ERG6 encodes the Candida albicans sterol 24-C-methyltransferase, a class I-like SAM-dependent Erg6/SMT-family enzyme of the late ergosterol pathway. The enzyme transfers a methyl group from S-adenosyl-L-methionine to C-24 of zymosterol to form fecosterol, the first committed C-24-methylation step after zymosterol production; purified native CaErg6 is a homooligomeric enzyme that prefers zymosterol and is inhibited by sterol substrate analogs. ERG6 disruption or reduced expression causes zymosterol accumulation and membrane/sterol phenotypes in Candida, consistent with a core endoplasmic-reticulum-associated role in ergosterol biosynthesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003838 sterol 24-C-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places sterol 24-C-methyltransferase activity on PTN002226525, the eukaryotic sterol methyltransferase node that contains fungal ERG6 proteins and Arabidopsis SMT1; C. albicans Erg6 itself is a seed for this IBD and has direct enzymatic support. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002226525 SUPPORTS TRANSFER PTN002226525 contains the Candida, budding-yeast, and plant sterol methyltransferase seeds used for the exact C-24 SMT activity. Supporting Evidence: PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. PMID:37005772 CaERG6, a crucial sterol 24-C-methyltransferase involved in the biosynthesis of ubiquitous ergosterol in C. albicans file:interpro/panther/PTHR44068/PTHR44068-paint.tsv PTHR44068 PTN002226525 GO:0003838 F IBD false AGI_LocusCode:AT5G13710|CGD:CAL0000189580|SGD:S000004467 taxon:2759 20181004 file:interpro/panther/PTHR44068/PTHR44068-review.yaml PAINT places sterol 24-C-methyltransferase activity on the sterol SMT node that contains fungal Erg6 proteins and plant SMT1 |
| GO:0003838 sterol 24-C-methyltransferase activity | IDA PMID:20946868 Purification, characterization and inhibition of sterol C24-... | ACCEPT | Summary: Ganapathy and colleagues purified native C. albicans 24-SMT and showed that zymosterol is its preferred substrate and that zymosterol incubation yields fecosterol. Supporting Evidence: PMID:20946868 Solubilized sterol C24-methyltransferase (24-SMT) was purified to homogeneity from a cell extract of the yeast Candida albicans PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. |
| GO:0003838 sterol 24-C-methyltransferase activity | IDA PMID:37005772 Biosensor-Enabled Discovery of CaERG6 Inhibitors and Their A... | ACCEPT | Summary: Liu et al. treated CaERG6 as a biochemically characterized C-24 SMT target in an inhibitor screen; the cached record is abstract-only, but the abstract states the same CaERG6 sterol 24-C-methyltransferase activity and ergosterol-pathway role. Supporting Evidence: PMID:37005772 CaERG6, a crucial sterol 24-C-methyltransferase involved in the biosynthesis of ubiquitous ergosterol in C. albicans PMID:37160123 The results of enzyme assays, photoaffinity labeling, molecular simulation, mutagenesis, and cellular thermal shift assays support H55 as an allosteric inhibitor of Erg6. PMID:38764175 d28 displayed the most potent antivirulence ability (MHIC50 = 0.25 ΞΌg/mL) by targeting Erg6 |
| GO:0003838 sterol 24-C-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation from EC 2.1.1.41/Rhea 21128 and curated yeast Erg6 orthology; this exactly matches the C. albicans enzyme reaction. Supporting Evidence: file:CANAL/ERG6/ERG6-uniprot.txt Reaction=zymosterol + S-adenosyl-L-methionine = fecosterol + S- PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. |
| GO:0003838 sterol 24-C-methyltransferase activity | IGI PMID:9593144 Sequencing, disruption, and characterization of the Candida ... | ACCEPT | Summary: Jensen-Pergakes et al. cloned C. albicans ERG6 by functional complementation of an S. cerevisiae erg6 mutant and disrupted both Candida alleles; the orthologous complementation result supports the same SMT activity. Supporting Evidence: PMID:9593144 The Candida albicans ERG6 gene was isolated by complementation of a S. cerevisiae erg6 mutant by using a C. albicans genomic library. |
| GO:0003838 sterol 24-C-methyltransferase activity | IMP PMID:37098889 Erg6 Acts as a Downstream Effector of the Transcription Fact... | ACCEPT | Summary: Jin et al. showed that ERG6 expression is reduced in a flo8 mutant that accumulates the Erg6 substrate zymosterol, and that ectopic ERG6 overexpression lowers zymosterol in that background; the perturbation is consistent with direct CaErg6 C-24 SMT activity. Supporting Evidence: PMID:37098889 overexpression of ERG6 in the flo8-deficient strain decreased the level of zymosterol |
| GO:0003838 sterol 24-C-methyltransferase activity | IMP PMID:9593144 Sequencing, disruption, and characterization of the Candida ... | ACCEPT | Summary: C. albicans erg6 mutants from the original cloning/disruption study show sterol-pathway drug phenotypes, and the paper explicitly identified the Candida gene by complementation of S. cerevisiae erg6. Supporting Evidence: PMID:9593144 The Candida albicans ERG6 gene was isolated by complementation of a S. cerevisiae erg6 mutant by using a C. albicans genomic library. PMID:9593144 The resulting erg6 strains were shown to be hypersusceptible to a number of sterol synthesis and metabolic inhibitors |
