ERG26 (YGL001C) encodes the sterol-4alpha-carboxylate 3-dehydrogenase (decarboxylating) (C-3 sterol dehydrogenase/C-4 decarboxylase, EC 1.1.1.170), an NAD(P)-dependent enzyme of the 3beta-HSD family. In each of the two C-4 demethylation rounds it oxidises the 3beta-hydroxyl of the 4alpha-carboxysterol produced by Erg25, which drives decarboxylation and yields a 3-keto sterol (3-dehydro-4-methylzymosterol, then zymosterone) for reduction by Erg27. Erg26 is a peripheral ER membrane protein that associates with Erg25, Erg27 and the scaffold Erg28 in the C-4 demethylation complex. ERG26 is essential: in heme-competent cells loss of Erg26 causes accumulation of carboxysterols and toxic oxygenated sterol intermediates that block growth even with exogenous sterol, and a temperature-sensitive erg26 allele also perturbs glycerolipid and phospholipid synthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from a fungal ERG26 node (PTN000820972; C. albicans and S. cerevisiae ERG26). Erg26 has its own experimental support for the C-3 dehydrogenase/C-4 decarboxylase activity; inheritance is sound. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- PMID:11279045 microsomes isolated from erg26-1 cells contained greatly reduced 4alpha-carboxysterol-C3 dehydrogenase activity when compared with microsomes from wild type cells |
| GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity | IDA PMID:9811880 Characterization of the Saccharomyces cerevisiae ERG26 gene ... | ACCEPT | Summary: Gachotte et al. 1998 identified ERG26 (YGL001c) by similarity to Nocardia cholesterol dehydrogenase and showed that erg26 mutants accumulate the 4-carboxysterol substrates of the C-3 dehydrogenase/decarboxylase. The full text supports the activity mainly through substrate accumulation; Baudry et al. 2001 later showed microsomes from erg26-1 cells lack the dehydrogenase activity. Supporting Evidence: PMID:9811880 accumulate nonesterified carboxylic acid sterols such as 4beta, 14alpha-dimethyl-4alpha-carboxy-cholesta-8,24-dien-3be ta-ol and 4beta-methyl-4alpha-carboxy-cholesta-8,24-dien-3beta-o l, the predicted substrates for the C-3 sterol dehydrogenase PMID:11279045 microsomes isolated from erg26-1 cells contained greatly reduced 4alpha-carboxysterol-C3 dehydrogenase activity when compared with microsomes from wild type cells |
| GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, RHEA:33447, EC 1.1.1.170); correct for Erg26. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SGD_PWY:ERGOSTEROL-SYN-PWY-1, 'ergosterol biosynthesis') assigns 4alpha-carboxy-4beta-methyl-zymosterol (and, in the second round, 4alpha-carboxyzymosterol) + NAD(P)+ -> 3-keto sterol + CO2 + NAD(P)H (EC 1.1.1.170) to Erg26. Correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SGD_PWY:PWY-6074-1, 'zymosterol biosynthesis') assigns 4alpha-carboxy-4beta-methyl-zymosterol (and, in the second round, 4alpha-carboxyzymosterol) + NAD(P)+ -> 3-keto sterol + CO2 + NAD(P)H (EC 1.1.1.170) to Erg26. Correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0000252 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SGD_PWY:PWY3O-31704, 'superpathway of ergosterol biosynthesis I') assigns 4alpha-carboxy-4beta-methyl-zymosterol (and, in the second round, 4alpha-carboxyzymosterol) + NAD(P)+ -> 3-keto sterol + CO2 + NAD(P)H (EC 1.1.1.170) to Erg26. Correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0005515 protein binding | IPI PMID:11805826 Functional organization of the yeast proteome by systematic ... | REMOVE | Summary: Gavin et al. 2002 TAP-MS recovered Erg26 with MCM7, a replicative helicase subunit. There is no biological link between a sterol decarboxylase and the MCM complex; likely a nonspecific co-purification, and "protein binding" is uninformative regardless. Reason: Uninformative protein binding from high-throughput AP-MS with no functional context. Supporting Evidence: PMID:11805826 We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:12119386 Protein-protein interactions among C-4 demethylation enzymes... | REMOVE | Summary: Mo et al. 2002: Erg26 was found with Erg28 in a complex purified via Erg26-HA (direct co-IP failed because Erg26 solubilised poorly). Meaningful complex association, captured by the catalytic complex annotation; "protein binding" is uninformative. Reason: Uninformative protein binding; complex membership represented by GO:1902494. Supporting Evidence: PMID:12119386 a complex containing Erg25p/Erg26p/Erg27p/Erg28p was identified |
