ERG1 encodes Candida albicans squalene epoxidase, a particulate FAD-dependent monooxygenase of the squalene monooxygenase family that catalyzes epoxidation of squalene to 2,3-oxidosqualene in the ergosterol biosynthetic pathway. Candida ERG1 produces a 55 kDa particulate enzyme whose activity requires oxygen, FAD, and NADH or NADPH, is inhibited by allylamine antifungals, and is conserved with ER-membrane squalene monooxygenases from budding yeast, fission yeast, and animals. Repressing or conditionally disrupting ERG1 depletes ergosterol and accumulates squalene, consistent with ERG1 executing an essential early oxygenation step in fungal sterol synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004506 squalene monooxygenase activity | EXP PMID:3877503 Inhibition of squalene epoxidase by allylamine antimycotic c... | ACCEPT | Summary: Ryder and Dupont measured allylamine inhibition of the particulate Candida epoxidase; later cloning and heterologous expression identified this enzyme as the ERG1-encoded squalene epoxidase. Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt Squalene epoxidase; part of the third module of ergosterol PMID:3877503 potent inhibitors of the Candida epoxidases and showed apparently PMID:9161422 overexpressing the C. albicans protein SE activity was 10-fold higher than the |
| GO:0004506 squalene monooxygenase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT placed squalene monooxygenase activity on the broad PTHR10835 node PTN000089417 using experimentally annotated fungal and animal descendants, including C. albicans ERG1 and S. cerevisiae ERG1. That node placement matches the Candida biochemical and cloning evidence. Supporting Evidence: file:interpro/panther/PTHR10835/PTHR10835-paint.tsv PTHR10835 PTN000089417 GO:0004506 F IBD false file:genes/CANAL/ERG1/ERG1-uniprot.txt DR PANTHER; PTHR10835; SQUALENE MONOOXYGENASE; 1. file:genes/CANAL/ERG1/ERG1-uniprot.txt Squalene epoxidase; part of the third module of ergosterol |
| GO:0004506 squalene monooxygenase activity | IDA PMID:6378256 Properties of a particulate squalene epoxidase from Candida ... | ACCEPT | Summary: Direct assay of washed Candida microsomes showed oxygen-, FAD-, and NAD(P)H-dependent conversion of radiolabeled squalene to 2,3-oxidosqualene and lanosterol. Supporting Evidence: PMID:6378256 A washed 'microsomal' fraction converted radiolabelled squalene to 2,3-oxidosqualene and lanosterol. PMID:6378256 Minimum requirements for activity were molecular oxygen, NADH or |
| GO:0004506 squalene monooxygenase activity | IDA PMID:9161422 Cloning and expression of squalene epoxidase from the pathog... | ACCEPT | Summary: Favre and Ryder cloned the Candida SE/ERG1 ORF and increased squalene epoxidase activity by expressing the Candida protein in S. cerevisiae. Supporting Evidence: PMID:9161422 overexpressing the C. albicans protein SE activity was 10-fold higher than the |
| GO:0004506 squalene monooxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation from the squalene epoxidase InterPro signatures, RHEA:25282, and EC:1.14.14.17 is consistent with the experimentally demonstrated Candida activity. Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt Squalene epoxidase; part of the third module of ergosterol file:genes/CANAL/ERG1/ERG1-uniprot.txt DR InterPro; IPR013698; Squalene_epoxidase. |
| GO:0004506 squalene monooxygenase activity | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | ACCEPT | Summary: The raft-lipid study used conditional disruption of ERG1, while direct biochemical and cloning work establish that the affected gene product is Candida squalene epoxidase. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously PMID:6378256 A washed 'microsomal' fraction converted radiolabelled squalene to 2,3-oxidosqualene and lanosterol. PMID:9161422 overexpressing the C. albicans protein SE activity was 10-fold higher than the |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT placed ER activity on PTN000089417 for the same squalene monooxygenase clade that contains Candida ERG1. This agrees with the family review and with the ER-membrane localization of fungal squalene epoxidases. Supporting Evidence: file:interpro/panther/PTHR10835/PTHR10835-paint.tsv PTHR10835 PTN000089417 GO:0005783 C IBD false file:genes/CANAL/ERG1/ERG1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: EnsemblFungi transfer from S. cerevisiae ERG1 to endoplasmic reticulum is correct for a conserved squalene monooxygenase whose active fungal orthologs are ER-membrane enzymes. Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProtKB-SubCell mapping of the Swiss-Prot ER membrane location is consistent with Candida ERG1's particulate squalene epoxidase activity and with the PAINT ER assertion. Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane file:interpro/panther/PTHR10835/PTHR10835-paint.tsv PTHR10835 PTN000089417 GO:0005783 C IBD false |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Manual sequence-similarity transfer from S. cerevisiae Erg1 to the ER membrane is appropriate for Candida ERG1, a conserved multi-pass squalene epoxidase of PANTHER family PTHR10835. Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane file:genes/CANAL/ERG1/ERG1-uniprot.txt DR PANTHER; PTHR10835; SQUALENE MONOOXYGENASE; 1. |
