ATG-5 is the C. elegans ortholog of yeast Atg5 and mammalian ATG5. It is the acceptor of the ubiquitin-like protein LGG-3/ATG12, which is covalently attached to it through the E1-like ATG-7 and E2-like ATG-10, and the LGG-3-ATG-5 conjugate binds the N-termini of the coiled-coil proteins ATG-16.1 and ATG-16.2 to form the Atg12-Atg5-Atg16 complex. This complex associates with the forming phagophore and acts as the E3-like enzyme that promotes transfer of LGG-1/LGG-2 from ATG-3 to phosphatidylethanolamine. Loss of atg-5 abolishes LGG-1 lipidation and LGG-1 puncta formation and blocks autophagic degradation of protein aggregates in the embryo.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that ATG-5 participates in autophagosome assembly. Reason: Core process, supported by C. elegans evidence that loss of atg-5 abolishes LGG-1 lipidation and puncta formation (PMID:24185444). Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0000045 autophagosome assembly | IMP PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Zhang et al. showed that atg-5 loss of function abolishes LGG-1 lipidation and the formation of LGG-1 puncta. Reason: Direct C. elegans loss-of-function evidence for the core process. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0000045 autophagosome assembly | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Author statement in the same paper; duplicates the IMP row. Reason: Correct; redundant with the IMP annotation from the same paper. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of mitophagy, from yeast and S. pombe Atg5. Reason: Cargo-specific output of general autophagy machinery; untested for atg-5 in C. elegans. Non-core. |
| GO:0005515 protein binding | IPI PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | REMOVE | Summary: Pull-down/yeast two-hybrid interactions of ATG-5 with ATG-16.1 (Q19124) and ATG-16.2 (Q09406). Reason: The interactions are real and important (removal does not mean the interaction is false), but protein binding is uninformative. They define membership of the Atg12-Atg5-Atg16 complex (GO:0034274), which is annotated separately and captures them informatively; no more specific binding MF term fits. Supporting Evidence: PMID:24185444 ATG-16.1 and ATG-16.2 interact with themselves and each other and also directly associate with ATG-5. |
| GO:0005515 protein binding | IPI PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | REMOVE | Summary: Pull-down/yeast two-hybrid interactions of ATG-5 with ATG-16.1 (Q19124) and ATG-16.2 (Q09406). Reason: The interactions are real and important (removal does not mean the interaction is false), but protein binding is uninformative. They define membership of the Atg12-Atg5-Atg16 complex (GO:0034274), which is annotated separately and captures them informatively; no more specific binding MF term fits. Supporting Evidence: PMID:24185444 ATG-16.1 and ATG-16.2 interact with themselves and each other and also directly associate with ATG-5. |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (Atg5 family) mapping to cytoplasm. Reason: Correct general location for a cytoplasmic autophagy protein. |
| GO:0005737 cytoplasm | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Author statement of cytoplasmic localization. Reason: Correct; cytosol (also annotated) is the more precise term. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0005776 autophagosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference that ATG-5 is active at the autophagosome. Reason: The Atg12-Atg5-Atg16 complex acts on the forming phagophore and largely dissociates on completion; phagophore (GO:0061908, also annotated) is the precise location of the core activity. Not wrong under the broad GO autophagosome term, so retained as non-core. |
| GO:0005829 cytosol | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Author statement of cytosolic localization. Reason: Atg5 orthologs exist as a cytosolic pool of the conjugate complex; correct. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0006914 autophagy | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (Atg5 family) mapping to autophagy. Reason: Correct, general; specific process captured by autophagosome assembly. |
| GO:0006914 autophagy | IMP PMID:19705512 Autophagy in C. elegans. | ACCEPT | Summary: WormBook review of C. elegans autophagy; the cached copy is abstract-only and the underlying atg-5 phenotype is not visible. Reason: The assertion is correct and consistent with later direct atg-5 data (PMID:24185444); deferring to the curator on the specific evidence in the full WormBook chapter. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0006914 autophagy | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Author statement; ATG-5 is part of the autophagy machinery. Reason: Correct, general. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0006995 cellular response to nitrogen starvation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic inference of response to nitrogen starvation, from Dictyostelium atg5. Reason: Unicellular starvation framing not tested in C. elegans; non-core inherited annotation. |
| GO:0007033 vacuole organization | IEA GO_REF:0000117 | MODIFY | Summary: ARBA machine-learning annotation to vacuole organization. Reason: Vacuole organization is an ancestor of autophagosome assembly (via autophagosome organization); it is true but far too general. Replace with the specific process. Proposed replacements: autophagosome assembly |
| GO:0010506 regulation of autophagy | IMP PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | MODIFY | Summary: Loss of atg-5 abolishes LGG-1 lipidation and puncta formation (curated as regulation of autophagy). Reason: The phenotype is sound, but ATG-5 is a core structural/E3-like component of the conjugation machinery, not a regulator of autophagy. The direct process is autophagosome assembly (and the lipidation step). Proposed replacements: autophagosome assembly Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0016236 macroautophagy | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation to macroautophagy. Reason: Correct. |
