atg5

Summary: Atg5 is essential for autophagosome assembly as part of the Atg12-Atg5-Atg16 complex. This complex functions as an E3-like ligase promoting Atg8 lipidation, which is required for autophagosome membrane expansion. The IBA annotation is well-supported by phylogenetic inference from characterized orthologs and direct experimental evidence in S. pombe.

Reason: Core function of Atg5. The deep research confirms that the Atg12-Atg5-Atg16 complex "functions at the pre-autophagosomal structure to promote the lipidation of ATG8... a modification essential for autophagosome membrane dynamics and substrate recruitment." Direct experimental evidence in S. pombe from PMID:23950735 and PMID:19778961 supports the essential role in autophagosome formation.

Summary: Atg5 localizes to the phagophore assembly site (PAS) membrane where it functions as part of the Atg12-Atg5-Atg16 complex. This localization is dependent on Atg18a which recruits the complex to PI3P-enriched membranes.

Reason: Localization to PAS membrane is directly demonstrated in S. pombe by fluorescence microscopy studies. The IBA annotation is consistent with direct IDA evidence (PMID:23950735, PMID:31941401) showing PAS localization. [2026-08 re-review against GO issue #29437] The supporting evidence quoted here describes PAS puncta / PAS accumulation, not a membrane. GO:0034045 asserts, via bounding_layer_of, that a membrane bounds the phagophore assembly site; the PAS is a liquid-like protein condensate with no bounding bilayer (PMID:32025038), and the term additionally carries 'phagophore' and 'isolation membrane' as synonyms of the distinct term GO:0061908. This annotation derives solely from the UniProt SL-0221 subcellular location via GO_REF:0000044, which is the propagation source rather than independent evidence. Generalize to the structure the cited experiments actually show.

Proposed replacements: phagophore assembly site

Summary: Atg5 is required for mitophagy (selective autophagy of mitochondria) in S. pombe. This function is conserved across eukaryotes and directly demonstrated experimentally.

Reason: Mitophagy requires the core autophagy machinery including Atg5. This is directly supported by IMP evidence from PMID:27737912 in S. pombe. The IBA annotation correctly reflects this conserved function.

Summary: Aggrephagy (selective autophagy of protein aggregates) requires the core autophagy machinery including Atg5. This annotation is inferred from phylogenetic analysis with characterized orthologs in other species.

Reason: The Atg12-Atg5-Atg16 complex is required for all forms of macroautophagy including selective autophagy of aggregates. While there is no direct experimental evidence specifically for aggrephagy in S. pombe, the IBA inference from well-characterized orthologs is sound given the conserved molecular mechanism.

Summary: Atg5 associates with autophagosomes during their formation as part of the Atg12-Atg5-Atg16 complex. The complex dissociates after autophagosome completion.

Reason: Association with autophagosomes is inherent to Atg5 function in promoting autophagosome membrane expansion. This is supported by the demonstrated localization to PAS and role in Atg8 lipidation.

Summary: Piecemeal microautophagy of the nucleus (PMN) is a form of selective autophagy that degrades portions of the nuclear envelope. This annotation is inferred from budding yeast orthologs.

Reason: GO:0034727 specifically denotes piecemeal MICROautophagy of the nucleus (PMN), a microautophagic process well-characterized in S. cerevisiae but not directly demonstrated in S. pombe. The falcon deep research adds direct S. pombe evidence (Zou et al. 2023, PLOS Biology) that Atg5 is required for MACROautophagic nucleophagy: a nucleoplasmic reporter (Pus1-mECitrine) is processed in an Atg5-dependent manner and atg5Δ abolishes induced nuclear-cargo puncta. This strengthens the case that Atg5 participates in nucleophagy generally, but does not establish PMN (microautophagy) per se in fission yeast. Keep as non-core pending direct demonstration of the microautophagic (PMN) mechanism.

Summary: Atg5 localizes to the phagophore (isolation membrane) during autophagosome formation as part of the Atg12-Atg5-Atg16 complex.

Reason: Localization to the phagophore is consistent with Atg5's role in promoting Atg8 lipidation and autophagosome membrane expansion. This is supported by the direct IDA evidence for PAS localization (PMID:23950735, PMID:31941401).

