ATPAF1 (ATP11) is a mitochondrial assembly factor for F1F0 ATP synthase, the human homolog of yeast Atp11p. It acts as a molecular chaperone that binds unassembled F1 beta subunits (ATP5F1B), preventing their aggregation and keeping them competent to assemble with alpha subunits into the alpha3beta3 catalytic core. Human ATPAF1 complements the yeast atp11 mutant. It is expressed broadly and constitutively. Atpaf1-knockout mice survive but are smaller, with raised blood lactate, and their hearts have less F1, fewer ATP synthase dimers, abnormal cristae and impaired respiration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:11410595 Atp11p and Atp12p are assembly factors for the F(1)-ATPase i... | REMOVE | Summary: Protein binding (IPI) with ATP5F1B (F1 beta subunit), from the human ATP11 characterization. This is the chaperone-client interaction through which ATPAF1 keeps unassembled beta subunits from aggregating; it is captured by complex-stabilizing activity and F1 assembly. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. [file:human/ATPAF1/ATPAF1-uniprot.txt "CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1"] Supporting Evidence: file:human/ATPAF1/ATPAF1-uniprot.txt CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Protein binding (IPI) with ATP5F1B (F1 beta subunit), from the BioPlex affinity-purification network. This is the chaperone-client interaction through which ATPAF1 keeps unassembled beta subunits from aggregating; it is captured by complex-stabilizing activity and F1 assembly. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. [file:human/ATPAF1/ATPAF1-uniprot.txt "CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1"] Supporting Evidence: file:human/ATPAF1/ATPAF1-uniprot.txt CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with ATP5F1B (F1 beta subunit), from the BioPlex dual proteome-scale network. This is the chaperone-client interaction through which ATPAF1 keeps unassembled beta subunits from aggregating; it is captured by complex-stabilizing activity and F1 assembly. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. [file:human/ATPAF1/ATPAF1-uniprot.txt "CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1"] Supporting Evidence: file:human/ATPAF1/ATPAF1-uniprot.txt CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Protein binding (IPI) with ATP5F1B (F1 beta subunit), from a multimodal cell map. This is the chaperone-client interaction through which ATPAF1 keeps unassembled beta subunits from aggregating; it is captured by complex-stabilizing activity and F1 assembly. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. [file:human/ATPAF1/ATPAF1-uniprot.txt "CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1"] Supporting Evidence: file:human/ATPAF1/ATPAF1-uniprot.txt CC -!- SUBUNIT: Interacts with ATP5F1B; involved in the assembly of the F1 |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Mitochondrion (HTP). ATPAF1 colocalizes with the mitochondrial F1 beta subunit and acts on F1 assembly in mitochondria. Accepted. Reason: [PMID:34375736 "We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al."] [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] Supporting Evidence: PMID:34375736 We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al. PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrion (IBA). ATPAF1 colocalizes with the mitochondrial F1 beta subunit and acts on F1 assembly in mitochondria. Accepted. Reason: [PMID:34375736 "We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al."] [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000319591 SUPPORTS TRANSFER Mitochondrial assembly-factor family. Supporting Evidence: PMID:34375736 We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al. PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. |
| GO:0005739 mitochondrion | IEA GO_REF:0000002 | ACCEPT | Summary: Mitochondrion (IEA). ATPAF1 colocalizes with the mitochondrial F1 beta subunit and acts on F1 assembly in mitochondria. Accepted. Reason: [PMID:34375736 "We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al."] [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] Supporting Evidence: PMID:34375736 We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al. PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane (IEA, UniProt subcellular location). UniProt records ATPAF1 as a peripheral inner-membrane protein by similarity to mouse Q811I0, but I could not trace the experimental basis of the mouse call. The cited mouse knockout study shows