gpx1 encodes the only glutathione peroxidase-family protein of Schizosaccharomyces pombe, a 158-residue non-selenium (cysteine) GPx homologue that functions as an atypical 2-Cys peroxiredoxin. Gpx1 reduces hydrogen peroxide, alkyl hydroperoxides and phospholipid hydroperoxides using thioredoxin, not glutathione, as electron donor (EC 1.11.1.24). It is found in the cytosol and mitochondria. gpx1 transcription is induced by oxidative, osmotic and heat stress through the Sty1-Atf1 pathway and rises in stationary phase, where Gpx1 supports long-term survival and protects oxidation-labile iron-sulfur enzymes such as aconitase and sulfite reductase. In exponentially growing cells it is a minor peroxide scavenger compared with the peroxiredoxin Tpx1 and catalase. Recombinant Gpx1 also shows weak holdase (anti-aggregation) chaperone activity in vitro.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004601 peroxidase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the GPx family signature (IPR000889) to generic peroxidase activity. Correct but uninformative: Gpx1 is a thioredoxin-dependent peroxidase. Reason: Replace the parent term with the specific thioredoxin-dependent peroxiredoxin activity shown biochemically for Gpx1, as done for the S. cerevisiae GPx-like enzymes. Proposed replacements: thioredoxin-dependent peroxiredoxin activity Supporting Evidence: PMID:18162174 The Gpx1 protein has a peroxidase activity but preferred thioredoxin to glutathione as an electron donor when examined in vitro and in vivo, and therefore is a thioredoxin peroxidase. |
| GO:0004602 glutathione peroxidase activity | IDA NOT PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: NOT glutathione peroxidase activity (Lee et al. 2008). Gpx1 preferred thioredoxin to glutathione in vitro and in vivo and was reclassified as a thioredoxin peroxidase. Reason: The negative annotation is the key correction for this family member and is consistent with the UniProt CAUTION note. Unlike S. cerevisiae GPX1, for which GSH-dependent activity was kept as a second function, the S. pombe data argue against glutathione as a physiological reductant. Supporting Evidence: PMID:18162174 The Gpx1 protein has a peroxidase activity but preferred thioredoxin to glutathione as an electron donor when examined in vitro and in vivo, and therefore is a thioredoxin peroxidase. file:SCHPO/gpx1/gpx1-uniprot.txt CAUTION: Was originally thought to be a glutathione peroxidase |
| GO:0004602 glutathione peroxidase activity | IDA NOT PMID:20356456 Distinct functional roles of peroxiredoxin isozymes and glut... | ACCEPT | Summary: NOT glutathione peroxidase activity (Kim et al. 2010): recombinant S. pombe GPx showed thioredoxin-dependent peroxidase activity rather than GPx activity. Reason: Independent biochemical confirmation of the NOT annotation. Supporting Evidence: PMID:20356456 GPx also showed thioreoxin-dependent peroxidase activity rather than GPx activity. |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: Genome-wide YFP-fusion localization (Matsuyama et al. 2006 ORFeome) scored Gpx1 in the nucleus as well as cytoplasm. Reason: A small (18 kDa) soluble protein can equilibrate into the nucleus; no nuclear function is known. Retained as a non-core localization from a high-throughput screen. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. |
| GO:0005737 cytoplasm | EXP PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: Cytoplasmic localization from Lee et al. 2008, which UniProt cites for the Cytoplasm location. Reason: Consistent with the cytosolic Fe-S enzyme protection phenotype; abstract-only cache, deferring to the curator for the localization data. Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18162174}. |
| GO:0005737 cytoplasm | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP localization places Gpx1 in the cytoplasm. Reason: Agrees with the targeted study (PMID:18162174). Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18162174}. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping (SL-0086) of the experimentally supported Cytoplasm location. Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18162174}. |
| GO:0005739 mitochondrion | IDA PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: is_active_in mitochondrion (Lee et al. 2008). Gpx1 is reported in mitochondria and gpx1 mutants have reduced activity of mitochondrial aconitase. Reason: Abstract-only cache; the localization is recorded by UniProt from this paper and fits the phenotype. Deferring to the curator. Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt Mitochondrion {ECO:0000269|PubMed:18162174}. PMID:18162174 The mutant also exhibited some defect in the activity of aconitase, an oxidation-labile Fe-S enzyme in mitochondria. |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping of the Mitochondrion location, which UniProt attributes to Lee et al. 2008. Reason: Consistent with the aconitase (mitochondrial Fe-S enzyme) defect of gpx1 mutants. Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt Mitochondrion {ECO:0000269|PubMed:18162174}. PMID:18162174 The mutant also exhibited some defect in the activity of aconitase, an oxidation-labile Fe-S enzyme in mitochondria. |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP localization scoring Gpx1 as cytosolic. Reason: Agrees with targeted data. Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18162174}. |