Summary: Atg5 is a core component of the Atg12-Atg5-Atg16 complex. This is directly demonstrated in S. pombe by co-immunoprecipitation and biochemical studies.

Reason: This annotation is directly supported by experimental evidence in S. pombe. PMID:23950735 demonstrates that "S. pombe SPBC405.05/Atg16 protein interacts with Atg5 both in the presence and in the absence of Atg12" and "Atg5 mainly exists in the form of Atg12-Atg5 conjugate."

Summary: Atg5 is required for the autophagic response to nitrogen starvation, which is a key physiological trigger for macroautophagy in S. pombe.

Reason: Nitrogen starvation is the primary inducer of autophagy in fission yeast. PMID:19778961 directly demonstrates that autophagy-deficient mutants including atg5 mutants have impaired responses to nitrogen starvation. This is a core function of the autophagy pathway.

Summary: The Atg12-Atg5-Atg16 complex functions as an E3-like ligase for Atg8 lipidation. Atg5 contributes to this activity (note the "contributes_to" qualifier in GOA).

Reason: This is the core molecular function of Atg5. The deep research confirms that "the ATG12-ATG5-ATG16 complex functions as an E3-like ubiquitin ligase... promoting the conjugation of another ubiquitin-like protein, ATG8, to the membrane lipid phosphatidylethanolamine (PE)." The "contributes_to" qualifier is appropriate as the E3-like activity requires the intact complex.

Summary: Nuclear localization is inferred from UniProt subcellular location annotation. HDA evidence from PMID:16823372 also supports nuclear localization.

Reason: Nuclear localization is supported by the high-throughput localization study (PMID:16823372) that identified Atg5 in both nucleus and cytosol. While not the primary functional location (which is PAS), some nuclear presence is consistent with the dual localization observed.

Summary: Cytoplasmic localization is consistent with Atg5's role in autophagy, which occurs in the cytoplasm. This is supported by multiple lines of evidence.

Reason: Cytoplasmic localization is well-established for Atg5 and is consistent with its role in autophagosome formation. The IEA annotation from InterPro domain mapping and subcellular location is appropriate.

Summary: Involvement in autophagy is the defining function of Atg5. This general annotation is supported by extensive experimental evidence.

Reason: This is a core function annotation. While more specific terms like macroautophagy (GO:0016236) are also annotated, the general autophagy term is appropriate as a parent term that captures the essential function. Multiple IMP annotations support this.

Summary: This annotation is derived from the UniProtKB keyword "Protein transport" (KW-0653). It likely refers to the Cvt (cytoplasm-to-vacuole targeting) pathway.

Reason: While Atg5 is involved in the Cvt pathway in budding yeast (delivering proteins like Ape1 to the vacuole), this is a specialized function of the autophagy machinery. The term "protein transport" is overly general for describing Atg5's role. Keep as non-core since the primary function is autophagy, and the Cvt pathway is a related but secondary function.

Summary: Duplicate annotation of PAS membrane localization, this time from UniProt subcellular location mapping rather than IBA phylogenetic inference.

Reason: This annotation duplicates the IBA annotation but with different evidence. Both are valid and consistent with the demonstrated PAS localization. Multiple evidence codes supporting the same annotation is acceptable. [2026-08 re-review against GO issue #29437] The supporting evidence quoted here describes PAS puncta / PAS accumulation, not a membrane. GO:0034045 asserts, via bounding_layer_of, that a membrane bounds the phagophore assembly site; the PAS is a liquid-like protein condensate with no bounding bilayer (PMID:32025038), and the term additionally carries 'phagophore' and 'isolation membrane' as synonyms of the distinct term GO:0061908. This annotation derives solely from the UniProt SL-0221 subcellular location via GO_REF:0000044, which is the propagation source rather than independent evidence. Generalize to the structure the cited experiments actually show.

Proposed replacements: phagophore assembly site

Summary: This annotation is derived from the UniProtKB keyword "Meiosis" (KW-0469), which was assigned because atg5 is also known as mug77 (meiotically up-regulated gene 77). The gene is transcriptionally upregulated during meiosis.

