ATP10

Summary: IBA annotation for mitochondrial inner membrane localization. Atp10p is well-established as a mitochondrial inner membrane protein. Ackerman and Tzagoloff (PMID:2141026) showed the protein is associated with the mitochondrial membrane. Tzagoloff et al. (PMID:14998992) further demonstrated that Atp10p is an inner membrane component that interacts with newly synthesized Atp6p. UniProt also records subcellular location as mitochondrion inner membrane. The IBA annotation is phylogenetically consistent and well supported.

Reason: Core localization for Atp10p, supported by direct experimental evidence (PMID:2141026, PMID:14998992) and phylogenetic inference (IBA). The mitochondrial inner membrane is where Atp10p performs its assembly factor function.

Summary: IBA annotation for mitochondrial ATP synthase complex assembly. This is the core biological process function of Atp10p. The original characterization (PMID:2141026) identified ATP10 as a nuclear gene required for assembly of the mitochondrial F1-F0 complex, and the follow-up study (PMID:14998992) demonstrated that Atp10p specifically assists assembly of Atp6p into the F0 unit. The IBA is phylogenetically sound and well-supported by experimental data.

Reason: This is the core function of Atp10p. Both original and subsequent studies confirm its essential role in ATP synthase assembly, specifically the F0 sector (PMID:2141026, PMID:14998992).

Summary: IEA annotation for mitochondrial inner membrane based on UniProt subcellular location mapping. This is consistent with the IBA annotation and the experimental evidence. UniProt records Atp10p as a mitochondrion inner membrane protein. Redundant with the IBA annotation but not incorrect.

Reason: Consistent with the well-established inner membrane localization of Atp10p. The IEA is a broader qualifier (located_in) compared to the IBA (is_active_in), but both correctly place Atp10p at the mitochondrial inner membrane.

Summary: IPI annotation for generic protein binding, from the large-scale inter-species PPI study by Zhong et al. (PMID:27107014). The WITH/FROM column indicates interaction with UniProtKB:Q6RW13-2 (human AGTRAP isoform 2), a cross-species interaction from a yeast two-hybrid screen. This is a xenologous interaction with no physiological relevance; AGTRAP is a human angiotensin II receptor- associated protein with no known mitochondrial function. The term "protein binding" is uninformative per curation guidelines, and the underlying interaction is not biologically meaningful for Atp10p function.

Reason: GO:0005515 (protein binding) is uninformative per curation guidelines. The underlying evidence is a cross-species yeast two-hybrid interaction with human AGTRAP (Q6RW13-2), which has no physiological relevance to Atp10p function. Atp10p's biologically meaningful interaction is with Atp6p (PMID:14998992), which is better captured by the process annotation for ATP synthase assembly.

Summary: IDA annotation for mitochondrial membrane localization from the original characterization by Ackerman and Tzagoloff (PMID:2141026). They showed that the Atp10p protein is associated with the mitochondrial membrane using antibody detection and fractionation experiments. This is a valid but less specific annotation than the mitochondrial inner membrane (GO:0005743), which is also annotated with stronger evidence. Since the original paper did not specifically demonstrate inner vs. outer membrane localization, the broader term is appropriate for the evidence from that particular paper.

Reason: Valid IDA annotation reflecting the experimental evidence from the original characterization. While less specific than the inner membrane annotation (GO:0005743), it accurately represents what was demonstrated in this particular paper (PMID:2141026). The more specific inner membrane localization is supported by later work.

Summary: HDA annotation for cytoplasm localization from a large-scale proteomics study examining protein localization during DNA replication stress (PMID:22842922). This is a high-throughput study. While Atp10p is a mitochondrial protein, the cytoplasm annotation may reflect detection in the broader cytoplasmic compartment (mitochondria are within the cytoplasm). However, this is a relatively uninformative localization for a protein whose primary function is at the mitochondrial inner membrane. The HDA evidence code indicates high-throughput direct assay.

Reason: The cytoplasm annotation is technically not wrong (mitochondria reside within the cytoplasm), but it is uninformative for Atp10p, whose well-established localization is the mitochondrial inner membrane. This is a high-throughput result that does not add specificity beyond what is already captured by the mitochondrion and inner membrane annotations.

Summary: HDA annotation for mitochondrion localization from a quantitative mitochondrial proteome study during fermentative and respiratory growth (PMID:24769239). Detection of Atp10p in the mitochondrial proteome is fully consistent with its known biology as a mitochondrial inner membrane assembly factor.

Reason: Consistent with the well-established mitochondrial localization of Atp10p. Detection in the mitochondrial proteome confirms the known biology. This is a broader term than GO:0005743 (inner membrane) but correctly reflects the HDA evidence level.

Summary: HDA annotation for mitochondrion localization from a comprehensive mitochondrial proteomics study (PMID:16823961). Atp10p was detected in the yeast mitochondrial proteome, consistent with its known function as a mitochondrial assembly factor.

Reason: Consistent with known biology. Atp10p is an established mitochondrial protein and its detection in high-throughput mitochondrial proteomics is expected and correct.

