CG42331 (FBgn0259233; historical annotation symbols CG13632 and CG6879) encodes an uncharacterized animal-type haem peroxidase of Drosophila melanogaster. The gene makes two distinct polypeptides. CG42331-PB/PD (UniProt Q9VC42, 1615 aa) has an N-terminal signal peptide, and CG42331-PC (UniProt Q9VC41, 1439 aa) is an N-terminally truncated isoform that starts at residue 177 of the long form and so lacks the signal peptide. Both isoforms carry one complete animal haem peroxidase (An_peroxidase, PF03098) domain, followed by a long C-terminal region of about 850 residues that is largely disordered and has no recognised domains. The residues needed for catalysis are all present: the distal His proton acceptor, the transition-state Arg, the proximal His heme ligand, the Asp and Glu that link the heme covalently, and the Ca2+-binding loop. The protein is therefore predicted to be an active heme-dependent peroxidase that uses H2O2 to oxidise a substrate, but neither the substrate nor its physiological role is known. The long isoform is predicted to be secreted. In the PANTHER tree, CG42331 forms its own subfamily (SF109) within an insect-specific expansion of peroxidases. Its closest relatives are other fly paralogs: Pxd, CG4009, CG10211 and cardinal (cd), which acts in ommochrome pigment synthesis. It has no one-to-one ortholog in vertebrates or nematodes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003006 developmental process involved in reproduction | IEA GO_REF:0000117 | REMOVE | Summary: ARBA machine-learning association rule assigning a broad reproductive developmental process. No experimental or expression evidence links CG42331 to reproduction. Reason: This rests only on an ARBA association rule, presumably keyed on peroxidase family membership. The reproductive (chorion hardening/oogenesis) roles in this insect expansion belong to Pxt (SF4, a different lineage under PTN007509807) and to Pxd-clade proteins (SF86), not to the CG42331 lineage (SF109), which branches separately at the polytomy PTN008518854. The PAINT curators propagated only peroxidase activity (IBD at PTN000158755) across the family and no reproductive process, which we read as a deliberate decision. A process inherited from family membership would also not establish that this protein does any of the work of a reproductive process. Supporting Evidence: file:DROME/CG42331/CG42331-bioinformatics/RESULTS.md PTN008518854 is a Drosophila-specific duplication node and resolves as a polytomy of three lineages file:DROME/CG42331/CG42331-deep-research-falcon.md No 2023–2024 publication specifically establishing CG42331/Q9VC41 function, substrate, localization, pathway, or phenotype was identified in the searches. |
| GO:0004601 peroxidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Q9VC41 has one complete animal haem peroxidase domain (IPR019791, PF03098, PS50292). All the PROSITE-ProRule catalytic and heme-linking residues are conserved: Asp85, His86, Arg214, Glu217 and His318. The same term is assigned by IBA to the long isoform (Q9VC42), inherited from the PAINT node PTN000158755, which is seeded by experimentally characterised peroxidases including the fly paralog Pxd. Reason: Peroxidase activity is the core predicted function. The domain is intact and the catalytic residues are conserved, and the PAINT IBD for peroxidase activity sits at a deep node above the whole animal haem peroxidase clade that contains SF109. No evidence suggests that the activity has been lost in this lineage. The physiological electron donor is unknown, so the generic term is as specific as the evidence allows. The UniProt CAUTION line about missing conserved residues does not refer to any of the core catalytic residues, all of which are present (see RESULTS.md). Supporting Evidence: file:DROME/CG42331/CG42331-uniprot.txt Belongs to the peroxidase family. file:DROME/CG42331/CG42331-uniprot.txt Reaction=H2O2 + AH2 = A + 2 H2O; Xref=Rhea:RHEA:30275, file:DROME/CG42331/CG42331-bioinformatics/RESULTS.md The UniProt CAUTION line ("Lacks conserved residue(s) required for the propagation of feature annotation") therefore does not mean that a core catalytic residue is missing. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | UNDECIDED | Summary: UniProt's "Secreted" location comes from an ARBA rule. The long isoform of the same gene (Q9VC42, CG42331-PB/PD) has a predicted signal peptide (residues 1-22), so the gene's main product is plausibly secreted, like most animal haem peroxidases. The benchmark accession Q9VC41 (CG42331-PC), however, starts at residue 177 of the long form and has no signal peptide. Reason: Extracellular localisation is plausible for the signal-peptide-bearing isoform. For Q9VC41 itself, no secretion signal is evident and no localisation data exist. Whether the PC isoform is translated, and where it goes, cannot be decided from the available evidence. The only source is an ARBA prediction, which is not independent support. Supporting Evidence: file:DROME/CG42331/CG42331-bioinformatics/RESULTS.md Q9VC42 has a predicted signal peptide at residues 1..22, which Q9VC41 lacks. |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO mapping from