| GO:0005811 lipid droplet | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: S. cerevisiae Erg1 genuinely partitions to lipid droplets, and the EnsemblFungi orthology transfer may also hold for Candida ERG1. The ER membrane remains the supported site of catalytic activity. Reason: Lipid-droplet localization is plausible by orthology but is not the core active compartment for squalene monooxygenase. Supporting Evidence: file:genes/yeast/ERG1/ERG1-ai-review.yaml Erg1 is genuinely located on LDs, although the LD pool is enzymatically inactive. |
| GO:0005886 plasma membrane | IDA PMID:19824013 Analysis of Candida albicans plasma membrane proteome. | UNDECIDED | Summary: CGD curated ERG1 from a Candida plasma-membrane proteomics study, but the cached abstract does not expose the ERG1-specific peptide or protein-table evidence. ERG1's known biology points to the ER membrane, so the plasma-membrane row needs full-text or supplementary-table review. Reason: The publication cache is abstract-only and lacks the ERG1 hit; do not overrule this IDA row without checking the mass-spectrometry table. Supporting Evidence: PMID:19824013 After LC-MS/MS analysis using both a MALDI-TOF/TOF and a linear ion trap quadrupole, a total of 214 membrane proteins were identified |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT placed ergosterol biosynthetic process at the fungal node PTN000851137, seeded by Candida and budding-yeast ERG1. This fungal node is sound: ERG1 performs the squalene epoxidation step needed for ergosterol production. Supporting Evidence: file:interpro/panther/PTHR10835/PTHR10835-paint.tsv PTHR10835 PTN000851137 GO:0006696 P IBD false PMID:15845783 showed a total lack of ergosterol and instead |
| GO:0006696 ergosterol biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: EnsemblFungi transfer of ergosterol biosynthetic process from the budding-yeast ortholog is correct: Candida ERG1 catalyzes the corresponding early step and conditional depletion abolishes ergosterol accumulation. Supporting Evidence: PMID:15845783 showed a total lack of ergosterol and instead file:genes/CANAL/ERG1/ERG1-uniprot.txt Squalene epoxidase; part of the third module of ergosterol |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:15845783 Squalene epoxidase encoded by ERG1 affects morphogenesis and... | ACCEPT | Summary: Conditional ERG1 depletion caused loss of detectable ergosterol and accumulation of squalene, directly supporting ERG1's role in ergosterol biosynthesis. Supporting Evidence: PMID:15845783 showed a total lack of ergosterol and instead |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | ACCEPT | Summary: This raft-lipid paper perturbed ERG1 as an ergosterol-pathway gene; combined with sterol profiling of ERG1 conditional mutants, the process assertion is correct. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously PMID:15845783 showed a total lack of ergosterol and instead |
| GO:0006696 ergosterol biosynthetic process | ISS PMID:9161422 Cloning and expression of squalene epoxidase from the pathog... | ACCEPT | Summary: ISS transfer from S. cerevisiae ERG1 is valid because Candida ERG1 is the orthologous squalene epoxidase and the Candida conditional mutant accumulates squalene instead of ergosterol. Supporting Evidence: PMID:9161422 overexpressing the C. albicans protein SE activity was 10-fold higher than the PMID:15845783 showed a total lack of ergosterol and instead |
| GO:0009267 cellular response to starvation | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: The erg1 conditional mutant had morphological defects, but ERG1 executes sterol synthesis rather than the starvation-response program itself. Reason: A membrane-sterol defect can perturb starvation phenotypes indirectly; the evidence does not show that squalene epoxidase is a starvation-response effector. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO membrane assignment from the squalene epoxidase family is true but too general. Reason: ERG1 is better represented as an endoplasmic-reticulum membrane enzyme. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt SUBCELLULAR LOCATION: Microsome membrane |
| GO:0016125 sterol metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: ARBA sterol metabolism is correct in direction but too broad for a fungal ERG1 gene. Reason: ERG1 catalyzes a biosynthetic step in the ergosterol branch of sterol metabolism. Proposed replacements: ergosterol biosynthetic process Supporting Evidence: PMID:15845783 showed a total lack of ergosterol and instead |
| GO:0016126 sterol biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO sterol biosynthetic process is a correct but broad process-level parent for Candida squalene epoxidase, which performs an early ergosterol-biosynthetic reaction. Reason: ERG1 catalyzes squalene epoxidation in the ergosterol branch of sterol biosynthesis; replace the broad sterol-biosynthetic parent with the more specific ergosterol biosynthetic process. Proposed replacements: ergosterol biosynthetic process Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt Squalene epoxidase; part of the third module of ergosterol PMID:15845783 showed a total lack of ergosterol and instead |
