atg-4.2
C. elegans
Cysteine protease atg-4.2
What the model saw
Gene: atg-4.2 Organism: Caenorhabditis elegans Known functions: Cysteine protease atg-4.2. cysteine-type endopeptidase activity. cysteine-type peptidase activity. protein-phosphatidylethanolamide deconjugating activity.
View unredacted entry
Cysteine protease atg-4.2. cysteine-type endopeptidase activity. cysteine-type peptidase activity. protein-phosphatidylethanolamide deconjugating activity.
Solver output
ATG-4.2 is a cysteine protease ortholog of the ATG4 family, which plays a dual essential role in autophagy: it cleaves the C-terminus of ATG8/LC3 family proteins to expose a glycine required for lipidation (priming), and it also deconjugates ATG8 from phosphatidylethanolamine (PE) on autophagic membranes (delipidation), as indicated by its protein-phosphatidylethanolamide deconjugating activity. This ATG8 processing cycle is indispensable for autophagosome biogenesis and maturation. In C. elegans, autophagy is a well-established pro-longevity pathway; enhanced autophagic flux extends lifespan, and autophagy is required for lifespan extension by dietary restriction, reduced insulin/IGF-1 signaling, and germline removal. By enabling proper ATG8 lipidation/delipidation cycling, atg-4.2 supports functional macroautophagy, thereby promoting longevity. Loss of ATG4 function impairs autophagosome formation and reduces lifespan in multiple model organisms.
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-4.2 in C. elegans. The mechanistic reasoning is thorough and accurate: ATG-4.2 is an ATG4 family cysteine protease that processes ATG8/LC3 proteins (both priming via C-terminal cleavage and deconjugation from PE), which is essential for autophagosome biogenesis. The model correctly connects autophagy to pro-longevity effects in C. elegans through multiple pathways (IIS, dietary restriction, germline removal). The confidence of 0.78 is appropriate. The reasoning is well-grounded in the known biology of ATG4 proteases and C. elegans autophagy.
Raw API responses
solver
{
"reasoning": "ATG-4.2 is a cysteine protease ortholog of the ATG4 family, which plays a dual essential role in autophagy: it cleaves the C-terminus of ATG8/LC3 family proteins to expose a glycine required for lipidation (priming), and it also deconjugates ATG8 from phosphatidylethanolamine (PE) on autophagic membranes (delipidation), as indicated by its protein-phosphatidylethanolamide deconjugating activity. This ATG8 processing cycle is indispensable for autophagosome biogenesis and maturation. In C. elegans, autophagy is a well-established pro-longevity pathway; enhanced autophagic flux extends lifespan, and autophagy is required for lifespan extension by dietary restriction, reduced insulin/IGF-1 signaling, and germline removal. By enabling proper ATG8 lipidation/delipidation cycling, atg-4.2 supports functional macroautophagy, thereby promoting longevity. Loss of ATG4 function impairs autophagosome formation and reduces lifespan in multiple model organisms.",
"confidence": 0.78,
"key_pathways": [
"ATG8/LC3 lipidation-delipidation cycle",
"macroautophagy/autophagosome biogenesis",
"insulin/IGF-1 and dietary restriction longevity pathways"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for atg-4.2 in C. elegans. The mechanistic reasoning is thorough and accurate: ATG-4.2 is an ATG4 family cysteine protease that processes ATG8/LC3 proteins (both priming via C-terminal cleavage and deconjugation from PE), which is essential for autophagosome biogenesis. The model correctly connects autophagy to pro-longevity effects in C. elegans through multiple pathways (IIS, dietary restriction, germline removal). The confidence of 0.78 is appropriate. The reasoning is well-grounded in the known biology of ATG4 proteases and C. elegans autophagy.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}