COX20 encodes a mitochondrial inner-membrane assembly chaperone required for maturation and assembly of mitochondrially encoded Cox2, subunit 2 of cytochrome c oxidase (respiratory complex IV). Cox20 binds newly synthesized precursor Cox2, supports its Imp1-dependent processing and Cox18-linked topogenesis, stabilizes unassembled Cox2, and enables Cox2 incorporation into complex IV. Stress and programmed-cell-death phenotypes are supported but are secondary to this core Cox2/complex IV assembly function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved mitochondrial localization is correct for Cox20. Reason: Cox20 is a conserved mitochondrial complex IV assembly factor and yeast experimental evidence places it at the mitochondrial inner membrane. Supporting Evidence: PMID:10671482 Cox20p, a 23.8-kDa protein of the mitochondrial inner membrane file:interpro/panther/PTHR31586/PTHR31586-metadata.yaml Family Name: CYTOCHROME C OXIDASE PROTEIN 20 |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic complex IV assembly inference is well supported. Reason: Cox20 family members are cytochrome c oxidase assembly factors, and yeast Cox20 is experimentally required for Cox2 maturation and complex IV assembly. Supporting Evidence: PMID:10671482 Cox20p acts as a membrane-bound chaperone necessary for cleavage of pCox2p and for interaction of the mature protein with other subunits of cytochrome oxidase |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Automated inner-membrane localization is consistent with direct yeast evidence. Reason: Cox20 is an integral mitochondrial inner-membrane protein acting on Cox2 maturation intermediates. Supporting Evidence: PMID:10671482 a 23.8-kDa protein of the mitochondrial inner membrane |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based complex IV assembly annotation is correct. Reason: The Cox20 domain family is specific to cytochrome c oxidase assembly factors and is supported by yeast experimental evidence. Supporting Evidence: file:yeast/COX20/COX20-deep-research-falcon.md Cox20 functions in the Complex IV assembly pathway, specifically in the COX2 maturation/assembly module. |
| GO:0005515 protein binding | IPI PMID:10671482 Identification of Cox20p, a novel protein involved in the ma... | MODIFY | Summary: Cox20 physically binds Cox2, but generic protein binding is less informative than the specific chaperone activity. Reason: The same study shows Cox20 acts as a membrane-bound chaperone for Cox2 maturation and assembly; protein folding chaperone better captures this in situ membrane-protein maturation role than generic protein binding. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:10671482 Cox20p specifically binds the newly synthesized pCox2p |
| GO:0043069 negative regulation of programmed cell death | IDA PMID:31752220 A Role for COX20 in Tolerance to Oxidative Stress and Progra... | KEEP AS NON CORE | Summary: The stress assay supports reduced programmed-cell-death markers with COX20 expression, but this is not Cox20's core conserved function. Reason: The phenotype is defensible as a stress-context effect, likely downstream of Cox2/complex IV function and mitochondrial redox physiology. Supporting Evidence: PMID:31752220 Overexpression of COX20 reduced the presence of apoptotic cells |
| GO:0043069 negative regulation of programmed cell death | IMP PMID:31752220 A Role for COX20 in Tolerance to Oxidative Stress and Progra... | KEEP AS NON CORE | Summary: Mutant/overexpression phenotypes support a non-core role in programmed-cell-death tolerance under oxidative stress. Reason: The annotation should be preserved as context-specific stress biology, but core curation should emphasize Cox2 maturation and complex IV assembly. Supporting Evidence: PMID:31752220 deleting COX20 significantly increased the number of apoptotic and necrotic cells |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: High-throughput mitochondrial proteomics localization is consistent with Cox20 biology. Reason: Cox20's core function occurs in mitochondria, specifically at the inner membrane. Supporting Evidence: PMID:10671482 mitochondrial inner membrane |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | ACCEPT | Summary: Mitochondrial localization is correct. Reason: Multiple lines of evidence support mitochondrial localization, and the more precise inner-membrane annotation is also present. Supporting Evidence: PMID:10671482 mitochondrial inner membrane |
| GO:0005743 mitochondrial inner membrane | IDA PMID:10671482 Identification of Cox20p, a novel protein involved in the ma... | ACCEPT | Summary: Direct inner-membrane localization is central to Cox20 function. Reason: Cox20 must act at the inner membrane to bind newly synthesized Cox2 and support its processing/topogenesis. Supporting Evidence: PMID:10671482 Cox20p, a 23.8-kDa protein of the mitochondrial inner membrane |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:10671482 Identification of Cox20p, a novel protein involved in the ma... | ACCEPT | Summary: Mutant evidence directly supports complex IV assembly. Reason: Cox20 loss disrupts Cox2 maturation and cytochrome oxidase assembly, making this the core biological-process annotation. Supporting Evidence: PMID:10671482 Cox20p acts as a membrane-bound chaperone necessary for cleavage of pCox2p and for interaction of the mature protein with other subunits of cytochrome oxidase |
| GO:0051082 unfolded protein binding | IDA PMID:10671482 Identification of Cox20p, a novel protein involved in the ma... | MODIFY | Summary: The direct evidence supports Cox2-specific chaperoning rather than generic unfolded protein binding. Reason: Cox20 binds newly synthesized pCox2 and stabilizes/handles Cox2 assembly intermediates in the mitochondrial inner membrane, which is better captured as protein folding chaperone activity than as a cytosolic carrier role. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:10671482 Cox20p acts as a membrane-bound chaperone |
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Download this section (compressed HTML)Q: Which Cox2 maturation step is most directly dependent on Cox20 under normal respiratory growth: pCox2 processing, C-tail export, Cox2 stabilization, or handoff to later complex IV modules?
Suggested experts: mitochondrial assembly experts, yeast respiratory-chain biochemists
Q: Is the programmed-cell-death protection phenotype a direct Cox20 activity or an indirect consequence of altered Cox2/complex IV assembly and mitochondrial redox state?
Suggested experts: mitochondrial stress-response researchers
Experiment: Pulse-label mitochondrially translated Cox2 after acute Cox20 depletion and quantify pCox2 processing, C-tail export, Cox20-Cox18 association, and complex IV incorporation over time.
Hypothesis: Cox20 loss first destabilizes or misroutes Cox2 maturation intermediates before global complex IV assembly defects accumulate.
Type: time-resolved Cox2 assembly assay
Experiment: Test oxidative-stress and programmed-cell-death phenotypes in cox20 alleles that separate Cox2 binding, Imp1 processing support, and Cox18-linked topogenesis.
Hypothesis: COX20-dependent programmed-cell-death tolerance tracks with a specific Cox2 maturation step rather than an independent anti-apoptotic activity.
Type: stress epistasis assay
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Download this section (compressed HTML)Mitochondrial inner membrane protein; required for proteolytic processing of Cox2p and its assembly into cytochrome c oxidase
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