| GO:0005515 protein binding | IPI PMID:16300994 A systematic study of yeast sterol biosynthetic protein-prot... | REMOVE | Summary: Split-ubiquitin two-hybrid (Mo and Bard 2005) reported Erg26-Erg9 (squalene synthase). "protein binding" is uninformative. Reason: Uninformative protein binding term. Supporting Evidence: PMID:16300994 Our results not only confirmed several previous interactions, but also allowed us to identify novel interactions. |
| GO:0005515 protein binding | IPI PMID:16300994 A systematic study of yeast sterol biosynthetic protein-prot... | REMOVE | Summary: Split-ubiquitin two-hybrid (Mo and Bard 2005) reported Erg26-Erg24. "protein binding" is uninformative. Reason: Uninformative protein binding term. Supporting Evidence: PMID:16300994 Our results not only confirmed several previous interactions, but also allowed us to identify novel interactions. |
| GO:0005515 protein binding | IPI PMID:16300994 A systematic study of yeast sterol biosynthetic protein-prot... | REMOVE | Summary: Split-ubiquitin confirmation of Erg26-Erg28 (Mo and Bard 2005); complex membership already represented by the complex annotation. Reason: Uninformative protein binding; complex membership represented by GO:1902494. Supporting Evidence: PMID:16300994 Our results not only confirmed several previous interactions, but also allowed us to identify novel interactions. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Gavin et al. 2006 genome-wide AP-MS again linked Erg26 and MCM7. No functional connection is known; "protein binding" is uninformative. Reason: Uninformative protein binding from high-throughput AP-MS. Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Michaelis et al. 2023 AP-MS interactome recovered Erg26-Erg9. Reproducible but functionally uninformative as "protein binding". Reason: Uninformative protein binding from a high-throughput screen. Supporting Evidence: PMID:37968396 Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Michaelis et al. 2023 AP-MS interactome recovered Erg26-Erg24. Reproducible but functionally uninformative as "protein binding". Reason: Uninformative protein binding from a high-throughput screen. Supporting Evidence: PMID:37968396 Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry |
| GO:0005783 endoplasmic reticulum | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | ACCEPT | Summary: SWAT-GFP genome-wide imaging (Yofe et al. 2016) places Erg26 in the ER. Supporting Evidence: PMID:26928762 we were able to uncover the sub-cellular localization of hundreds of proteins never visualized before |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in ER from PTN000820972; consistent with the GFP data for Erg26. Supporting Evidence: PMID:11279045 GFP-Erg26p and GFP-Erg27p fusion proteins were localized to the endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | IDA PMID:11279045 The effect of the erg26-1 mutation on the regulation of lipi... | ACCEPT | Summary: Baudry et al. 2001 localised GFP-Erg26p to the ER. Supporting Evidence: PMID:11279045 GFP-Erg26p and GFP-Erg27p fusion proteins were localized to the endoplasmic reticulum |
| GO:0005783 endoplasmic reticulum | IDA PMID:12119386 Protein-protein interactions among C-4 demethylation enzymes... | ACCEPT | Summary: Mo et al. 2002 GFP fusions placed Erg26 in the ER, where it acts in the C-4 demethylation complex. Supporting Evidence: PMID:12119386 Green fluorescent protein-fusion protein localization studies showed that Erg26p, Erg27p, and Erg28p are all located in the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:11279045 The effect of the erg26-1 mutation on the regulation of lipi... | ACCEPT | Summary: Baudry et al. 2001 GFP-Erg26p ER localisation; Erg26 is a peripheral ER membrane protein. Supporting Evidence: PMID:11279045 GFP-Erg26p and GFP-Erg27p fusion proteins were localized to the endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:12119386 Protein-protein interactions among C-4 demethylation enzymes... | ACCEPT | Summary: Mo et al. 2002 showed Erg26 is membrane-associated by differential centrifugation and ER-localised by GFP. Supporting Evidence: PMID:12119386 Differential centrifugation showed that Erg26p, Erg27p, and Erg28p are all membrane-associated proteins. PMID:12119386 Green fluorescent protein-fusion protein localization studies showed that Erg26p, Erg27p, and Erg28p are all located in the endoplasmic reticulum. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0097) to ER membrane; correct (peripheral). Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IPI PMID:12119386 Protein-protein interactions among C-4 demethylation enzymes... | ACCEPT | Summary: Mo et al. 2002 complex purification from ER membranes; ER membrane location is correct even if IPI is an unusual evidence code for a CC. Supporting Evidence: PMID:12119386 a complex containing Erg25p/Erg26p/Erg27p/Erg28p was identified PMID:12119386 Differential centrifugation showed that Erg26p, Erg27p, and Erg28p are all membrane-associated proteins. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways-to-GO-CAM conversion (GO_REF:0000123, SGD_PWY:ERGOSTEROL-SYN-PWY-1, 'ergosterol biosynthesis') places every pathway reaction "is_active_in cytosol" by default. Erg26 is a peripheral ER membrane protein held in the Erg28-scaffolded C-4 demethylation complex, acting on membrane-embedded carboxysterols; its sterol/squalene substrate is embedded in the ER bilayer and the activity is measured in the microsomal (ER) membrane fraction, not in the soluble cytosol. Reason: Converter compartment default; the site of activity is the ER membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:12119386 Differential centrifugation showed that Erg26p, Erg27p, and Erg28p are all membrane-associated proteins. PMID:12119386 Green fluorescent protein-fusion protein localization studies showed that Erg26p, Erg27p, and Erg28p are all located in the endoplasmic reticulum. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways-to-GO-CAM conversion (GO_REF:0000123, SGD_PWY:PWY-6074-1, 'zymosterol biosynthesis') places every pathway reaction "is_active_in cytosol" by default. Erg26 is a peripheral ER membrane protein held in the Erg28-scaffolded C-4 demethylation complex, acting on membrane-embedded carboxysterols; its sterol/squalene substrate is embedded in the ER bilayer and the activity is measured in the microsomal (ER) membrane fraction, not in the soluble cytosol. Reason: Converter compartment default; the site of activity is the ER membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:12119386 Differential centrifugation showed that Erg26p, Erg27p, and Erg28p are all membrane-associated proteins. PMID:12119386 Green fluorescent protein-fusion protein localization studies showed that Erg26p, Erg27p, and Erg28p are all located in the endoplasmic reticulum. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways-to-GO-CAM conversion (GO_REF:0000123, SGD_PWY:PWY3O-31704, 'superpathway of ergosterol biosynthesis I') places every pathway reaction "is_active_in cytosol" by default. Erg26 is a peripheral ER membrane protein held in the Erg28-scaffolded C-4 demethylation complex, acting on membrane-embedded carboxysterols; its sterol/squalene substrate is embedded in the ER bilayer and the activity is measured in the microsomal (ER) membrane fraction, not in the soluble cytosol. Reason: Converter compartment default; the site of activity is the ER membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:12119386 Differential centrifugation showed that Erg26p, Erg27p, and Erg28p are all membrane-associated proteins. PMID:12119386 Green fluorescent protein-fusion protein localization studies showed that Erg26p, Erg27p, and Erg28p are all located in the endoplasmic reticulum. |
| GO:0006694 steroid biosynthetic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro IPR002225 (3beta-HSD family) mapping to steroid biosynthetic process; correct but general. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}. |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000820973 (fungal ERG26 node). Erg26 catalyses the decarboxylation step of C-4 demethylation in ergosterol synthesis; correct. Supporting Evidence: PMID:9811880 accumulate nonesterified carboxylic acid sterols such as 4beta, 14alpha-dimethyl-4alpha-carboxy-cholesta-8,24-dien-3be ta-ol and 4beta-methyl-4alpha-carboxy-cholesta-8,24-dien-3beta-o l, the predicted substrates for the C-3 sterol dehydrogenase |
| GO:0006696 ergosterol biosynthetic process | IDA PMID:9811880 Characterization of the Saccharomyces cerevisiae ERG26 gene ... | ACCEPT | Summary: Gachotte et al. 1998: erg26 disruptants are non-viable even with sterol supplementation unless heme synthesis is blocked, and accumulate carboxysterols; direct genetic and biochemical evidence for the ergosterol pathway role. Supporting Evidence: PMID:9811880 Segregants containing the YGL001c disruption were not viable after transfer to fresh, sterol-supplemented media. PMID:9811880 accumulate nonesterified carboxylic acid sterols such as 4beta, 14alpha-dimethyl-4alpha-carboxy-cholesta-8,24-dien-3be ta-ol and 4beta-methyl-4alpha-carboxy-cholesta-8,24-dien-3beta-o l, the predicted substrates for the C-3 sterol dehydrogenase |
