atg-3
C. elegans
Ubiquitin-like-conjugating enzyme ATG3
What the model saw
Gene: atg-3 Organism: Caenorhabditis elegans Known functions: Ubiquitin-like-conjugating enzyme ATG3. Atg8-family conjugating enzyme activity. ubiquitin-like protein transferase activity.
View unredacted entry
Ubiquitin-like-conjugating enzyme ATG3. Atg8-family conjugating enzyme activity. ubiquitin-like protein transferase activity.
Solver output
ATG-3 is the C. elegans ortholog of the E2-like conjugating enzyme required for lipidation of ATG8-family proteins (e.g., LGG-1/LGG-2 in worms). This lipidation step—transferring phosphatidylethanolamine to ATG8—is essential for autophagosome membrane elongation and closure, making ATG-3 a core, non-redundant component of the macroautophagy pathway. Functional macroautophagy is required for lifespan extension in multiple C. elegans longevity paradigms, including daf-2/insulin signaling mutants, dietary restriction, and germline-less glp-1 mutants. Loss of atg-3 blocks autophagosome formation and shortens lifespan, while its normal activity supports proteostasis and organelle quality control. Therefore, the normal function of atg-3 promotes longevity by enabling autophagic flux.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted pro_longevity for atg-3 in C. elegans. The mechanistic reasoning is accurate and detailed: ATG-3 is indeed the E2-like conjugating enzyme required for ATG8 lipidation (PE conjugation), which is essential for autophagosome biogenesis. The model correctly identifies that loss of atg-3 blocks autophagy and shortens lifespan, and that autophagy is required for lifespan extension in multiple longevity paradigms (daf-2 mutants, dietary restriction, glp-1 mutants). The key pathways listed are all relevant and correct. High confidence (0.88) is appropriate given the well-established role of autophagy in C. elegans longevity.
Raw API responses
solver
{
"reasoning": "ATG-3 is the C. elegans ortholog of the E2-like conjugating enzyme required for lipidation of ATG8-family proteins (e.g., LGG-1/LGG-2 in worms). This lipidation step—transferring phosphatidylethanolamine to ATG8—is essential for autophagosome membrane elongation and closure, making ATG-3 a core, non-redundant component of the macroautophagy pathway. Functional macroautophagy is required for lifespan extension in multiple C. elegans longevity paradigms, including daf-2/insulin signaling mutants, dietary restriction, and germline-less glp-1 mutants. Loss of atg-3 blocks autophagosome formation and shortens lifespan, while its normal activity supports proteostasis and organelle quality control. Therefore, the normal function of atg-3 promotes longevity by enabling autophagic flux.",
"confidence": 0.88,
"key_pathways": [
"ATG8 lipidation / autophagosome biogenesis",
"macroautophagy flux",
"DAF-16/FOXO longevity pathway (autophagy arm)"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for atg-3 in C. elegans. The mechanistic reasoning is accurate and detailed: ATG-3 is indeed the E2-like conjugating enzyme required for ATG8 lipidation (PE conjugation), which is essential for autophagosome biogenesis. The model correctly identifies that loss of atg-3 blocks autophagy and shortens lifespan, and that autophagy is required for lifespan extension in multiple longevity paradigms (daf-2 mutants, dietary restriction, glp-1 mutants). The key pathways listed are all relevant and correct. High confidence (0.88) is appropriate given the well-established role of autophagy in C. elegans longevity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}