SFA1 (YDL168W) encodes the S. cerevisiae class III alcohol dehydrogenase, also called glutathione-dependent formaldehyde dehydrogenase or S-(hydroxymethyl)glutathione dehydrogenase (EC 1.1.1.284). It is a cytosolic medium-chain zinc ADH that binds two Zn2+ per subunit. Its principal activity is the NAD(P)+-dependent oxidation of S-(hydroxymethyl)glutathione, the spontaneous adduct of formaldehyde and glutathione, to S-formylglutathione, the first step of glutathione-dependent formaldehyde detoxification. sfa1 mutants are formaldehyde-sensitive and SFA1 overexpression confers hyper-resistance; SFA1 is induced by formaldehyde, ethanol and methyl methanesulfonate. Like other class III ADHs it is also an NADH-dependent S-nitrosoglutathione (GSNO) reductase. Loss of SFA1 raises GSNO and protein S-nitrosothiol levels and causes nitrosative-stress sensitivity. Independently of glutathione, Sfa1p oxidises long-chain primary alcohols and, in the reductive direction, can reduce Ehrlich-pathway fusel aldehydes to fusel alcohols. Here it is one of six redundant enzymes, together with Adh1-5p. SFA1 is also one of the oxidoreductase genes regulated by the HOG pathway through the CRE-binding factor Sko1 under osmotic stress, and it is induced by oxidative stress in a Yap1-dependent manner.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the class I/III zinc ADH node PTN000191653 (human ADH1-5, mouse/rat Adh, Arabidopsis, fly, zebrafish, yeast SFA1). Sfa1p oxidises long-chain primary alcohols with NAD+ independently of glutathione, so the inherited activity holds for this class III enzyme, although its main substrate is S-(hydroxymethyl)glutathione. Supporting Evidence: PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA file:yeast/SFA1/SFA1-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IDA PMID:8483449 Molecular structure and genetic regulation of SFA, a gene re... | ACCEPT | Summary: Wehner et al. purified Sfa1p and showed that it oxidises long-chain alcohols with NAD+ (Km 2 mM for octanol). This is direct evidence for primary alcohol dehydrogenase activity. Supporting Evidence: PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: RHEA:10736/10740 and EC 1.1.1.1 mapping from the UniProt catalytic-activity lines, which rest on Wehner et al.; correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IMP PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. 2003 multiple-mutant analysis showed that Sfa1p alone, with all ADH1-5 and AAD genes deleted, suffices to reduce Ehrlich-pathway aldehydes to their fusel alcohols. This is the aldehyde-reduction direction of the NAD-dependent ADH activity. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY3O-4105 (valine degradation), final Ehrlich step (aldehyde + NADH -> fusel alcohol, EC 1.1.1.1). Dickinson et al. showed genetically that Sfa1p can perform this reduction. Correct MF; Sfa1p is one of six redundant enzymes for this step. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) file:yeast/SFA1/SFA1-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY3O-4109 (isoleucine degradation), final Ehrlich step (aldehyde + NADH -> fusel alcohol, EC 1.1.1.1). Dickinson et al. showed genetically that Sfa1p can perform this reduction. Correct MF; Sfa1p is one of six redundant enzymes for this step. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) file:yeast/SFA1/SFA1-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY3O-4112 (leucine degradation), final Ehrlich step (aldehyde + NADH -> fusel alcohol, EC 1.1.1.1). Dickinson et al. showed genetically that Sfa1p can perform this reduction. Correct MF; Sfa1p is one of six redundant enzymes for this step. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) file:yeast/SFA1/SFA1-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY3O-4115 (phenylalanine degradation), final Ehrlich step (aldehyde + NADH -> fusel alcohol, EC 1.1.1.1). Dickinson et al. showed genetically that Sfa1p can perform this reduction. Correct MF; Sfa1p is one of six redundant enzymes for this step. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) file:yeast/SFA1/SFA1-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Global GFP-fusion screen places Sfa1p in the cytoplasm; correct. Supporting Evidence: PMID:14562095 Here we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins. file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell (SL-0086) mapping of the cytoplasmic localisation; correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005737 cytoplasm | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY-1801-1 (formaldehyde oxidation II, glutathione-dependent) places glutathione-dependent formaldehyde oxidation in the cytoplasm. Correct; cytosol is more precise. