yueD

Summary: IBA to sepiapterin reductase from the PTHR44085 node.

Reason: The IBA node groups bacterial benzil/carbonyl reductases with animal SPRs. No Bacillus family member has been assayed with sepiapterin, and the characterized B. cereus ortholog acts on aromatic diketones. Whether the PAINT node placement correctly includes this low-identity bacterial branch cannot be settled without the tree; it needs PAINT-curator review rather than removal on similarity grounds.

Summary: Keyword-mapped cytoplasm location; consistent with a soluble SDR lacking targeting signals.

Reason: Soluble SDR-family reductase with no signal peptide or transmembrane segment. B. subtilis YueD itself has never been localized, so the supporting quote below is from the 41%-identical B. cereus ortholog, where a GFP fusion was imaged directly; it is cited as the inference source, not as evidence about this protein. UniProt reaches the same conclusion the same way (ECO:0000250|UniProtKB:Q8RJB2).

Summary: ISS from B. cereus YueD (GFP-cytoplasm).

Reason: Soluble SDR; transfer from a 41%-identical characterized ortholog is reasonable.

Summary: IBA to tetrahydrobiopterin biosynthetic process.

Reason: Bacillus subtilis is not known to synthesize tetrahydrobiopterin, and there is no evidence it has the dedicated animal BH4 pathway. A process cannot be inherited into an organism that lacks the pathway, even if the enzyme could reduce sepiapterin in vitro (PATHWAY_CONTEXT_IGNORED).

Summary: Combined IEA driven by RHEA:25968 mapped to the EC 1.1.1.- grouping class.

Reason: This IEA is generated from the RHEA:25968 narrowMatch xref on the grouping class GO:0016616, which was added when GO:0102306 was obsoleted. It is not wrong, but it is uninformative; a RHEA reaction mapped to an EC-incomplete grouping class yields annotations that say nothing about substrate class. Replace with GO:0004090 (and fix the xref upstream: RHEA:25968 should be a narrowMatch of GO:0004090, as its sister reaction RHEA:31891 already is). As with the ISS row, this protein has never been assayed, so the quote below is from the B. cereus ortholog and stands as the inference source. Homology at 41% identity carries the reaction class but not the substrate: GO:0004090 names a chemistry (NADPH-dependent reduction of a ketone to a secondary alcohol) that every characterized member of this family performs, whereas GO:0004757 would assert a specific pterin substrate that no Bacillus family member has been tested on. That asymmetry is why this row is refined to a broad reaction term while the sepiapterin reductase IBA is left UNDECIDED.

Proposed replacements: carbonyl reductase (NADPH) activity

Summary: ISS from B. cereus YueD benzil reductase activity.

Reason: Transfer from the 41%-identical B. cereus enzyme is reasonable at the level of an NADPH carbonyl reductase, but the grouping class is uninformative. Use GO:0004090, matching the specific activity of the donor. (Benzil-specific GO:0102306 was obsoleted as non-physiological.)

Proposed replacements: carbonyl reductase (NADPH) activity