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atg-5

C. elegans

Autophagy-related protein 5

What the model saw

Gene: atg-5
Organism: Caenorhabditis elegans
Known functions: Autophagy-related protein 5. Atg8-family ligase activity. protein binding.
View unredacted entry
Autophagy-related protein 5. Atg8-family ligase activity. protein binding.

Solver output

Predicted influence
Pro-longevity
Confidence
92%
Mechanism
Disabled macroautophagy
Reasoning

ATG-5 is a core autophagy protein that functions as part of the ATG12–ATG5–ATG16 E3-like ligase complex, which catalyzes the conjugation of ATG8/LC3 family proteins to phosphatidylethanolamine on the phagophore membrane — a critical step in autophagosome elongation and closure. This Atg8-family ligase activity is essential for productive macroautophagy flux. In C. elegans, autophagy is required for lifespan extension downstream of multiple longevity pathways, including DAF-2/insulin signaling, dietary restriction, and mitochondrial stress; loss of atg-5 suppresses these longevity phenotypes. By enabling efficient clearance of damaged proteins and organelles, ATG-5 directly supports proteostasis and opposes the accumulation of cellular damage associated with aging.

Key pathways
macroautophagy / autophagosome biogenesisATG12-ATG5-ATG16 conjugation complexDAF-2/IIS longevity pathway (autophagy branch)
Longevity influence
Pro-longevity
Lifespan effect
Decrease

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

Answer
Correct
Mechanism
Correct
Reasoning quality
5/5
Failure mode
Correct
Notes

The model correctly predicted pro_longevity for atg-5 in C. elegans with high confidence (0.92). The mechanistic reasoning is excellent and accurate: ATG-5 functions as part of the ATG12-ATG5-ATG16 E3-like ligase complex, catalyzes ATG8 lipidation, is essential for autophagosome formation, and loss of atg-5 suppresses lifespan extension in multiple longevity pathways. The model correctly identifies that autophagy is required downstream of DAF-2/insulin signaling, dietary restriction, and mitochondrial stress pathways. All key pathways identified are relevant and accurate.

Raw API responses

solver

{
  "reasoning": "ATG-5 is a core autophagy protein that functions as part of the ATG12–ATG5–ATG16 E3-like ligase complex, which catalyzes the conjugation of ATG8/LC3 family proteins to phosphatidylethanolamine on the phagophore membrane — a critical step in autophagosome elongation and closure. This Atg8-family ligase activity is essential for productive macroautophagy flux. In C. elegans, autophagy is required for lifespan extension downstream of multiple longevity pathways, including DAF-2/insulin signaling, dietary restriction, and mitochondrial stress; loss of atg-5 suppresses these longevity phenotypes. By enabling efficient clearance of damaged proteins and organelles, ATG-5 directly supports proteostasis and opposes the accumulation of cellular damage associated with aging.",
  "confidence": 0.92,
  "key_pathways": [
    "macroautophagy / autophagosome biogenesis",
    "ATG12-ATG5-ATG16 conjugation complex",
    "DAF-2/IIS longevity pathway (autophagy branch)"
  ],
  "mechanism_class": "disabled_macroautophagy",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model correctly predicted pro_longevity for atg-5 in C. elegans with high confidence (0.92). The mechanistic reasoning is excellent and accurate: ATG-5 functions as part of the ATG12-ATG5-ATG16 E3-like ligase complex, catalyzes ATG8 lipidation, is essential for autophagosome formation, and loss of atg-5 suppresses lifespan extension in multiple longevity pathways. The model correctly identifies that autophagy is required downstream of DAF-2/insulin signaling, dietary restriction, and mitochondrial stress pathways. All key pathways identified are relevant and accurate.",
  "failure_mode": "correct",
  "answer_correct": true,
  "mechanism_correct": true,
  "reasoning_quality": 5,
  "ground_truth_questionable": false
}