ATG-2 is the C. elegans member of the ATG2 family, a very large (2290 aa) rod-shaped bridge-like lipid transfer protein of the chorein/VPS13 superfamily. By homology with yeast Atg2 and human ATG2A, ATG-2 tethers the rim of the expanding phagophore (isolation membrane) to the endoplasmic reticulum and moves glycerophospholipids from the ER to the phagophore, supplying membrane for its growth. ATG-2 binds the PROPPIN EPG-6 (WIPI3/4 ortholog) directly, and the ATG-2/EPG-6 complex is needed for PI3P-positive omegasomes to progress to closed autophagosomes; atg-2 mutants accumulate enlarged early autophagic structures, mislocalise ATG-9 and ATG-13, and fail to degrade protein aggregates such as PGL granules during embryogenesis. In neurons, ATG-2 acts cell-autonomously in the autophagy needed for presynaptic assembly.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for autophagosome assembly from the ATG2 family node. Reason: Core process, confirmed in C. elegans: atg-2 mutants arrest at the omegasome-to-autophagosome step. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0000045 autophagosome assembly | NAS PMID:21802374 The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates p... | ACCEPT | Summary: Author statement that ATG-2 acts in autophagosome formation. Reason: Correct; matches the mutant phenotype and the conserved ATG2 lipid-supply function. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0000407 phagophore assembly site | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for phagophore assembly site. Reason: ATG2 proteins localise to the PAS/phagophore edge with the PROPPIN; in C. elegans ATG-2 acts with EPG-6 at early autophagic structures. Supporting Evidence: PMID:30185561 Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the PI3P-enriched ER-phagophore junction |
| GO:0000422 autophagy of mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for autophagy of mitochondrion. Reason: IBA from the ATG2 family node. ATG-2 belongs to the core autophagosome-forming machinery, which is shared by bulk and selective macroautophagy; no C. elegans study has tested ATG-2 in this particular selective pathway, so this is kept as non-core. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0000425 pexophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for pexophagy (yeast Atg2 donor). Reason: IBA from the ATG2 family node. ATG-2 belongs to the core autophagosome-forming machinery, which is shared by bulk and selective macroautophagy; no C. elegans study has tested ATG-2 in this particular selective pathway, so this is kept as non-core. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0005515 protein binding | IPI PMID:21802374 The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates p... | REMOVE | Summary: Direct binding of ATG-2 to EPG-6. Reason: Removal does not mean the interaction is false: it is real and conserved (Atg2-Atg18 in yeast, ATG2A-WIPI4 in human), but "protein binding" says nothing about function. The interaction is captured more informatively as membership of the ATG2-ATG18 complex (GO:0062079, NEW) and by the ATG-2 lipid-transfer activity it positions. Supporting Evidence: PMID:21802374 EPG-6 directly interacts with ATG-2 |
| GO:0005737 cytoplasm | IDA PMID:21802374 The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates p... | ACCEPT | Summary: Cytoplasmic localisation reported in Lu et al. 2011. Reason: Correct but general; ATG-2 is a soluble peripheral membrane protein. Supporting Evidence: file:worm/atg-2/atg-2-uniprot.txt Cytoplasm |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoplasm. Reason: Consistent with the IDA row. Supporting Evidence: file:worm/atg-2/atg-2-uniprot.txt Cytoplasm |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to ER membrane. Reason: Same basis as the ISS row. Supporting Evidence: file:worm/atg-2/atg-2-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of ER membrane localisation from yeast Atg2. Reason: One end of ATG2 binds the ER at ER-phagophore contacts, and this geometry is conserved from yeast to human. Not yet shown for C. elegans ATG-2 directly. Supporting Evidence: file:worm/atg-2/atg-2-uniprot.txt Endoplasmic reticulum membrane PMID:30911189 Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation |
| GO:0005811 lipid droplet | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location mapping to lipid droplet. Reason: Same basis as the ISS row. Supporting Evidence: file:worm/atg-2/atg-2-uniprot.txt Lipid droplet |
| GO:0005811 lipid droplet | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer of lipid droplet localisation from human ATG2A. Reason: Human ATG2A/B localise to lipid droplets through C-terminal amphipathic helices; this is a secondary location, not tested in C. elegans, and is unrelated to the core autophagosome-assembly role. Supporting Evidence: file:worm/atg-2/atg-2-uniprot.txt Lipid droplet |
| GO:0006914 autophagy | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based autophagy annotation. Reason: Correct but very general; the specific process supported for ATG-2 is autophagosome assembly. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0010508 positive regulation of autophagy | IMP PMID:25124690 PI3P phosphatase activity is required for autophagosome matu... | MODIFY | Summary: IMP from the MTM-3 paper, which used atg-2 mutants in epistasis analysis. Reason: ATG-2 is a core component of the autophagosome-forming machinery, not a regulator of autophagy. The mutant data show that autophagy fails without it, which places it in autophagosome assembly; the regulatory term misstates the role. Proposed replacements: autophagosome assembly Supporting Evidence: PMID:25124690 MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes |
| GO:0016236 macroautophagy | NAS PMID:21802374 The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates p... | ACCEPT | Summary: Author statement that ATG-2 acts in macroautophagy. Reason: Correct; parent of the core autophagosome assembly annotation. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0032266 phosphatidylinositol-3-phosphate binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for PtdIns(3)P binding, seeded by yeast Atg2. Reason: Yeast Atg2 binds PI3P directly through its N-terminal/APT region, and ATG2 proteins act at the PI3P-enriched ER-phagophore junction. C. elegans ATG-2 has not been assayed, but no evidence argues it is outside the clade that inherited this activity. Non-core relative to lipid transfer. Supporting Evidence: PMID:30185561 Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the PI3P-enriched ER-phagophore junction |