| GO:0016236 macroautophagy | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Author statement; ATG-5 functions in macroautophagy. Reason: Correct. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0019776 Atg8-family ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that ATG-5 contributes to Atg8-family ligase (E3-like) activity as part of the Atg12-Atg5-Atg16 complex. Reason: Core molecular function, correctly qualified as contributes_to: the E3-like activity belongs to the LGG-3-ATG-5 conjugate within the complex. C. elegans data show atg-5 is required for LGG-1 lipidation. Supporting Evidence: PMID:24185444 The Atg12βAtg5 conjugate possesses an E3-like activity for Atg8 lipidation by promoting the transfer of Atg8 from Atg3 to PE. PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0034045 obsolete phagophore assembly site membrane | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic inference to phagophore assembly site membrane, a term now obsolete in GO (QuickGO: replaced_by GO:7770114 phagophore membrane, because the PAS is not a membrane-bounded compartment). Reason: The intended location, the membrane of the forming autophagosome, is correct for the Atg12-Atg5-Atg16 complex; update to the replacement term. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000315667 SUPPORTS TRANSFER ATG5 clade node; location inference is sound, only the GO term has since been obsoleted in favour of phagophore membrane. Proposed replacements: phagophore membrane |
| GO:0034045 obsolete phagophore assembly site membrane | IEA GO_REF:0000044 | MODIFY | Summary: UniProt SubCell mapping (preautophagosomal structure membrane) to the now-obsolete PAS membrane term. Reason: Update to the GO replacement term phagophore membrane. Proposed replacements: phagophore membrane Supporting Evidence: file:worm/atg-5/atg-5-uniprot.txt Preautophagosomal structure membrane |
| GO:0034045 obsolete phagophore assembly site membrane | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | MODIFY | Summary: Author statement mapped to the now-obsolete PAS membrane term. Reason: Update to the GO replacement term phagophore membrane. Proposed replacements: phagophore membrane |
| GO:0034274 Atg12-Atg5-Atg16 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that ATG-5 is part of the Atg12-Atg5-Atg16 complex. Reason: Core complex membership; supported in C. elegans by direct binding of ATG-5 to ATG-16.1 and ATG-16.2. Supporting Evidence: PMID:24185444 ATG-16.1 and ATG-16.2 interact with themselves and each other and also directly associate with ATG-5. |
| GO:0034274 Atg12-Atg5-Atg16 complex | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | ACCEPT | Summary: Author statement of complex membership. Reason: Correct, consistent with the binding data in the same paper. Supporting Evidence: PMID:24185444 ATG-16.1 and ATG-16.2 interact with themselves and each other and also directly associate with ATG-5. |
| GO:0034727 piecemeal microautophagy of the nucleus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic inference of piecemeal microautophagy of the nucleus from the eukaryotic ATG5 node PANTHER:PTN000315667 (S. cerevisiae Atg5, SGD:S000006070). Reason: Piecemeal microautophagy of the nucleus (GO:0034727) is a budding-yeast process at nucleus-vacuole junctions (Nvj1-Vac8) not documented 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 ATG5 root node PANTHER:PTN000315667 over-propagates a yeast-specific organelle topology to nematode ATG-5, whose conserved role is LGG-3/ATG12 conjugation and LGG-1/LGG-2 lipidation in autophagosome assembly (GO:0000045). Marked as over-annotated for consistency with human/ATG5, SCHPO/atg5, worm/atg-2, worm/atg-4.1, worm/atg-9, worm/atg-13, and worm/unc-51. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000315667 Β· PTN000315667 SUPPORTS SOURCE BUT NOT TARGET Eukaryotic ATG5 root node (PANTHER:PTN000315667) is too deep for GO:0034727 (piecemeal microautophagy of the nucleus), which depends on budding-yeast nucleus-vacuole junctions absent in C. elegans. SGD:S000006070 Β· Saccharomyces cerevisiae ATG5 SUPPORTS SOURCE BUT NOT TARGET S. cerevisiae Atg5 participates in yeast PMN via the shared Atg8 lipidation machinery, but the NVJ microautophagic process does not transfer to nematodes. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. file:worm/atg-5/atg-5-uniprot.txt Most likely a component of an atg-5-lgg-3-atg-16 complex that promotes autophagosome formation by associating with lgg-2, but not lgg-1, at the preautophagosomal membrane (PubMed:24185444). |
| GO:0035973 aggrephagy | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of aggrephagy. Reason: Aggrephagy of embryonic protein aggregates (PGL granules, SQST-1) is the principal assay of basal autophagy in C. elegans, and loss of atg-5 blocks LGG-1 lipidation and puncta formation needed for it. Accepted as a key physiological process of ATG-5 in worms. Supporting Evidence: PMID:24185444 Here we demonstrate that loss of function of atg-5 abolishes LGG-1 lipidation and puncta formation. |
| GO:0061908 phagophore | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that ATG-5 is active at the phagophore. Reason: Precise location of the E3-like activity of the Atg12-Atg5-Atg16 complex. |
| GO:1990234 transferase complex | NAS PMID:24185444 The two C. elegans ATG-16 homologs have partially redundant ... | MODIFY | Summary: Author statement mapped to transferase complex. Reason: Transferase complex is a parent (via catalytic complex) of the Atg12-Atg5-Atg16 complex; correct but uninformative. Use the specific complex. Proposed replacements: Atg12-Atg5-Atg16 complex |
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Download this section (compressed HTML)Q: Is LGG-3 conjugation to ATG-5 required for every ATG-5 function in C. elegans, and has the LGG-3-ATG-5 conjugate been detected biochemically in worms?
Experiment: Detect the LGG-3-ATG-5 conjugate by immunoblot in wild-type, atg-7 and atg-10 mutants, and test whether a non-conjugatable ATG-5 (acceptor Lys mutant) rescues LGG-1 lipidation in atg-5 mutants.
Type: genetics and biochemistry
atg-5 encodes, by alternative splicing, two isoforms of an ortholog of the autophagic budding yeast protein Atg5p, and of human ATG5 (OMIM:604261); ATG-5 has no obvious function in mass RNAi assays.
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