CMC2

Summary: Phylogenetic propagation of mitochondrial localization across the CMC1/CMC2 family.

Reason: Correct but generic; the intermembrane space rows from EXP, IDA, IEA and TAS evidence are more informative.

Summary: UniProt-derived inner membrane localization. Cmc2 is a peripheral membrane protein on the intermembrane space face.

Reason: Consistent with UniProt, which records peripheral membrane association, but in slight tension with the Bax-release proteomics that recovers Cmc2 as releasable. Best read as peripheral association; the intermembrane space term is primary.

Summary: UniProt-derived intermembrane space localization.

Reason: Consistent with the EXP and IDA evidence on the target.

Summary: Mutant phenotype evidence that Cmc2 is essential for cytochrome c oxidase biogenesis, from the study that identified it as a Cmc1 homologue and demonstrated the Cmc1-Cmc2 interaction.

Reason: The primary functional evidence for this gene. Core biological process.

Summary: High-throughput mitochondrial localization.

Reason: Correct but generic; subsumed by the intermembrane space rows. No supporting_text is attached: the cached record is a proteome-scale survey that does not name this protein in its text, so no verbatim quotation can carry the claim.

Summary: Nuclear localization from the genome-wide C-terminal GFP fusion library, contradicted by every other localization source for this protein.

Reason: Flagged because it conflicts with everything else known about this protein, not because the evidence behind it could not be inspected. CMC2 is a twin CX9C substrate of the MIA40-ERV1 disulfide relay, and there is no described route by which such a protein reaches the nucleus: import commits it to the intermembrane space, where its two disulfides are oxidatively trapped. The call is contradicted by Bax-release IMS proteomics (EXP), direct assay localization (IDA), the phylogenetic and InterPro assignments, Reactome, and the UniProt subcellular location, and no other source of any kind places this protein in the nucleus. Cmc2 is additionally a peripheral inner-membrane protein complexed with Cmc1. The most likely explanation is that C-terminal GFP fusion blocked import and the mislocalized fusion was scored outside mitochondria - the same library gives this protein a cytoplasmic call too. Marked over-annotated rather than removed so a curator with access to the original images can make the final call; REMOVE would be defensible. No supporting_text is attached: the cached record is abstract-only and does not name this protein, so no verbatim quotation can carry the claim - the paper's contribution here is the genome-wide localization call itself, which lives in its image dataset.

Summary: Cytoplasmic localization from the genome-wide C-terminal GFP fusion library. A cytosolic pool is expected for a MIA40 substrate, which dwells in the cytosol before import.

Reason: Mia40-pathway substrates genuinely occupy the cytosol before import - twin CX9C proteins remain there for several minutes while awaiting the disulfide relay - so a cytosolic signal for this protein is biologically expected rather than anomalous. The C-terminal GFP tag used by this library can also block import, so this row may partly report a tagging artifact, but nothing known about the protein contradicts a genuine cytosolic pool. Accepted as a correct compartment and kept non-core because the functionally relevant pool - the one that acts on the copper delivery pathway - is the intermembrane space one. No supporting_text is attached: the cached record is abstract-only and does not name this protein, so no verbatim quotation can carry the claim - the paper's contribution here is the genome-wide localization call itself, which lives in its image dataset.

Summary: Direct experimental placement in the intermembrane space by Bax-release proteomics.

Reason: Targeted IMS proteomics with high coverage of the known soluble IMS proteome, and the strongest single localization evidence for this protein.

Summary: Reactome traceable author statement placing Cmc2 in the intermembrane space.

Reason: Consistent with the direct evidence; adds nothing independent.

Summary: SGD's explicit 'no data' placeholder for molecular function.

Reason: Correct and worth preserving. No catalytic or binding activity has been demonstrated for this protein, and the ND placeholder is an accurate statement of the state of knowledge. It should be retired only when a real molecular function is shown, not replaced with a generic binding term. The same honest-unknown pattern holds across COA4, COX23, CMC2 and PET191 - four intermembrane space assembly factors in this pathway whose molecular functions remain genuinely undetermined. For Cmc2 specifically, UniProt's suggestion that it may act in copper trafficking to cytochrome c oxidase and Sod1 is explicitly hedged and undemonstrated; it must not be converted into a metallochaperone or copper-binding annotation. No supporting_text is attached: this row asserts the absence of demonstrated activity, and no quotation can evidence an absence. The argument for keeping it is the reasoning above, not a citation.

Summary: Direct assay intermembrane space localization from the family-wide twin Cx9C survey, which also established MIA40-dependent import for this protein.

Reason: Consistent with all other localization evidence and mechanistically grounded in the import route. No supporting_text is attached: this reference is abstract-only in the cache and its abstract never places the protein in this compartment, so no verbatim quotation can carry the claim. The localization rests on the other rows for this term, not on this one.

Summary: Evidence for a role in respiratory chain complex assembly at the general level; the gene's complex IV-specific role is annotated separately.

Reason: Faithful to the cited study, which assayed respiratory chain function generally rather than complex IV specifically, so this is a correct annotation and not a defect. The gene also carries the complex IV-specific GO:0033617 from focused studies, so nothing is lost by leaving this parent term in place. Treated the same way as the redundant-parent GO:0008535 row on COX19: a correct-but-general parent is kept non-core, not rewritten. Re-pointing it would be a curation-policy change rather than a correction.