| GO:0034045 obsolete phagophore assembly site membrane | IEA GO_REF:0000044 | MODIFY | Summary: UniProt subcellular-location mapping to the now-obsolete phagophore assembly site membrane term. Reason: As for the ISS row. Proposed replacements: phagophore membrane Supporting Evidence: PMID:30911189 Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation |
| GO:0034045 obsolete phagophore assembly site membrane | ISS GO_REF:0000024 | MODIFY | Summary: ISS to the now-obsolete term phagophore assembly site membrane. Reason: GO:0034045 is obsolete (QuickGO, checked 2026-10). ATG2 binds the phagophore rim, so the intended location is GO:7770114 phagophore membrane, the replacement used for human ATG2A. Proposed replacements: phagophore membrane Supporting Evidence: PMID:30911189 Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation |
| GO:0034727 piecemeal microautophagy of the nucleus | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA for piecemeal microautophagy of the nucleus, seeded only by yeast Atg2. Reason: Piecemeal microautophagy of the nucleus is a budding-yeast process at nucleus-vacuole junctions, which depend on yeast-specific proteins (Vac8, Nvj1). There is no evidence for this process in C. elegans, so propagating it to ATG-2 is an over-annotation, as was judged for human ATG9A. Propagation Review Root cause: NO FAILURE NON CORE Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000324023 SUPPORTS SOURCE BUT NOT TARGET Yeast Atg2 participates in PMN, but the process depends on yeast nucleus-vacuole junction machinery not known in nematodes. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for protein-membrane adaptor activity, seeded by S. pombe Atg2. Reason: ATG2 family proteins bridge two membranes: one tip binds the phagophore rim (with the PROPPIN) and the other the ER. This membrane-tethering activity is conserved and is part of how ATG2 supplies lipid. Supporting Evidence: PMID:30911189 Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation PMID:30185561 WIPI4 binds to one of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle to another PI3P-free vesicle |
| GO:0061709 reticulophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for reticulophagy (yeast Atg2 donor). Reason: IBA from the ATG2 family node. ATG-2 belongs to the core autophagosome-forming machinery, which is shared by bulk and selective macroautophagy; no C. elegans study has tested ATG-2 in this particular selective pathway, so this is kept as non-core. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0061723 glycophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for glycophagy (Drosophila Atg2 donor). Reason: IBA from the ATG2 family node. ATG-2 belongs to the core autophagosome-forming machinery, which is shared by bulk and selective macroautophagy; no C. elegans study has tested ATG-2 in this particular selective pathway, so this is kept as non-core. Supporting Evidence: PMID:21802374 epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures |
| GO:0061908 phagophore | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for phagophore. Reason: ATG2 binds the rim of the expanding phagophore, which it supplies with lipid. Supporting Evidence: PMID:30911189 Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation |
| GO:0120013 lipid transfer activity | ISS PMID:30952800 ATG2 transports lipids to promote autophagosome biogenesis. | NEW | Summary: ATG2-family lipid transfer activity, transferred from human ATG2A and fission-yeast Atg2. Reason: Lipid transfer is the defining biochemical activity of ATG2 proteins: human ATG2A and S. pombe Atg2 bind many glycerophospholipids in an N-terminal hydrophobic channel and transfer them between membranes in vitro, and the lipid-transfer region is sufficient to rescue autophagosome formation. C. elegans ATG-2 is a full-length ATG2 family member (Chorein/ATG2_CAD domains) whose loss blocks phagophore expansion, so the activity is expected to be conserved. Comparator: human ATG2A and ATG2B carry GO:0120013. UniProt also describes ATG-2 as a lipid transfer protein by similarity. ATG-2 itself does the transfer, so this is the gene doing the work, not a requirement. Supporting Evidence: PMID:30952800 ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro PMID:30911189 These results suggest that Atg2 acts as a lipid-transfer protein that supplies phospholipids for autophagosome formation file:worm/atg-2/atg-2-uniprot.txt Lipid transfer protein involved in autophagosome assembly |
| GO:0062079 ATG2-ATG18 complex | IPI PMID:21802374 The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates p... | NEW | Summary: ATG-2 binds EPG-6 directly, forming the C. elegans counterpart of the Atg2-Atg18 complex. Reason: Direct ATG-2-EPG-6 binding and shared mutant phenotypes (Lu et al. 2011), with later work naming the ATG-2/EPG-6 complex. GO:0062079 is the ATG2-PROPPIN complex term, also carried by human ATG2A. Supporting Evidence: PMID:21802374 EPG-6 directly interacts with ATG-2 PMID:25124690 MTM-3 acts downstream of the ATG-2/EPG-6 complex and upstream of EPG-5 to promote autophagosome maturation into autolysosomes |
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Download this section (compressed HTML)Q: Does C. elegans ATG-2 transfer lipids in vitro like human ATG2A, and does it use EPG-6, ATG-18, or both to reach the phagophore rim?
Experiment: Purify the C. elegans ATG-2 N-terminal lipid-transfer region (alone and with EPG-6) and measure FRET-based phospholipid transfer between donor and PI3P-containing acceptor liposomes.
Hypothesis: Worm ATG-2 transfers phospholipids, and EPG-6 increases transfer to PI3P-containing membranes.
Type: In vitro lipid transfer assay
atg-2 encodes a large (2,275-residue) protein orthologous to theautophagic budding yeast protein Atg2p, and to human ATG2A and ATG2B;ATG-2 is expressed in larval and adult pharynx, intestine, body wall muscles, and neurons, as well as adult reproductive system; ATG-2 has noobvious phenotype in mass RNAi assays.
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