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005739 mitochondrion | HDA PMID:14576278 The proteome of Saccharomyces cerevisiae mitochondria. | KEEP AS NON CORE | Summary: Sickmann et al. mitochondrial proteome (MS of purified mitochondria). Sfa1p is an abundant cytosolic enzyme (~8,000 molecules per cell) and GFP-tagged Sfa1p is cytoplasmic. Detection in mitochondrial preparations may reflect a minor associated pool or contamination; no mitochondrial function has been shown. Supporting Evidence: PMID:14576278 We performed a comprehensive approach to determine the proteome of Saccharomyces cerevisiae mitochondria. file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | KEEP AS NON CORE | Summary: Reinders et al. PROMITO mitochondrial proteome. Sfa1p is an abundant cytosolic enzyme (~8,000 molecules per cell) and GFP-tagged Sfa1p is cytoplasmic. Detection in mitochondrial preparations may reflect a minor associated pool or contamination; no mitochondrial function has been shown. Supporting Evidence: PMID:16823961 A total of 851 different proteins (PROMITO dataset) were identified file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt SubCell (SL-0173) mapping of the mitochondrial localisation, which UniProt took from the PROMITO proteome. Sfa1p is an abundant cytosolic enzyme (~8,000 molecules per cell) and GFP-tagged Sfa1p is cytoplasmic. Detection in mitochondrial preparations may reflect a minor associated pool or contamination; no mitochondrial function has been shown. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Mitochondrion {ECO:0000269|PubMed:16823961}. file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA cytosol from the class I/III ADH node (human ADH1A/1B/1C/ADH5 and others). Class III ADH is cytosolic, and Sfa1p is cytoplasmic by GFP; correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion places the Sfa1p reaction of PWY3O-214 (tryptophan degradation) in the cytosol. Consistent with the cytoplasmic GFP localisation. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion places the Sfa1p reaction of PWY3O-4105 (valine degradation) in the cytosol. Consistent with the cytoplasmic GFP localisation. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion places the Sfa1p reaction of PWY3O-4109 (isoleucine degradation) in the cytosol. Consistent with the cytoplasmic GFP localisation. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion places the Sfa1p reaction of PWY3O-4112 (leucine degradation) in the cytosol. Consistent with the cytoplasmic GFP localisation. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion places the Sfa1p reaction of PWY3O-4115 (phenylalanine degradation) in the cytosol. Consistent with the cytoplasmic GFP localisation. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. |
| GO:0006550 L-isoleucine catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways conversion from PWY3O-4109 (isoleucine degradation): reduction of the isoleucine-derived fusel aldehyde to the fusel alcohol. Dickinson et al. 2003 showed for leucine, phenylalanine and tryptophan that any of ADH1-5 or SFA1 can perform this last Ehrlich step; for isoleucine there is no Sfa1p-specific evidence. Sfa1p is at most a minor, redundant contributor next to the Adh isozymes. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. 2003 genetic interaction with ADH5: in strains lacking the ADH and AAD genes, Sfa1p alone sufficed for reduction of 3-methylbutanal to isoamyl alcohol in leucine catabolism. Sfa1p performs the final Ehrlich step but is redundant with the ethanol dehydrogenases. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. 2003 genetic interaction with ADH1: in strains lacking the ADH and AAD genes, Sfa1p alone sufficed for reduction of 3-methylbutanal to isoamyl alcohol in leucine catabolism. Sfa1p performs the final Ehrlich step but is redundant with the ethanol dehydrogenases. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. 