ATP10

UniProt ID: P18496
Organism: Saccharomyces cerevisiae
Review Status: COMPLETE
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Gene Description

ATP10 (Atp10p) is a nuclear-encoded mitochondrial inner membrane protein required for assembly of the F0 sector of the mitochondrial F1-F0 ATP synthase complex. It functions as a specific assembly factor (chaperone) for Atp6p (subunit 6), binding newly synthesized Atp6p on mitochondrial ribosomes and facilitating its incorporation into a partially assembled ATPase subcomplex (PMID:14998992). Atp10p is not a subunit of the mature ATPase complex itself, nor is it a general-purpose chaperone; it acts specifically on Atp6p during the assembly process (PMID:2141026). Mutations in ATP10 cause loss of rutamycin sensitivity and defective F0 assembly (PMID:2141026).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005743 mitochondrial inner membrane
IBA
GO_REF:0000033 		ACCEPT
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.
Supporting Evidence:
PMID:2141026
The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex.
PMID:14998992
Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F(0) sector of the ATPase.
file:yeast/ATP10/ATP10-deep-research-falcon.md
Falcon deep research identifies ATP10 as a mitochondrial inner membrane Atp6-specific assembly factor for ATP synthase F0 biogenesis.
GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly
IBA
GO_REF:0000033 		ACCEPT
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).
Supporting Evidence:
PMID:2141026
A yeast nuclear gene (ATP10) is reported whose product is essential for the assembly of a functional mitochondrial ATPase complex.
PMID:14998992
Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits.
GO:0005743 mitochondrial inner membrane
IEA
GO_REF:0000044 		ACCEPT
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.
Supporting Evidence:
PMID:2141026
The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex.
GO:0005515 protein binding
IPI
PMID:27107014
An inter-species protein-protein interaction network across ... 		MARK AS OVER ANNOTATED
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.
Supporting Evidence:
PMID:27107014
systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network
GO:0031966 mitochondrial membrane
IDA
PMID:2141026
ATP10, a yeast nuclear gene required for the assembly of the... 		ACCEPT
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.
Supporting Evidence:
PMID:2141026
The antibody recognizes a 30-kDa protein present in wild type mitochondria. The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex.
GO:0005737 cytoplasm
HDA
PMID:22842922
Dissecting DNA damage response pathways by analysing protein... 		KEEP AS NON CORE
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.
Supporting Evidence:
PMID:22842922
high-throughput microscopic screening of the yeast GFP fusion collection to develop a systems-level view of protein reorganization following drug-induced DNA replication stress
GO:0005739 mitochondrion
HDA
PMID:24769239
Quantitative variations of the mitochondrial proteome and ph... 		ACCEPT
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.
Supporting Evidence:
PMID:24769239
we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast grown on fermentative (glucose or galactose) and respiratory (lactate) media
GO:0005739 mitochondrion
HDA
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimen... 		ACCEPT
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.
Supporting Evidence:
PMID:16823961
A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE
GO:0005739 mitochondrion
HDA
PMID:22842922
Dissecting DNA damage response pathways by analysing protein... 		ACCEPT
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.
Supporting Evidence:
PMID:22842922
high-throughput microscopic screening of the yeast GFP fusion collection to develop a systems-level view of protein reorganization following drug-induced DNA replication stress
GO:0005743 mitochondrial inner membrane
IPI
PMID:14998992
Atp10p assists assembly of Atp6p into the F0 unit of the yea... 		ACCEPT
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.
Supporting Evidence:
PMID:14998992
Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F(0) sector of the ATPase.
PMID:14998992
following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p
GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly
IMP
PMID:14998992
Atp10p assists assembly of Atp6p into the F0 unit of the yea... 		ACCEPT
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.
Supporting Evidence:
PMID:14998992
Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type.
PMID:2141026
Mutations in ATP10 induce a loss of rutamycin sensitivity in the mitochondrial ATPase but do not affect respiratory enzymes. This phenotype has been correlated with a defect in the F0 sector of the ATPase.
GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly
IPI
PMID:14998992
Atp10p assists assembly of Atp6p into the F0 unit of the yea... 		ACCEPT
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.
Supporting Evidence:
PMID:14998992
following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p. This interaction is required for the integration of Atp6p into a partially assembled subcomplex of the ATPase.
GO:0051082 unfolded protein binding
IPI
PMID:14998992
Atp10p assists assembly of Atp6p into the F0 unit of the yea... 		MARK AS OVER ANNOTATED
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.
Supporting Evidence:
PMID:14998992
Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits.
PMID:14998992
Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F(0) sector of the ATPase.
PMID:2141026
These data suggest that the ATP10 product is not a subunit of the ATPase complex but rather is required for the assembly of the F0 sector of the complex.
GO:0140777 protein-containing complex stabilizing activity
IPI
PMID:14998992
Atp10p assists assembly of Atp6p into the F0 unit of the yea... 		NEW
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.
Supporting Evidence:
PMID:14998992
Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type.
PMID:14998992
Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits.

Core Functions

Atp10p stabilizes newly synthesized Atp6p during assembly of the F0 sector of the mitochondrial ATP synthase. It binds Atp6p after translation on mitochondrial ribosomes and facilitates its incorporation into an intermediate ATPase subcomplex. In the absence of Atp10p, Atp6p is rapidly degraded. This is a protein-containing complex stabilizing activity, not a general chaperone or foldase function.

Molecular Function:
protein-containing complex stabilizing activity
Directly Involved In:
mitochondrial proton-transporting ATP synthase complex assembly
Cellular Locations:
mitochondrial inner membrane
Supporting Evidence:
  • PMID:14998992
    Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits.
  • file:yeast/ATP10/ATP10-deep-research-falcon.md
    Falcon deep research emphasizes Atp6 stabilization and incorporation into F0 assembly intermediates as the core ATP10 function.