| GO:0006696 ergosterol biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA rule ARBA00087364 assigning ergosterol biosynthetic process; correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0006696 ergosterol biosynthetic process | NAS PMID:32679672 Regulation of Ergosterol Biosynthesis in Saccharomyces cerev... | ACCEPT | Summary: Jorda and Puig 2020 review names Erg25-Erg26-Erg27 as the C-4 demethylation complex of ergosterol synthesis. Supporting Evidence: PMID:32679672 the C-14 reductase Erg24 and the C-4 demethylation complex Erg25-Erg26-Erg27 |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SGD_PWY:ERGOSTEROL-SYN-PWY-1, 'ergosterol biosynthesis') places Erg26 at the C-3 dehydrogenation/C-4 decarboxylation steps of ergosterol biosynthesis; correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0006696 ergosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SGD_PWY:PWY3O-31704, 'superpathway of ergosterol biosynthesis I') places Erg26 at the C-3 dehydrogenation/C-4 decarboxylation steps of ergosterol biosynthesis; correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: InterPro IPR002225 mapping to the general class "oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor". Correct parent; the specific activity is the decarboxylating 3beta-hydroxysteroid dehydrogenase. Reason: General parent of the established activity. Proposed replacements: 3-beta-hydroxysteroid dehydrogenase [NAD(P)+]/C4-decarboxylase activity Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3- PMID:11279045 microsomes isolated from erg26-1 cells contained greatly reduced 4alpha-carboxysterol-C3 dehydrogenase activity when compared with microsomes from wild type cells |
| GO:0036197 zymosterol biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (SGD_PWY:PWY-6074-1, 'zymosterol biosynthesis'): Erg26 catalyses step 4 of the lanosterol -> zymosterol sequence; correct. Supporting Evidence: file:yeast/ERG26/ERG26-uniprot.txt PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from |
| GO:0102175 3-beta-hydroxysteroid dehydrogenase (NAD+)/C4-decarboxylase activity | IMP PMID:9811880 Characterization of the Saccharomyces cerevisiae ERG26 gene ... | KEEP AS NON CORE | Summary: IMP from Gachotte et al. 1998 to the NAD+-specific child term (GO:0102175, is_a GO:0000252). The mutant phenotype (carboxysterol accumulation) establishes the decarboxylating dehydrogenase step but not its cofactor; the full text only cites earlier NAD-depletion experiments from other systems, and UniProt/Rhea write the yeast reaction with NAD(P)+. The parent term is fully supported; the NAD+ specificity is not demonstrated for Erg26. Reason: Function correct, but cofactor specificity (NAD+ vs NADP+) is not established by the cited evidence; the cofactor-neutral parent GO:0000252 is used as the core term. Supporting Evidence: PMID:9811880 accumulate nonesterified carboxylic acid sterols such as 4beta, 14alpha-dimethyl-4alpha-carboxy-cholesta-8,24-dien-3be ta-ol and 4beta-methyl-4alpha-carboxy-cholesta-8,24-dien-3beta-o l, the predicted substrates for the C-3 sterol dehydrogenase PMID:9811880 Several groups have demonstrated the accumulation of carboxylic acid sterol intermediates by incubating radiolabeled substrates with microsomes depleted in NAD cofactors |
| GO:1902494 catalytic complex | IPI PMID:12119386 Protein-protein interactions among C-4 demethylation enzymes... | ACCEPT | Summary: Mo et al. 2002 affinity-purified a complex containing Erg25, Erg26, Erg27 and Erg28 (sterol C-4 demethylation complex). No specific GO term exists, so "catalytic complex" is the best available CC. Supporting Evidence: PMID:12119386 a complex containing Erg25p/Erg26p/Erg27p/Erg28p was identified |
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Q: Is the reproducible Erg26-MCM7 co-purification in two Gavin AP-MS datasets an artefact, or does it reflect a moonlighting interaction?
C-3 sterol dehydrogenase; catalyzes the second of three steps required to remove two C-4 methyl groups from an intermediate in ergosterol biosynthesis; human homolog NSDHL implicated in CK syndrome, and can complement yeast null mutant; molecular target of natural product and antifungal compound FR171456
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