Summary: Phylogenetic inference that ATG-7 participates in autophagosome assembly. As the E1 for both the LGG-1/LGG-2 lipidation system and the LGG-3-ATG-5 system, ATG-7 catalyses steps that autophagosome biogenesis depends on; C. elegans data show that LGG-1 and LGG-2 lipidation requires ATG-7 and ATG-3.

Reason: Core process for the E1 of the autophagic conjugation systems, conserved from yeast to mammals; consistent with C. elegans evidence that ATG-7 mediates Atg8-homolog lipidation (PMID:27046254) and that atg-7 is required for autophagy-dependent dauer morphogenesis (PMID:12958363).

Summary: Phylogenetic inference that ATG-7 acts at the phagophore assembly site, based on yeast Atg7 and human ATG7.

Reason: Atg7 is recruited to the PAS in yeast and the inference is placed at the ATG7 clade node; C. elegans ATG-7 lies inside that clade and no evidence of divergence is known. Acceptable as the site where the E1 acts, although C. elegans-specific localization data are lacking.

Summary: UniProt subcellular-location mapping (preautophagosomal structure) from a family rule.

Reason: Same assertion as the IBA row; consistent with the conserved function of Atg7.

Summary: Phylogenetic inference of a role in mitophagy based on mammalian ATG7.

Reason: ATG-7 is general autophagy core machinery and so is plausibly required for mitophagy, as in mammals and yeast, but no C. elegans study cited here tests atg-7 in mitophagy. Mitophagy is one of several cargo-specific outputs of the core function, not the core function itself.

Summary: Phylogenetic inference of cytoplasmic localization across E1-like enzymes.

Reason: ATG-7 is a soluble cytoplasmic enzyme; consistent with UniProt annotation and with its function in activating cytosolic LGG-1/LGG-2/LGG-3.

Summary: Combined automated annotation (InterPro Atg7 family plus SubCell) to cytoplasm.

Reason: Correct and consistent with the IBA row.

Summary: Melendez et al. showed that dauer formation, which is associated with increased autophagy, requires the C. elegans orthologs of APG1, APG7, APG8 and AUT10, in a daf-2 background (genetic interaction).

Reason: Early in vivo demonstration that atg-7 is needed for autophagy in C. elegans. The broad term is appropriate for this kind of genetic evidence; the more specific mechanistic role is captured by autophagosome assembly and the E1 activities.

Summary: Phylogenetic inference of a role in the cellular response to nitrogen starvation, from the ATG7 clade (Dictyostelium donor).

Reason: Starvation-induced autophagy is conserved, and ATG-7 is required for starvation/dietary-restriction-dependent autophagy outputs in worms (PMID:17912023), but nitrogen starvation per se is a unicellular framing and has not been tested in C. elegans. Kept as a non-core inherited annotation.

Summary: Jia and Levine showed that bec-1 and Ce-atg7 are required for the extended lifespan of the eat-2 dietary-restriction mutant.

Reason: Lifespan determination is a downstream organismal phenotype of losing autophagy, not the molecular role of ATG-7; retained as a non-core physiological role.

Summary: InterPro-based assignment of the generic ubiquitin-like modifier activating enzyme activity from the E1-like ThiF domain.

Reason: Correct but general. ATG-7 is the specific E1 for the Atg8-family proteins (LGG-1/LGG-2) and for Atg12 (LGG-3); the specific child terms are already asserted by IBA and are the informative descriptions.

Proposed replacements: Atg8 activating enzyme activity Atg12 activating enzyme activity

Summary: Erdelyi et al. showed that autophagy and apoptosis are redundantly required for normal development and viability (genetic interaction with an apoptosis-pathway gene).

Reason: A developmental requirement revealed only in combination with loss of apoptosis; a pleiotropic consequence of losing autophagy rather than a core function of ATG-7.

Summary: Phylogenetic inference that ATG-7 activates the Atg12-family protein (LGG-3 in C. elegans), based on yeast Atg7, mouse and human ATG7.