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
PMID:14998992
Atp10p assists assembly of Atp6p into the F0 unit of the yeast mitochondrial ATPase.
  • Atp10p cross-links to newly synthesized Atp6p on mitochondrial ribosomes
    "following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p"
  • The Atp10p-Atp6p interaction is required for integration of Atp6p into a partially assembled ATPase subcomplex
    "This interaction is required for the integration of Atp6p into a partially assembled subcomplex of the ATPase"
  • In an atp10 null mutant, Atp6p is less stable and more rapidly degraded
    "Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type"
  • Authors propose Atp10p is an Atp6p-specific chaperone facilitating Atp6p incorporation into the F0 sector
    "we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits"
PMID:16823961
Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.
PMID:2141026
ATP10, a yeast nuclear gene required for the assembly of the mitochondrial F1-F0 complex.
  • ATP10 encodes a 30 kDa protein essential for assembly of a functional mitochondrial ATPase complex
    "A yeast nuclear gene (ATP10) is reported whose product is essential for the assembly of a functional mitochondrial ATPase complex"
  • Mutations in ATP10 cause loss of rutamycin sensitivity indicating defective F0 sector
    "Mutations in ATP10 induce a loss of rutamycin sensitivity in the mitochondrial ATPase but do not affect respiratory enzymes. This phenotype has been correlated with a defect in the F0 sector of the ATPase"
  • ATP10 product is not a subunit of the ATPase but is required for F0 assembly
    "These data suggest that the ATP10 product is not a subunit of the ATPase complex but rather is required for the assembly of the F0 sector of the complex"
  • The protein is associated with the mitochondrial membrane but does not co-fractionate with F1 or F1-F0
    "The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex"
PMID:22842922
Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress.
PMID:24769239
Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae.
PMID:27107014
An inter-species protein-protein interaction network across vast evolutionary distance.
  • Cross-species Y2H interaction reported between yeast Atp10p and human AGTRAP isoform 2; not physiologically relevant
    "systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network"
file:yeast/ATP10/ATP10-deep-research-falcon.md
Falcon deep research report on ATP10
  • Falcon synthesis identifies ATP10 as an Atp6-specific mitochondrial ATP synthase F0 assembly factor and not a general unfolded-protein chaperone.

Suggested Questions for Experts

Q: Should ATP10 receive GO:0140777 protein-containing complex stabilizing activity as a curated molecular-function annotation, replacing the less informative unfolded protein binding term?

Suggested experts: Tzagoloff A, Ackerman SH

Suggested Experiments

Experiment: Measure Atp6p binding, degradation, and incorporation into ATP synthase assembly intermediates in ATP10 mutants and in strains carrying targeted Atp10p interface substitutions.

Hypothesis: Atp10p stabilizes newly synthesized Atp6p during a discrete F0 assembly step rather than functioning as a general chaperone.

Type: mitochondrial ATP synthase assembly assay

📚 Additional Documentation

Deep Research Falcon

(ATP10-deep-research-falcon.md)

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gene_id: ATP10
gene_symbol: ATP10
uniprot_accession: P18496
protein_description: 'RecName: Full=Mitochondrial ATPase complex subunit ATP10;'
gene_info: Name=ATP10; OrderedLocusNames=YLR393W; ORFNames=L8084.8;
organism_full: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
protein_family: Belongs to the ATP10 family. .
protein_domains: ATP10. (IPR007849); ATP-synt_10 (PF05176)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: P18496
  • Protein Description: RecName: Full=Mitochondrial ATPase complex subunit ATP10;
  • Gene Information: Name=ATP10; OrderedLocusNames=YLR393W; ORFNames=L8084.8;
  • Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
  • Protein Family: Belongs to the ATP10 family. .
  • Key Domains: ATP10. (IPR007849); ATP-synt_10 (PF05176)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "ATP10" matches the protein description above
  2. Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'ATP10' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene ATP10 (gene ID: ATP10, UniProt: P18496) in yeast.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: P18496
  • Protein Description: RecName: Full=Mitochondrial ATPase complex subunit ATP10;
  • Gene Information: Name=ATP10; OrderedLocusNames=YLR393W; ORFNames=L8084.8;
  • Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
  • Protein Family: Belongs to the ATP10 family. .
  • Key Domains: ATP10. (IPR007849); ATP-synt_10 (PF05176)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "ATP10" matches the protein description above
  2. Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'ATP10' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene ATP10 (gene ID: ATP10, UniProt: P18496) in yeast.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: ATP10 (UniProt P18496; gene ATP10; systematic ORF YLR393W) in Saccharomyces cerevisiae S288c

0) Mandatory target verification (gene/protein identity)

The literature retrieved and analyzed here concerns the yeast nuclear gene ATP10 and its protein product Atp10p, described as a mitochondrial inner membrane assembly factor required for biogenesis of the F\u2081F\u2092-ATP synthase (complex V) and acting specifically in F\u2092 (membrane) sector assembly by assisting the mitochondrially encoded Atp6 (subunit a). This matches the UniProt target description you provided (P18496; mitochondrial ATPase complex subunit ATP10; S. cerevisiae S288c; ATP10 family). Primary experimental evidence explicitly studies “ATP10/Atp10p” in yeast and is not confounded with unrelated ATP10 symbols from other organisms (tzagoloff2004atp10passistsassembly pages 1-2, ackerman1990atp10ayeast pages 1-2).

Scope note: In the retrieved full-text evidence, the systematic locus YLR393W and domain annotations (e.g., PF05176) are not explicitly stated; these are therefore treated as verified by UniProt context supplied in the prompt rather than re-derived from the papers.

1) Key concepts and definitions (current understanding)

1.1 What ATP10 is (definition)

ATP10/Atp10p is an ATP synthase assembly factor (a non-stoichiometric, non-structural biogenesis factor) required to assemble the mitochondrial ATP synthase, particularly the F\u2092 sector. It is explicitly described as a mitochondrial inner membrane component necessary for biogenesis of the hydrophobic F\u2092 sector (tzagoloff2004atp10passistsassembly pages 1-1, helfenbein2003atp22anuclear pages 6-7).

A central modern definition is that Atp10p behaves as an Atp6-specific chaperone/escort, physically interacting with newly synthesized Atp6 to keep it assembly-competent and to promote its productive incorporation into F\u2092 assembly intermediates (tzagoloff2004atp10passistsassembly pages 1-1).

1.2 What ATP10 is not

Multiple sources emphasize that Atp10p is not a structural subunit of the mature ATP synthase and not the protease responsible for Atp6 N-terminal processing (tzagoloff2004atp10passistsassembly pages 1-1, rak2009assemblyoff0 pages 5-6). Instead, Atp6 precursor processing is linked to Atp23 (with dual roles in processing and assembly), whereas Atp10’s role is chaperone-like and transient during assembly (franco2020modularassemblyof pages 10-13, kabala2022assemblydependenttranslationof pages 1-2).

1.3 Functional context: ATP synthase assembly, modules, and safety

Assembly of the mitochondrial ATP synthase must be tightly controlled because partially assembled membrane proton channels can dissipate membrane potential. A specific rationale given is that subunit-specific assembly factors (like Atp10p) help avoid the accumulation of potentially harmful F\u2092 intermediates that could uncouple/proton-leak (tzagoloff2004atp10passistsassembly pages 6-7).

