Pet191 is a 108-residue twin CX9C protein required for cytochrome c oxidase maturation in yeast, and the ortholog of human COA5. It resides in the mitochondrial intermembrane space associated with the inner membrane, where its motif cysteines are present in disulfide linkages within a large oligomeric complex; the motif cysteines are functionally important. Pet191 is unusual among twin CX9C proteins in that its import is independent of the MIA40 pathway. It has been proposed to stabilize an early cytochrome c oxidase assembly intermediate until displaced by copper metallochaperone action, but no molecular function has been demonstrated.
| 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 and inner membrane rows are more informative. Supporting Evidence: PMID:18503002 The twin-Cx(9)C motif protein Pet191 is essential for cytochrome c oxidase |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic propagation of the complex IV assembly role, seeded partly from this gene's own experimental annotations and from human COA5. Reason: Directly supported on the target by IMP evidence in two independent studies three decades apart. Core biological process. The gene's own SGD id in the WITH/FROM is expected and correct. Supporting Evidence: PMID:18503002 The twin-Cx(9)C motif protein Pet191 is essential for cytochrome c oxidase |
| GO:0005758 mitochondrial intermembrane space | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt-derived intermembrane space localization. Reason: Consistent with the IDA evidence on the target, including Bax-release IMS proteomics. Supporting Evidence: PMID:22984289 From the known 31 soluble IMS proteins, 29 proteins...were reproducibly identified, corresponding to a coverage of >90% |
| GO:0005743 mitochondrial inner membrane | IDA PMID:18503002 Pet191 is a cytochrome c oxidase assembly factor in Saccharo... | KEEP AS NON CORE | Summary: Direct assay inner membrane localization: Pet191 is associated with the inner membrane within a large oligomeric complex. Reason: A genuine direct observation, and consistent with UniProt's note that Pet191 is imported into the intermembrane space. Best read as peripheral association on the intermembrane space face; the intermembrane space term is the primary compartment. Supporting Evidence: PMID:18503002 present in disulfide linkages within a large oligomeric complex associated with...the mitochondrial inner membrane. The import of Pet191 differs from that of |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | KEEP AS NON CORE | 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. |
| GO:0005739 mitochondrion | HDA PMID:16823961 Toward the complete yeast mitochondrial proteome: multidimen... | KEEP AS NON CORE | Summary: High-throughput mitochondrial localization from a second proteomic survey. Reason: Same as the other HDA row: correct organelle, subsumed by the sub-compartment evidence. 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. |
| 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 intermembrane space assembly factors in this pathway whose molecular functions remain genuinely undetermined. For Pet191 specifically, UniProt's description of it stabilizing an early assembly intermediate until displaced by a copper metallochaperone is a model rather than a demonstrated activity, and should not be converted into a chaperone or 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. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:22984289 Intermembrane space proteome of yeast mitochondria. | ACCEPT | Summary: Direct assay intermembrane space localization 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:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:18503002 Pet191 is a cytochrome c oxidase assembly factor in Saccharo... | ACCEPT | Summary: Mutant phenotype evidence that Pet191 is essential for cytochrome c oxidase maturation, with the twin Cx9C motif cysteines functionally important. Reason: The primary modern characterization of this gene. It also establishes the striking exception that Pet191 import is independent of the Mia40 pathway, unlike every other twin Cx9C protein in this set - a mechanistic difference worth carrying into any family-level inference. Core biological process. Supporting Evidence: PMID:18503002 The twin-Cx(9)C motif protein Pet191 is essential for cytochrome c oxidase |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IMP PMID:8381337 Sequence and chromosomal localization of two PET genes requi... | ACCEPT | Summary: Mutant phenotype evidence from the original cloning of PET191 as a gene required for assembly of active cytochrome c oxidase whose product is not a subunit of the final complex. Reason: The founding evidence for this gene, and an early explicit statement that Pet191 is an assembly factor rather than a structural subunit. Supporting Evidence: PMID:8381337 are required for the assembly of active...yet their gene products are not subunits |
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Download this section (compressed HTML)Q: Pet191 import is independent of the MIA40 pathway, unlike every other twin CX9C protein in this pathway. What is the import route, and does the difference reflect a distinct functional role?
Suggested experts: Winge lab, Herrmann lab
Q: What is the large oligomeric complex in which Pet191 resides? Its composition has never been determined, and it is the most obvious route to a molecular function for this protein.
Suggested experts: Winge lab, Barrientos lab
Q: Human COA5 is the ortholog and is disease-associated. Is the yeast evidence sufficient to support annotation transfer, given the divergent import route?
Suggested experts: GO Consortium PAINT curators
Experiment: Determine the composition of the Pet191 complex by blue-native PAGE followed by mass spectrometry, in wild-type and in strains blocked at defined steps of complex IV assembly.
Hypothesis: The Pet191-containing oligomeric complex is an early cytochrome c oxidase assembly intermediate.
Type: biochemical
Experiment: Screen import mutants for failure to accumulate Pet191 in mitochondria, and test in vitro import of Pet191 into mitochondria depleted of candidate receptors.
Hypothesis: Pet191 uses an import receptor distinct from MIA40.
Type: genetic
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