ATG7

Summary: Phylogenetic inference-based annotation (IBA) correctly assigns ATG7 to the phagophore assembly site based on ortholog curation. ATG7 localizes to the preautophagosomal/phagophore assembly site (PAS) where autophagosome biogenesis occurs.

Reason: Robust IBA annotation supported by experimental evidence showing ATG7 localization to the PAS (PMID:18497569). ATG7 is a core component of the autophagy machinery that functions at the phagophore assembly site. This is consistent with the UniProt annotation "Preautophagosomal structure" and represents a key subcellular localization.

Summary: cytoplasm is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: protein modification by small protein conjugation is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: mitophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: autophagosome assembly is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: Atg12 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: cellular response to nitrogen starvation is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: Atg8 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: piecemeal microautophagy of the nucleus is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: phagophore assembly site is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: cytoplasm is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: autophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: ubiquitin-like modifier activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: ATG7 functions in autophagy-specific trafficking pathways; this broad protein transport term is overly generic for its mechanism.

Reason: Removed because GO:0015031 does not capture the selective autophagy machinery role of ATG7, which is better represented by autophagy/Cvt/mitophagy terms.

Summary: General microautophagy annotation is broader than the directly supported ATG7 microautophagy role.

Reason: Marked as over-annotated because ATG7 is strongly supported for nucleophagy (piecemeal microautophagy of nucleus), while generic microautophagy is less specifically evidenced.

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.

Reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.

Proposed replacements: ubiquitin-like protein binding

Summary: identical protein binding is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: identical protein binding is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: nucleophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: Potential zinc-ion association is not a central, well-established molecular activity for ATG7.

Reason: Kept as non-core to retain computational signal without elevating to a core function pending stronger direct biochemical evidence.

Summary: cytosol is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: Mitochondrial localization from high-throughput datasets is not well supported for ATG7 as a resident compartment assignment.

Reason: Removed because ATG7 is primarily a cytosolic autophagy E1-like enzyme; its role in mitophagy does not require stable mitochondrial localization.

Summary: Mitochondrial localization from high-throughput datasets is not well supported for ATG7 as a resident compartment assignment.

Reason: Removed because ATG7 is primarily a cytosolic autophagy E1-like enzyme; its role in mitophagy does not require stable mitochondrial localization.

Summary: The generic C-terminal protein lipidation term is correct in essence for ATG7, which catalyzes the E1 step of Atg8-phosphatidylethanolamine conjugation, but is less specific than available GO terms.

Reason: ATG7 is the E1-like enzyme that activates Atg8 and transfers it to the E2 Atg3, which completes conjugation of the Atg8 C-terminal glycine to phosphatidylethanolamine; ATG7 therefore performs an obligate catalytic step of Atg8 lipidation, and the lipidation process term is appropriate. The MODIFY is a specialization, not a correction: GO:0061739 protein lipidation involved in autophagosome assembly is a child of the annotated GO:0006501 and names the specific Atg8-PE lipidation that ATG7 drives (the originally proposed id, GO:0061683, was an erroneous id for an unrelated, now-obsolete term). GO:0061739 is scoped to autophagosome assembly, whereas Atg8-PE conjugation in yeast also serves the Cvt pathway; GO has no Cvt-specific lipidation term, and ATG7's Cvt role is captured separately by its ACCEPTed cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) annotations, so the narrower term is still the best available specialization.

Proposed replacements: protein lipidation involved in autophagosome assembly

Summary: The cited paper shows Atg12p-dependent membrane association of Apg7p-GFP without identifying the compartment; the extrinsic-component term encodes protein topology rather than a location.

Reason: Two problems, neither of which impugns the curator's underlying observation. First, the term: GO:0097632 asserts protein topology, which GO has already ruled is not a cellular component - its siblings GO:0097633 and GO:0097634 and its autophagosome counterpart GO:0097635 were obsoleted on exactly that ground, and GO:0097632 was missed (GO issue #23424, and #29437 R4). It is also defined as part_of GO:0034045, which asserts a bounding membrane the phagophore assembly site does not have (PMID:32025038). Second, the evidence: the cached record is abstract-only, and the abstract supports Apg12p-dependent membrane association and starvation-dependent pelleting without naming a compartment, so the specific claim of PAS-membrane topology is not something this reviewer can verify. Prior review cited the paper's title as its supporting text and justified the location by ATG7's E1-like enzymatic function, which is not localization evidence. Generalize to the compartment, which this gene already carries independently as an IDA from PMID:18497569.

Proposed replacements: phagophore assembly site

Summary: phagophore assembly site is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: autophagy of mitochondrion is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: cytosol is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: The generic C-terminal protein lipidation term is correct in essence for ATG7, which catalyzes the E1 step of Atg8-phosphatidylethanolamine conjugation, but is less specific than available GO terms.

Reason: ATG7 is the E1-like enzyme that activates Atg8 and transfers it to the E2 Atg3, which completes conjugation of the Atg8 C-terminal glycine to phosphatidylethanolamine; ATG7 therefore performs an obligate catalytic step of Atg8 lipidation, and the lipidation process term is appropriate. The MODIFY is a specialization, not a correction: GO:0061739 protein lipidation involved in autophagosome assembly is a child of the annotated GO:0006501 and names the specific Atg8-PE lipidation that ATG7 drives (the originally proposed id, GO:0061683, was an erroneous id for an unrelated, now-obsolete term). GO:0061739 is scoped to autophagosome assembly, whereas Atg8-PE conjugation in yeast also serves the Cvt pathway; GO has no Cvt-specific lipidation term, and ATG7's Cvt role is captured separately by its ACCEPTed cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) annotations, so the narrower term is still the best available specialization.