2) Molecular function and mechanism (best-supported model)

2.1 Physical interaction with Atp6 (subunit a)

A key mechanistic result is that, after Atp6 is synthesized on mitochondrial ribosomes, Atp6 can be cross-linked to Atp10p, providing direct evidence of physical association in vivo and supporting a chaperone/escort model (tzagoloff2004atp10passistsassembly pages 1-1). Consistent with this, reviews and later mechanistic papers describe Atp10 forming a physical complex with newly translated/unassembled Atp6 and promoting its later interaction with the c-ring (Atp9 ring) (franco2020modularassemblyof pages 10-13, rak2009assemblyoff0 pages 5-6, kabala2022assemblydependenttranslationof pages 1-2).

Visual evidence from the 2004 JBC study includes (i) cross-linking/co-immunoprecipitation evidence for Atp10–Atp6 association and (ii) an assembly model diagram placing Atp10 as an Atp6-directed chaperone in late F\u2092 assembly (tzagoloff2004atp10passistsassembly media 861c4845, tzagoloff2004atp10passistsassembly media bd9776b0).

2.2 Atp10’s assembly step: late F\u2092 biogenesis / Atp6 stabilization and incorporation

Functional evidence indicates that without ATP10:
- Atp6 becomes unstable and is degraded more rapidly, and
- specific Atp6-containing assembly intermediates fail to form (tzagoloff2004atp10passistsassembly pages 1-1, tzagoloff2004atp10passistsassembly pages 4-5).

Mechanistically, Atp10 is required for formation of an Atp6-containing oligomeric intermediate (reported as a 54-kDa complex in the 2004 study) while Atp9 oligomerization can proceed independently, indicating Atp10’s specificity toward Atp6-dependent steps (tzagoloff2004atp10passistsassembly pages 4-5).

2.3 Placement in modular assembly pathways

A widely used conceptual framework is the modular assembly model in yeast, in which distinct intermediates form and then merge. In this view:
- an Atp6/Atp8/peripheral-stalk (stator) intermediate forms as a module, and Atp10 associates with this Atp6/Atp8 complex, and
- an F\u2081 + Atp9 ring intermediate forms via a separate route, with later convergence to the mature enzyme (rak2011modularassemblyof pages 1-2, rak2011modularassemblyof pages 8-9).

Reviews synthesize this further by noting that incorporation of the Atp9 ring into larger complexes is accompanied by release of Atp10 (consistent with a transient assembly role) and that Atp10 function overlaps or cooperates with Atp23 in late F\u2092 assembly steps (franco2020modularassemblyof pages 10-13, rak2009assemblyoff0 pages 5-6).

3) Subcellular localization and topology

3.1 Localization (supported)

Atp10p is described as a mitochondrial inner membrane component involved in F\u2092 (membrane sector) biogenesis (tzagoloff2004atp10passistsassembly pages 1-1, helfenbein2003atp22anuclear pages 6-7).

3.2 Membrane topology (limited in retrieved text)

The retrieved evidence does not provide a definitive, explicit statement of Atp10p’s matrix-facing vs intermembrane-space-facing topology. Therefore, any topology beyond “inner membrane associated” should be treated as provisional unless confirmed by additional topology-specific experiments (e.g., protease protection), which were not captured in the accessible text segments.

4) Genetic and biochemical phenotypes of ATP10 loss-of-function

4.1 Respiratory growth phenotype

Classic pet mutants in ATP10 show very poor growth on non-fermentable carbon sources (e.g., glycerol), consistent with loss of oxidative phosphorylation capacity (ackerman1990atp10ayeast pages 2-3, ackerman1990atp10ayeast pages 3-3).

4.2 Coupling/inhibitor sensitivity phenotypes (rutamycin/oligomycin)

Because inhibitor sensitivity depends on functional coupling between F\u2081 and F\u2092:
- Wild-type mitochondrial ATPase is strongly rutamycin-inhibitable, whereas ATP10 mutants show markedly reduced rutamycin inhibition—supporting defective F\u2081–F\u2092 coupling/assembly (ackerman1990atp10ayeast pages 3-4, ackerman1990atp10ayeast pages 3-3).
- Independent quantitative data in ATP10 mutant backgrounds show reduced oligomycin inhibition of ATPase activity compared with wild type (zeng2007themetalloproteaseencoded pages 2-3).

4.3 Genetic stability / petite frequency

In the Ackerman & Tzagoloff characterization, the ATP10 mutant isolate E103 showed accumulation of only about 10–15% cytoplasmic petite derivatives upon prolonged subculturing, indicating the respiratory defect is not dominated by rampant mtDNA loss in that context (ackerman1990atp10ayeast pages 2-3).

5) Quantitative statistics and experimental data (selected)

5.1 ATPase activity differences (WT vs atp10)

Ackerman & Tzagoloff (1990) report markedly reduced mitochondrial ATPase specific activity in atp10 mutants, e.g.:
- WT: 5.40 units/mg vs atp10 mutant E103: 0.77 units/mg (ackerman1990atp10ayeast pages 4-5).

They also report ATPase distribution differences between mitochondrial and post-mitochondrial fractions (WT 20 and 3 vs mutant 12 and 9 in one described experiment), consistent with altered F\u2081 association/coupling (ackerman1990atp10ayeast pages 3-4).

5.2 Rutamycin inhibition (coupling readout)

In the same study, rutamycin inhibition was reported as:
- WT: ~70–80% inhibited
- atp10 mutants: ~10–20% inhibited (ackerman1990atp10ayeast pages 3-3, ackerman1990atp10ayeast pages 3-4).

5.3 Oligomycin inhibition (additional quantitative evidence)

A table in Zeng et al. (2007) includes ATPase measurements (no inhibitor vs + oligomycin) showing:
- WT: 4.70 \u2192 0.42 (\u223c91% inhibition)
- W303 ATP10 mutant entries: inhibition reduced to 6%, 32%, or 42% (with reduced absolute ATPase activity) (zeng2007themetalloproteaseencoded pages 2-3).

5.4 Atp6 stability/assembly (qualitative with strong visual support)

Tzagoloff et al. (2004) provide evidence that Atp6 steady-state levels are markedly reduced and newly synthesized Atp6 is degraded more rapidly in an atp10 null mutant, consistent with Atp10 functioning to protect Atp6 from proteolysis and/or incorporate it into protease-resistant assembly intermediates (tzagoloff2004atp10passistsassembly pages 1-1, tzagoloff2004atp10passistsassembly media 4e9d59c3). The precise degradation rate constants were not extracted from available figure text.

6) Recent developments and latest research context (prioritizing 2023–2024 where possible)

6.1 Direct ATP10-specific advances in 2023–2024: limited in retrieved full text

Within the retrieved 2023–2024 papers, explicit ATP10-focused mechanistic advances were not recoverable from the accessible text segments. A 2024 systems-level chemogenomic study on weak-acid tolerance emphasizes the importance of functional mitochondria/ATP supply for stress tolerance but does not, in the sections accessed here, specify ATP10 itself as a named determinant (mota2024sharedandmore pages 19-20).

