PET100 is a small (73 aa) single-pass mitochondrial inner-membrane protein that functions as a Complex IV (cytochrome c oxidase, COX)-specific assembly chaperone. It is the human ortholog of yeast Pet100p and belongs to the PET100 family. PET100 is non-catalytic; it promotes incorporation of the early nuclear-encoded COX subunits (the COX7/COX8 group, exemplified by its conserved interaction with COX subunit VIIa, COX7A2) into an early COX assembly intermediate, forming a ~300 kDa subcomplex with Complex IV subunits in the mitochondrial inner membrane. Loss of PET100 function causes isolated mitochondrial complex IV deficiency (mitochondrial complex IV deficiency nuclear type 12; Leigh syndrome), with reduced COX levels and activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005743 mitochondrial inner membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assignment of PET100 to the mitochondrial inner membrane, consistent with its yeast ortholog Pet100p and with direct experimental evidence in human. This is the correct, specific subcellular location and a core aspect of PET100 biology. Reason: PET100 is experimentally localized to the mitochondrial inner membrane, where it acts as a COX assembly chaperone. The IBA is fully concordant with the human experimental data. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a PMID:22356826 corroborating the conserved interaction of fungal Pet100p-subunit VIIa that takes place in the inner mitochondrial membrane of yeast |
| GO:0044183 protein folding chaperone | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA molecular-function annotation as a "protein folding chaperone". PET100 is a COX-specific assembly/scaffolding chaperone that promotes incorporation of early COX subunits, but there is no evidence that it catalyzes or assists protein folding per se. This over-interprets its assembly role as a folding activity. Reason: PET100 has no demonstrated protein-folding-catalysis function; its documented role is binding COX subunits (e.g. COX7A2) and promoting their incorporation into the assembling complex. Notably the UniProt-listed PAN-GO molecular function is the binding term GO:0051082 (unfolded protein binding), not folding activity. The IBA is not overtly wrong (PET100 is chaperone-like) so it is retained as an over-annotation rather than removed, per curation policy for phylogenetically reviewed annotations. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: SGD:S000002486 · PET100 (S. cerevisiae Pet100p) Yeast Pet100p is a COX-specific assembly chaperone; the phylogenetic MF transfer over-labels this assembly/scaffolding role as protein-folding activity. Supporting Evidence: PMID:22356826 The subunit VIIa of COX (encoded by the COX7A2 gene) was specifically co-purified with PET100 |
| GO:0051131 chaperone-mediated protein complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IBA biological-process annotation describing PET100's chaperone-mediated role in assembling a protein complex. This accurately captures the mechanism by which PET100 promotes incorporation of COX subunits into Complex IV and complements the more specific GO:0033617. Reason: PET100 acts as a chaperone that mediates assembly of the cytochrome c oxidase complex, interacting with COX7A2 and forming an early ~300 kDa COX subcomplex. This is a valid, mechanism-oriented characterization consistent with the literature. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a PMID:22356826 The subunit VIIa of COX (encoded by the COX7A2 gene) was specifically co-purified with PET100 |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation to Complex IV assembly. This is the core biological process of PET100: it is a COX-specific assembly factor essential for Complex IV maturation and assembly, and its loss causes isolated Complex IV deficiency. Reason: Strongly supported by experimental data in human (PET100 mutations cause isolated complex IV deficiency; PET100 forms an early COX subcomplex) and by orthology to yeast Pet100p, a COX assembly factor. This is the central function of the gene. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a PMID:22356826 The subunit VIIa of COX (encoded by the COX7A2 gene) was specifically co-purified with PET100 |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to mitochondrion (from InterPro/UniProt SubCell mapping). Correct but general; the specific location is the mitochondrial inner membrane. Reason: PET100 is a mitochondrial protein; this parent term is accurate. It is retained as a correct, if less specific, location annotation alongside the inner-membrane term. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (SubCell mapping) annotation to the mitochondrial inner membrane. This is the correct specific location, independently supported experimentally. Reason: Concordant with the experimental EXP and IBA inner-membrane annotations; PET100 is a single-pass inner-membrane protein. Supporting Evidence: file:human/PET100/PET100-uniprot.txt Mitochondrion inner membrane |
| GO:0006457 protein folding | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Electronic annotation to "protein folding", derived by inter-ontology logical inference from the "protein folding chaperone" MF (GO:0044183). It inherits the over-interpretation of PET100's assembly role as a folding process. Reason: This BP is an automatic consequence of the over-annotated GO:0044183 MF (see the with/from GO:0044183). PET100 promotes assembly/incorporation of COX subunits but is not documented to participate in protein folding. Marked as over-annotated rather than removed because the underlying chaperone characterization is not overtly wrong. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a |
| GO:0016020 membrane | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Electronic annotation to the root "membrane" term (from the SubCell "single-pass membrane protein" mapping). Uninformative given the specific mitochondrial inner-membrane annotation. Reason: "membrane" is an unspecific location that adds no information beyond the more precise GO:0005743 (mitochondrial inner membrane). It reflects the generic single-pass-membrane-protein SubCell keyword rather than a distinct localization. Supporting Evidence: file:human/PET100/PET100-uniprot.txt Single-pass membrane protein |
| GO:0033617 mitochondrial respiratory chain complex IV assembly | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation to Complex IV assembly, based on the Pet100 domain (IPR018625). Concordant with the IBA and experimental evidence for the core function. Reason: The InterPro Pet100 signature is a reliable predictor of Complex IV assembly function; this duplicate of the core BP is correct. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput proteomics (mitochondrial proteome) localization to mitochondrion. Correct but general; consistent with the specific inner-membrane location. Reason: Independent HTP proteomic support for PET100's mitochondrial localization. Retained as a correct parent-level location. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a |
| GO:0005743 mitochondrial inner membrane | EXP PMID:24462369 A founder mutation in PET100 causes isolated complex IV defi... | ACCEPT | Summary: Experimental (EXP) localization of PET100 to the mitochondrial inner membrane, where it forms a ~300 kDa subcomplex with Complex IV subunits. This is the definitive, experimentally established core location. Reason: Directly demonstrated in the disease study establishing PET100's function; the strongest evidence for the inner-membrane location and the anchor for the other inner-membrane annotations. Supporting Evidence: PMID:24462369 located in the mitochondrial inner membrane and forms a |
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Download this section (compressed HTML)Q: Which specific early COX subunits (COX7A2/COX7B/COX8A and orthologs) does human PET100 directly engage, and does it act sequentially or as a scaffold that couples their incorporation into the assembling Complex IV?
Q: Does PET100 have any binding-type molecular function that could be captured by a more informative GO term than "protein folding chaperone", and if so what is its structural basis given the single transmembrane helix?
Experiment: Perform complexome profiling / BN-PAGE with quantitative mass spectrometry in PET100-null versus wild-type cells to define which COX assembly intermediate stalls in the absence of PET100 and which subunits fail to be incorporated.
Experiment: Use crosslinking mass spectrometry or co-immunoprecipitation of tagged PET100 to map its direct interaction partners among COX subunits and other assembly factors, and to test the proposed role in incorporating the early COX7/COX8 subunit group.
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