erg11 (SPAC13A11.02c; also called cyp51/cyp1) encodes the essential sterol 14alpha-demethylase (CYP51, EC 1.14.14.154) of Schizosaccharomyces pombe, a heme-thiolate cytochrome P450 anchored in the ER membrane by an N-terminal helix. Using O2 and electrons from NADPH-cytochrome P450 reductase, it removes the 14alpha-methyl group of lanosterol in three oxidations (releasing formate), producing the Delta14 sterol that Erg24 reduces next. Its activity depends on the heme-binding protein Dap1, which binds Erg11 and positively regulates it. Erg11 is distributed through the cortical ER and nuclear envelope, is the target of azole antifungals, and is induced by the Sre1 SREBP pathway under low sterol/low oxygen.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004497 monooxygenase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (P450 domains) monooxygenase activity; correct parent but the specific P450 activity is known. Reason: Generic parent; specific sterol 14-demethylase activity applies. Proposed replacements: sterol 14-demethylase activity Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. file:SCHPO/erg11/erg11-uniprot.txt Reaction=lanosterol + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 = |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO iron ion binding for P450s. The iron is bound as heme (heme binding is the accurate term); kept as non-core. Reason: Iron is held within heme; non-core cofactor statement. Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; |
| GO:0005515 protein binding | IPI PMID:17276356 Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. | REMOVE | Summary: IPI with Dap1 (Hughes et al. 2007): Dap1 is a hemoprotein that binds Erg11 and is required for its activity. The interaction matters, but 'protein binding' does not describe Erg11's function; the regulatory relationship belongs on Dap1. Reason: Uninformative protein binding term; the interaction itself is not disputed. Supporting Evidence: PMID:17276356 binds and positively regulates Cyp51A1 and Cyp61A1, two P450s required for |
| GO:0005783 endoplasmic reticulum | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome HDA ER localisation; correct. Supporting Evidence: PMID:16823372 Next, we determined the localization of 4,431 proteins, corresponding to |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell ER (from the ORFeome); correct. Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: PomBase ISS ER membrane from S. cerevisiae Erg11; also shown directly as an integral ER-membrane protein in S. pombe ER-phagy studies. Supporting Evidence: PMID:37939137 yep1Ξ cells also exhibited a severe defect in the autophagic processing of GFP-tagged integral ER membrane protein Erg11 into free GFP |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA ergosterol biosynthetic process (PTN001209323). Lanosterol 14-demethylation is an essential ergosterol step; erg11 deletion is lethal in S. pombe. Supporting Evidence: PMID:27585850 Erg11 is a P450 enzyme that catalyzes the key step, lanosterol-14Ξ±-demethylation, in the biosynthesis of ergosterol PMID:27585850 Tetrad dissection showed that the deletion is lethal |
| GO:0008398 sterol 14-demethylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (RHEA/EC 1.14.14.154) sterol 14-demethylase activity; correct. Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt Reaction=lanosterol + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 = |
| GO:0008398 sterol 14-demethylase activity | ISS GO_REF:0000024 | ACCEPT | Summary: PomBase ISS from S. cerevisiae Erg11 (CYP51); the core activity, also used in the PomBase GO-CAM. Supporting Evidence: PMID:27585850 Erg11 is a P450 enzyme that catalyzes the key step, lanosterol-14Ξ±-demethylation, in the biosynthesis of ergosterol file:SCHPO/erg11/erg11-uniprot.txt Reaction=lanosterol + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 = |
| GO:0016020 membrane | IEA GO_REF:0000044 | MODIFY | Summary: UniProt SubCell 'membrane'; ER membrane is supported. Reason: Generic membrane; use ER membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:37939137 yep1Ξ cells also exhibited a severe defect in the autophagic processing of GFP-tagged integral ER membrane protein Erg11 into free GFP |
| GO:0016126 sterol biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway sterol biosynthetic process; correct. Supporting Evidence: PMID:27585850 Erg11 is a P450 enzyme that catalyzes the key step, lanosterol-14Ξ±-demethylation, in the biosynthesis of ergosterol |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA oxidoreductase activity from a deep P450 node (PTN001209376). True but uninformative compared with sterol 14-demethylase activity. Reason: Very general parent; non-core. Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. |
| GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO 'oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen'; generic P450 term. Reason: Generic parent; specific activity applies. Proposed replacements: sterol 14-demethylase activity Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt Reaction=lanosterol + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 = |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO heme binding; P450 heme-thiolate cofactor (UniProt cofactor heme). Correct. Supporting Evidence: file:SCHPO/erg11/erg11-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; |
| GO:0020037 heme binding | TAS PMID:17276356 Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. | ACCEPT | Summary: TAS (Hughes et al. 2007) heme binding; the paper treats Erg11 (Cyp51) as a heme-dependent P450. Correct. Supporting Evidence: PMID:17276356 binds and positively regulates Cyp51A1 and Cyp61A1, two P450s required for file:SCHPO/erg11/erg11-uniprot.txt Name=heme; Xref=ChEBI:CHEBI:30413; |
| GO:0032541 cortical endoplasmic reticulum | EXP PMID:37939137 The ortholog of human REEP1-4 is required for autophagosomal... | ACCEPT | Summary: EXP (Zhao et al. 2023): Erg11-GFP localises to the cortical ER and nuclear envelope. Supporting Evidence: PMID:37939137 As Ost4 and Erg11 localize to both the cortical ER and the nuclear envelope |
| GO:0032541 cortical endoplasmic reticulum | IDA PMID:36799444 Inner nuclear membrane proteins Lem2 and Bqt4 interact with ... | ACCEPT | Summary: IDA (Hirano et al. 2023, abstract only): Erg11 was found as a Lem2-binding lipid-synthesis enzyme and its localisation examined; cortical ER localisation agrees with independent data. Accepted per curator. Supporting Evidence: PMID:36799444 Cho2, Ole1 and Erg11 for Lem2 |
| GO:0097038 perinuclear endoplasmic reticulum | EXP PMID:37939137 The ortholog of human REEP1-4 is required for autophagosomal... | ACCEPT | Summary: EXP (Zhao et al. 2023): Erg11-GFP is on the nuclear envelope (perinuclear ER) as well as cortical ER. Supporting Evidence: PMID:37939137 As Ost4 and Erg11 localize to both the cortical ER and the nuclear envelope |
| GO:0097038 perinuclear endoplasmic reticulum | IDA PMID:36799444 Inner nuclear membrane proteins Lem2 and Bqt4 interact with ... | ACCEPT | Summary: IDA (Hirano et al. 2023) perinuclear ER, consistent with Erg11 interacting with the inner nuclear membrane protein Lem2. Accepted per curator (abstract only). Supporting Evidence: PMID:36799444 Cho2, Ole1 and Erg11 for Lem2 |
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