MCR1

UniProt ID: Q59M70
Organism: Candida albicans SC5314
Review Status: COMPLETE
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Gene Description

Candida albicans MCR1 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 eukaryotic node, but the NADH-specific child is already captured by the target's Rhea/EC row.
Reason: PTN000452207 places a molecular-function assertion at a broad eukaryotic node seeded by characterized S. cerevisiae MCR1 and by S. cerevisiae PGA3, a plasma-membrane-associated coenzyme-Q6 reductase in the same PTHR19370:SF143 subfamily as AIM33. The node can support only the NAD(P)H-dependent GO:0004128 parent, while Candida MCR1 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
Sources checked:
PANTHER:PTN000452207 Β· PANTHER:PTN000452207 SUPPORTS TRANSFER
PTN000452207 carries a conserved cytochrome-b5 reductase parent term that C. albicans MCR1 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/CANAL/MCR1/MCR1-uniprot.txt
Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + NAD(+) + H(+); Xref=Rhea:RHEA:46680
GO:0005575 cellular_component
ND
GO_REF:0000015
ACCEPT
Summary: Root cellular component ND annotation: when it was made, no cellular component had been curated for this gene product from literature.
Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the cellular component is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: REMOVE. The gene's notes record a literature search for direct C. albicans MCR1 work that found only expression/proteome or catalog records, none localizing the protein.
Supporting Evidence:
file:CANAL/MCR1/MCR1-notes.md
expression/proteome or product-catalog records rather than MCR1 functional
GO:0005739 mitochondrion
IBA
GO_REF:0000033
ACCEPT
Summary: Candida MCR1 inherits mitochondrial localization from a broad eukaryotic PTN000452207 placement that excludes the descendant AIM33/PGA3 clade.
Reason: C. albicans MCR1 inherits the PTN000452207 mitochondrial assertion, an ancestral eukaryotic node seeded by S. cerevisiae MCR1, while PAINT explicitly withholds that localization from the descendant AIM33/PGA3 node. The inferred mitochondrial outer-membrane localization on the Candida 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
The broad PTN000452207 node carries mitochondrion as a conserved parent localization that C. albicans MCR1 can inherit, while the descendant AIM33/PGA3 branch has an explicit IRD blocking transfer to that plasma-membrane subclade.
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
file:interpro/panther/PTHR19370/PTHR19370-paint.tsv
PTHR19370 PTN001064672 GO:0005739 C IRD true
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 MCR1 family member.
Reason: The C. albicans 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 Candida MCR1.
Supporting Evidence:
file:genes/CANAL/MCR1/MCR1-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 Candida evidence currently makes the process a core MCR1 function.
Reason: The PAINT assertion comes from an S. cerevisiae MCR1 seed and C. albicans 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 Candida MCR1 function here because MCR1 has not been assayed in Candida, 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 C. albicans target, but Candida MCR1 lacks direct process evidence.
Supporting Evidence:
file:interpro/panther/PTHR19370/PTHR19370-paint.tsv
PTHR19370 PTN000452208 GO:0006696 P IBD false
GO:0008150 biological_process
ND
GO_REF:0000015
ACCEPT
Summary: Root biological process ND annotation: when it was made, no biological process had been curated for this gene product from literature.
Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the biological process is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: REMOVE. The gene's notes record a literature search for direct C. albicans MCR1 work that found only expression/proteome or catalog records, none identifying a process.
Supporting Evidence:
file:CANAL/MCR1/MCR1-notes.md
expression/proteome or product-catalog records rather than MCR1 functional
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: 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 and is entailed by GO:0090524 on this protein.
Supporting Evidence:
file:genes/CANAL/MCR1/MCR1-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 Candida 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; the separate GO:0016491 row is a true but too-general parent.
Supporting Evidence:
file:genes/CANAL/MCR1/MCR1-uniprot.txt
Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + NAD(+) + H(+); Xref=Rhea:RHEA:46680

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/CANAL/MCR1/MCR1-uniprot.txt
    Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] + NAD(+) + H(+); Xref=Rhea:RHEA:46680

References

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Notes

(MCR1-notes.md)

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