shop

UniProt ID: Q9VWP4
Organism: Drosophila melanogaster
Review Status: DRAFT
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Gene Description

shop (shopper, CG7280) encodes the Drosophila melanogaster sulfite oxidase, a homolog of human SUOX. It is a molybdopterin- and heme-containing enzyme of the mitochondrial intermembrane space that oxidizes sulfite to sulfate, passing electrons via its cytochrome b5 domain to cytochrome c. It performs the terminal step of the oxidation of sulfur from cysteine catabolism and hydrogen sulfide. shop mutants have strongly reduced sulfite oxidase activity and elevated sulfite; Shopper is specifically required in ensheathing glia, where excess sulfite disturbs glutamate homeostasis and larval locomotion. shop mutants model isolated sulfite oxidase deficiency: they are sensitive to dietary cysteine, sulfite and thiosulfate, and a cysteine-depleted diet normalizes their metabolism and rescues development and survival.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		MODIFY
Summary: Mitochondrion by phylogenetic inference (PTN000452464; donors fly shop, rat Suox).
Reason: Correct but general. Shopper is a SUOX homolog, and SUOX enzymes reside in the mitochondrial intermembrane space, which is already annotated to shop (TAS). The specific compartment is preferred; applied to all mitochondrion rows.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
GO:0005739 mitochondrion
IDA
PMID:30158546
The sulfite oxidase Shopper controls neuronal activity by re... 		MODIFY
Summary: HA-tagged Shopper co-localizes with mitoGFP in S2 cells and glia.
Reason: Experimental mitochondrial localization at the resolution of light microscopy. Correct but general. Shopper is a SUOX homolog, and SUOX enzymes reside in the mitochondrial intermembrane space, which is already annotated to shop (TAS). The specific compartment is preferred; applied to all mitochondrion rows.
Supporting Evidence:
PMID:30158546
In S2 cells, ShopperHA is found in a punctate pattern co-localizing with the mitochondrial marker mitoGFP
GO:0005739 mitochondrion
IEA
GO_REF:0000117 		MODIFY
Summary: Mitochondrion from ARBA.
Reason: Correct but general. Shopper is a SUOX homolog, and SUOX enzymes reside in the mitochondrial intermembrane space, which is already annotated to shop (TAS). The specific compartment is preferred; applied to all mitochondrion rows.
GO:0005758 mitochondrial intermembrane space
IEA
GO_REF:0000044 		ACCEPT
Summary: Mitochondrial intermembrane space from the UniProt subcellular location vocabulary.
Reason: Specific compartment of SUOX-family enzymes; consistent with the fly mitochondrial localization data.
Supporting Evidence:
PMID:30158546
shopper encodes a homolog of the human sulfite oxidase named SUOX, which localizes to the intermembrane space of mitochondria.
GO:0005758 mitochondrial intermembrane space
TAS
PMID:30158546
The sulfite oxidase Shopper controls neuronal activity by re... 		ACCEPT
Summary: Author statement that SUOX-family sulfite oxidase localizes to the intermembrane space.
Reason: Correct specific compartment.
Supporting Evidence:
PMID:30158546
shopper encodes a homolog of the human sulfite oxidase named SUOX, which localizes to the intermembrane space of mitochondria.
GO:0006790 sulfur compound metabolic process
IBA
GO_REF:0000033 		MODIFY
Summary: Sulfur compound metabolic process by phylogenetic inference (PTN008570343).
Reason: Correct but very general; the specific process supported by fly genetics is sulfide oxidation (GO:0019418, defined as conversion of sulfide to sulfite or sulfate), already annotated (IMP).
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Proposed replacements: sulfide oxidation
GO:0006790 sulfur compound metabolic process
IEA
GO_REF:0000041 		MODIFY
Summary: Sulfur compound metabolic process from UniPathway.
Reason: Correct but general; replace with sulfide oxidation as for the IBA row.
Proposed replacements: sulfide oxidation
GO:0008482 sulfite oxidase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Sulfite oxidase activity by phylogenetic inference (PTN008570343; donors fly shop, rat Suox, Arabidopsis SOX).
Reason: Core activity, also shown directly in flies; shop appearing among its own donors reflects its experimental annotation.
Propagation Review
Root cause: NO FAILURE CORE
Supporting Evidence:
PMID:30158546
The sulfite oxidase activity is drastically reduced upon lack of shopper either by ubiquitous suppression (Act5C-Gal4) or in shopper-deficient animals (Df(1)shopper+4) compared to controls.
GO:0008482 sulfite oxidase activity
IDA
PMID:30158546
The sulfite oxidase Shopper controls neuronal activity by re... 		ACCEPT
Summary: Sulfite oxidase activity measured in larval extracts; reduced in shop mutants/RNAi and increased on overexpression.
Reason: Direct fly evidence for the core activity.
Supporting Evidence:
PMID:30158546
The sulfite oxidase activity is drastically reduced upon lack of shopper either by ubiquitous suppression (Act5C-Gal4) or in shopper-deficient animals (Df(1)shopper+4) compared to controls.
GO:0008482 sulfite oxidase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Sulfite oxidase activity from ARBA, Rhea RHEA:24600 and EC 1.8.3.1.
Reason: Core activity.
Supporting Evidence:
PMID:30158546
The sulfite oxidase activity is drastically reduced upon lack of shopper either by ubiquitous suppression (Act5C-Gal4) or in shopper-deficient animals (Df(1)shopper+4) compared to controls.
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000002 		MODIFY
Summary: Oxidoreductase activity from InterPro.
Reason: Uninformative parent; replace with sulfite oxidase activity, already annotated.
Proposed replacements: sulfite oxidase activity
GO:0019418 sulfide oxidation
IMP
PMID:38416643
Identifying potential dietary treatments for inherited metab... 		ACCEPT
Summary: shop mutants (isolated sulfite oxidase deficiency model) show cysteine/sulfite/thiosulfate-sensitive phenotypes.
Reason: Sulfite oxidase performs the final step of sulfide oxidation (sulfite to sulfate, within the GO definition "conversion of sulfide to sulfite or sulfate"); fly genetics show that shop mutants are sensitive to sulfite and thiosulfate. Core process.
Supporting Evidence:
PMID:38416643
Adding sulfite (the substrate of sulfite oxidase) or thiosulfate to the Cys-free diet significantly reduced the health of shop larvae (and not controls)
GO:0020037 heme binding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Heme binding by phylogenetic inference (PTN008570343; donor rat Suox).
Reason: Animal sulfite oxidases carry an N-terminal cytochrome b5 heme domain that relays electrons to cytochrome c; correct cofactor term, non-core.
Propagation Review
Root cause: NO FAILURE NON CORE
GO:0020037 heme binding
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: Heme binding from the cytochrome b5 heme-binding InterPro domain.
Reason: Correct cofactor term; non-core, as for the IBA row.
GO:0030151 molybdenum ion binding
IEA
GO_REF:0000002 		MODIFY
Summary: Molybdenum ion binding from InterPro.
Reason: Molybdenum is bound as part of the molybdopterin cofactor rather than as a free ion; molybdopterin cofactor binding (GO:0043546), already annotated (IBA), is the more accurate term.
Proposed replacements: molybdopterin cofactor binding
GO:0030642 intracellular sulfate ion homeostasis
IMP
PMID:30158546
The sulfite oxidase Shopper controls neuronal activity by re... 		MARK AS OVER ANNOTATED
Summary: Intracellular sulfate ion homeostasis inferred from shop mutants (Otto et al. 2018).
Reason: The cached full text reports reduced sulfite oxidase activity and elevated sulfite levels in shop mutants, not measurements of sulfate; a change in metabolite levels caused by loss of the enzyme reflects its catalytic activity, not a role in sulfate homeostasis. The term is likely an over-interpretation, though supplementary data were not checked.
Supporting Evidence:
PMID:30158546
In addition to the sulfite oxidase activity levels, we tested the sulfite levels and found corresponding phenotypes.
GO:0043546 molybdopterin cofactor binding
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: Molybdopterin cofactor binding by phylogenetic inference (PTN008570343).
Reason: Sulfite oxidase is a molybdopterin enzyme; correct and specific cofactor term, non-core.
Propagation Review
Root cause: NO FAILURE NON CORE
GO:0070013 intracellular organelle lumen
IEA
GO_REF:0000117 		MODIFY
Summary: Intracellular organelle lumen from ARBA.
Reason: Correct but very general; the specific lumen is the mitochondrial intermembrane space, already annotated.

