PET191

UniProt ID: Q02772
Organism: Saccharomyces cerevisiae
Review Status: DRAFT
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Gene Description

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.

Existing Annotations Review

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

Core Functions

Twin CX9C assembly factor for cytochrome c oxidase, residing in the mitochondrial intermembrane space in association with the inner membrane as part of a large oligomeric complex in which its motif cysteines are disulfide linked. Required for cytochrome c oxidase maturation but not a subunit of the mature enzyme. Unlike other twin CX9C proteins of this pathway, its import does not require the MIA40 relay. Its molecular activity is undetermined.

Supporting Evidence:

References

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Suggested Questions for Experts

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

Suggested Experiments

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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