A 2023/2024 eLife article on phosphate budgeting and mitochondrial repression was retrieved, but the accessible portions reviewed did not contain explicit ATP10 mentions; it does, however, illustrate modern quantitative phenotyping (e.g., oxygen consumption rate, mitochondrial phosphate pools) that is increasingly used to connect metabolic state to mitochondrial function (vengayil2024thedeubiquitinaseubp3usp10 pages 11-12, vengayil2024thedeubiquitinaseubp3usp10 pages 12-13).

6.2 Most recent explicit mechanistic framing available in this evidence set

The most recent work in the retrieved corpus that explicitly describes Atp10’s mechanistic role is Kabala et al. 2022 (Genetics), which places Atp10 (and Atp23) in the context of assembly-dependent translation feedback for mitochondrially encoded ATP synthase subunits, describing Atp10 as physically associating with newly translated Atp6 and promoting Atp6 interaction with the c-ring (kabala2022assemblydependenttranslationof pages 1-2).

7) Current applications and real-world implementations

7.1 ATP10 mutants as tools to study complex V biogenesis and coupling

ATP10 mutants are used as classical nuclear respiratory-deficient (pet) mutants to dissect ATP synthase assembly via biochemical fractionation, inhibitor sensitivity, and reconstitution experiments (ackerman1990atp10ayeast pages 1-2, ackerman1990atp10ayeast pages 3-4).

7.2 ATP10 perturbation as a probe of mitochondrially encoded subunit regulation

Modern work uses assembly-factor mutants (including ATP10-linked steps) to investigate how assembly defects feedback to mitochondrial translation output, helping to explain how subunits encoded in two genomes are produced in appropriate stoichiometry (kabala2022assemblydependenttranslationof pages 1-2).

8) Expert synthesis and interpretation

Collectively, the strongest evidence supports ATP10 as a late-stage, subunit-specific assembly factor for ATP synthase F\u2092 assembly. It appears to (i) bind newly made Atp6, (ii) prevent its premature degradation, and (iii) facilitate its incorporation into Atp6/Atp8/stator intermediates and subsequent productive association with the Atp9 ring to complete the proton channel (tzagoloff2004atp10passistsassembly pages 1-1, tzagoloff2004atp10passistsassembly pages 4-5, rak2011modularassemblyof pages 1-2, franco2020modularassemblyof pages 10-13).

This interpretation is consistent across primary mechanistic experiments (cross-linking and assembly intermediates), genetic/biochemical phenotyping (respiratory growth defect; inhibitor insensitivity), and integrative modular-assembly models (tzagoloff2004atp10passistsassembly pages 1-1, rak2011modularassemblyof pages 8-9, rak2009assemblyoff0 pages 5-6).

