COX17

Summary: Phylogenetic propagation of intermembrane space localization across the COX17 family, seeded partly from this gene's own experimental annotations.

Reason: Corroborated on the target by EXP proteomics, IDA and TAS. The gene's own SGD id in the WITH/FROM is expected: its experimental annotations are among the descendant evidences behind the IBD.

Summary: Phylogenetic propagation of the complex IV assembly role.

Reason: Directly supported on the target by IMP and IDA evidence. Core biological process.

Summary: Phylogenetic propagation of copper chaperone activity, the defining molecular function of this family.

Reason: Directly demonstrated on the target: purified Cox17 transfers copper specifically to Sco1 and Cox11 in vitro. Core molecular function.

Summary: InterPro-derived copper ion binding from the COX17 family signature IPR007745.

Reason: Correct and directly demonstrated on the target by spectroscopy and calorimetry. Less specific than the cuprous ion binding IDA row, but not wrong.

Summary: InterPro- and UniProt-derived intermembrane space localization.

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

Summary: InterPro-derived copper chaperone activity from IPR007745.

Reason: Correct; the COX17 family signature genuinely predicts this activity and the target has direct experimental support.

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.

Summary: Copper ion transport, from the in vitro demonstration of copper transfer from Cox17 to Sco1 and Cox11.

Reason: A fair reading of the transfer experiments, but the informative statement is the chaperone activity term, which names the mechanism rather than the generic movement of copper. Retained as a correct but less specific process framing.

Summary: Reactome traceable author statement placing Cox17 in the intermembrane space.

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

Summary: Direct assay of copper chaperone activity: purified Cu-Cox17 transfers copper specifically to Sco1 and Cox11, with no transfer to non-cognate acceptors.

Reason: The single best piece of evidence for the core molecular function, and the experiment that established Cox17 as the common copper source for both the CuA and CuB branches.

Summary: High-throughput mitochondrial localization.

Reason: Correct but generic; the intermembrane space rows are more informative.

Summary: High-throughput mitochondrial localization from a second proteomic survey.

Reason: Same as the other HDA row: correct organelle, but subsumed by the sub-compartment evidence.

Summary: Direct assay of Cu(I) binding by isothermal titration calorimetry, with solution structures of the apo and Cu(I)-loaded protein.

Reason: Cuprous ion binding is the chemically precise term and is directly demonstrated. Preferable to the generic copper ion binding IEA row.

Summary: Direct assay localization to the intermembrane space in the study that purified and characterized Cox17.

Reason: Primary experimental localization, later confirmed by IMS proteomics.

Summary: Cytosolic localization from the same purification and localization study. Cox17 genuinely partitions between cytosol and intermembrane space.

Reason: Not an artifact: dual cytosolic and IMS distribution is a real, repeatedly reported property of Cox17 and is recorded in UniProt. Kept non-core because the functionally relevant pool - the one that metallates Sco1 and Cox11 - is the intermembrane space pool.

Summary: Mutant phenotype evidence for copper chaperone activity, supported by spectroscopic demonstration of a bound cuprous-thiolate cluster.

Reason: Independent support for the core molecular function by a different method and group.

Summary: Direct assay evidence for a role in complex IV assembly, from the copper transfer study.

Reason: Consistent with the IMP evidence and with the mechanism: Cox17 supplies the copper that Sco1 and Cox11 insert into Cox2 and Cox1.

Summary: Mutant phenotype evidence: cox17 mutants are respiratory deficient with a block in production of functional cytochrome oxidase, while still expressing both mitochondrially and nuclearly encoded subunits.

Reason: The original characterization of the gene, and the basis for placing Cox17 at a late post-translational step of assembly. Core biological process.

Summary: Protein farnesylation, attributed to Cox17 from a paper that is entirely about a different gene, COX10 (heme A:farnesyltransferase).

Reason: Three independent problems make this a mis-attribution rather than an annotation whose full text merely differs from its abstract. First, the cited reference is titled and abstracted wholly about cloning the human COX10 homolog by complementation of a yeast cox10 mutant; COX10 and COX17 differ by one digit. Second, the term is wrong even for COX10: GO:0018343 is defined as covalent attachment of a farnesyl group to a PROTEIN, whereas heme A:farnesyltransferase farnesylates heme, not protein - so no gene in that paper performs the annotated activity. Third, the row was assigned by MGI against a Saccharomyces cerevisiae UniProt accession. Cox17 is a 69 aa twin CX9C copper chaperone with no farnesyltransferase activity, and the substantial Cox17 literature is uniformly about copper binding and transfer. This is not a case of second-guessing a curator who read a full text that the cache lacks: the annotated activity is absent from the cited work altogether. Recommend reporting to the assigning group. Note that the supporting_text below deliberately quotes PMID:8662933 rather than the cited PMID:8078902: quoting the miscited paper would defeat the point, since the finding is precisely that it supports nothing here. The quote instead establishes what COX17 does.

Summary: Mitochondrial localization sourced from the same mis-attributed COX10 reference as the farnesylation row. The compartment is correct; the evidence chain is not.

Reason: Cox17 is genuinely mitochondrial, and the term is independently supported by two HDA rows, so - unlike the farnesylation row from the same reference - this annotation is not factually wrong and is treated consistently with the other GO:0005739 rows. Its provenance is nonetheless unsound: PMID:8078902 is about COX10 (heme A:farnesyltransferase), not COX17. The row should be re-sourced to a valid reference rather than relied upon as independent evidence. Flagged with the farnesylation row in suggested_questions.