ERG10 encodes the cytosolic acetoacetyl-CoA thiolase (acetyl-CoA C-acetyltransferase, EC 2.3.1.9) of Saccharomyces cerevisiae, a homotetrameric member of the thiolase family with conserved active-site cysteines (C91, C384). Erg10 catalyses the Claisen condensation of two acetyl-CoA molecules to acetoacetyl-CoA, the first committed step of the mevalonate pathway that supplies isoprenoid precursors for ergosterol, dolichol, ubiquinone and prenylated proteins. ERG10 is a single-copy essential gene; null alleles abolish acetoacetyl-CoA thiolase activity and cause mevalonate auxotrophy. Its expression rises when cellular sterol levels are low and in the cold.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003985 acetyl-CoA C-acetyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the acetoacetyl-CoA thiolase node PTN000432378 (cytosolic ACAT2-type thiolases, seeded with Erg10 itself among others). Erg10 has direct biochemical and genetic evidence for this activity, so the inherited assignment is correct. Supporting Evidence: PMID:7989303 null alleles of ERG10 produced no detectable acetoacetyl-CoA thiolase enzyme activity file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | IDA PMID:5571829 Two forms of acetoacetyl coenzyme A thiolase in yeast. I. Se... | ACCEPT | Summary: Kornblatt & Rudney separated and characterised the yeast acetoacetyl-CoA thiolase activities (kinetic constants cited by UniProt). Abstract not cached; the activity is fully corroborated by the later ERG10 cloning work, so the curator's IDA is accepted. Supporting Evidence: PMID:5571829 Two forms of acetoacetyl coenzyme A thiolase in yeast. I. Separation and properties. file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | IDA PMID:7989303 ERG10 from Saccharomyces cerevisiae encodes acetoacetyl-CoA ... | ACCEPT | Summary: Hiser et al. showed thiolase activity scales with ERG10 copy number and is absent in null alleles; this is the defining experiment for Erg10 as the acetoacetyl-CoA thiolase. Core MF. Supporting Evidence: PMID:7989303 null alleles of ERG10 produced no detectable acetoacetyl-CoA thiolase enzyme activity PMID:7989303 Acetoacetyl-CoA thiolase activity corresponded to the number of copies of ERG10 present in cell extracts |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from RHEA:21036 / EC 2.3.1.9, matching the UniProt catalytic-activity record for Erg10; correct. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways ERGOSTEROL-SYN-PWY-1 (superpathway of ergosterol biosynthesis), in which Erg10 catalyses the acetyl-CoA condensation; correct MF. Supporting Evidence: PMID:7989303 null alleles of ERG10 produced no detectable acetoacetyl-CoA thiolase enzyme activity |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways IPPSYN-PWY (isopentenyl diphosphate biosynthesis, mevalonate route); Erg10 performs step 1; correct. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Metabolic intermediate biosynthesis; (R)-mevalonate |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-5177 (glutaryl-CoA degradation), where the thiolase reaction is drawn in the cleavage direction. The MF term itself (the reversible thiolase reaction) is correct for Erg10 even though the pathway context is doubtful in yeast (see the BP row from the same pathway). Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, |
| GO:0003985 acetyl-CoA C-acetyltransferase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY-922 (mevalonate pathway I); Erg10 catalyses its first step; correct. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Metabolic intermediate biosynthesis; (R)-mevalonate |
| GO:0005634 nucleus | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: Huh et al. genome-wide GFP survey scored Erg10-GFP in the nucleus (in addition to cytoplasm). Small soluble enzymes often give diffuse nucleocytoplasmic signal; no nuclear function is known, so this is retained only as a non-core location. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories |
| GO:0005737 cytoplasm | IDA PMID:5571830 Two forms of acetoacetyl coenzyme A thiolase in yeast. II. I... | ACCEPT | Summary: Kornblatt & Rudney (part II) fractionated yeast thiolases and placed the Erg10-type acetoacetyl-CoA thiolase in the cytosolic (extramitochondrial) fraction; consistent with the cytoplasmic assignment in Hiser et al. Supporting Evidence: PMID:5571830 Intracellular location PMID:7989303 was demonstrated to encode cytoplasmic aceto-acetyl-CoA thiolase |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning IEA for cytoplasm; correct but less specific than the experimentally supported cytosol. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005773 vacuole | NAS PMID:28904410 Recent Advances in Ergosterol Biosynthesis and Regulation Me... | REMOVE | Summary: NAS 'is_active_in vacuole' attributed to a 2017 ergosterol review. The cached text of this review contains no statement placing Erg10 in the vacuole, and all experimental data (fractionation, cloning study, UniProt) place the thiolase in the cytosol, where the mevalonate pathway starts. A vacuolar site of activity is unsupported and contradicted. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol PMID:7989303 was demonstrated to encode cytoplasmic aceto-acetyl-CoA thiolase |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (Cytoplasm, cytosol; from PMID:5571830) to cytosol; correct and the primary location. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: is_active_in cytosol from YeastPathways ERGOSTEROL-SYN-PWY-1; consistent with experimental cytosolic location of Erg10. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: is_active_in cytosol from YeastPathways IPPSYN-PWY; consistent with experimental cytosolic location. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: is_active_in cytosol from YeastPathways PWY-5177; the location is right for Erg10 even though the glutaryl-CoA degradation context is doubtful. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: is_active_in cytosol from YeastPathways PWY-922 (mevalonate pathway); correct. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from fungal node PTN001052717 seeded by Erg10; Erg10 supplies acetoacetyl-CoA for the mevalonate branch that feeds ergosterol synthesis; correct. Supporting Evidence: PMID:7989303 were isolated in a screen for mevalonate auxotrophs in Saccharomyces cerevisiae PMID:7989303 null alleles of ERG10 produced no detectable acetoacetyl-CoA thiolase enzyme activity |
| GO:0006696 ergosterol biosynthetic process | IDA PMID:5571829 Two forms of acetoacetyl coenzyme A thiolase in yeast. I. Se... | ACCEPT | Summary: Curator IDA from the Kornblatt & Rudney biochemical characterisation of the thiolase (abstract not cached). Erg10 activity is the entry step to sterol synthesis; accepted, deferring to the curator. Supporting Evidence: PMID:5571829 Two forms of acetoacetyl coenzyme A thiolase in yeast. I. Separation and properties. file:yeast/ERG10/ERG10-uniprot.txt Metabolic intermediate biosynthesis; (R)-mevalonate |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:200835 Ertosterol biosynthesis in Saccharomyces cerevisiae: mutants... | ACCEPT | Summary: Karst & Lacroute isolated thermosensitive ergosterol-auxotrophic mutants in early pathway steps. The cached abstract assigns their 'erg10' complementation group to squalene synthetase deficiency, reflecting historic allele nomenclature, so the cached text cannot confirm the exact gene; full text not available. The BP itself is correct for ERG10 (mevalonate auxotrophs, essential thiolase), so the curator's IMP is accepted. Supporting Evidence: PMID:200835 Thermosensitive mutants, auxotrophic for ergosterol synthesis, have been isolated PMID:7989303 were isolated in a screen for mevalonate auxotrophs in Saccharomyces cerevisiae |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways ERGOSTEROL-SYN-PWY-1; Erg10 catalyses the first step; correct. Supporting Evidence: PMID:7989303 null alleles of ERG10 produced no detectable acetoacetyl-CoA thiolase enzyme activity |
| GO:0008299 isoprenoid biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: RCA from YeastPathways IPPSYN-PWY. Correct but general; Erg10 acts specifically in the mevalonate route to isopentenyl diphosphate, for which a more precise term exists. Proposed replacements: isopentenyl diphosphate biosynthetic process, mevalonate pathway Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Metabolic intermediate biosynthesis; (R)-mevalonate PMID:7989303 were isolated in a screen for mevalonate auxotrophs in Saccharomyces cerevisiae |
| GO:0016740 transferase activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA to generic 'transferase activity'; true but uninformative given the precisely known thiolase reaction. Proposed replacements: acetyl-CoA C-acetyltransferase activity Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro thiolase-like superfamily (IPR016039) mapping to 'acyltransferase activity'; correct parent, but the specific activity is known. Proposed replacements: acetyl-CoA C-acetyltransferase activity Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | MODIFY | Summary: InterPro thiolase family signatures mapped to 'acyltransferase activity, transferring groups other than amino-acyl groups'; correct parent of the specific acetoacetyl-CoA thiolase activity. Proposed replacements: acetyl-CoA C-acetyltransferase activity Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt Reaction=2 acetyl-CoA = acetoacetyl-CoA + CoA; Xref=Rhea:RHEA:21036, PMID:7989303 This identity included the active site cysteines located at amino acids 91 and 384 in the Erg10 protein. |
| GO:0046395 carboxylic acid catabolic process | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways PWY-5177 (glutaryl-CoA degradation, part of lysine catabolism templates), which uses the thiolase in the acetoacetyl-CoA cleavage direction. There is no yeast-specific evidence that Erg10 participates in glutaryl-CoA/lysine catabolism; its physiological direction is acetoacetyl-CoA synthesis for the mevalonate pathway. Likely a pathway-template inference rather than a real role. Supporting Evidence: file:yeast/ERG10/ERG10-uniprot.txt PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21037; PMID:7989303 were isolated in a screen for mevalonate auxotrophs in Saccharomyces cerevisiae |
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