9) Evidence summary table

Category Localization Molecular function Pathway/module Key interaction(s) Mutant phenotype Quantitative data Key references
Identity Mitochondrial inner membrane Nuclear-encoded ATP synthase assembly factor, not a stoichiometric ATP synthase subunit Complex V (F1Fo-ATP synthase) biogenesis Defined as ATP10/Atp10p required for F1Fo assembly in yeast Respiratory-deficient pet mutant class when defective Complementing gene contains a 792-bp ORF encoding a ~30.3 kDa protein; complementing insert narrowed from ~8 kb to 2.2 kb (ackerman1990atp10ayeast pages 4-5) Ackerman & Tzagoloff 1990; Tzagoloff et al. 2004 (tzagoloff2004atp10passistsassembly pages 1-1, ackerman1990atp10ayeast pages 1-2)
Localization Mitochondrial inner membrane Post-translational assembly factor acting on membrane sector F0 Late F0 assembly Associates with newly synthesized mitochondrial Atp6p after translation Loss disrupts membrane assembly of F0 while F1 remains only loosely membrane associated Inner-membrane localization stated explicitly; no matrix/intermembrane-space topology detail recovered in accessible text (tzagoloff2004atp10passistsassembly pages 1-1, helfenbein2003atp22anuclear pages 6-7) Tzagoloff et al. 2004; Helfenbein et al. 2003 (tzagoloff2004atp10passistsassembly pages 1-1, helfenbein2003atp22anuclear pages 6-7)
Molecular function Inner membrane site of action Atp6p-specific chaperone/assembly factor that maintains Atp6p in an assembly-competent state and promotes its incorporation into F0 Ordered/modular ATP synthase assembly Newly translated Atp6p can be cross-linked to Atp10p In atp10 null mitochondria, Atp6-containing assembly intermediates fail to form and Atp6 is destabilized The Atp6-containing 54-kDa oligomer is absent in atp10 null mitochondria (tzagoloff2004atp10passistsassembly pages 4-5, tzagoloff2004atp10passistsassembly pages 1-1) Tzagoloff et al. 2004 (tzagoloff2004atp10passistsassembly pages 4-5, tzagoloff2004atp10passistsassembly pages 1-1)
Pathway/module Inner membrane F0 assembly zone Functions specifically in Atp6 incorporation rather than Atp9 ring formation Modular assembly model with separate Atp6/Atp8/stator and F1/Atp9-ring intermediates Atp10p is associated with the Atp6p/Atp8p complex and promotes later interaction with the Atp9 ring Assembly arrest occurs after c-ring formation but before productive Atp6 integration Atp6p/Atp8p intermediate sediments at ~150–200 kDa; smaller Atp6-containing oligomer reported at 54 kDa (rak2011modularassemblyof pages 8-9, rak2011modularassemblyof pages 1-2, tzagoloff2004atp10passistsassembly pages 4-5) Rak et al. 2011; Tzagoloff et al. 2004 (rak2011modularassemblyof pages 8-9, rak2011modularassemblyof pages 1-2, tzagoloff2004atp10passistsassembly pages 4-5)
Key interaction(s) Mitochondrial inner membrane Transient assembly interactions, not permanent residence in mature enzyme Late F0 assembly and proton-channel completion Physical complex with newly translated Atp6; functionally linked to Atp23 and to Atp9-ring joining atp10 mutants accumulate Atp6-deficient subcomplexes Review consensus: Atp10 promotes favorable interaction of Atp6 with the 9(10)-ring; extra ATP23 can partially rescue atp10 defects (franco2020modularassemblyof pages 10-13, rak2009assemblyoff0 pages 5-6, kabala2022assemblydependenttranslationof pages 1-2) Rak 2009; Franco 2020; Kabala et al. 2022 (franco2020modularassemblyof pages 10-13, rak2009assemblyoff0 pages 5-6, kabala2022assemblydependenttranslationof pages 1-2)
Mutant phenotype Mitochondria / respiratory growth context Defect is primarily in F0 assembly/coupling rather than total F1 synthesis Oxidative phosphorylation F1 remains partly mitochondria-associated but functionally uncoupled from normal F0 assembly Very poor growth on non-fermentable carbon sources such as glycerol; respiratory deficiency After mechanical breakage, ~50% of F1 remains with mitochondrial fraction in mutant; ATPase units in mitochondrial/post-mitochondrial fractions were 12/9 in mutant vs 20/3 in WT (ackerman1990atp10ayeast pages 3-4) Ackerman & Tzagoloff 1990 (ackerman1990atp10ayeast pages 3-4)
Quantitative data Isolated mitochondria ATPase activity strongly reduced in atp10 mutants ATP synthase functional output Defective inhibitor-sensitive coupling to F0 Partial inhibitor sensitivity indicates impaired but not absent coupling Mitochondrial ATPase specific activity: 5.40 units/mg in WT vs 0.77 units/mg in atp10 mutant El03; mutant ATPase was about 50% of WT in another assay context (ackerman1990atp10ayeast pages 4-5, ackerman1990atp10ayeast pages 2-3) Ackerman & Tzagoloff 1990 (ackerman1990atp10ayeast pages 4-5, ackerman1990atp10ayeast pages 2-3)
Quantitative data ATPase assays with rutamycin/oligomycin Inhibitor sensitivity reports coupling state of assembled ATP synthase F0-dependent ATPase inhibition WT enzyme strongly inhibitor-sensitive, atp10 mutant only partially so Supports defective F0 assembly and coupling Rutamycin inhibition: WT ~70–80% vs atp10 mutants ~10–20%; oligomycin table values: WT 4.70 to 0.42 ATPase units (91% inhibition) vs ATP10 mutant isolates with 1.90→1.78 (6%), 2.63→1.80 (32%), and 1.80→1.05 (42%) (ackerman1990atp10ayeast pages 3-4, zeng2007themetalloproteaseencoded pages 2-3, ackerman1990atp10ayeast pages 3-3) Ackerman & Tzagoloff 1990; Zeng et al. 2007 (ackerman1990atp10ayeast pages 3-4, zeng2007themetalloproteaseencoded pages 2-3, ackerman1990atp10ayeast pages 3-3)
Quantitative data Long-term culture / genetic stability atp10 lesions are recessive nuclear mutations with limited petite accumulation Respiratory mutant maintenance Not an mtDNA-instability-first phenotype Mutants remain relatively genetically stable despite respiratory defect Only ~10–15% cytoplasmic petite derivatives accumulate on prolonged subculturing (ackerman1990atp10ayeast pages 2-3, ackerman1990atp10ayeast pages 3-3) Ackerman & Tzagoloff 1990 (ackerman1990atp10ayeast pages 2-3, ackerman1990atp10ayeast pages 3-3)
Key references Mitochondrial ATP synthase assembly literature Current consensus: Atp10 is a transient, Atp6-directed assembly factor, not the Atp6 processing protease and not a structural subunit F0/complex V biogenesis; assembly-dependent translational feedback Atp10 acts with Atp23 and Atp9-ring assembly logic in modern models atp10 mutants are used experimentally to dissect ATP synthase assembly and ATP6/ATP9 translational feedback Most recent explicit mechanistic source retrieved is 2022, which places Atp10 in assembly-dependent regulation of Atp6/Atp9 expression (kabala2022assemblydependenttranslationof pages 1-2) Kabala et al. 2022; Franco 2020; Rak et al. 2011 (kabala2022assemblydependenttranslationof pages 1-2, franco2020modularassemblyof pages 10-13, rak2011modularassemblyof pages 8-9)

Table: This table condenses the key identity, localization, mechanism, pathway placement, interaction partners, mutant phenotypes, and quantitative measurements for S. cerevisiae ATP10/Atp10p. It is designed as a citation-traceable reference for functional annotation of the UniProt P18496 protein.

10) Key cited sources (with URLs and publication dates)

  • Ackerman SH, Tzagoloff A. ATP10, a yeast nuclear gene required for the assembly of the mitochondrial F1-F0 complex. J Biol Chem. 1990-06. https://doi.org/10.1016/S0021-9258(19)38763-0 (ackerman1990atp10ayeast pages 2-3, ackerman1990atp10ayeast pages 4-5)
  • Tzagoloff A, Barrientos A, Neupert W, Herrmann JM. Atp10p Assists Assembly of Atp6p into the F0 Unit of the Yeast Mitochondrial ATPase. J Biol Chem. 2004-05. https://doi.org/10.1074/jbc.M401506200 (tzagoloff2004atp10passistsassembly pages 1-1, tzagoloff2004atp10passistsassembly media bd9776b0)
  • Rak M, Zeng X, Brière J-J, Tzagoloff A. Assembly of F0 in Saccharomyces cerevisiae. Biochim Biophys Acta. 2009-01. https://doi.org/10.1016/j.bbamcr.2008.07.001 (rak2009assemblyoff0 pages 5-6)
  • Rak M, Gokova S, Tzagoloff A. Modular assembly of yeast mitochondrial ATP synthase. EMBO J. 2011-03. https://doi.org/10.1038/emboj.2010.364 (rak2011modularassemblyof pages 1-2, rak2011modularassemblyof pages 8-9)
  • Franco LVR, Su C-H, Tzagoloff A. Modular assembly of yeast mitochondrial ATP synthase and cytochrome oxidase. Biological Chemistry. 2020-05. https://doi.org/10.1515/hsz-2020-0112 (franco2020modularassemblyof pages 10-13)
  • Kabala AM et al. Assembly-dependent translation of subunits 6 (Atp6) and 9 (Atp9) of ATP synthase in yeast mitochondria. Genetics. 2022-01. https://doi.org/10.1093/genetics/iyac007 (kabala2022assemblydependenttranslationof pages 1-2)
  • Zeng X, Neupert W, Tzagoloff A. The Metalloprotease Encoded by ATP23 Has a Dual Function in Processing and Assembly of Subunit 6 of Mitochondrial ATPase. Mol Biol Cell. 2007-02. https://doi.org/10.1091/mbc.e06-09-0801 (zeng2007themetalloproteaseencoded pages 2-3)
  • Mota MN et al. Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids. Microbial Cell Factories. 2024-02. https://doi.org/10.1186/s12934-024-02309-0 (mota2024sharedandmore pages 19-20)

Limitations of this report (transparency)

1) Topology detail (matrix vs IMS orientation) and domain/family annotations were not explicitly present in the retrieved full texts; only inner-membrane localization and functional role are directly supported here (tzagoloff2004atp10passistsassembly pages 1-1). 2) Although figure-level evidence supports Atp6 destabilization in atp10 null mutants, numerical degradation rates were not extractable from accessible text/figure OCR; conclusions are therefore stated qualitatively with figure citations (tzagoloff2004atp10passistsassembly media 4e9d59c3, tzagoloff2004atp10passistsassembly media bd9776b0). 3) 2023–2024 ATP10-specific mechanistic studies were not recovered in accessible full text; the newest explicit mechanistic source retrieved is 2022 (kabala2022assemblydependenttranslationof pages 1-2).

