par-5
C. elegans
14-3-3 domain-containing protein;14-3-3-like protein 1
What the model saw
Gene: par-5 Organism: Caenorhabditis elegans Known functions: 14-3-3 domain-containing protein;14-3-3-like protein 1. protein binding.
View unredacted entry
14-3-3 domain-containing protein;14-3-3-like protein 1. protein binding.
Solver output
PAR-5 is a 14-3-3 family protein in C. elegans, orthologous to mammalian 14-3-3 proteins. 14-3-3 proteins are well-established regulators of the FOXO transcription factor DAF-16 in the insulin/IGF-1 signaling (IIS) pathway. Specifically, 14-3-3 proteins bind phosphorylated DAF-16/FOXO (phosphorylated by AKT downstream of DAF-2/IGF-1R), sequestering it in the cytoplasm and suppressing its transcriptional activity. However, PAR-5 (along with FTT-2) has also been shown to act as a positive regulator of DAF-16 nuclear localization and longevity in certain contexts, particularly under reduced IIS, where 14-3-3 proteins can scaffold DAF-16 for nuclear import. Genetic studies in C. elegans demonstrate that par-5 loss shortens lifespan and reduces stress resistance, consistent with a pro-longevity role. The primary mechanism connects to deregulated nutrient sensing via the IIS/DAF-16 axis, a canonical hallmark of aging pathway.
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 par-5 as pro_longevity with good confidence (0.72). The mechanistic reasoning is solid - PAR-5 is indeed a 14-3-3 protein that plays a role in DAF-16/FOXO regulation in the IIS pathway. The model correctly notes the nuanced dual role of 14-3-3 proteins (cytoplasmic sequestration vs. nuclear import scaffolding) and correctly identifies that par-5 loss shortens lifespan. The mechanism class of "deregulated_nutrient_sensing" is appropriate given the IIS pathway connection. The reasoning is well-articulated and biologically accurate. Minor note: the model's description of the dual role of 14-3-3 proteins is somewhat complex and could be clearer, but overall the reasoning is sound.
Raw API responses
solver
{
"reasoning": "PAR-5 is a 14-3-3 family protein in C. elegans, orthologous to mammalian 14-3-3 proteins. 14-3-3 proteins are well-established regulators of the FOXO transcription factor DAF-16 in the insulin/IGF-1 signaling (IIS) pathway. Specifically, 14-3-3 proteins bind phosphorylated DAF-16/FOXO (phosphorylated by AKT downstream of DAF-2/IGF-1R), sequestering it in the cytoplasm and suppressing its transcriptional activity. However, PAR-5 (along with FTT-2) has also been shown to act as a positive regulator of DAF-16 nuclear localization and longevity in certain contexts, particularly under reduced IIS, where 14-3-3 proteins can scaffold DAF-16 for nuclear import. Genetic studies in C. elegans demonstrate that par-5 loss shortens lifespan and reduces stress resistance, consistent with a pro-longevity role. The primary mechanism connects to deregulated nutrient sensing via the IIS/DAF-16 axis, a canonical hallmark of aging pathway.",
"confidence": 0.72,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"DAF-16/FOXO transcription factor regulation",
"14-3-3 protein scaffolding"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted par-5 as pro_longevity with good confidence (0.72). The mechanistic reasoning is solid - PAR-5 is indeed a 14-3-3 protein that plays a role in DAF-16/FOXO regulation in the IIS pathway. The model correctly notes the nuanced dual role of 14-3-3 proteins (cytoplasmic sequestration vs. nuclear import scaffolding) and correctly identifies that par-5 loss shortens lifespan. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate given the IIS pathway connection. The reasoning is well-articulated and biologically accurate. Minor note: the model's description of the dual role of 14-3-3 proteins is somewhat complex and could be clearer, but overall the reasoning is sound.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}