Proposed replacements: protein lipidation involved in autophagosome assembly

Summary: The generic C-terminal protein lipidation term is correct in essence for ATG7, which catalyzes the E1 step of Atg8-phosphatidylethanolamine conjugation, but is less specific than available GO terms.

Reason: ATG7 is the E1-like enzyme that activates Atg8 and transfers it to the E2 Atg3, which completes conjugation of the Atg8 C-terminal glycine to phosphatidylethanolamine; ATG7 therefore performs an obligate catalytic step of Atg8 lipidation, and the lipidation process term is appropriate. The MODIFY is a specialization, not a correction: GO:0061739 protein lipidation involved in autophagosome assembly is a child of the annotated GO:0006501 and names the specific Atg8-PE lipidation that ATG7 drives (the originally proposed id, GO:0061683, was an erroneous id for an unrelated, now-obsolete term). GO:0061739 is scoped to autophagosome assembly, whereas Atg8-PE conjugation in yeast also serves the Cvt pathway; GO has no Cvt-specific lipidation term, and ATG7's Cvt role is captured separately by its ACCEPTed cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) annotations, so the narrower term is still the best available specialization.

Proposed replacements: protein lipidation involved in autophagosome assembly

Summary: The generic C-terminal protein lipidation term is correct in essence for ATG7, which catalyzes the E1 step of Atg8-phosphatidylethanolamine conjugation, but is less specific than available GO terms.

Reason: ATG7 is the E1-like enzyme that activates Atg8 and transfers it to the E2 Atg3, which completes conjugation of the Atg8 C-terminal glycine to phosphatidylethanolamine; ATG7 therefore performs an obligate catalytic step of Atg8 lipidation, and the lipidation process term is appropriate. The MODIFY is a specialization, not a correction: GO:0061739 protein lipidation involved in autophagosome assembly is a child of the annotated GO:0006501 and names the specific Atg8-PE lipidation that ATG7 drives (the originally proposed id, GO:0061683, was an erroneous id for an unrelated, now-obsolete term). GO:0061739 is scoped to autophagosome assembly, whereas Atg8-PE conjugation in yeast also serves the Cvt pathway; GO has no Cvt-specific lipidation term, and ATG7's Cvt role is captured separately by its ACCEPTed cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) annotations, so the narrower term is still the best available specialization.

Proposed replacements: protein lipidation involved in autophagosome assembly

Summary: The generic C-terminal protein lipidation term is correct in essence for ATG7, which catalyzes the E1 step of Atg8-phosphatidylethanolamine conjugation, but is less specific than available GO terms.

Reason: ATG7 is the E1-like enzyme that activates Atg8 and transfers it to the E2 Atg3, which completes conjugation of the Atg8 C-terminal glycine to phosphatidylethanolamine; ATG7 therefore performs an obligate catalytic step of Atg8 lipidation, and the lipidation process term is appropriate. The MODIFY is a specialization, not a correction: GO:0061739 protein lipidation involved in autophagosome assembly is a child of the annotated GO:0006501 and names the specific Atg8-PE lipidation that ATG7 drives (the originally proposed id, GO:0061683, was an erroneous id for an unrelated, now-obsolete term). GO:0061739 is scoped to autophagosome assembly, whereas Atg8-PE conjugation in yeast also serves the Cvt pathway; GO has no Cvt-specific lipidation term, and ATG7's Cvt role is captured separately by its ACCEPTed cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) annotations, so the narrower term is still the best available specialization.

Proposed replacements: protein lipidation involved in autophagosome assembly

Summary: The generic C-terminal protein lipidation term is correct in essence for ATG7, which catalyzes the E1 step of Atg8-phosphatidylethanolamine conjugation, but is less specific than available GO terms.

Reason: ATG7 is the E1-like enzyme that activates Atg8 and transfers it to the E2 Atg3, which completes conjugation of the Atg8 C-terminal glycine to phosphatidylethanolamine; ATG7 therefore performs an obligate catalytic step of Atg8 lipidation, and the lipidation process term is appropriate. The MODIFY is a specialization, not a correction: GO:0061739 protein lipidation involved in autophagosome assembly is a child of the annotated GO:0006501 and names the specific Atg8-PE lipidation that ATG7 drives (the originally proposed id, GO:0061683, was an erroneous id for an unrelated, now-obsolete term). GO:0061739 is scoped to autophagosome assembly, whereas Atg8-PE conjugation in yeast also serves the Cvt pathway; GO has no Cvt-specific lipidation term, and ATG7's Cvt role is captured separately by its ACCEPTed cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) annotations, so the narrower term is still the best available specialization.

Proposed replacements: protein lipidation involved in autophagosome assembly

Summary: autophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: membrane is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: macroautophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: macroautophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: Atg12 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: Atg8 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: cytoplasm to vacuole targeting by the Cvt pathway is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: cytoplasm to vacuole targeting by the Cvt pathway is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: protein modification by small protein conjugation is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.

Summary: piecemeal microautophagy of the nucleus is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.

Reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.