| GO:0003838 sterol 24-C-methyltransferase activity | ISS PMID:9593144 Sequencing, disruption, and characterization of the Candida ... | ACCEPT | Summary: Orthology to S. cerevisiae Erg6 is correct; C. albicans ERG6 was cloned by rescuing an S. cerevisiae erg6 mutant, and purified C. albicans Erg6 subsequently confirmed the same zymosterol-to-fecosterol activity. Supporting Evidence: PMID:9593144 The Candida albicans ERG6 gene was isolated by complementation of a S. cerevisiae erg6 mutant by using a C. albicans genomic library. PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PTN002226525 carries an ER IBD for Erg6/SMT proteins. Budding-yeast Erg6 is ER- and lipid-droplet-associated, the C. albicans enzyme catalyzes the membrane sterol C-24 methylation step, and UniProt records the late pathway as mainly occurring at the ER membrane, so the ER activity site is appropriate. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002226525 SUPPORTS TRANSFER PTN002226525 is the same SMT node that carries the exact activity and is seeded by fungal Erg6 proteins with ER support. Supporting Evidence: file:CANAL/ERG6/ERG6-uniprot.txt consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. file:interpro/panther/PTHR44068/PTHR44068-paint.tsv PTHR44068 PTN002226525 GO:0005783 C IBD false SGD:S000004467|UniProtKB:Q4FKJ2|dictyBase:DDB_G0288907 taxon:2759 20250904 file:interpro/panther/PTHR44068/PTHR44068-review.yaml ER localization is sound on the sterol SMT branch |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from S. cerevisiae Erg6 to the Candida ortholog. This agrees with the PAINT ER node and with the late Erg pathway being ER-membrane associated. Supporting Evidence: file:CANAL/ERG6/ERG6-uniprot.txt consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane. |
| GO:0005811 lipid droplet | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer from S. cerevisiae Erg6, which is a strong lipid-droplet marker and active in lipid-particle preparations. The localization is plausible for Candida Erg6, but direct C. albicans localization evidence is absent from the cached set, so lipid droplets are retained as non-core. Supporting Evidence: PMID:10515935 This is very likely for Erg6p ( 27 ) and Erg7p ( 4a ), which are enzymatically active in lipid particle preparations. PMID:24868093 Sec61 and Erg6 are negative and positive controls, respectively. |
| GO:0005886 plasma membrane | IDA PMID:19824013 Analysis of Candida albicans plasma membrane proteome. | UNDECIDED | Summary: Cabezon et al. used plasma-membrane proteomics and LC-MS/MS to identify C. albicans membrane proteins, but the cached record is abstract-only and does not name Erg6, making the per-protein evidence and possible ER/lipid-droplet carryover impossible to adjudicate. Reason: Direct C. albicans evidence for a plasma-membrane pool could not be verified from the cached abstract; the assignment should be revisited with the full text and supplementary peptide 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:0006694 steroid biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO maps the SMT C-terminal signature to the broad steroid biosynthetic process; for fungal Erg6 the supported descendant is ergosterol biosynthetic process. Reason: GO:0006694 is true but too general for a fungal sterol C-24 methyltransferase; GO:0006696 is the specific pathway already supported experimentally and by PAINT. Proposed replacements: ergosterol biosynthetic process Supporting Evidence: PMID:20946868 Solubilized sterol C24-methyltransferase (24-SMT) was purified to homogeneity from a cell extract of the yeast Candida albicans PMID:37005772 CaERG6, a crucial sterol 24-C-methyltransferase involved in the biosynthesis of ubiquitous ergosterol in C. albicans |
| GO:0006696 ergosterol biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places ergosterol biosynthesis on the fungal SMT node PTN000802684, seeded by C. albicans, S. cerevisiae, and S. pombe Erg6 proteins. The Candida enzyme directly makes fecosterol from zymosterol in the late ergosterol pathway. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000802684 SUPPORTS TRANSFER Fungal node seeded by C. albicans ERG6, S. cerevisiae ERG6, and S. pombe erg6 for ergosterol biosynthesis. Supporting Evidence: PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. file:CANAL/ERG6/ERG6-uniprot.txt PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from file:interpro/panther/PTHR44068/PTHR44068-paint.tsv PTHR44068 PTN000802684 GO:0006696 P IBD false CGD:CAL0000189580|PomBase:SPBC16E9.05|SGD:S000004467 taxon:4751 20181004 file:interpro/panther/PTHR44068/PTHR44068-review.yaml The fungal Erg6 branch produces C-24 methylated sterols on the route to ergosterol |
| GO:0006696 ergosterol biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation from curated fungal Erg6 orthologs; the process is correct for Candida ERG6 and agrees with the PAINT fungal node. Supporting Evidence: PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. file:CANAL/ERG6/ERG6-uniprot.txt PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from |
