ATPAF2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference placing ATPAF2 activity in the mitochondrion. Consistent with all experimental and computational evidence; ATPAF2 is imported into mitochondria and acts on the F1 sector of ATP synthase. Reason: Correct compartment, appropriately general. A more specific location (mitochondrial matrix / inner membrane) is captured in core_functions and by other annotations. Supporting Evidence: file:human/ATPAF2/ATPAF2-uniprot.txt Mitochondrion inner membrane
GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that ATPAF2 is involved in assembly of the mitochondrial proton-transporting ATP synthase (Complex V). This is the core biological process of the gene, and matches the yeast Atp12p ortholog and human experimental data. Reason: Specific, well-supported BP capturing the central role of ATPAF2 as an F1 assembly factor. This is a core function. Supporting Evidence: PMID:11410595 proteins required for assembly of the PMID:14701807 Atp12p binds to unassembled
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation from UniProt Subcellular Location mapping. UniProt records ATPAF2 as a peripheral inner-membrane protein, consistent with its role acting on the soluble F1 sector at the matrix face of the inner membrane. Reason: Consistent with the experimentally reported subcellular location; the protein is a peripheral membrane protein associated with the inner membrane. Supporting Evidence: file:human/ATPAF2/ATPAF2-uniprot.txt Mitochondrion inner membrane
GO:0006457 protein folding	IEA GO_REF:0000108	ACCEPT	Summary: Electronic inference (from the protein folding chaperone MF) that ATPAF2 participates in protein folding. ATPAF2 is a molecular chaperone that binds unassembled F1 alpha subunit and suppresses its aggregation, so a folding-related BP is reasonable, though the specific assembly BP terms are more informative. Reason: Not incorrect; the chaperone assists proper folding/assembly of the F1 alpha subunit. The more specific and core process is ATP synthase complex assembly (GO:0033615). Supporting Evidence: PMID:14701807 Wild type HuAtp12p suppresses the aggregation of thermally
GO:0043461 proton-transporting ATP synthase complex assembly	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-to-GO electronic annotation (IPR011419, ATP12 family) assigning the general ATP synthase assembly process. Correct but less specific than the mitochondrial-specific term GO:0033615. Reason: Correct parent-level BP consistent with the ATP12 family assignment; redundant with the more specific mitochondrial term but not wrong. Supporting Evidence: PMID:11410595 proteins required for assembly of the
GO:0005515 protein binding	IPI PMID:11410595 Atp11p and Atp12p are assembly factors for the F(1)-ATPase i...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation to an F1 subunit (ATP5F1A, P25705). This is the physiologically meaningful interaction underlying ATPAF2 function - binding the F1 alpha subunit during assembly. However, the bare protein binding term is uninformative; the informative molecular function is protein folding chaperone (GO:0044183). Reason: Bare protein binding conveys no functional specificity. The interaction is real and biologically relevant (F1 alpha subunit), but the chaperone MF term captures the actual function. Retained rather than removed per curation policy. Supporting Evidence: PMID:11410595 the human proteins
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a large-scale next-generation-sequencing interactome (Y2H) dataset. Uninformative and captures partners not established as physiological for a mitochondrial matrix assembly chaperone. Reason: Uninformative protein binding from a high-throughput interactome screen; no specific function conveyed. Retained per policy.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a proteome-scale human interactome map. Many recorded partners (zinc-finger transcription factors, keratins, nuclear proteins) are not physiological for a mitochondrial assembly chaperone. Reason: Uninformative high-throughput protein binding; no specific function. Retained per policy.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an interactome-perturbation study. Uninformative and dominated by non-mitochondrial partners. Reason: Uninformative high-throughput protein binding; no specific function. Retained per policy.
GO:0005515 protein binding	IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat...	MARK AS OVER ANNOTATED	Summary: Protein binding from a mitochondrial protein-interaction mapping (AE-MS) study that captured the ATPAF2-ATP5F1A interaction among respiratory chain assembly factors. Functionally relevant partner, but the bare protein binding term is uninformative. Reason: The interaction (F1 alpha subunit) is physiologically meaningful, but the generic protein binding term does not capture the chaperone function (GO:0044183). Retained per policy.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a proteome-scale interactome/community-detection study. Uninformative for molecular function. Reason: Uninformative high-throughput protein binding; no specific function. Retained per policy.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from an interactome-perturbation framework. Records the ATP5F1B (P06576) interaction, which is physiologically relevant, but the generic term conveys no function. Reason: Uninformative protein binding; the relevant F1-subunit interaction is better captured by the chaperone MF and assembly BP. Retained per policy.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a population-scale interaction-disruption study. Includes the ATP5F1B interaction but the generic term is uninformative. Reason: Uninformative high-throughput protein binding; no specific function. Retained per policy.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare protein binding from the HuRI reference binary interactome (Y2H). Large set of partners, most not physiological for a mitochondrial matrix chaperone. Reason: Uninformative high-throughput protein binding; no specific function. Retained per policy.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from the BioPlex dual proteome-scale AP-MS network. Records the ATP5F1B interaction; the generic term is uninformative. Reason: Uninformative protein binding; specific function captured elsewhere. Retained per policy.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a multimodal cell-map / interactome study. Records the ATP5F1B interaction; the generic term is uninformative. Reason: Uninformative protein binding; no specific function conveyed. Retained per policy.
