GO_REF:0000015

Use of the ND evidence code for Gene Ontology (GO) terms

Placeholder annotation indicating no experimental molecular function data curated

GO_REF:0000033

Annotation inferences using phylogenetic trees

IBA annotations inferred from well-characterized orthologs using PANTHER phylogenetic trees
Includes human, mouse, worm, zebrafish, and budding yeast ATG5 orthologs

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

Maps UniProtKB keywords to GO terms automatically
Source of the problematic meiotic cell cycle annotation from Meiosis keyword

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

Maps UniProtKB subcellular location annotations to GO cellular component terms

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

Combines multiple IEA sources including InterPro domain mapping

PMID:16823372

ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.

Systematic localization study of S. pombe proteins

"we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome"
Detected Atg5 in nucleus and cytosol

"we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein"

PMID:19778961

Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial sporulation during nitrogen starvation.

Demonstrated that autophagy is required for efficient sporulation under nitrogen starvation

"Autophagy-deficient Schizosaccharomyces pombe mutants undergo partial sporulation during nitrogen starvation"
Showed that autophagy-defective cells can partially sporulate when excess amino acids supplied

"up to 30 % of autophagy-defective cells with amino acid auxotrophy were able to recover sporulation when an excess of required amino acids was supplied"
Clarified that autophagy provides nutrients during sporulation rather than being a meiotic regulator

"fission yeast may store sufficient intracellular nitrogen to allow partial sporulation under nitrogen-limiting conditions, although the majority of the nitrogen source is supplied by autophagy"

PMID:23950735

Global analysis of fission yeast mating genes reveals new autophagy factors.

Identified Atg10, Atg16, and Atg14 in S. pombe

"Three core components of the autophagy machinery, Atg10, Atg16, and Atg14, have not been identified in S. pombe"
Demonstrated Atg5-Atg16 interaction

"S. pombe SPBC405.05/Atg16 protein interacts with Atg5 both in the presence and in the absence of Atg12"
Showed Atg5 mainly exists as Atg12-Atg5 conjugate

"We have shown that in S. pombe, Atg5 mainly exists in the form of Atg12–Atg5 conjugate, and physically interacts with Atg16"
Demonstrated Atg18a is required for PAS targeting of Atg12-Atg5-Atg16 complex

"Atg18a is required for the recruitment of the Atg12–Atg5·Atg16 complex to PAS"
Characterized puncta formation by Atg5 under starvation

"atg18aΔ abolished the starvation-induced puncta formation by Atg5 and Atg16"

PMID:27737912

Atg20- and Atg24-family proteins promote organelle autophagy in fission yeast.

Demonstrated mitophagy and reticulophagy in S. pombe

"in a distantly related fungal organism, the fission yeast Schizosaccharomyces pombe, autophagy of ER and mitochondria is induced by nitrogen starvation"
Showed these selective autophagy processes require core Atg proteins including Atg5

"Autophagy cargos include not only soluble cytosolic materials but also bulky organelles, such as ER and mitochondria"

PMID:31941401

Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop to promote autophagy.

Showed Atg5 accumulates at PAS puncta

"PAS accumulation of Atg2, Atg18b, Atg24b, Atg5, Atg16, and Atg8 reduced by the Atg38 AIM mutation was recovered by expressing"
Demonstrated Atg38 AIM mutation reduces PAS accumulation of Atg5

"PAS accumulation of Atg2, Atg18b, Atg24b, Atg5, Atg16, and Atg8 reduced by the Atg38 AIM mutation"
Established role of Atg5 in autophagosome formation feedback loop

"we revealed that the Atg38-Atg8 interaction establishes a positive feedback loop between Atg8 and the PtdIns3K complex I to facilitate autophagosome formation"

file:SCHPO/atg5/atg5-deep-research-falcon.md

Falcon deep research report on S. pombe atg5 (O74971)

S. pombe Atg5 is a core autophagy factor in the Atg12 conjugation system that acts with Atg12 as the E3 enzyme for Atg8 lipidation (Atg8-PE), the membrane-anchored form required for autophagosome biogenesis; it is best understood as a scaffold/adaptor subunit rather than a catalyst with independent small-molecule substrate turnover.

"Atg5 is described as acting with Atg12 as an **E3 enzyme** for Atg8 lipidation, i.e., for forming Atg8 conjugated to phosphatidylethanolamine (Atg8–PE), a membrane-anchored form required for proper autophagosome biogenesis."
The Atg12-Atg5 conjugate binds Atg16 noncovalently to form the Atg12-Atg5-Atg16 complex, which acts as an E3-like ligase for Atg8/LC3 conjugation to PE on the phagophore membrane.

"The Atg12–Atg5 conjugate binds Atg16 noncovalently to form the Atg12–Atg5–Atg16 complex, which functions as an E3-like ligase for Atg8/LC3 conjugation to PE on the phagophore membrane."
In fission yeast, Atg16 promotes PAS localization of Atg12-Atg5, and Atg18a targets the Atg12-Atg5-Atg16 complex to the PAS (phagophore assembly site).

"Atg16 is reported to promote PAS localization of Atg12–Atg5, and Atg18a is reported to target the Atg12–Atg5·Atg16 complex to the PAS"
Zou et al. 2023 (PLOS Biology) provide direct S. pombe evidence that Atg5 is required for selective-autophagy (nucleophagy/ER-phagy) flux: a nucleoplasmic reporter (Pus1-mECitrine) is processed in an Atg5-dependent manner, and atg5Δ abolishes induced nuclear-cargo puncta.

"No Pus1 or Bqt4 puncta were observed in atg5Δ cells and yep1Δ atg5Δ cells"
Residue-level mechanism (conserved-yeast inference): Atg12 is transferred through Atg7 and Atg10 and then covalently conjugated to Atg5 via an isopeptide bond (Atg12 Gly186 to Atg5 Lys149), defining Atg5 as the Atg12 acceptor subunit.

"Atg12 is transferred through Atg7 and Atg10, and then covalently conjugated to Atg5 via an isopeptide bond (Atg12 Gly186 to Atg5 Lys149 in the described yeast system)"
Recent mechanistic work (2024 Science Advances, conserved inference) places the ATG12-ATG5-ATG16L1 E3-like ligase in a three-step membrane-docking model with ATG3 for LC3/Atg8 delivery, with the ATG12-ATG5 unit allosterically enhancing ATG3-LC3 thioester reactivity for transfer to PE.

"the ATG12–ATG5 unit enhances exposure/reactivity of the ATG3–LC3 thioester intermediate for transfer to PE"
Interpretive caution from Flanagan et al. 2013: while Atg5's core role is conserved, the surrounding conjugation network can have lineage-specific variations (an Atg10-like E2 had cell-cycle roles and was not required for autophagy in S. pombe).

"while Atg5’s core role is conserved, the surrounding conjugation network can have lineage-specific variations"