only mitochondrial colocalization with the F1 beta subunit. Yeast Atp11p is described as a chaperone acting on soluble F1 subunits before they join the membrane-bound F(o). A peripheral inner-membrane association is plausible but not established in the cited sources. Kept as non-core. Reason: [file:human/ATPAF1/ATPAF1-uniprot.txt "CC {ECO:0000250|UniProtKB:Q811I0}; Peripheral membrane protein"] [PMID:34375736 "We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al."] [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] Supporting Evidence: file:human/ATPAF1/ATPAF1-uniprot.txt CC {ECO:0000250|UniProtKB:Q811I0}; Peripheral membrane protein PMID:34375736 We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al. PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. |
| GO:0005743 mitochondrial inner membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mitochondrial inner membrane (ISS, from mouse ATPAF1). UniProt records ATPAF1 as a peripheral inner-membrane protein by similarity to mouse Q811I0, but I could not trace the experimental basis of the mouse call. The cited mouse knockout study shows only mitochondrial colocalization with the F1 beta subunit. Yeast Atp11p is described as a chaperone acting on soluble F1 subunits before they join the membrane-bound F(o). A peripheral inner-membrane association is plausible but not established in the cited sources. Kept as non-core. Reason: [file:human/ATPAF1/ATPAF1-uniprot.txt "CC {ECO:0000250|UniProtKB:Q811I0}; Peripheral membrane protein"] [PMID:34375736 "We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al."] [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q811I0 UNRESOLVED Mouse Atpaf1; the experimental basis of its inner-membrane location could not be traced from the cited sources. Supporting Evidence: file:human/ATPAF1/ATPAF1-uniprot.txt CC {ECO:0000250|UniProtKB:Q811I0}; Peripheral membrane protein PMID:34375736 We confirmed that ATPAF1 was co-localized with the mitochondrial Ξ²-subunit ATP5B via immunofluorescence staining, which was consistent with previous studies (Saito et al. PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. |
| GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Mitochondrial proton-transporting ATP synthase complex assembly (IBA). Atp11p/ATPAF1 is required to assemble the alpha and beta subunits into F1, and Atpaf1-knockout mouse hearts have less F1 and fewer ATP synthase dimers. Core process. Reason: [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] [PMID:34375736 "Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart."] [PMID:34375736 "The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000319591 SUPPORTS TRANSFER Atp11 family node; F1 assembly is the conserved function. Supporting Evidence: PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. PMID:34375736 Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart. PMID:34375736 The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals. |
| GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Mitochondrial proton-transporting ATP synthase complex assembly (ISS, from mouse ATPAF1). Atp11p/ATPAF1 is required to assemble the alpha and beta subunits into F1, and Atpaf1-knockout mouse hearts have less F1 and fewer ATP synthase dimers. Core process. Reason: [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] [PMID:34375736 "Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart."] [PMID:34375736 "The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q811I0 SUPPORTS TRANSFER Mouse Atpaf1; knockout impairs ATP synthase assembly (PMID:34375736). Supporting Evidence: PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. PMID:34375736 Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart. PMID:34375736 The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals. |
| GO:0065003 protein-containing complex assembly | IEA GO_REF:0000002 | ACCEPT | Summary: Protein-containing complex assembly (IEA). Atp11p/ATPAF1 is required to assemble the alpha and beta subunits into F1, and Atpaf1-knockout mouse hearts have less F1 and fewer ATP synthase dimers. Correct but general (an ancestor of the accepted GO:0033615); accepted. Reason: [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] [PMID:34375736 "Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart."] [PMID:34375736 "The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals."] Supporting Evidence: PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. PMID:34375736 Western blots and Blue-Native electrophoresis (BN-PAGE) demonstrated a decreased F1 content and ATP synthase dimers in the Atpaf1-KO heart. PMID:34375736 The results provide strong support that ATPAF1 is essential for ATP synthase assembly and mitochondrial oxidative phosphorylation, thus playing a crucial role in maintaining cardiac structure and function in animals. |
