CG18547 encodes a 345-residue soluble aldo-keto reductase (AKR) of the GH17980p-related family (PANTHER PTHR42686), whose characterised members are NAD(P)+-dependent sugar and pyridoxal dehydrogenases (plant L-galactose dehydrogenase, yeast D-arabinose dehydrogenase ARA2). It retains the complete AKR Asp-Tyr-Lys-His catalytic tetrad and is therefore expected to be an active NAD(P)-dependent oxidoreductase, but its physiological substrate, cofactor preference and reaction direction have not been determined. CG18547 is one of three tandem Drosophila paralogs (with CG3397 and CG12224) that are co-orthologous to Caenorhabditis elegans mec-14; the family is absent from vertebrates. Its transcript marks a glutathione S-transferase-rich subpopulation of larval lymph gland prohemocytes. It sits outside the plant and fungal clades in which L-galactose dehydrogenase and erythroascorbate synthesis functions are established, so those pathway roles are not expected in the fly.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0010349 L-galactose dehydrogenase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO transfer of the plant L-galactose dehydrogenase activity via the LGALDH-like signature; CG18547 lies outside the plant clade to which PAINT confined this activity. Reason: IPR044479 (LGALDH-like) matches the whole PTHR42686-type AKR group, which also contains D-arabinose, D-threo-aldose and pyridoxal dehydrogenases, so the signature does not fix substrate. In the PANTHER tree CG18547 diverges from Arabidopsis LGALDH at the Eukaryota node; PAINT placed GO:0010349 only at the land-plant node PTN000920391 and gave the fly gene just the generic oxidoreductase term from the subfamily root. L-galactose oxidation is a step of the plant ascorbate pathway, for which there is no evidence in insects. The catalytic tetrad is intact, so some sugar dehydrogenase activity is possible, but the L-galactose-specific claim is an over-transfer. Supporting Evidence: file:DROME/CG18547/CG18547-bioinformatics/RESULTS.md is propagated to O81884 from PTN000920391 (plant node) file:DROME/CG18547/CG18547-bioinformatics/RESULTS.md LCA with Arabidopsis LGALDH (O81884) is PTN000199432 (Eukaryota) |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT root-node (PTN002448388) inference of oxidoreductase activity, consistent with a complete AKR catalytic tetrad in CG18547. Reason: CG18547 descends from PTN002448388, the PTHR42686:SF1 root at which PAINT placed only the generic oxidoreductase term, using Arabidopsis LGALDH and yeast ARA2 as experimental descendants. The fly protein retains Asp71, Tyr76, Lys102 and His143 aligned to the LGALDH tetrad, so catalytic competence is expected. Because characterised members in the subfamily act on different substrates and PAINT declined to place a more specific term at a node ancestral to the fly gene, this broad term is as precise as the evidence allows. Supporting Evidence: file:DROME/CG18547/CG18547-bioinformatics/RESULTS.md CG18547 retains the complete Asp-Tyr-Lys-His tetrad file:DROME/CG18547/CG18547-uniprot.txt DR Pfam; PF00248; Aldo_ket_red; 1. |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro AKR signature mapping to oxidoreductase activity; concordant with the IBA row. Reason: The full-length AKR domain (Pfam PF00248, residues 38-314) with an intact catalytic tetrad supports generic oxidoreductase activity. Same claim as the IBA row and accepted consistently. Supporting Evidence: file:DROME/CG18547/CG18547-uniprot.txt DR InterPro; IPR020471; AKR. file:DROME/CG18547/CG18547-bioinformatics/RESULTS.md CG18547 retains the complete Asp-Tyr-Lys-His tetrad |
| GO:0070485 dehydro-D-arabinono-1,4-lactone biosynthetic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Sequence-similarity transfer of yeast ARA2's erythroascorbate-pathway role; the fly gene sits in the metazoan clade, outside the fungal node where PAINT placed this process. Reason: Dehydro-D-arabinono-1,4-lactone (D-erythroascorbate) synthesis is a fungal pathway in which ARA2 oxidises D-arabinose and ALO1 completes the route. In the PANTHER tree CG18547 and ARA2 share only the Opisthokont ancestor PTN000199433, and PAINT propagated ARA2's D-arabinose dehydrogenase and GO:0070485 terms only from the fungal node PTN000920371, a deliberate omission for the metazoan clade. There is no evidence that Drosophila makes erythroascorbate. The AKR fold supports oxidoreductase chemistry but not participation in this pathway. Supporting Evidence: file:DROME/CG18547/CG18547-bioinformatics/RESULTS.md LCA with yeast ARA2 (Q04212) is PTN000199433 (Opisthokonts) file:DROME/CG18547/CG18547-bioinformatics/RESULTS.md Neither specific function was placed at a node ancestral to CG18547. |
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Download this section (compressed HTML)Q: Do the three tandem Drosophila paralogs CG18547, CG3397 and CG12224 share a substrate, and is their function related to that of the C. elegans co-ortholog mec-14 in touch receptor neurons?
Q: Should modules/erythroascorbate_biosynthesis use the fungal PAINT node PTN000920371 rather than the whole PTHR42686 family as the selector for the Ara2-type step, given that the family includes metazoan and plant members that do not perform it?
Experiment: Express and purify recombinant CG18547 and screen aldoses, aldehydes and pyridoxal with NAD+ and NADP+ (oxidative) and NADH/NADPH (reductive) to define substrate and cofactor specificity; include a Tyr76Phe tetrad mutant as a catalytic-dead control.
Type: biochemical assay
Experiment: Generate a CG18547 null (and CG18547/CG3397/CG12224 triple) and test lymph gland prohemocyte composition, oxidative-stress tolerance and metabolite profiles against a genomic-rescue control.
Type: genetic loss of function
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