2003 genetic interaction with ADH2: in strains lacking the ADH and AAD genes, Sfa1p alone sufficed for reduction of 3-methylbutanal to isoamyl alcohol in leucine catabolism. Sfa1p performs the final Ehrlich step but is redundant with the ethanol dehydrogenases. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. 2003 genetic interaction with ADH3: in strains lacking the ADH and AAD genes, Sfa1p alone sufficed for reduction of 3-methylbutanal to isoamyl alcohol in leucine catabolism. Sfa1p performs the final Ehrlich step but is redundant with the ethanol dehydrogenases. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. 2003 genetic interaction with ADH4: in strains lacking the ADH and AAD genes, Sfa1p alone sufficed for reduction of 3-methylbutanal to isoamyl alcohol in leucine catabolism. Sfa1p performs the final Ehrlich step but is redundant with the ethanol dehydrogenases. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY3O-4112 (leucine degradation); supported for Sfa1p by the Dickinson et al. 2003 genetics. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006559 L-phenylalanine catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways conversion from PWY3O-4115 (phenylalanine degradation). Dickinson et al. 2003 showed that Sfa1p is one of six enzymes (ADH1-5, SFA1) able to reduce the phenylalanine-derived aldehyde to its fusel alcohol. Real but redundant, non-core participation. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006569 L-tryptophan catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways conversion from PWY3O-214 (tryptophan degradation). Dickinson et al. 2003 showed that Sfa1p is one of six enzymes (ADH1-5, SFA1) able to reduce the tryptophan-derived aldehyde to its fusel alcohol. Real but redundant, non-core participation. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006574 L-valine catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways conversion from PWY3O-4105 (valine degradation): reduction of the valine-derived fusel aldehyde to the fusel alcohol. Dickinson et al. 2003 showed for leucine, phenylalanine and tryptophan that any of ADH1-5 or SFA1 can perform this last Ehrlich step; for valine there is no Sfa1p-specific evidence. Sfa1p is at most a minor, redundant contributor next to the Adh isozymes. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0008270 zinc ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA zinc ion binding from class I/III ADHs. Medium-chain zinc ADHs bind a catalytic and a structural Zn2+; Sfa1p has the conserved ligands. Correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Note=Binds 2 Zn(2+) ions per subunit. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR002328 ADH zinc-binding site; IPR014183 class III ADH). Correct for this zinc ADH. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Note=Binds 2 Zn(2+) ions per subunit. |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | ACCEPT | Summary: Russell et al. defined the yeast zinc proteome by combined domain and motif searches and included Sfa1p. Computational, but consistent with the conserved zinc ADH ligands. Supporting Evidence: PMID:30358795 The yeast zinc proteome of 582 known or potential zinc-binding proteins was identified using a bioinformatics analysis file:yeast/SFA1/SFA1-uniprot.txt Name=Zn(2+); Xref=ChEBI:CHEBI:29105; |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO root oxidoreductase activity from the ADH zinc-binding site (IPR002328). True but uninformative; the specific activity is S-(hydroxymethyl)glutathione dehydrogenase. Reason: Too general; use the specific glutathione-dependent formaldehyde dehydrogenase activity. Proposed replacements: S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + PMID:7649298 Alcohol dehydrogenase class III (glutathione-dependent formaldehyde dehydrogenase) from Saccharomyces cerevisiae was purified and analyzed structurally and enzymatically. |
| GO:0033833 hydroxymethylfurfural reductase (NADH) activity | IMP PMID:16652391 A 5-hydroxymethyl furfural reducing enzyme encoded by the Sa... | UNDECIDED | Summary: Petersson et al. screened 15 candidate reductase genes by overexpression for 5-hydroxymethylfurfural (HMF) reduction, and identified ADH6 as the responsible enzyme. The abstract does not describe the SFA1 result behind this IMP NADH-dependent HMF reductase activity annotation, and the full text is not cached. Class III ADH could plausibly reduce HMF weakly with NADH, but the data cannot be checked here. Supporting Evidence: PMID:16652391 Based on the expression data, a subset of 15 reductase genes was chosen to be further examined using an overexpression strain collection. PMID:16652391 Strains overexpressing ADH6 had increased HMF conversion activity |
