mcr1

Summary: PTN000452207 deliberately places broad cytochrome-b5 reductase activity at a mixed MCR1/PGA3 eukaryotic node; the NADH-specific child is already captured by the target's Rhea/EC row.

Reason: The PTN000452207 molecular-function assertion is seeded by S. cerevisiae MCR1 and PGA3 at a broad eukaryotic node, so GO:0004128 is an appropriate conserved parent for the mixed node rather than a failed MCR1-specific inference. A. fumigatus mcr1 is separately mapped to EC 1.6.2.2 and the NADH-dependent Rhea reaction used for GO:0090524, making this IBA a correct but non-core parent row.

Summary: PTN000452207 places the MCR1-like subfamily in mitochondria and is consistent with the characterized mitochondrial S. cerevisiae Mcr1 ortholog.

Reason: A. fumigatus mcr1 sits in PTHR19370:SF171 with S. cerevisiae MCR1, whose product is experimentally mitochondrial, and the PAINT node is seeded by fungal MCR1-like proteins. Mitochondrion is an appropriate parent of the inferred mitochondrial outer-membrane localization.

Summary: The UniProt subcellular-location transfer to the mitochondrial outer membrane matches the N-terminally anchored MCR1 family member.

Reason: The A. fumigatus Swiss-Prot record infers a single-pass mitochondrial outer-membrane protein, and the S. cerevisiae ortholog has an experimentally characterized outer-membrane isoform. This is the most specific localization currently available for A. fumigatus mcr1.

Summary: PTN000452208 propagates an inherited S. cerevisiae MCR1 ergosterol-biosynthesis assertion, but no A. fumigatus evidence currently makes the process a core mcr1 function.

Reason: The PAINT assertion comes from an S. cerevisiae MCR1 seed and A. fumigatus mcr1 is in the same MCR1-like branch, so the IBA is retained as an in-clade inherited process annotation. It is not promoted to a core A. fumigatus mcr1 function here because mcr1 has not been assayed in A. fumigatus, and the available CYP51 reconstitution evidence used purified C. albicans CYP51 plus yeast cytochrome b5 and NADH cytochrome-b5 reductase; the abstract does not identify that reductase as a mitochondrial MCR1-like enzyme.

Summary: The ARBA/InterPro method correctly detects a pyridine nucleotide cytochrome reductase, but its oxidoreductase parent is less informative than the Rhea-supported cytochrome-b5 reductase child.

Reason: mcr1 has the conserved CBR-like domains and its UniProt record already maps the protein to the NADH:cytochrome-b5 oxidoreductase reaction. The broad GO:0016491 parent loses the electron donor and acceptor specificity.

Proposed replacements: cytochrome-b5 reductase activity, acting on NADH

Summary: The Rhea/EC mapping captures the expected NADH-dependent cytochrome-b5 reductase activity for A. fumigatus mcr1.

Reason: EC 1.6.2.2 and RHEA:46680 specify reduction of ferricytochrome b5 using NADH. This is the precise molecular-function term for mcr1's conserved cytochrome-b5 reductase domains and should replace the broader GO:0016491 parent term.