| GO:0030447 filamentous growth | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: ERG1 repression perturbs hyphal formation, but the enzyme's direct work is squalene epoxidation in ergosterol biosynthesis. Reason: The hyphal phenotype follows membrane-sterol depletion and is better treated as a downstream phenotype than as a core ERG1 biological process. Supporting Evidence: PMID:15845783 conditional erg1 mutant strains were unable PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously |
| GO:0036170 filamentous growth of a population of unicellular organisms in response to starvation | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: The conditional mutant had starvation-medium filamentation defects, but the causal biochemical lesion is loss of ergosterol synthesis. Reason: This response-specific filamentation term overstates perturbation evidence from a sterol-pathway mutant. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously |
| GO:0036171 filamentous growth of a population of unicellular organisms in response to chemical stimulus | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: Chemical-induced filamentation defects are consistent with defective ergosterol-rich membranes, not a direct function of the ERG1 enzyme in responding to the filamentation stimulus. Reason: ERG1 supplies ergosterol; the evidence does not show that squalene epoxidase executes the chemical stimulus-response program. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously |
| GO:0036180 filamentous growth of a population of unicellular organisms in response to biotic stimulus | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: Biotic-stimulus filamentation was inferred from conditional ERG1 perturbation, but the directly supported function is still ergosterol biosynthesis. Reason: A hyphal-growth defect caused by sterol depletion is indirect for this stimulus-specific filamentous growth process. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously |
| GO:0036187 cell growth mode switching, budding to filamentous | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: Budding-to-filamentous switching defects in ERG1-depleted cells are downstream of sterol depletion rather than a direct regulatory activity of squalene epoxidase. Reason: The conditional-mutant phenotype is real, but ERG1's direct process is the ergosterol-biosynthetic reaction that supports membrane composition. Supporting Evidence: PMID:16246085 conditionally disrupting ERG1 or in sphingolipid composition by homozygously |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Squalene epoxidase is an FAD-dependent monooxygenase, and the InterPro2GO FAD-binding assertion is appropriate for the conserved protein family. Reason: FAD binding is a genuine cofactor interaction, but the core molecular function is squalene monooxygenase activity. Supporting Evidence: file:genes/CANAL/ERG1/ERG1-uniprot.txt Name=FAD; Xref=ChEBI:CHEBI:57692; |
| GO:0051668 localization within membrane | IMP PMID:16246085 Membrane raft lipid constituents affect drug susceptibilitie... | MARK AS OVER ANNOTATED | Summary: Conditional ERG1 perturbation mislocalized the Cdr1 efflux transporter, but that is a consequence of altered sterol-rich membrane domains. Reason: ERG1 helps build the membrane lipid environment; it is not itself a Cdr1 localization factor executing localization within membrane. Supporting Evidence: PMID:16246085 leads to improper surface localization of |
| GO:0071466 cellular response to xenobiotic stimulus | IMP PMID:16607011 Conserved fungal genes as potential targets for broad-spectr... | MARK AS OVER ANNOTATED | Summary: Reducing CaERG1 expression caused specific terbinafine hypersensitivity, confirming target engagement but not showing that squalene epoxidase executes a xenobiotic-response program. Reason: Terbinafine hypersensitivity follows depletion of its target; the direct ERG1 process is ergosterol biosynthesis. Supporting Evidence: PMID:16607011 Taken together, these results established that reduced expression of Ca ERG1 resulted in cells that were hypersensitive only to the target-specific inhibitor terbinafine. |
| GO:0071466 cellular response to xenobiotic stimulus | IMP PMID:17604452 Genome-wide fitness test and mechanism-of-action studies of ... | MARK AS OVER ANNOTATED | Summary: The CaFT screens report drug hypersensitivity profiles for ergosterol-biosynthesis inhibitors, a perturbation readout rather than direct participation by ERG1 in xenobiotic response. Reason: A heterozygous deletion fitness defect under an inhibitor is indirect for GO:0071466; it is expected for an ergosterol-pathway gene without making xenobiotic response a core ERG1 function. Supporting Evidence: PMID:17604452 The profiles of additional inhibitors of ergosterol biosynthesis, including terbinafine, lovastatin, and dyclonine, are described in Text S1 |
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