atg-4.1
C. elegans
Cysteine protease atg-4.1
What the model saw
Gene: atg-4.1 Organism: Caenorhabditis elegans Known functions: Cysteine protease atg-4.1. cysteine-type endopeptidase activity. cysteine-type peptidase activity. protein-phosphatidylethanolamide deconjugating activity.
View unredacted entry
Cysteine protease atg-4.1. cysteine-type endopeptidase activity. cysteine-type peptidase activity. protein-phosphatidylethanolamide deconjugating activity.
Solver output
ATG-4.1 is the C. elegans ortholog of the ATG4 cysteine protease family, which performs two essential roles in autophagy: (1) the proteolytic cleavage (priming) of pro-ATG8/LGG-1 to expose a C-terminal glycine required for lipidation, and (2) the deconjugating (delipidating) activity reflected in its protein-phosphatidylethanolamine deconjugating annotation, which recycles ATG8 from the outer autophagosomal membrane. Both activities are indispensable for autophagosome biogenesis and flux. In C. elegans, macroautophagy is a well-established pro-longevity pathway; loss of autophagy genes (e.g., lgg-1, bec-1, atg-18) shortens lifespan, while enhanced autophagy extends it. Because atg-4.1 is a core enzymatic regulator enabling ATG8 conjugation/deconjugation cycling, its normal function supports productive autophagic flux and thus promotes longevity.
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-4.1 in C. elegans. The mechanistic reasoning is thorough and accurate: ATG4 family cysteine proteases prime ATG8/LGG-1 by cleaving the C-terminal residue to expose glycine for lipidation, and also deconjugate ATG8-PE from the outer autophagosomal membrane for recycling. Both functions are essential for autophagy flux. The model correctly connects autophagy to pro-longevity effects in C. elegans, citing relevant parallel genes (lgg-1, bec-1, atg-18). The confidence level of 0.82 is appropriate. Overall, this is an excellent prediction with correct answer and sound mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "ATG-4.1 is the C. elegans ortholog of the ATG4 cysteine protease family, which performs two essential roles in autophagy: (1) the proteolytic cleavage (priming) of pro-ATG8/LGG-1 to expose a C-terminal glycine required for lipidation, and (2) the deconjugating (delipidating) activity reflected in its protein-phosphatidylethanolamine deconjugating annotation, which recycles ATG8 from the outer autophagosomal membrane. Both activities are indispensable for autophagosome biogenesis and flux. In C. elegans, macroautophagy is a well-established pro-longevity pathway; loss of autophagy genes (e.g., lgg-1, bec-1, atg-18) shortens lifespan, while enhanced autophagy extends it. Because atg-4.1 is a core enzymatic regulator enabling ATG8 conjugation/deconjugation cycling, its normal function supports productive autophagic flux and thus promotes longevity.",
"confidence": 0.82,
"key_pathways": [
"ATG8/LGG-1 lipidation cycle (macroautophagy)",
"autophagosome biogenesis",
"protein-PE deconjugation and ATG8 recycling"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for atg-4.1 in C. elegans. The mechanistic reasoning is thorough and accurate: ATG4 family cysteine proteases prime ATG8/LGG-1 by cleaving the C-terminal residue to expose glycine for lipidation, and also deconjugate ATG8-PE from the outer autophagosomal membrane for recycling. Both functions are essential for autophagy flux. The model correctly connects autophagy to pro-longevity effects in C. elegans, citing relevant parallel genes (lgg-1, bec-1, atg-18). The confidence level of 0.82 is appropriate. Overall, this is an excellent prediction with correct answer and sound mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}