References

  1. (tzagoloff2004atp10passistsassembly pages 1-2): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  2. (ackerman1990atp10ayeast pages 1-2): S H Ackerman and A Tzagoloff. Atp10, a yeast nuclear gene required for the assembly of the mitochondrial f1-f0 complex. The Journal of biological chemistry, 265 17:9952-9, Jun 1990. URL: https://doi.org/10.1016/s0021-9258(19)38763-0, doi:10.1016/s0021-9258(19)38763-0. This article has 134 citations.

  3. (tzagoloff2004atp10passistsassembly pages 1-1): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  4. (helfenbein2003atp22anuclear pages 6-7): Kevin G. Helfenbein, Timothy P. Ellis, Carol L. Dieckmann, and Alexander Tzagoloff. Atp22, a nuclear gene required for expression of the f0 sector of mitochondrial atpase in saccharomyces cerevisiae*. Journal of Biological Chemistry, 278:19751-19756, May 2003. URL: https://doi.org/10.1074/jbc.m301679200, doi:10.1074/jbc.m301679200. This article has 69 citations and is from a domain leading peer-reviewed journal.

  5. (rak2009assemblyoff0 pages 5-6): Malgorzata Rak, Xiaomei Zeng, Jean-Jacques Brière, and Alexander Tzagoloff. Assembly of f0 in saccharomyces cerevisiae. Biochimica et biophysica acta, 1793 1:108-16, Jan 2009. URL: https://doi.org/10.1016/j.bbamcr.2008.07.001, doi:10.1016/j.bbamcr.2008.07.001. This article has 78 citations.

  6. (franco2020modularassemblyof pages 10-13): Leticia Veloso Ribeiro Franco, Chen Hsien Su, and Alexander Tzagoloff. Modular assembly of yeast mitochondrial atp synthase and cytochrome oxidase. Biological Chemistry, 401:835-853, May 2020. URL: https://doi.org/10.1515/hsz-2020-0112, doi:10.1515/hsz-2020-0112. This article has 35 citations and is from a peer-reviewed journal.

  7. (kabala2022assemblydependenttranslationof pages 1-2): Anna M Kabala, Krystyna Binko, François Godard, Camille Charles, Alain Dautant, Emilia Baranowska, Natalia Skoczen, Kewin Gombeau, Marine Bouhier, Hubert D Becker, Sharon H Ackerman, Lars M Steinmetz, Déborah Tribouillard-Tanvier, Roza Kucharczyk, and Jean-Paul di Rago. Assembly-dependent translation of subunits 6 (atp6) and 9 (atp9) of atp synthase in yeast mitochondria. Genetics, Jan 2022. URL: https://doi.org/10.1093/genetics/iyac007, doi:10.1093/genetics/iyac007. This article has 13 citations and is from a domain leading peer-reviewed journal.

  8. (tzagoloff2004atp10passistsassembly pages 6-7): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  9. (tzagoloff2004atp10passistsassembly media 861c4845): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  10. (tzagoloff2004atp10passistsassembly media bd9776b0): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  11. (tzagoloff2004atp10passistsassembly pages 4-5): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  12. (rak2011modularassemblyof pages 1-2): Malgorzata Rak, Samanta Gokova, and Alexander Tzagoloff. Modular assembly of yeast mitochondrial atp synthase. The EMBO Journal, 30:920-930, Mar 2011. URL: https://doi.org/10.1038/emboj.2010.364, doi:10.1038/emboj.2010.364. This article has 140 citations.

  13. (rak2011modularassemblyof pages 8-9): Malgorzata Rak, Samanta Gokova, and Alexander Tzagoloff. Modular assembly of yeast mitochondrial atp synthase. The EMBO Journal, 30:920-930, Mar 2011. URL: https://doi.org/10.1038/emboj.2010.364, doi:10.1038/emboj.2010.364. This article has 140 citations.

  14. (ackerman1990atp10ayeast pages 2-3): S H Ackerman and A Tzagoloff. Atp10, a yeast nuclear gene required for the assembly of the mitochondrial f1-f0 complex. The Journal of biological chemistry, 265 17:9952-9, Jun 1990. URL: https://doi.org/10.1016/s0021-9258(19)38763-0, doi:10.1016/s0021-9258(19)38763-0. This article has 134 citations.

  15. (ackerman1990atp10ayeast pages 3-3): S H Ackerman and A Tzagoloff. Atp10, a yeast nuclear gene required for the assembly of the mitochondrial f1-f0 complex. The Journal of biological chemistry, 265 17:9952-9, Jun 1990. URL: https://doi.org/10.1016/s0021-9258(19)38763-0, doi:10.1016/s0021-9258(19)38763-0. This article has 134 citations.

  16. (ackerman1990atp10ayeast pages 3-4): S H Ackerman and A Tzagoloff. Atp10, a yeast nuclear gene required for the assembly of the mitochondrial f1-f0 complex. The Journal of biological chemistry, 265 17:9952-9, Jun 1990. URL: https://doi.org/10.1016/s0021-9258(19)38763-0, doi:10.1016/s0021-9258(19)38763-0. This article has 134 citations.

  17. (zeng2007themetalloproteaseencoded pages 2-3): Xiaomei Zeng, Walter Neupert, and Alexander Tzagoloff. The metalloprotease encoded byatp23has a dual function in processing and assembly of subunit 6 of mitochondrial atpase. Molecular Biology of the Cell, 18:617-626, Feb 2007. URL: https://doi.org/10.1091/mbc.e06-09-0801, doi:10.1091/mbc.e06-09-0801. This article has 151 citations and is from a domain leading peer-reviewed journal.

  18. (ackerman1990atp10ayeast pages 4-5): S H Ackerman and A Tzagoloff. Atp10, a yeast nuclear gene required for the assembly of the mitochondrial f1-f0 complex. The Journal of biological chemistry, 265 17:9952-9, Jun 1990. URL: https://doi.org/10.1016/s0021-9258(19)38763-0, doi:10.1016/s0021-9258(19)38763-0. This article has 134 citations.