| GO:0006696 ergosterol biosynthetic process | IGI PMID:9593144 Sequencing, disruption, and characterization of the Candida ... | ACCEPT | Summary: The original Candida study cloned ERG6 by complementation of S. cerevisiae erg6 and disrupted Candida ERG6, directly connecting CaERG6 to the fungal ergosterol pathway. Supporting Evidence: PMID:9593144 The Candida albicans ERG6 gene was isolated by complementation of a S. cerevisiae erg6 mutant by using a C. albicans genomic library. |
| GO:0006696 ergosterol biosynthetic process | IMP PMID:37098889 Erg6 Acts as a Downstream Effector of the Transcription Fact... | ACCEPT | Summary: ERG6 overexpression in a flo8 mutant reduces zymosterol accumulation and partially restores biofilm/virulence phenotypes, consistent with Erg6 controlling flux through the zymosterol-to-fecosterol step of ergosterol synthesis. Supporting Evidence: PMID:37098889 overexpression of ERG6 in the flo8-deficient strain decreased the level of zymosterol PMID:37098889 Erg6 appears to be an important downstream effector of Flo8 in the regulation of C. albicans biofilm formation and in vivo virulence. |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO general methyltransferase activity from the sterol methyltransferase signatures; the specific supported activity is GO:0003838. Reason: GO:0008168 is a distant parent of the exact sterol 24-C-methyltransferase activity and should be refined. Proposed replacements: sterol 24-C-methyltransferase activity Supporting Evidence: PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. |
| GO:0008757 S-adenosylmethionine-dependent methyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: The SAM-dependent methyltransferase signature correctly identifies the cofactor chemistry, but GO:0003838 captures Erg6's sterol substrate and exact reaction. Reason: GO:0008757 is true but too general relative to the experimentally supported sterol 24-C-methyltransferase activity. Proposed replacements: sterol 24-C-methyltransferase activity Supporting Evidence: PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. |
| GO:0016126 sterol biosynthetic process | IEA GO_REF:0000041 | MODIFY | Summary: UniPathway maps the ergosterol-from-zymosterol pathway to the broad sterol biosynthetic process. PTN002226525 independently carries the same parent term, but the fungal PTN000802684 node and Candida experiments support the more informative ergosterol biosynthetic process. Reason: GO:0016126 is the correct parent but should be refined to GO:0006696 for fungal Erg6. Proposed replacements: ergosterol biosynthetic process Supporting Evidence: file:CANAL/ERG6/ERG6-uniprot.txt PATHWAY: Steroid metabolism; ergosterol biosynthesis; ergosterol from |
| GO:0036196 zymosterol metabolic process | IDA PMID:37005772 Biosensor-Enabled Discovery of CaERG6 Inhibitors and Their A... | ACCEPT | Summary: Erg6 directly consumes zymosterol and produces fecosterol; the zymosterol metabolic process row is the step-level biological-process view of the same enzyme activity. Supporting Evidence: PMID:20946868 The product of the enzyme incubated with zymosterol was fecosterol. PMID:37005772 CaERG6, a crucial sterol 24-C-methyltransferase involved in the biosynthesis of ubiquitous ergosterol in C. albicans PMID:40698822 disruption of either Osh2-mediated transport or Erg6-dependent conversion leads to intracellular zymosterol accumulation. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The Ensembl Compara transfer is plausible. S. cerevisiae Erg6 self-interacts in several interaction assays, and purified native C. albicans SMT eluted as an approximately 178 kDa complex but ran as an approximately 43 kDa protein by SDS-PAGE, consistent with a homotetramer. The homomeric state is not a separate core molecular function, so it is retained as non-core. Supporting Evidence: PMID:20946868 The purified enzyme has an apparent molecular mass of 178 kDa on gel permeation chromatography and 43 kDa on SDS/PAGE, indicating that it is composed of four identical subunits. |
| 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: Xu et al. detected altered fluconazole fitness of ERG6 deletion strains in CaFT/spot-test assays, but Erg6 is a sterol-pathway enzyme whose expression or dosage changes alter membrane composition and drug susceptibility; it is not itself an execution step in a xenobiotic-response program. Reason: The phenotype supports a link between Erg6-dependent sterol composition and compound sensitivity, not direct participation of the Erg6 enzyme in the cellular response to xenobiotic stimulus. Supporting Evidence: PMID:17604452 In addition, the ERG6 strain showed relative resistance as indicated by the significant negative z-scores at higher concentrations |
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Download this section (compressed HTML)Q: Does C. albicans Erg6 also have a lipid-droplet pool as in S. cerevisiae, or is the ER the dominant detectable site of the late Erg6 reaction?
Q: Does the CaFT fluconazole phenotype of ERG6 reflect altered drug uptake, altered sterol-pathway flux, or both?
Experiment: Tag native ERG6 in C. albicans, image it with ER and lipid-droplet markers, and pair localization with subcellular sterol methyltransferase assays to test whether lipid droplets carry an active Erg6 pool.
Hypothesis: Candida Erg6 is active at the ER and may also be active on lipid droplets.
Type: subcellular localization
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