the haem peroxidase superfamily signature. No data link CG42331 to oxidative stress responses. Reason: Animal haem peroxidases use H2O2 as a co-substrate for biosynthetic and defensive oxidations, such as extracellular matrix cross-linking, chorion hardening, pigment synthesis and halide oxidation. Using H2O2 is not the same as responding to oxidative stress. The PAINT curators did not propagate this process across PTHR11475, and nothing specific to CG42331 supports it. Supporting Evidence: file:DROME/CG42331/CG42331-deep-research-falcon.md Membership in a haem-peroxidase family suggests a possible oxidation/peroxide-related role, but participation in ROS defense, extracellular crosslinking, cyclooxygenase metabolism, or neurogenesis is unproven. |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000104 | MODIFY | Summary: UniRule-based assignment of the generic oxidoreductase term. It is true, but it is a broad ancestor of the peroxidase activity that the domain and active-site evidence support. Reason: The term is correct but too general. The evidence supports the more specific peroxidase activity (GO:0004601), which this gene already carries. Proposed replacements: peroxidase activity Supporting Evidence: file:DROME/CG42331/CG42331-uniprot.txt Belongs to the peroxidase family. |
| GO:0020037 heme binding | IEA GO_REF:0000002 | ACCEPT | Summary: Animal haem peroxidases bind heme b covalently through ester links from a conserved Asp and Glu, and coordinate it through the proximal His. In Q9VC41, Asp85, Glu217 and His318 are all conserved. Reason: Heme is the catalytic cofactor of the peroxidase domain, and the residues that bind it are conserved. This annotation correctly records cofactor binding. Supporting Evidence: file:DROME/CG42331/CG42331-uniprot.txt Name=heme b; Xref=ChEBI:CHEBI:60344; Evidence={ECO:0000256|PROSITE- file:DROME/CG42331/CG42331-bioinformatics/RESULTS.md Asp85 and Glu217 are the covalent heme links. |
| GO:0022412 cellular process involved in reproduction in multicellular organism | IEA GO_REF:0000117 | REMOVE | Summary: ARBA association rule. There is no evidence for a reproductive role of CG42331. Reason: Same reasoning as for GO:0003006. The reproductive roles in this fly peroxidase expansion belong to other lineages (Pxt in SF4, and the Pxd clade). PAINT did not propagate any reproductive process to this node, and no expression, mutant or biochemical data for CG42331 support the term. Supporting Evidence: file:DROME/CG42331/CG42331-bioinformatics/RESULTS.md Its sister lineages within PTN007509807 are cysu (SF106) and the Pxt (SF4) plus Irc (SF125) clade. |
| GO:0048646 anatomical structure formation involved in morphogenesis | IEA GO_REF:0000117 | REMOVE | Summary: ARBA association rule for a very broad developmental process. No phenotype or expression data exist for CG42331. Reason: There is no gene-specific evidence. A morphogenesis process inherited from family membership is uninformative, and it would not establish participation even if a phenotype were found. Morphogenetic roles in the family, such as Pxn in basement membrane formation or cysu in wing cuticle, belong to other subfamilies. Supporting Evidence: file:DROME/CG42331/CG42331-deep-research-falcon.md CG42331/Q9VC41 ≠ Cysu/CG5873. |
| GO:0098869 cellular oxidant detoxification | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Inferred automatically from peroxidase activity by an inter-ontology link. Animal haem peroxidases are mostly extracellular enzymes that use H2O2 to drive specific oxidations, not cellular detoxification systems. Reason: The automatic link from peroxidase activity to oxidant detoxification fits peroxiredoxins and glutathione peroxidases, but does not fit secreted animal haem peroxidases. These use H2O2 for biosynthetic or defensive oxidations, such as cross-linking, pigment formation and hypohalous acid production. Nothing indicates that CG42331 protects cells by detoxifying peroxide. Supporting Evidence: file:DROME/CG42331/CG42331-deep-research-falcon.md Membership in a haem-peroxidase family suggests a possible oxidation/peroxide-related role, but participation in ROS defense, extracellular crosslinking, cyclooxygenase metabolism, or neurogenesis is unproven. |
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Download this section (compressed HTML)Q: Is the CG42331-PC transcript (which encodes Q9VC41, without the signal peptide) translated, and if so, is the product intracellular? This would test whether the extracellular location applies to all products of the gene.
Q: What substrate does CG42331 oxidise, and does the long disordered C-terminal region target it to a particular extracellular structure (for example cuticle, matrix or a pigment granule)?
Experiment: Express the peroxidase domain recombinantly and measure guaiacol/ABTS peroxidase activity, with a His86 (distal His) mutant as a negative control.
Type: biochemical enzyme assay
Experiment: Tag the endogenous gene and compare where the PB/PD and PC isoforms localise in tissues where the gene is expressed (for example the esophagus, according to Bgee).
Type: localization
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