| GO:0005829 cytosol | IDA PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: is_active_in cytosol (Lee et al. 2008). The gpx1 mutant loses activity of cytosolic sulfite reductase in stationary phase, consistent with a cytosolic peroxidase pool. Supporting Evidence: PMID:18162174 Activity of sulfite reductase, a labile Fe-S enzyme in the cytosol, was also dramatically lowered in the mutant in the stationary phase. file:SCHPO/gpx1/gpx1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18162174}. |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO (GPx family) response to oxidative stress. gpx1 is stress-induced and Gpx1 scavenges H2O2 when overexpressed. Reason: True but a broad response term; the direct process is hydrogen peroxide detoxification. Supporting Evidence: PMID:10455235 gpx1(+) mRNA was induced by various stresses, including oxidative stress, osmostress and heat stress. PMID:10455235 These results suggest that Gpx1 acts as a scavenger of H(2)O(2) in vivo. |
| GO:0008379 obsolete thioredoxin peroxidase activity | IDA PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | MODIFY | Summary: Thioredoxin peroxidase activity (Lee et al. 2008); GO:0008379 is obsolete. Reason: The activity is now represented by GO:0140824 thioredoxin-dependent peroxiredoxin activity, which GOA already carries for Gpx1 from the same paper. Proposed replacements: thioredoxin-dependent peroxiredoxin activity Supporting Evidence: PMID:18162174 The Gpx1 protein has a peroxidase activity but preferred thioredoxin to glutathione as an electron donor when examined in vitro and in vivo, and therefore is a thioredoxin peroxidase. |
| GO:0034599 cellular response to oxidative stress | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for the fungal/animal GPx family. gpx1 mRNA is induced by oxidative stress and Gpx1 reduces peroxides. Reason: Inherited and consistent with the S. pombe data, although Gpx1 is a minor contributor during exponential growth. Supporting Evidence: PMID:10455235 gpx1(+) mRNA was induced by various stresses, including oxidative stress, osmostress and heat stress. PMID:24521463 Gpx1, the only glutathione peroxidase encoded by the S. pombe genome, only has a minor secondary role when extracellular peroxides are added. |
| GO:0042744 hydrogen peroxide catabolic process | IDA PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: Hydrogen peroxide catabolic process from the in vitro peroxidase assays of Lee et al. 2008. Reason: Direct consequence of the thioredoxin-dependent H2O2 reduction activity. Supporting Evidence: PMID:18162174 The Gpx1 protein has a peroxidase activity but preferred thioredoxin to glutathione as an electron donor when examined in vitro and in vivo, and therefore is a thioredoxin peroxidase. PMID:18162174 Besides H(2)O(2), it can reduce alkyl and phospholipid hydroperoxides. |
| GO:0045454 cell redox homeostasis | IMP PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | KEEP AS NON CORE | Summary: cell redox homeostasis (IMP): gpx1 mutants show reduced activity of oxidation-labile Fe-S enzymes (aconitase, sulfite reductase) and reduced long-term survival. Reason: Supported phenotype, but a broad downstream process; the core process is peroxide detoxification. Supporting Evidence: PMID:18162174 The mutant also exhibited some defect in the activity of aconitase, an oxidation-labile Fe-S enzyme in mitochondria. |
| GO:0061692 cellular detoxification of hydrogen peroxide | IDA PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: Cellular detoxification of hydrogen peroxide (Lee et al. 2008); Gpx1 reduces H2O2 and organic hydroperoxides with thioredoxin and supports stationary-phase survival. Reason: Core process, consistent with overexpression rescue of catalase-mutant H2O2 sensitivity (PMID:10455235). Supporting Evidence: PMID:18162174 The Gpx1 protein has a peroxidase activity but preferred thioredoxin to glutathione as an electron donor when examined in vitro and in vivo, and therefore is a thioredoxin peroxidase. PMID:10455235 These results suggest that Gpx1 acts as a scavenger of H(2)O(2) in vivo. |
| GO:0140824 thioredoxin-dependent peroxiredoxin activity | EXP PMID:18162174 Gpx1 is a stationary phase-specific thioredoxin peroxidase i... | ACCEPT | Summary: Thioredoxin-dependent peroxiredoxin activity: Gpx1 reduces H2O2, alkyl and phospholipid hydroperoxides and prefers thioredoxin to glutathione. Reason: Core molecular function. Supporting Evidence: PMID:18162174 The Gpx1 protein has a peroxidase activity but preferred thioredoxin to glutathione as an electron donor when examined in vitro and in vivo, and therefore is a thioredoxin peroxidase. PMID:18162174 Besides H(2)O(2), it can reduce alkyl and phospholipid hydroperoxides. |
| GO:0140824 thioredoxin-dependent peroxiredoxin activity | IDA PMID:20356456 Distinct functional roles of peroxiredoxin isozymes and glut... | ACCEPT | Summary: Kim et al. 2010 confirmed thioredoxin-dependent peroxidase activity of recombinant S. pombe GPx. Reason: Independent confirmation of the core activity. Supporting Evidence: PMID:20356456 GPx also showed thioreoxin-dependent peroxidase activity rather than GPx activity. |
| GO:0140824 thioredoxin-dependent peroxiredoxin activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA from the UniProt catalytic activity (RHEA:62620, EC 1.11.1.24), which is itself based on Lee et al. 2008. Supporting Evidence: file:SCHPO/gpx1/gpx1-uniprot.txt EC=1.11.1.24 {ECO:0000269|PubMed:18162174}; |
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Download this section (compressed HTML)Q: Which thioredoxin (trx1, trx2/mitochondrial) reduces Gpx1 in each compartment, and is the mitochondrial pool generated by an alternative translation start or by a cryptic targeting signal?
Q: Does Gpx1 act as a peroxide sensor or redox relay for a transcription factor in stationary phase, analogous to S. cerevisiae Hyr1/Gpx3 and Yap1?
Experiment: Compare stationary-phase survival, aconitase activity and lipid peroxidation in gpx1 deletion strains complemented with wild-type Gpx1 or peroxidatic/resolving cysteine mutants, and with cytosol- or mitochondria-restricted Gpx1.
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