Atg8a
D. melanogaster
Autophagy-related 8a
What the model saw
Gene: Atg8a Organism: Drosophila melanogaster Known functions: Autophagy-related 8a. GABA receptor binding. phosphatidylethanolamine binding. protein binding. protein kinase binding. protein tag activity. ubiquitin protein ligase binding.
View unredacted entry
Autophagy-related 8a. GABA receptor binding. phosphatidylethanolamine binding. protein binding. protein kinase binding. protein tag activity. ubiquitin protein ligase binding.
Solver output
Atg8a is the Drosophila ortholog of mammalian LC3/GABARAP, a central effector of macroautophagy. Its phosphatidylethanolamine (PE) binding activity reflects the lipidation step (Atg8–PE conjugation) that is essential for autophagosome membrane elongation and closure. Its protein tag activity underlies selective autophagy cargo recognition via LIR-motif interactions, and its ubiquitin ligase and protein kinase binding activities place it at the hub of autophagy initiation and cargo-receptor signaling. Overexpression of Atg8a in Drosophila neurons and fat body has been shown to extend lifespan, while loss of function accelerates age-related neurodegeneration and shortens lifespan. By maintaining proteostasis and organelle quality control through autophagosome biogenesis, Atg8a opposes the accumulation of damaged proteins and organelles that drive aging.
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 Atg8a in Drosophila melanogaster with high confidence (0.93). The mechanistic reasoning is excellent and accurate: Atg8a is indeed the Drosophila LC3/GABARAP ortholog, its PE-binding/lipidation role in autophagosome biogenesis is correctly described, and the model accurately cites that overexpression extends lifespan while loss-of-function shortens it and accelerates neurodegeneration. The key pathways identified are all relevant and correct. The mechanism_class label "disabled_macroautophagy" is slightly odd as a label (it seems to describe what happens when the gene is lost rather than the gene's function class), but the actual reasoning text is fully correct.
Raw API responses
solver
{
"reasoning": "Atg8a is the Drosophila ortholog of mammalian LC3/GABARAP, a central effector of macroautophagy. Its phosphatidylethanolamine (PE) binding activity reflects the lipidation step (Atg8–PE conjugation) that is essential for autophagosome membrane elongation and closure. Its protein tag activity underlies selective autophagy cargo recognition via LIR-motif interactions, and its ubiquitin ligase and protein kinase binding activities place it at the hub of autophagy initiation and cargo-receptor signaling. Overexpression of Atg8a in Drosophila neurons and fat body has been shown to extend lifespan, while loss of function accelerates age-related neurodegeneration and shortens lifespan. By maintaining proteostasis and organelle quality control through autophagosome biogenesis, Atg8a opposes the accumulation of damaged proteins and organelles that drive aging.",
"confidence": 0.93,
"key_pathways": [
"macroautophagy / autophagosome biogenesis (Atg8-PE lipidation)",
"selective autophagy cargo recognition (LIR-motif / ubiquitin receptor pathway)",
"TOR-regulated autophagy induction"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Atg8a in Drosophila melanogaster with high confidence (0.93). The mechanistic reasoning is excellent and accurate: Atg8a is indeed the Drosophila LC3/GABARAP ortholog, its PE-binding/lipidation role in autophagosome biogenesis is correctly described, and the model accurately cites that overexpression extends lifespan while loss-of-function shortens it and accelerates neurodegeneration. The key pathways identified are all relevant and correct. The mechanism_class label \"disabled_macroautophagy\" is slightly odd as a label (it seems to describe what happens when the gene is lost rather than the gene's function class), but the actual reasoning text is fully correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}