CG30022 encodes the Drosophila melanogaster ortholog of ETHE1, the mitochondrial persulfide dioxygenase (sulfur dioxygenase), a non-heme Fe(II)-dependent member of the metallo-beta-lactamase (glyoxalase II-like) superfamily. By orthology it oxidizes glutathione persulfide (S-sulfanylglutathione), formed when sulfide:quinone oxidoreductase oxidizes hydrogen sulfide, to sulfite with release of glutathione, the second step of the mitochondrial sulfide oxidation pathway, in the mitochondrial matrix. Its activity, localization and physiological role have not been examined experimentally in flies. In UniProt the gene is also annotated with the name CG9026.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005506 iron ion binding | ISS GO_REF:0000024 | MODIFY | Summary: Iron ion binding transferred from human ETHE1. Reason: Correct but general; ETHE1 uses a mononuclear Fe(II) center, so ferrous iron binding (GO:0008198) is the specific term (same replacement used for Tmlh and Adi1). Cofactor, not core. Proposed replacements: ferrous iron binding |
| GO:0005654 nucleoplasm | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Nucleoplasm transferred from human ETHE1. Reason: Nuclear localization of human ETHE1 comes from an early study of overexpressed protein (originally named HSCO), whereas the catalytic function is in the mitochondrial matrix, where the human protein is localized experimentally. No fly data support a nuclear pool; over-annotation for the fly ortholog. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | MODIFY | Summary: Mitochondrion from ARBA/UniProt subcellular location. Reason: Correct but general; human ETHE1 is a mitochondrial matrix enzyme (experimental matrix annotation in GOA) and its substrate is generated by SQOR on the matrix face of the inner membrane, so mitochondrial matrix is the appropriate term. Applied to both mitochondrion rows. Proposed replacements: mitochondrial matrix Supporting Evidence: file:DROME/CG30022/CG30022-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | MODIFY | Summary: Mitochondrion transferred from human ETHE1. Reason: Correct but general; replace with mitochondrial matrix, as for the IEA row. Proposed replacements: mitochondrial matrix |
| GO:0006749 glutathione metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Glutathione metabolic process from InterPro IPR044528 (ETHE1-like). Reason: Glutathione is released when the persulfide is oxidized, so the term is not wrong, but the process the enzyme performs is sulfide oxidation (GO:0019418, already annotated ISS); glutathione acts as a carrier rather than being produced or consumed net. Replace with sulfide oxidation. Proposed replacements: sulfide oxidation |
| GO:0006749 glutathione metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Glutathione metabolic process transferred from human ETHE1. Reason: As for the IEA row: glutathione is a persulfide carrier here, and the specific process is sulfide oxidation (GO:0019418), already annotated. Proposed replacements: sulfide oxidation |
| GO:0019418 sulfide oxidation | ISS GO_REF:0000024 | ACCEPT | Summary: Sulfide oxidation transferred from human ETHE1 (O95571). Reason: ETHE1 oxidizes the SQOR-derived persulfide to sulfite, a step of mitochondrial sulfide oxidation; by orthology. Core process. |
| GO:0050313 sulfur dioxygenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Sulfur dioxygenase activity from ARBA/InterPro and EC 1.13.11.18. Reason: Specific core activity of the ETHE1 family. The record's catalytic-activity line rests only on an ARBA rule, so support here is family classification: CG30022 falls in the PANTHER mitochondrial persulfide dioxygenase ETHE1 subfamily and carries the persulfide dioxygenase-like MBL-fold signature, and this family's characterized members are sulfur (persulfide) dioxygenases. Untested in flies. Supporting Evidence: file:DROME/CG30022/CG30022-uniprot.txt PANTHER; PTHR43084:SF1; PERSULFIDE DIOXYGENASE ETHE1, MITOCHONDRIAL; 1. file:DROME/CG30022/CG30022-uniprot.txt InterPro; IPR044528; POD-like_MBL-fold. |
| GO:0050313 sulfur dioxygenase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sulfur dioxygenase activity transferred from human ETHE1 (O95571). Reason: Core activity by orthology to human ETHE1; untested in flies. The record's catalytic-activity line is ARBA-only, so the cited support is family classification: membership of the PANTHER mitochondrial persulfide dioxygenase ETHE1 subfamily, whose characterized members carry this activity. Supporting Evidence: file:DROME/CG30022/CG30022-uniprot.txt PANTHER; PTHR43084:SF1; PERSULFIDE DIOXYGENASE ETHE1, MITOCHONDRIAL; 1. file:DROME/CG30022/CG30022-uniprot.txt InterPro; IPR044528; POD-like_MBL-fold. |
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Download this section (compressed HTML)Q: Do CG30022 mutant flies accumulate sulfide, thiosulfate and C4/C5 acylcarnitines as in ETHE1-deficient ethylmalonic encephalopathy?
Q: UniProt lists two entries for this gene (A0ACM8PZC4 and Q86PD3) and gives the name CG9026 on one; which is the canonical product?
Experiment: Generate CG30022 null flies and measure tissue H2S, thiosulfate and persulfide levels; assay recombinant CG30022 with glutathione persulfide.
Hypothesis: CG30022 is the fly persulfide dioxygenase and its loss causes sulfide toxicity.
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