hcs1 (SPAC4F8.14c; UniProt P54874) encodes 3-hydroxy-3-methylglutaryl-CoA synthase (EC 2.3.3.10). It condenses acetoacetyl-CoA with acetyl-CoA to give HMG-CoA, the second step of the mevalonate pathway. hcs1 is a single-copy essential gene, and disruptants grow only when mevalonate is supplied. The enzyme is cytosolic in a genome-wide screen.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004421 hydroxymethylglutaryl-CoA synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference from characterised HMG-CoA synthases; sound. Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0004421 hydroxymethylglutaryl-CoA synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/RHEA mapping; consistent. Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0004421 hydroxymethylglutaryl-CoA synthase activity | IMP PMID:8750242 Molecular cloning and sequencing of the hcs gene, which enco... | ACCEPT | Summary: hcs disruption is lethal and rescued by mevalonate, consistent with loss of HMG-CoA synthase. Supporting Evidence: PMID:8750242 hcs-defective mutant could be grown on a medium containing 5 mg/ml mevalonate PMID:8750242 suggesting that the hcs gene is essential for growth |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: ORFeome YFP screen recorded nuclear signal for hcs1. Soluble metabolic enzymes often show diffuse nucleocytoplasmic signal in this screen; no nuclear role is known. Reason: Experimental HDA kept, but not part of the core function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005783 endoplasmic reticulum | IC PMID:8750242 Molecular cloning and sequencing of the hcs gene, which enco... | KEEP AS NON CORE | Summary: Curator inference of ER from the ergosterol pathway. HMG-CoA synthase is soluble and cytosolic in fungi, and the screen places hcs1 in the cytosol. The ER is where the pathway continues, but not where this enzyme acts. Reason: Location inferred from pathway context rather than shown for the enzyme. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP screen placed hcs1 in the cytosol, consistent with a soluble metabolic enzyme. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0006084 acetyl-CoA metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: HMGCS consumes acetyl-CoA; acetyl-CoA metabolism is correct but not informative. Kept non-core, as in the S. cerevisiae ERG13 review. Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0006084 acetyl-CoA metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping; as above. Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0006084 acetyl-CoA metabolic process | IMP PMID:8750242 Molecular cloning and sequencing of the hcs gene, which enco... | KEEP AS NON CORE | Summary: Mevalonate-rescuable lethality; the more informative process is mevalonate-pathway IPP synthesis. Supporting Evidence: PMID:8750242 hcs-defective mutant could be grown on a medium containing 5 mg/ml mevalonate |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference (fungal node seeded by the S. cerevisiae ortholog); the enzyme supplies mevalonate-pathway isoprenoid units for ergosterol, consistent with the S. cerevisiae review. Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: Correct but broad parent of mevalonate-pathway isoprenoid synthesis, which is also annotated. Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro-derived parent of the specific activity, which is already annotated. Reason: Too general. Proposed replacements: hydroxymethylglutaryl-CoA synthase activity Supporting Evidence: file:SCHPO/hcs1/hcs1-uniprot.txt (PubMed:8750242). Hcs1 condenses acetyl-CoA with acetoacetyl-CoA to |
| GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process | IMP PMID:8750242 Molecular cloning and sequencing of the hcs gene, which enco... | KEEP AS NON CORE | Summary: Curator inference that the enzyme acts upstream in FPP biosynthesis. Correct pathway context, but the enzyme does not make FPP; its direct process is mevalonate-pathway IPP synthesis. Supporting Evidence: PMID:8750242 hcs-defective mutant could be grown on a medium containing 5 mg/ml mevalonate |
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