mcr-1

UniProt ID: Q7SFY2
Organism: Neurospora crassa OR74A
Review Status: COMPLETE
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Gene Description

Neurospora crassa mcr-1 encodes the MCR1-like member of the fungal NADH-cytochrome b5 reductase family. The protein has the conserved cytochrome-b5 reductase FAD- and NADH-binding regions and a predicted N-terminal transmembrane segment, and is inferred to act as a mitochondrial NADH-dependent cytochrome-b5 reductase.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004128 cytochrome-b5 reductase activity, acting on NAD(P)H
IBA
GO_REF:0000033
TOO GENERAL
Summary: PTN000452207 supports a broad cytochrome-b5 reductase activity at a mixed MCR1/PGA3 eukaryotic node, but 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 the IBA is not a failed MCR1-specific inference. It can support only the NAD(P)H-dependent cytochrome-b5 reductase parent, while Neurospora mcr-1 is separately mapped to EC 1.6.2.2 and the NADH-dependent Rhea reaction used for GO:0090524; the broad GO:0004128 claim is therefore true but entailed by the accepted NADH-specific child term for this target.
Propagation Review
Root cause: NO FAILURE NON CORE
Failure modes: GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN000452207 Β· PANTHER:PTN000452207 SUPPORTS TRANSFER
This broad MCR1/PGA3 node carries a conserved cytochrome-b5 reductase parent term that N. crassa mcr-1 can inherit as an ancestor of the more precise target-specific Rhea/EC row.
Supporting Evidence:
file:interpro/panther/PTHR19370/PTHR19370-paint.tsv
PTHR19370 PTN000452207 GO:0004128 F IBD false
file:genes/NEUCR/mcr-1/mcr-1-uniprot.txt
Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: PTN000452207 places the MCR1-like subfamily in mitochondria and is consistent with the characterized mitochondrial S. cerevisiae Mcr1 ortholog.
Reason: N. crassa mcr-1 sits in PTHR19370:SF171 with S. cerevisiae MCR1, whose product is experimentally sorted to two submitochondrial compartments; PAINT placed the mitochondrion assertion at a eukaryotic node seeded by S. cerevisiae MCR1 and two T. brucei cytochrome-b5 reductase-like proteins. The inferred mitochondrial outer-membrane localization on the N. crassa UniProt record makes mitochondrion the right activity-site granularity for this IBA.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000452207 Β· PANTHER:PTN000452207 SUPPORTS TRANSFER
This node covers the N. crassa mcr-1 subfamily and carries the mitochondrial localization inherited from experimentally characterized S. cerevisiae MCR1 and non-fungal eukaryotic reductase seeds.
Supporting Evidence:
file:interpro/panther/PTHR19370/PTHR19370-paint.tsv
PTHR19370 PTN000452207 GO:0005739 C IBD false
PMID:8001120
The S. cerevisiae gene MCR1 encodes two mitochondrial isoforms of
GO:0005741 mitochondrial outer membrane
IEA
GO_REF:0000044
ACCEPT
Summary: The UniProt subcellular-location transfer to the mitochondrial outer membrane matches the N-terminally anchored mcr-1 family member.
Reason: The N. crassa 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 Neurospora mcr-1.
Supporting Evidence:
file:genes/NEUCR/mcr-1/mcr-1-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion outer membrane {ECO:0000250};
PMID:8001120
This precursor protein is inserted into the outer membrane
GO:0006696 ergosterol biosynthetic process
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: PTN000452208 propagates an inherited S. cerevisiae MCR1 ergosterol-biosynthesis assertion, but no Neurospora evidence currently makes the process a core mcr-1 function.
Reason: The PAINT assertion comes from an S. cerevisiae MCR1 seed and N. crassa mcr-1 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 Neurospora mcr-1 function here because mcr-1 has not been assayed in Neurospora, and the available CYP51 reconstitution evidence used the microsomal cytochrome-b5/NADH-cytochrome-b5-reductase system that corresponds to the ER CBR1 paralog branch rather than this mitochondrial MCR1 branch.
Propagation Review
Root cause: NO FAILURE NON CORE
Sources checked:
PANTHER:PTN000452208 Β· PANTHER:PTN000452208 SUPPORTS TRANSFER
This node propagates the ergosterol-biosynthesis assertion from an S. cerevisiae MCR1 source to an in-clade N. crassa target, but Neurospora mcr-1 lacks direct process evidence.
Supporting Evidence:
file:interpro/panther/PTHR19370/PTHR19370-paint.tsv
PTHR19370 PTN000452208 GO:0006696 P IBD false
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000002
TOO GENERAL
Summary: InterPro correctly detects a pyridine nucleotide cytochrome reductase, but its oxidoreductase parent is less informative than the Rhea-supported cytochrome-b5 reductase child.
Reason: mcr-1 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 and is entailed by GO:0090524 on this protein.
Supporting Evidence:
file:genes/NEUCR/mcr-1/mcr-1-uniprot.txt
InterPro; IPR001834; CBR-like.
GO:0090524 cytochrome-b5 reductase activity, acting on NADH
IEA
GO_REF:0000120
ACCEPT
Summary: The Rhea/EC mapping captures the expected NADH-dependent cytochrome-b5 reductase activity for Neurospora mcr-1.
Reason: EC 1.6.2.2 and RHEA:46680 specify reduction of ferricytochrome b5 using NADH. This is the precise molecular-function term for mcr-1's conserved cytochrome-b5 reductase domains and subsumes the broader GO:0004128 and GO:0016491 parent terms that are also present in GOA.
Supporting Evidence:
file:genes/NEUCR/mcr-1/mcr-1-uniprot.txt
Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +

Core Functions

Predicted FAD-dependent reduction of ferricytochrome b5 using NADH as electron donor in a mitochondrial MCR1-clade protein.

Supporting Evidence:
  • file:interpro/panther/PTHR19370/PTHR19370-paint.tsv
    PTHR19370 PTN000452207 GO:0004128 F IBD false
  • file:genes/NEUCR/mcr-1/mcr-1-uniprot.txt
    Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +

References

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Notes

(mcr-1-notes.md)

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