Reason: One of the two defining E1 activities of Atg7 orthologs; C. elegans ATG-7 is within the ATG7 clade with the conserved C-terminal active-site cysteine (UniProt ACT_SITE 523). Direct biochemistry on worm ATG-7 with LGG-3 has not been reported, but the phylogenetic inference is sound.

Summary: Phylogenetic inference that ATG-7 activates Atg8-family proteins (LGG-1, LGG-2).

Reason: Core molecular function. C. elegans data show that LGG-1 and LGG-2 lipidation is mediated by ATG-7 and ATG-3, and that LGG-1 and LGG-2 differ in their affinities for ATG-7.

Summary: Jia et al. showed that inactivation of autophagy genes increases accumulation of polyQ40 aggregates in muscle and Htn-Q150 aggregates in ASH neurons.

Reason: Autophagic degradation of aggregate-prone proteins is a genuine output of ATG-7 function; aggrephagy would be a more specific description, but the abstract-only cache does not show which assay supports the atg-7 row, so the curator's term is kept as a non-core downstream process.

Summary: Deep-node phylogenetic inference across the E1 family that ATG-7 takes part in protein modification by small-protein conjugation.

Reason: Correct: ATG-7 catalyses the first step of LGG-3 conjugation to ATG-5 and of LGG-1/LGG-2 conjugation to PE. The term is general but appropriate for a family-wide E1 node.

Summary: Phylogenetic inference of piecemeal microautophagy of the nucleus from the eukaryotic ATG7 node PANTHER:PTN000102341 (S. cerevisiae Atg7, SGD:S000001214).

Reason: Piecemeal microautophagy of the nucleus (GO:0034727) is defined from budding-yeast nucleus-vacuole junctions (Nvj1-Vac8), and there is no evidence for this process in C. elegans. While some reviews (human/ATG2A, ATG2B, ATG12, ULK1) left GO:0034727 UNDECIDED on whether macroautophagic nuclear turnover could be treated as a functional equivalent, GO's ontology hierarchy places the general parent term GO:0044804 (nucleophagy) under GO:0016236 (macroautophagy) for autophagosome-mediated nuclear cargo degradation, whereas GO:0034727 (piecemeal microautophagy of the nucleus) is its GO:0016237 (microautophagy)-scoped child (defined by direct endosomal, lysosomal, or vacuolar membrane invagination without prior autophagosome sequestration). Placing GO:0034727 at the eukaryotic ATG7 root node PANTHER:PTN000102341 over-propagates a yeast-specific organelle-contact process to nematode ATG-7, whose conserved role is E1-like activation of LGG-1/LGG-2 and LGG-3 during autophagosome assembly (GO:0000045). Marked as over-annotated for consistency with human/ATG7, worm/atg-5, worm/atg-2, worm/atg-4.1, worm/atg-9, worm/atg-13, and worm/unc-51.

Summary: atg-7 (APG7 ortholog) is required for normal dauer morphogenesis in a daf-2 background.

Reason: Dauer development depends on autophagy, but this is a developmental consequence of the core autophagic function.

Summary: Manil-Segalen et al. used autophagy mutants including atg-7 while dissecting LGG-1/LGG-2 function in allophagy; loss of atg-7 blocks autophagosome formation.

Reason: The underlying observation (atg-7 needed for autophagosome formation) is sound, but ATG-7 is a catalytic core component of the assembly machinery, not a regulator of it. The direct process term GO:0000045 is the appropriate description.

Proposed replacements: autophagosome assembly

Summary: ATG-7, with ATG-3, mediates the phosphatidylethanolamine conjugation of LGG-1 and LGG-2 in C. elegans.

Reason: ATG-7 performs a catalytic step of Atg8-family lipidation (E1 thioester formation), so it passes the participation test. Comparator check: human ATG7 (O95352) has an IDA row on the precomposed GO:0061739, decomposed to this genus, and yeast Atg7 carries C-terminal protein lipidation (GO:0006501) by IDA/IMP. The autophagosome-assembly context is carried by the core functions (GO:0000045). C. elegans ATG-7 otherwise has no lipidation process term.