Summary: HDA annotation for mitochondrion localization from the same DNA replication stress proteomics study that also yielded the cytoplasm annotation (PMID:22842922). Detection of Atp10p in the mitochondrial fraction is expected and consistent with its known biology.

Reason: Consistent with the well-established mitochondrial localization. Duplicate in terms of GO ID with the other HDA annotations from PMID:24769239 and PMID:16823961, but from a different study providing independent HDA evidence.

Summary: IPI annotation for mitochondrial inner membrane localization from Tzagoloff et al. (PMID:14998992). The WITH/FROM column indicates SGD:S000007268 (Atp6p), suggesting the inner membrane localization was inferred from the physical interaction between Atp10p and the inner membrane-integrated Atp6p. The cross-linking experiments demonstrated that Atp10p interacts with Atp6p at the mitochondrial inner membrane. This is strong evidence for inner membrane localization.

Reason: The IPI evidence demonstrates that Atp10p physically interacts with Atp6p (an inner membrane protein) at the mitochondrial inner membrane. The cross-linking data from PMID:14998992 provides direct evidence for this localization.

Summary: IMP annotation for mitochondrial ATP synthase complex assembly from Tzagoloff et al. (PMID:14998992). The mutant phenotype evidence shows that in an atp10 null mutant, Atp6p is less stable and more rapidly degraded, leading to defective F0 assembly. The original paper (PMID:2141026) also showed that mutations in ATP10 cause loss of rutamycin sensitivity, indicating defective F0 sector. This is the core function of Atp10p.

Reason: Strong IMP evidence demonstrating that loss of Atp10p leads to impaired Atp6p stability and defective ATP synthase assembly. This is the central biological process function of Atp10p.

Summary: IPI annotation for mitochondrial ATP synthase complex assembly from Tzagoloff et al. (PMID:14998992), with Atp6p (SGD:S000007268) in the WITH/FROM column. The physical interaction between Atp10p and Atp6p (demonstrated by cross-linking) is directly relevant to the assembly process: Atp10p binds newly synthesized Atp6p and facilitates its incorporation into an intermediate ATPase subcomplex.

Reason: The IPI evidence from cross-linking experiments demonstrates a direct physical interaction between Atp10p and Atp6p during the assembly process. This interaction is the mechanistic basis for Atp10p's role in ATP synthase assembly.

Summary: IPI annotation for unfolded protein binding from Tzagoloff et al. (PMID:14998992), with Atp6p (SGD:S000007268) in the WITH/FROM column. The authors proposed that Atp10p functions as an "Atp6p-specific chaperone" based on cross-linking experiments showing Atp10p interacts with newly synthesized Atp6p. However, Atp10p is not a general unfolded protein binder -- it is a highly specific assembly factor for a single client (Atp6p). It does not bind a range of unfolded proteins, nor does it possess a recognizable chaperone domain. The term GO:0051082 implies a broader substrate specificity than what is demonstrated. Atp10p's function is better described as stabilizing Atp6p during assembly and facilitating its incorporation into the F0 subcomplex, which is an assembly factor activity rather than a general chaperone/unfolded protein binding activity. This is consistent with how other mitochondrial assembly factors (PET100, COX20, SHY1) in this project have been handled, where GO:0051082 was marked as over-annotated. GO:0044183 (protein folding chaperone) is also inappropriate because Atp10p does not actively fold proteins. The most appropriate MF annotation would be GO:0140777 (protein-containing complex stabilizing activity), which captures the stabilization of unassembled subunits during complex assembly, analogous to what IBA already provides for the closely related ATP11 gene.

Reason: Atp10p is a specific assembly factor for Atp6p, not a general unfolded protein binder. The literature (PMID:14998992) explicitly describes it as an "Atp6p-specific chaperone" with a single known client. GO:0051082 implies broader substrate binding that is not supported by evidence. Atp10p does not possess a recognizable chaperone domain and does not actively fold proteins; it stabilizes Atp6p during F0 assembly. This is consistent with the handling of other mitochondrial assembly factors in the UPB project (PET100, COX20, SHY1), where GO:0051082 was marked as over-annotated. GO:0044183 (protein folding chaperone) is also not appropriate because Atp10p does not catalyze protein folding. A better MF annotation would be GO:0140777 (protein-containing complex stabilizing activity), which is already used for the related assembly factor ATP11.

Proposed replacements: protein-containing complex stabilizing activity

Summary: NEW annotation. Atp10p stabilizes newly synthesized Atp6p and facilitates its incorporation into an intermediate ATPase subcomplex (PMID:14998992). In the absence of Atp10p, Atp6p is less stable and more rapidly degraded. This stabilization of an unassembled subunit during complex assembly is precisely what GO:0140777 (protein-containing complex stabilizing activity) captures. The closely related assembly factor ATP11 already has an IBA annotation for this term. This is the most appropriate MF term for Atp10p's molecular function.

Reason: Atp10p stabilizes newly synthesized Atp6p, preventing its degradation and facilitating its incorporation into the ATP synthase F0 sector (PMID:14998992). This is a protein-containing complex stabilizing activity. The related assembly factor ATP11 already carries this annotation via IBA. This term better captures Atp10p's molecular function than GO:0051082 (unfolded protein binding), which overstates the generality of its binding activity.