GO:0044183 protein folding chaperone	IDA PMID:14701807 The molecular chaperone, Atp12p, from Homo sapiens. In vitro...	ACCEPT	Summary: Direct experimental (IDA) annotation that ATPAF2 is a protein folding chaperone. Purified recombinant human Atp12p suppresses aggregation of a model substrate (thermally inactivated citrate synthase), and binds unassembled F1 alpha subunit to prevent non-productive aggregation during F1 assembly. This is the core molecular function. Reason: Informative, experimentally supported molecular function that captures the chaperone activity - far more useful than bare protein binding. This is the core MF of ATPAF2. Supporting Evidence: PMID:14701807 Wild type HuAtp12p suppresses the aggregation of thermally PMID:14701807 Atp12p binds to unassembled
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput proteomics (HTP) detection of ATPAF2 in a high-confidence human mitochondrial proteome. Corroborates mitochondrial localization. Reason: Consistent with experimental and phylogenetic evidence for mitochondrial localization. Supporting Evidence: PMID:34800366 high-confidence human mitochondrial proteome
GO:0005743 mitochondrial inner membrane	IGI PMID:11410595 Atp11p and Atp12p are assembly factors for the F(1)-ATPase i...	ACCEPT	Summary: Genetic-interaction (IGI) annotation placing ATPAF2 activity at the mitochondrial inner membrane, based on functional analysis of the human ATP12 relative to yeast atp12/ATP11 (P22135). Consistent with UniProt's peripheral inner-membrane assignment; ATPAF2 acts on the F1 sector at the matrix face of the inner membrane. Reason: Correct localization for a peripheral inner-membrane assembly factor. Supporting Evidence: file:human/ATPAF2/ATPAF2-uniprot.txt Mitochondrion inner membrane
GO:0033615 mitochondrial proton-transporting ATP synthase complex assembly	IGI PMID:11410595 Atp11p and Atp12p are assembly factors for the F(1)-ATPase i...	ACCEPT	Summary: Genetic-interaction (IGI) annotation to the core assembly process, from functional characterization of human ATP11/ATP12 showing they function like their yeast counterparts in F1 assembly. This is a core function. Reason: Well-supported, specific core BP for ATPAF2. Duplicates the IBA entry, which is acceptable. Supporting Evidence: PMID:11410595 the human proteins PMID:11410595 proteins required for assembly of the
GO:0005515 protein binding	IPI PMID:28719601 CLIC, a tool for expanding biological pathways based on co-e...	MARK AS OVER ANNOTATED	Summary: IPI protein-binding annotation for the interaction with FMC1 (Q96HJ9), a co-factor implicated in mitochondrial ATP synthase F1 assembly, identified via co-expression (CLIC). Functionally relevant partner, but the bare protein binding term is uninformative. Reason: The FMC1 interaction is biologically plausible in the F1 assembly context, but generic protein binding conveys no molecular function. Retained per policy. Supporting Evidence: PMID:28719601 functional connection between protein C7orf55 (FMC1) and the mitochondrial ATP
GO:0016607 nuclear speck	IDA GO_REF:0000054	REMOVE	Summary: IDA nuclear speck localization from a LIFEdb GFP-fusion screen of an overexpressed construct. This contradicts the well-established mitochondrial localization of ATPAF2, which carries an N-terminal mitochondrial transit peptide and is a validated component of the mitochondrial proteome. Nuclear speck localization is a mislocalization artifact of the overexpressed fusion protein. Reason: Inconsistent with the mitochondrial-matrix / inner-membrane biology of this transit-peptide-containing assembly chaperone; a GFP-fusion overexpression artifact (GO_REF:0000054 automated fusion-localization pipeline), not evidence of a physiological nuclear function. This is not an experimental annotation whose full text is inaccessible, so removal is appropriate. Supporting Evidence: file:human/ATPAF2/ATPAF2-uniprot.txt Mitochondrion inner membrane
GO:0043461 proton-transporting ATP synthase complex assembly	NAS PMID:14757859 Respiratory chain complex V deficiency due to a mutation in ...	ACCEPT	Summary: Non-traceable author statement (NAS) that ATPAF2/ATP12 is involved in ATP synthase assembly, from the clinical report describing the first pathogenic mutation in a human nuclear-encoded ATPase assembly gene (causing complex V deficiency). Correct process; the disease phenotype directly implicates ATPAF2 in ATP synthase assembly. Reason: Correct BP, supported by disease genetics; loss of ATPAF2 function impairs complex V, consistent with an assembly role. Parent-level term redundant with the more specific mitochondrial term. Supporting Evidence: PMID:14757859 the first report of a pathogenic mutation in a human nuclear PMID:14757859 believed to be the cause of the impaired complex V activity
GO:0005759 mitochondrial matrix	IC PMID:14701807 The molecular chaperone, Atp12p, from Homo sapiens. In vitro...	NEW	Summary: Proposed anatomical location. ATPAF2 is a soluble chaperone that binds the unassembled F1 alpha subunit and prevents its aggregation; F1 assembly occurs on the matrix face of the inner membrane, and UniProt classifies ATPAF2 as a peripheral (not integral) inner-membrane protein. It therefore functions in the mitochondrial matrix compartment. This complements the mitochondrion and inner-membrane annotations with the more precise sub-compartment. Reason: The existing location annotations (mitochondrion; inner membrane) are correct but do not capture that ATPAF2 acts as a soluble matrix-side chaperone on the F1 sector. Added to reflect the core_functions location. Supporting Evidence: PMID:14701807 Atp12p binds to unassembled file:human/ATPAF2/ATPAF2-uniprot.txt Mitochondrion inner membrane

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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