:0003987. Supporting Evidence: file:yeast/ACS1/ACS1-uniprot.txt Reaction=acetate + ATP + CoA = acetyl-CoA + AMP + diphosphate; |
| GO:0016880 acid-ammonia (or amide) ligase activity | IDA PMID:18305111 Discovery of amide (peptide) bond synthetic activity in Acyl... | KEEP AS NON CORE | Summary: IDA from Abe et al., who discovered that adenylate-forming acyl-CoA synthetases, including an acetyl-CoA synthetase, form N-acyl-cysteine amide bonds when L-cysteine replaces CoA. This is an in vitro side reaction of the adenylate intermediate with a non-physiological acceptor; no in vivo role is known. The abstract does not name the source of the acetyl-CoA synthetase; deferring to the curator on the identity, it is retained as a non-core, promiscuous activity. Supporting Evidence: PMID:18305111 this unexpected enzyme activity was also observed for acetyl-CoA synthetase and firefly luciferase PMID:18305111 When l-cysteine was used as a substrate instead of CoA, N-acyl-l-cysteine was surprisingly detected as a reaction product. |
| GO:0016880 acid-ammonia (or amide) ligase activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IEA from ARBA model ARBA00089271, which generalises the in vitro amide-bond side activity (PMID:18305111) to acetyl-CoA synthetases. Propagating a non-physiological promiscuous activity across the family is an over-generalisation, but the activity is experimentally observed for acetyl-CoA synthetase (IDA row), so it is kept consistently as non-core rather than removed. Supporting Evidence: PMID:18305111 When l-cysteine was used as a substrate instead of CoA, N-acyl-l-cysteine was surprisingly detected as a reaction product. |
| GO:0019654 pyruvate fermentation to acetate | IMP PMID:1363452 Cloning and disruption of a gene required for growth on acet... | MODIFY | Summary: IMP: De Virgilio et al. showed that acs1 disruption abolishes growth on acetate as sole carbon source. GO:0019654 "pyruvate fermentation to acetate" names an anaerobic, ATP-yielding route that ends in acetate; Acs1p does not take part in producing acetate but activates acetate to acetyl-CoA during aerobic growth on acetate. The phenotype supports a role in acetate catabolism (utilisation of acetate as carbon source). Reason: Wrong direction/pathway: the mutant phenotype is failure to assimilate acetate, not failure to form it by fermentation. Replace with acetate catabolic process. Proposed replacements: acetate catabolic process Supporting Evidence: PMID:1363452 As expected, the mutant was unable to grow on acetate as sole carbon source. |
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Download this section (compressed HTML)Q: Is the mitochondrial pool of Acs1p detected by proteomics catalytically relevant, given that mitochondrial and nucleocytosolic acetyl-CoA pools are biochemically isolated?
Experiment: Compartment-restricted (NLS/NES or mitochondrial-targeted) ACS1 alleles in an acs2-ts background to test which Acs1p pool supports acetate growth and histone acetylation.
Acetyl-coA synthetase isoform; along with Acs2p, acetyl-CoA synthetase isoform is the nuclear source of acetyl-coA for histone acetylation; expressed during growth on nonfermentable carbon sources and under aerobic conditions; metabolites mediate the formation of filament assemblies in meiotic cells, storing Acs1p in an inactive state and promoting efficient return to growth after starvation
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