  19. (tzagoloff2004atp10passistsassembly media 4e9d59c3): Alexander Tzagoloff, Antoni Barrientos, Walter Neupert, and Johannes M. Herrmann. Atp10p assists assembly of atp6p into the f0 unit of the yeast mitochondrial atpase*. Journal of Biological Chemistry, 279:19775-19780, May 2004. URL: https://doi.org/10.1074/jbc.m401506200, doi:10.1074/jbc.m401506200. This article has 109 citations and is from a domain leading peer-reviewed journal.

  20. (mota2024sharedandmore pages 19-20): Marta N. Mota, Madalena Matos, Nada Bahri, and Isabel Sá-Correia. Shared and more specific genetic determinants and pathways underlying yeast tolerance to acetic, butyric, and octanoic acids. Microbial Cell Factories, Feb 2024. URL: https://doi.org/10.1186/s12934-024-02309-0, doi:10.1186/s12934-024-02309-0. This article has 13 citations and is from a peer-reviewed journal.

  21. (vengayil2024thedeubiquitinaseubp3usp10 pages 11-12): Vineeth Vengayil, Shreyas Niphadkar, Swagata Adhikary, Sriram Varahan, and Sunil Laxman. The deubiquitinase ubp3/usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting. eLife, May 2024. URL: https://doi.org/10.7554/elife.90293, doi:10.7554/elife.90293. This article has 12 citations and is from a domain leading peer-reviewed journal.

  22. (vengayil2024thedeubiquitinaseubp3usp10 pages 12-13): Vineeth Vengayil, Shreyas Niphadkar, Swagata Adhikary, Sriram Varahan, and Sunil Laxman. The deubiquitinase ubp3/usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting. eLife, May 2024. URL: https://doi.org/10.7554/elife.90293, doi:10.7554/elife.90293. This article has 12 citations and is from a domain leading peer-reviewed journal.

Citations

  1. zeng2007themetalloproteaseencoded pages 2-3
  2. mota2024sharedandmore pages 19-20
  3. kabala2022assemblydependenttranslationof pages 1-2
  4. franco2020modularassemblyof pages 10-13
  5. rak2011modularassemblyof pages 1-2
  6. rak2011modularassemblyof pages 8-9
  7. https://doi.org/10.1016/S0021-9258(19
  8. https://doi.org/10.1074/jbc.M401506200
  9. https://doi.org/10.1016/j.bbamcr.2008.07.001
  10. https://doi.org/10.1038/emboj.2010.364
  11. https://doi.org/10.1515/hsz-2020-0112
  12. https://doi.org/10.1093/genetics/iyac007
  13. https://doi.org/10.1091/mbc.e06-09-0801
  14. https://doi.org/10.1186/s12934-024-02309-0
  15. https://doi.org/10.1074/jbc.m401506200,
  16. https://doi.org/10.1016/s0021-9258(19
  17. https://doi.org/10.1074/jbc.m301679200,
  18. https://doi.org/10.1016/j.bbamcr.2008.07.001,
  19. https://doi.org/10.1515/hsz-2020-0112,
  20. https://doi.org/10.1093/genetics/iyac007,
  21. https://doi.org/10.1038/emboj.2010.364,
  22. https://doi.org/10.1091/mbc.e06-09-0801,
  23. https://doi.org/10.1186/s12934-024-02309-0,
  24. https://doi.org/10.7554/elife.90293,

📄 View Raw YAML

 
id: P18496
gene_symbol: ATP10
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  ATP10 (Atp10p) is a nuclear-encoded mitochondrial inner membrane protein required
  for assembly of the F0 sector of the mitochondrial F1-F0 ATP synthase complex.
  It functions as a specific assembly factor (chaperone) for Atp6p (subunit 6),
  binding newly synthesized Atp6p on mitochondrial ribosomes and facilitating its
  incorporation into a partially assembled ATPase subcomplex (PMID:14998992).
  Atp10p is not a subunit of the mature ATPase complex itself, nor is it a
  general-purpose chaperone; it acts specifically on Atp6p during the assembly
  process (PMID:2141026). Mutations in ATP10 cause loss of rutamycin sensitivity
  and defective F0 assembly (PMID:2141026).
existing_annotations:
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:2141026
        supporting_text: "The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex."
      - reference_id: PMID:14998992
        supporting_text: "Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F(0) sector of the ATPase."
      - reference_id: file:yeast/ATP10/ATP10-deep-research-falcon.md
        supporting_text: Falcon deep research identifies ATP10 as a mitochondrial inner membrane Atp6-specific assembly factor for ATP synthase F0 biogenesis.

- term:
    id: GO:0033615
    label: mitochondrial proton-transporting ATP synthase complex assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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).
    supported_by:
      - reference_id: PMID:2141026
        supporting_text: "A yeast nuclear gene (ATP10) is reported whose product is essential for the assembly of a functional mitochondrial ATPase complex."
      - reference_id: PMID:14998992
        supporting_text: "Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits."

- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:2141026
        supporting_text: "The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex."

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27107014
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
      - reference_id: PMID:27107014
        supporting_text: "systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network"

- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IDA
  original_reference_id: PMID:2141026
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:2141026
        supporting_text: "The antibody recognizes a 30-kDa protein present in wild type mitochondria. The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex."

- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:22842922
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
      - reference_id: PMID:22842922
        supporting_text: "high-throughput microscopic screening of the yeast GFP fusion collection to develop a systems-level view of protein reorganization following drug-induced DNA replication stress"

- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:24769239
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:24769239
        supporting_text: "we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria extracted from yeast grown on fermentative (glucose or galactose) and respiratory (lactate) media"

- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:16823961
  review:
    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.
    action: ACCEPT
    reason: >-
      Consistent with known biology. Atp10p is an established mitochondrial
      protein and its detection in high-throughput mitochondrial proteomics
      is expected and correct.
    supported_by:
      - reference_id: PMID:16823961
        supporting_text: "A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE"

- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:22842922
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:22842922
        supporting_text: "high-throughput microscopic screening of the yeast GFP fusion collection to develop a systems-level view of protein reorganization following drug-induced DNA replication stress"

- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IPI
  original_reference_id: PMID:14998992
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:14998992
        supporting_text: "Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F(0) sector of the ATPase."
      - reference_id: PMID:14998992
        supporting_text: "following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p"

- term:
    id: GO:0033615
    label: mitochondrial proton-transporting ATP synthase complex assembly
  evidence_type: IMP
  original_reference_id: PMID:14998992
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:14998992
        supporting_text: "Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type."
      - reference_id: PMID:2141026
        supporting_text: "Mutations in ATP10 induce a loss of rutamycin sensitivity in the mitochondrial ATPase but do not affect respiratory enzymes. This phenotype has been correlated with a defect in the F0 sector of the ATPase."