| GO:0033859 furaldehyde metabolic process | IMP PMID:16652391 A 5-hydroxymethyl furfural reducing enzyme encoded by the Sa... | UNDECIDED | Summary: Petersson et al. screened 15 candidate reductase genes by overexpression for 5-hydroxymethylfurfural (HMF) reduction, and identified ADH6 as the responsible enzyme. The abstract does not describe the SFA1 result behind this IMP furaldehyde metabolism annotation, and the full text is not cached. Class III ADH could plausibly reduce HMF weakly with NADH, but the data cannot be checked here. Supporting Evidence: PMID:16652391 Based on the expression data, a subset of 15 reductase genes was chosen to be further examined using an overexpression strain collection. PMID:16652391 Strains overexpressing ADH6 had increased HMF conversion activity |
| GO:0046294 formaldehyde catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA at PTN000191653 with donors mouse Adh5 (MGI:87929), UniProtKB:P25437 and SFA1 itself. Glutathione-dependent formaldehyde detoxification is the conserved ancestral role of class III ADH; correct. Supporting Evidence: PMID:7649298 This supports a general role of the enzyme in formaldehyde detoxication rather than in long-chain alcohol turnover. |
| GO:0046294 formaldehyde catabolic process | IDA PMID:8483449 Molecular structure and genetic regulation of SFA, a gene re... | ACCEPT | Summary: Wehner et al.: sfa1 disruptants degrade formaldehyde more slowly and are formaldehyde-sensitive, while SFA1 overexpression increases formaldehyde consumption and resistance. The purified protein oxidises formaldehyde in the presence of glutathione. Core process. Supporting Evidence: PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA PMID:8483449 In sfa::LEU2 disruption mutants, sensitivity to formaldehyde is correlated with reduced degradation of the chemical. |
| GO:0046294 formaldehyde catabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the class III ADH family (IPR014183). Correct; formaldehyde detoxification is the main physiological role. Supporting Evidence: PMID:7649298 This supports a general role of the enzyme in formaldehyde detoxication rather than in long-chain alcohol turnover. |
| GO:0046294 formaldehyde catabolic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways conversion from PWY-1801-1 (formaldehyde oxidation II, glutathione-dependent): S-(hydroxymethyl)glutathione oxidation by Sfa1p is the first enzymatic step of glutathione-dependent formaldehyde oxidation; correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + PMID:8483449 In sfa::LEU2 disruption mutants, sensitivity to formaldehyde is correlated with reduced degradation of the chemical. |
| GO:0047018 indole-3-acetaldehyde reductase (NADH) activity | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways conversion from PWY3O-214 (tryptophan degradation): indole-3-acetaldehyde + NADH -> tryptophol. Dickinson et al. 2003 showed that Sfa1p is among the enzymes that can do the final reduction in tryptophol formation. It is a substrate-specific restatement of the NAD-dependent ADH activity, and Sfa1p is redundant with ADH1-5. Supporting Evidence: PMID:12499363 can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0051903 S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA at PTN000191653 from class III ADHs (human ADH5 P11766, mouse Adh5, Arabidopsis ADH2/GSNOR, fly Fdh, SFA1 itself). This is the defining activity of class III ADH. SFA1 among the donors reflects its own experimental grounding. Supporting Evidence: PMID:7649298 Alcohol dehydrogenase class III (glutathione-dependent formaldehyde dehydrogenase) from Saccharomyces cerevisiae was purified and analyzed structurally and enzymatically. file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + |
| GO:0051903 S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity | IDA PMID:8483449 Molecular structure and genetic regulation of SFA, a gene re... | ACCEPT | Summary: Wehner et al.: purified Sfa1p oxidises formaldehyde only in the presence of glutathione, i.e. via the S-(hydroxymethyl)glutathione adduct, with NAD+. Core activity. Supporting Evidence: PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA |
