Cox23 is a 151-residue intermembrane space protein required for cytochrome c oxidase assembly, and a homologue of the copper chaperone Cox17. Deletion causes respiratory deficiency; the defect is rescued by high copper in the medium, but only when COX17 is simultaneously present on a high-copy plasmid, placing Cox23 in the mitochondrial copper delivery pathway upstream of or alongside Cox17 rather than as an independent copper donor. A spontaneous suppressor screen later showed that a mutation in Cox1 abrogates the requirement for Cox23, indicating that Cox23 acts on a Cox1-containing assembly intermediate. Cox23 is distributed between the cytosol and the intermembrane space. Despite two decades of genetics, no molecular function has been demonstrated, and SGD's ND placeholder on GO:0003674 remains the accurate summary.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation of mitochondrial localization. Reason: Correct but generic; the intermembrane space rows from EXP, IDA and IEA evidence are more informative. The is_active_in qualifier on an organelle-level term adds little. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and |
| GO:0033108 mitochondrial respiratory chain complex assembly | IBA GO_REF:0000033 | KEEP AS NON CORE | 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: This is a phylogenetic assertion about the ancestral node, not a claim from a single study, and at that level the general term is correct rather than defective. 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. This row is an IBA, which makes rewriting it worse than merely unnecessary: the term records what the PAINT curator judged the ancestral node to support, and target-specific IMP evidence for a more specific term does not license asserting that specificity at the node. Raised for PAINT in suggested_questions instead. Supporting Evidence: PMID:15145942 shown to be required for the expression of cytochrome oxidase |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt-derived cytoplasmic localization. Cox23 genuinely partitions between cytosol and intermembrane space. Reason: A real dual distribution reported in the original characterization and recorded in UniProt, not a tagging artifact. Kept non-core because the functional pool is the intermembrane space one. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt-derived intermembrane space localization. Reason: Consistent with EXP and IDA evidence on the target. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:15145942 COX23, a homologue of COX17, is required for cytochrome oxid... | ACCEPT | Summary: Direct assay placement in the intermembrane space in the study that named and characterized Cox23. Reason: Primary experimental localization, independently confirmed by Bax-release IMS proteomics. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:15145942 COX23, a homologue of COX17, is required for cytochrome oxid... | ACCEPT | Summary: Mutant phenotype evidence that Cox23 is required for expression of cytochrome oxidase, with the respiratory defect rescued by copper only in the presence of high-copy COX17. Reason: The founding evidence for this gene and the basis for placing it in the copper delivery pathway. The COX17 dependence of the copper rescue is the key genetic result: it argues Cox23 acts through the copper pathway rather than as an independent donor. Core biological process. Supporting Evidence: PMID:15145942 shown to be required for the expression of cytochrome oxidase |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:28357365 Cox1 mutation abrogates need for Cox23 in cytochrome c oxida... | ACCEPT | Summary: Mutant phenotype evidence from a suppressor screen showing that a Cox1 mutation abrogates the requirement for Cox23. Reason: Independent IMP confirmation by a different group, and mechanistically informative: it places Cox23's action on a Cox1-containing assembly intermediate, consistent with the AlphaFold-predicted COX23-COX1 contact reported in 2026 - though that prediction has had no experimental follow-up. Supporting Evidence: PMID:28357365 Cox23 is a known conserved assembly factor for cytochrome c oxidase, although...we isolated spontaneous suppressors of the |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | KEEP AS NON CORE | Summary: Cytoplasmic localization from the genome-wide C-terminal GFP fusion library. Reason: Unlike the equivalent rows on COA4 and CMC2, this one is not treated as an artifact, because for Cox23 a cytosolic pool is independently supported by a genuine IDA row from the original characterization and is recorded in UniProt. The GFP-library caveat still applies - C-terminal tagging of small twin CX9C proteins readily blocks MIA40-dependent import and strands the fusion outside mitochondria, so this row adds little independent weight - but the compartment call itself is sound. Kept non-core because the functionally relevant pool is the intermembrane space one. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and...predominantly of cytosolic proteins |
| GO:0005758 mitochondrial intermembrane space | EXP PMID:22984289 Intermembrane space proteome of yeast mitochondria. | ACCEPT | 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. Supporting Evidence: PMID:22984289 From the known 31 soluble IMS proteins, 29 proteins...were reproducibly identified, corresponding to a coverage of >90% |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | 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 of the intermembrane space assembly factors in this pathway whose molecular functions remain genuinely undetermined. 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. |
| GO:0005737 cytoplasm | IDA PMID:15145942 COX23, a homologue of COX17, is required for cytochrome oxid... | KEEP AS NON CORE | Summary: Direct assay cytoplasmic localization from the original characterization. Reason: A genuine dual distribution, unlike the HDA row for the same term. Kept non-core because the intermembrane space pool is the functionally relevant one. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and |
| GO:0005739 mitochondrion | IDA PMID:15145942 COX23, a homologue of COX17, is required for cytochrome oxid... | KEEP AS NON CORE | Summary: Direct assay mitochondrial localization from the original characterization. Reason: Correct but subsumed by the intermembrane space rows. Supporting Evidence: PMID:15145942 Cox23p, like Cox17p, is detected in the intermembrane space of mitochondria and |
| GO:0033108 mitochondrial respiratory chain complex assembly | IMP PMID:19703468 Systematic analysis of the twin cx(9)c protein family. | KEEP AS NON CORE | 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. Supporting Evidence: PMID:19703468 most of these proteins for the assembly or stability of respiratory chain |
Loading supporting content…
Download this section (compressed HTML)Q: Cox23 is one of four intermembrane space assembly factors in this pathway (with COA4, CMC2, PET191) carrying an ND molecular_function placeholder. Is a new GO molecular function term needed for accessory factors that support metallochaperone action without binding metal themselves?
Suggested experts: GO molecular function curation group
Q: AlphaFold-Multimer predicts a conserved COX23-COX1 interaction (doi:10.1038/s41467-026-77112-z), which would fit the Cox1 suppressor genetics. This is a prediction with no experimental follow-up in that paper. Is it worth testing directly?
Suggested experts: Winge lab, Barrientos lab
Q: Should the GO:0033108 IBA on COX23 be re-pointed to the complex IV-specific GO:0033617? Two focused IMP studies give this gene complex IV specificity, but the IBA records the PAINT curator's judgement about the ancestral node, which did not assert that specificity. Re-pointing it would be a claim about the clade, not about this gene.
Suggested experts: GO Consortium PAINT curators
Experiment: Test the predicted Cox23-Cox1 interaction by co-immunoprecipitation from crosslinked mitochondria, as was done successfully for Coa4-Cox11, and ask whether the interaction is lost in the suppressor Cox1 mutant background.
Hypothesis: Cox23 acts on a Cox1-containing assembly intermediate through a direct contact with Cox1.
Type: biochemical
Loading supporting content…
Download this section (compressed HTML)