erg1 (SPBC713.12) encodes squalene epoxidase (squalene monooxygenase, EC 1.14.14.17) of Schizosaccharomyces pombe, an FAD-dependent, multi-pass ER-membrane flavoenzyme that uses O2 and electrons from NADPH-cytochrome P450 reductase to convert squalene to (S)-2,3-epoxysqualene, the substrate of lanosterol synthase Erg7. It is the first oxygen-requiring step of ergosterol synthesis and the target of allylamine antifungals such as terbinafine; loss or inhibition of Erg1 causes squalene accumulation. Its expression rises under anaerobic conditions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004506 squalene monooxygenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA squalene monooxygenase activity from PTN000089417 (SQLE family, human SQLE, mouse/rat Sqle, C. albicans ERG1 and S. cerevisiae ERG1). erg1 is the single SQLE-family protein of S. pombe; correct. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt SIMILARITY: Belongs to the squalene monooxygenase family. file:SCHPO/erg1/erg1-uniprot.txt Reaction=squalene + reduced [NADPH--hemoprotein reductase] + O2 = (S)- PMID:33223513 Moreover, inhibition of Erg1 leads to the intracellular accumulation of squalene, a toxic metabolite that leads to rapid cell death PMID:23145048 terbinafine significantly decreased lanosterol level and increased squalene level in wild-type cells |
| GO:0004506 squalene monooxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro, RHEA:25282, EC 1.14.14.17); matches the IBA and the squalene-accumulation phenotype. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt Reaction=squalene + reduced [NADPH--hemoprotein reductase] + O2 = (S)- file:SCHPO/erg1/erg1-uniprot.txt DISRUPTION PHENOTYPE: Leads to the accumulation of squalene. |
| GO:0005737 cytoplasm | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | TOO GENERAL | Summary: ORFeome HDA assigned 'cytoplasm'. Since the ER is part of the cytoplasm in GO this is not wrong, but the enzyme is an integral ER-membrane protein and the ER/ER-membrane rows are the informative ones. Reason: Correct by ontology structure but too general relative to the accepted ER and ER-membrane rows. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to |
| GO:0005774 vacuolar membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: UniProt SubCell mapping to vacuolar membrane, which derives from the ORFeome overexpressed-YFP screen. No other evidence places squalene epoxidase in the vacuole and its substrate/partners (squalene, CPR ccr1, Erg7) are ER-resident; a vacuolar rim signal for an overexpressed polytopic ER protein is more likely turnover/mislocalisation than a site of activity. Reason: Single high-throughput observation; not a site of function. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to |
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome HDA ER localisation; consistent with the multi-pass ER enzyme. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in ER (PTN000089417; donors incl. S. japonicus SJAG_00370). Correct. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to ER membrane; correct for a multi-pass squalene epoxidase. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: PomBase ISS from S. cerevisiae Erg1 (ER/microsomal membrane); correct and used in the PomBase GO-CAM. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ergosterol biosynthetic process (PTN000851137). Squalene epoxidation is an obligate step of ergosterol synthesis; disruption/inhibition causes squalene accumulation. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt DISRUPTION PHENOTYPE: Leads to the accumulation of squalene. PMID:33223513 Moreover, inhibition of Erg1 leads to the intracellular accumulation of squalene, a toxic metabolite that leads to rapid cell death |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO 'membrane' from the FAD-binding domain IPR013698. True but uninformative; ER membrane is known. Reason: Generic membrane; ER membrane is supported. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0016125 sterol metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA sterol metabolic process. Erg1 acts biosynthetically; the specific process is ergosterol biosynthesis. Reason: Generic metabolic term; use the specific biosynthetic process. Proposed replacements: ergosterol biosynthetic process Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt DISRUPTION PHENOTYPE: Leads to the accumulation of squalene. |
| GO:0016126 sterol biosynthetic process | IEA GO_REF:0000120 | MODIFY | Summary: InterPro2GO/UniPathway sterol biosynthetic process; true but less specific than ergosterol biosynthesis, which captures the fungal product pathway and is already accepted from PTN000851137. Reason: Generic sterol biosynthesis term; use the specific fission-yeast ergosterol biosynthetic process. Proposed replacements: ergosterol biosynthetic process Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt PATHWAY: Steroid metabolism; ergosterol biosynthesis. |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO FAD binding (IPR013698). Squalene epoxidase is an FAD flavoprotein (UniProt cofactor FAD); correct cofactor-binding statement. Reason: Genuine cofactor binding; non-core. Supporting Evidence: file:SCHPO/erg1/erg1-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; |
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Download this section (compressed HTML)Q: UniProt states erg1 anaerobic induction is sre1-dependent, but Todd et al. 2006 report it as Sre1-independent; which transcription factor drives erg1 induction in hypoxia?
Experiment: Profile erg1 expression by anaerobic time-course RNA-seq or RT-qPCR in candidate transcription-factor deletion strains, including sre1 deletion as the published negative control, and test direct promoter occupancy by ChIP-qPCR under aerobic and anaerobic conditions.
Hypothesis: The Sre1-independent anaerobic induction of fission-yeast erg1 is driven by another hypoxia-responsive transcription factor.
Type: anaerobic transcript profiling and promoter occupancy
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