| GO:0051903 S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro2GO/EC 1.1.1.284 mapping (IPR014183, class III ADH); correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + |
| GO:0080007 S-nitrosoglutathione reductase (NADH) activity | EXP PMID:11260719 A metabolic enzyme for S-nitrosothiol conserved from bacteri... | ACCEPT | Summary: Liu et al. purified the S-nitrosoglutathione-metabolising activity from S. cerevisiae and identified it as glutathione-dependent formaldehyde dehydrogenase. Deletion abolished GSNO-consuming activity, raised GSNO and protein-SNO levels, and caused nitrosative-stress sensitivity. A second core activity. Supporting Evidence: PMID:11260719 and show that it is the glutathione-dependent formaldehyde dehydrogenase PMID:11260719 Deleting the reductase gene in yeast and mice abolishes the GSNO-consuming activity |
| GO:0080007 S-nitrosoglutathione reductase (NADH) activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA:78371 mapping of the UniProt GSNO reductase reaction, which rests on Liu et al. 2001; correct. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-nitrosoglutathione + NADH + H(+) = S- PMID:11260719 Deleting the reductase gene in yeast and mice abolishes the GSNO-consuming activity |
| GO:0106321 S-(hydroxymethyl)glutathione dehydrogenase (NADP+) activity | EXP PMID:7649298 Class III alcohol dehydrogenase from Saccharomyces cerevisia... | ACCEPT | Summary: Fernandez et al. purified yeast class III ADH and characterised its formaldehyde/S-(hydroxymethyl)glutathione kinetics (Km 0.04 mM for the glutathione adduct). UniProt records the NADP+-linked reaction from this paper. NAD+ is the main cofactor, but class III ADHs accept NADP+. Supporting Evidence: PMID:7649298 Alcohol dehydrogenase class III (glutathione-dependent formaldehyde dehydrogenase) from Saccharomyces cerevisiae was purified and analyzed structurally and enzymatically. file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + |
| GO:0106321 S-(hydroxymethyl)glutathione dehydrogenase (NADP+) activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA:19981 mapping of the NADP+-dependent S-(hydroxymethyl)glutathione dehydrogenase reaction from UniProt; consistent with Fernandez et al. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NADP(+) = S-formylglutathione + |
| GO:0106322 S-(hydroxymethyl)glutathione dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | ACCEPT | Summary: RHEA:19985 mapping of the NAD+-dependent S-(hydroxymethyl)glutathione dehydrogenase reaction; correct, and the physiologically main cofactor. Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NAD(+) = S-formylglutathione + PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA |
| GO:0106322 S-(hydroxymethyl)glutathione dehydrogenase (NAD+) activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from UniProtKB:P06525, the entry UniProt cites for the NAD+-linked reaction. The NAD+-linked reaction is in any case supported directly: Sfa1p oxidises formaldehyde with NAD+ only in the presence of glutathione (Wehner et al.). Supporting Evidence: file:yeast/SFA1/SFA1-uniprot.txt Reaction=S-(hydroxymethyl)glutathione + NAD(+) = S-formylglutathione + PMID:8483449 it oxidizes long-chain alcohols and, in the presence of glutathione, is able to oxidize FA |
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Download this section (compressed HTML)Q: How much does Sfa1p contribute to fusel alcohol formation in wild-type cells, where Adh1p dominates aldehyde reduction?
Q: Does Sfa1p have a genuine mitochondrial pool, or is its detection in mitochondrial proteomes contamination from the abundant cytosolic enzyme?
Experiment: Measure isoamyl alcohol and 2-phenylethanol production in adh1-5 aad strains with and without SFA1, under conditions that induce SFA1 (formaldehyde, ethanol), to estimate its in vivo Ehrlich-pathway flux.
Experiment: Assay purified Sfa1p with 5-hydroxymethylfurfural and NADH to resolve whether it is a physiologically relevant HMF reductase.
Bifunctional alcohol dehydrogenase and formaldehyde dehydrogenase; formaldehyde dehydrogenase activity is glutathione-dependent; functions in formaldehyde detoxification and formation of long chain and complex alcohols, regulated by Hog1p-Sko1p; protein abundance increases in response to DNA replication stress
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