Core Functions

Sulfite oxidase activity: molybdopterin-dependent oxidation of sulfite to sulfate in the mitochondrial intermembrane space, the terminal step of sulfur oxidation from cysteine and sulfide; required in ensheathing glia to keep sulfite low.

Molecular Function:
sulfite oxidase activity
Directly Involved In:
sulfide oxidation
Cellular Locations:
mitochondrial intermembrane space
Supporting Evidence:
  • PMID:30158546
    The sulfite oxidase activity is drastically reduced upon lack of shopper either by ubiquitous suppression (Act5C-Gal4) or in shopper-deficient animals (Df(1)shopper+4) compared to controls.
  • PMID:30158546
    shopper encodes a homolog of the human sulfite oxidase named SUOX, which localizes to the intermembrane space of mitochondria.

References

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Suggested Questions for Experts

Q: Why is Shopper function specifically required in ensheathing glia, and is sulfite toxicity or downstream glutamate imbalance the proximate cause of the locomotor defect?

Suggested Experiments

Experiment: Measure sulfite, thiosulfate and sulfate in glia-specific shop knockdown larvae by LC-MS and test rescue by targeting a heterologous sulfite oxidase to the intermembrane space.

Hypothesis: Sulfite accumulation in ensheathing glia, rather than sulfate deficiency, drives the shop phenotype.

Deep Research

Falcon

(shop-deep-research-falcon.md)

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FlyBase

(shop-deep-research-flybase.md)
FlyBase gene description for shop (DROME) FlyBase

FlyBase gene description for shop (DROME)

shopper (shop) encodes a mitochondrial sulfite oxidase that catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the hydrogen sulfide oxidation.

📚 Additional Documentation

Notes

(shop-notes.md)

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