Reason: This annotation represents an over-annotation. The "Meiosis" keyword was assigned because atg5/mug77 is transcriptionally upregulated during meiosis, NOT because the protein directly participates in the meiotic cell cycle machinery. Atg5 is autophagy machinery that is upregulated during meiosis/sporulation because autophagy is required during this nutrient-stress condition to recycle cellular components. The deep research confirms: "The fission yeast atg5 deletion mutant cannot grow on minimal media or under nitrogen starvation conditions" and "autophagy-deficient mutants undergo partial sporulation" - this indicates autophagy supports sporulation by providing nutrients, not that Atg5 is a meiotic regulator. GO:0051321 implies direct involvement in meiotic progression, which is not the case for an autophagy component.

Summary: This is a placeholder "No biological Data" (ND) annotation indicating no molecular function annotation has been curated from literature.

Reason: The ND annotation should be replaced with the appropriate molecular function annotation. The IBA annotation for GO:0019776 (Atg8-family ligase activity) already captures the molecular function. The ND annotation is outdated given the available IBA annotation with contributes_to qualifier.

Proposed replacements: Atg8-family ligase activity

Summary: Direct experimental evidence for localization to the phagophore assembly site (PAS) in S. pombe from fluorescence microscopy studies.

Reason: This IDA annotation provides direct experimental evidence for PAS localization. PMID:31941401 demonstrates that Atg5 accumulates at PAS puncta and this accumulation is affected by Atg38 AIM mutations.

Summary: Direct mutant phenotype evidence demonstrating Atg5 is required for mitophagy in S. pombe.

Reason: This IMP annotation provides direct experimental evidence that atg5 mutants are defective in mitophagy. PMID:27737912 demonstrates that "autophagy of ER and mitochondria is induced by nitrogen starvation" and requires Atg proteins.

Summary: Direct mutant phenotype evidence demonstrating Atg5 is required for reticulophagy (ER-phagy) in S. pombe.

Reason: This IMP annotation provides direct experimental evidence that atg5 mutants are defective in selective autophagy of the endoplasmic reticulum. This is consistent with Atg5's role in the core autophagy machinery required for all forms of macroautophagy. The falcon deep research adds direct S. pombe evidence from Zou et al. 2023 (PLOS Biology) that atg5Δ abolishes formation of induced ER-phagy/nucleophagy cargo puncta and blocks reporter processing.

Summary: Direct mutant phenotype evidence demonstrating Atg5 is required for macroautophagy in S. pombe under nitrogen starvation.

Reason: This is a core function annotation with direct experimental evidence. PMID:19778961 demonstrates that autophagy-deficient mutants including atg5 show defective autophagy during nitrogen starvation. Macroautophagy is the primary function of Atg5.

Summary: Direct experimental evidence for localization to the phagophore assembly site (PAS) from fluorescence microscopy in S. pombe.

Reason: This IDA annotation provides direct experimental evidence for PAS localization. PMID:23950735 shows that "atg18a abolished the starvation-induced puncta formation by Atg5 and Atg16" indicating Atg5 normally forms PAS puncta.

Summary: Direct mutant phenotype evidence demonstrating Atg5 is required for macroautophagy in S. pombe. This study identified new autophagy factors and characterized their roles.

Reason: This IMP annotation provides direct experimental evidence. PMID:23950735 demonstrates that atg5 mutants have defective CFP-Atg8 processing and impaired autophagy. "Disruption phenotype: Impairs atg8-processing" according to UniProt.

Summary: High-throughput localization study detected Atg5 in the nucleus using systematic ORF tagging and fluorescence microscopy.

Reason: This HDA annotation is from a well-established systematic localization study in S. pombe. While the nucleus is not the primary functional location for Atg5, the detection is valid. Dual localization in nucleus and cytosol is consistent with the study findings.

Summary: High-throughput localization study detected Atg5 in the cytosol using systematic ORF tagging and fluorescence microscopy.

Reason: This HDA annotation is from a well-established systematic localization study. Cytosolic localization is consistent with Atg5's role in cytoplasmic autophagy and is well-supported by the study methodology.