| GO:0140777 protein-containing complex stabilizing activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein-containing complex stabilizing activity (IBA). ATPAF1/Atp11p is a molecular chaperone that binds unassembled F1 beta subunits and keeps them assembly-competent. Human ATPAF1 complements the yeast atp11 mutant, and endogenous F1 beta co-immunoprecipitates with ATPAF1 in human HEK293 cells. Core function. Reason: [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] [PMID:11410595 "Here we report the isolation of the cDNAs and the characterization of the human genes for Atp11p and Atp12p and show that the human proteins function like their yeast counterparts."] [PMID:34375736 "Co-IP experiments showed that the endogenous Ξ²-subunit interacts with ATPAF1 (Fig."] [file:human/ATPAF1/ATPAF1-uniprot.txt "CC -!- FUNCTION: Has a complex stabilizing activity in the assembly of the"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000319591 SUPPORTS TRANSFER Atp11 family node seeded by yeast Atp11p and mouse Atpaf1; human ATPAF1 complements yeast atp11 (PMID:11410595). Supporting Evidence: PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. PMID:11410595 Here we report the isolation of the cDNAs and the characterization of the human genes for Atp11p and Atp12p and show that the human proteins function like their yeast counterparts. PMID:34375736 Co-IP experiments showed that the endogenous Ξ²-subunit interacts with ATPAF1 (Fig. file:human/ATPAF1/ATPAF1-uniprot.txt CC -!- FUNCTION: Has a complex stabilizing activity in the assembly of the |
| GO:0140777 protein-containing complex stabilizing activity | ISS GO_REF:0000024 | ACCEPT | Summary: Protein-containing complex stabilizing activity (ISS, from mouse ATPAF1). ATPAF1/Atp11p is a molecular chaperone that binds unassembled F1 beta subunits and keeps them assembly-competent. Human ATPAF1 complements the yeast atp11 mutant, and endogenous F1 beta co-immunoprecipitates with ATPAF1 in human HEK293 cells. Core function. Reason: [PMID:12206899 "Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p."] [PMID:11410595 "Here we report the isolation of the cDNAs and the characterization of the human genes for Atp11p and Atp12p and show that the human proteins function like their yeast counterparts."] [PMID:34375736 "Co-IP experiments showed that the endogenous Ξ²-subunit interacts with ATPAF1 (Fig."] [file:human/ATPAF1/ATPAF1-uniprot.txt "CC -!- FUNCTION: Has a complex stabilizing activity in the assembly of the"] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q811I0 SUPPORTS TRANSFER Mouse Atpaf1 (ortholog); knockout reduces F1 content and ATP synthase dimers (PMID:34375736). Supporting Evidence: PMID:12206899 Our work, which employs the yeast Saccharomyces cerevisiae as a model system for studies of mitochondrial function, has provided evidence that assembly of the mitochondrial alpha and beta subunits into the F(1) oligomer requires two molecular chaperone proteins called Atp11p and Atp12p. PMID:11410595 Here we report the isolation of the cDNAs and the characterization of the human genes for Atp11p and Atp12p and show that the human proteins function like their yeast counterparts. PMID:34375736 Co-IP experiments showed that the endogenous Ξ²-subunit interacts with ATPAF1 (Fig. file:human/ATPAF1/ATPAF1-uniprot.txt CC -!- FUNCTION: Has a complex stabilizing activity in the assembly of the |
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Download this section (compressed HTML)Q: Is human ATPAF1 a soluble matrix chaperone, as Atp11p is in yeast, or peripherally associated with the inner membrane, and do ATPAF1 variants cause ATP synthase deficiency in patients?
Q: Should ATPAF1's anti-aggregation holdase role (protein folding chaperone, GO:0044183, used in its affinage grounding) be annotated in addition to complex-stabilizing activity? GOA currently carries only GO:0140777, which captures the client-specific assembly role.
Experiment: Use protease protection and carbonate extraction of human mitochondria to place ATPAF1 in the matrix or on the inner membrane, and screen ATP synthase-deficient patients for ATPAF1 variants.
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