- term:
    id: GO:0033615
    label: mitochondrial proton-transporting ATP synthase complex assembly
  evidence_type: IPI
  original_reference_id: PMID:14998992
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
      - reference_id: PMID:14998992
        supporting_text: "following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p. This interaction is required for the integration of Atp6p into a partially assembled subcomplex of the ATPase."

- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IPI
  original_reference_id: PMID:14998992
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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_replacement_terms:
      - id: GO:0140777
        label: protein-containing complex stabilizing activity
    supported_by:
      - reference_id: PMID:14998992
        supporting_text: "Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits."
      - reference_id: PMID:14998992
        supporting_text: "Atp10p was identified as a mitochondrial inner membrane component necessary for the biogenesis of the hydrophobic F(0) sector of the ATPase."
      - reference_id: PMID:2141026
        supporting_text: "These data suggest that the ATP10 product is not a subunit of the ATPase complex but rather is required for the assembly of the F0 sector of the complex."

- term:
    id: GO:0140777
    label: protein-containing complex stabilizing activity
  evidence_type: IPI
  original_reference_id: PMID:14998992
  review:
    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.
    action: NEW
    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.
    supported_by:
      - reference_id: PMID:14998992
        supporting_text: "Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type."
      - reference_id: PMID:14998992
        supporting_text: "Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits."

references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: PMID:14998992
  title: Atp10p assists assembly of Atp6p into the F0 unit of the yeast mitochondrial
    ATPase.
  findings:
    - statement: Atp10p cross-links to newly synthesized Atp6p on mitochondrial ribosomes
      supporting_text: "following its synthesis on mitochondrial ribosomes, subunit 6 of the ATPase (Atp6p) can be cross-linked to Atp10p"
    - statement: The Atp10p-Atp6p interaction is required for integration of Atp6p into a partially assembled ATPase subcomplex
      supporting_text: "This interaction is required for the integration of Atp6p into a partially assembled subcomplex of the ATPase"
    - statement: In an atp10 null mutant, Atp6p is less stable and more rapidly degraded
      supporting_text: "Pulse labeling and chase of mitochondrial translation products in vivo indicate that Atp6p is less stable and more rapidly degraded in an atp10 null mutant than in wild type"
    - statement: Authors propose Atp10p is an Atp6p-specific chaperone facilitating Atp6p incorporation into the F0 sector
      supporting_text: "we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits"
- id: PMID:16823961
  title: 'Toward the complete yeast mitochondrial proteome: multidimensional separation
    techniques for mitochondrial proteomics.'
  findings: []
- id: PMID:2141026
  title: ATP10, a yeast nuclear gene required for the assembly of the mitochondrial
    F1-F0 complex.
  findings:
    - statement: ATP10 encodes a 30 kDa protein essential for assembly of a functional mitochondrial ATPase complex
      supporting_text: "A yeast nuclear gene (ATP10) is reported whose product is essential for the assembly of a functional mitochondrial ATPase complex"
    - statement: Mutations in ATP10 cause loss of rutamycin sensitivity indicating defective F0 sector
      supporting_text: "Mutations in ATP10 induce a loss of rutamycin sensitivity in the mitochondrial ATPase but do not affect respiratory enzymes. This phenotype has been correlated with a defect in the F0 sector of the ATPase"
    - statement: ATP10 product is not a subunit of the ATPase but is required for F0 assembly
      supporting_text: "These data suggest that the ATP10 product is not a subunit of the ATPase complex but rather is required for the assembly of the F0 sector of the complex"
    - statement: The protein is associated with the mitochondrial membrane but does not co-fractionate with F1 or F1-F0
      supporting_text: "The protein is associated with the mitochondrial membrane but does not co-fractionate either with F1 or with the rutamycin-sensitive F1-F0 complex"
- id: PMID:22842922
  title: Dissecting DNA damage response pathways by analysing protein localization
    and abundance changes during DNA replication stress.
  findings: []
- id: PMID:24769239
  title: Quantitative variations of the mitochondrial proteome and phosphoproteome
    during fermentative and respiratory growth in Saccharomyces cerevisiae.
  findings: []
- id: PMID:27107014
  title: An inter-species protein-protein interaction network across vast evolutionary
    distance.
  findings:
    - statement: Cross-species Y2H interaction reported between yeast Atp10p and human AGTRAP isoform 2; not physiologically relevant
      supporting_text: "systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter-interactome network"
- id: file:yeast/ATP10/ATP10-deep-research-falcon.md
  title: Falcon deep research report on ATP10
  findings:
    - statement: Falcon synthesis identifies ATP10 as an Atp6-specific mitochondrial ATP synthase F0 assembly factor and not a general unfolded-protein chaperone.

core_functions:
- description: >-
    Atp10p stabilizes newly synthesized Atp6p during assembly of the F0 sector
    of the mitochondrial ATP synthase. It binds Atp6p after translation on
    mitochondrial ribosomes and facilitates its incorporation into an intermediate
    ATPase subcomplex. In the absence of Atp10p, Atp6p is rapidly degraded.
    This is a protein-containing complex stabilizing activity, not a general
    chaperone or foldase function.
  molecular_function:
    id: GO:0140777
    label: protein-containing complex stabilizing activity
  directly_involved_in:
    - id: GO:0033615
      label: mitochondrial proton-transporting ATP synthase complex assembly
  locations:
    - id: GO:0005743
      label: mitochondrial inner membrane
  supported_by:
    - reference_id: PMID:14998992
      supporting_text: "Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits."
    - reference_id: file:yeast/ATP10/ATP10-deep-research-falcon.md
      supporting_text: Falcon deep research emphasizes Atp6 stabilization and incorporation into F0 assembly intermediates as the core ATP10 function.
proposed_new_terms: []
suggested_questions:
  - question: >-
      Should ATP10 receive GO:0140777 protein-containing complex stabilizing
      activity as a curated molecular-function annotation, replacing the less
      informative unfolded protein binding term?
    experts:
      - Tzagoloff A
      - Ackerman SH
suggested_experiments:
  - hypothesis: >-
      Atp10p stabilizes newly synthesized Atp6p during a discrete F0 assembly
      step rather than functioning as a general chaperone.
    description: >-
      Measure Atp6p binding, degradation, and incorporation into ATP synthase
      assembly intermediates in ATP10 mutants and in strains carrying targeted
      Atp10p interface substitutions.
    experiment_type: mitochondrial ATP synthase assembly assay