TOS3
S. cerevisiae
serine/threonine protein kinase TOS3
What the model saw
Gene: TOS3 Organism: Saccharomyces cerevisiae Known functions: serine/threonine protein kinase TOS3. ATP binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
serine/threonine protein kinase TOS3. ATP binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
TOS3 (Target Of Sbf 3) is a serine/threonine protein kinase in S. cerevisiae that functions as an upstream activating kinase of Snf1 (the yeast ortholog of AMPK). By phosphorylating and activating Snf1/AMPK, TOS3 promotes energy-sensing signaling that is critical for metabolic adaptation under nutrient limitation. Snf1/AMPK activation is well-established as a pro-longevity pathway in yeast, suppressing TORC1 activity and promoting autophagy and stress resistance. Thus, TOS3's normal kinase activity feeds into the Snf1-AMPK axis, which opposes the pro-aging effects of excess nutrient signaling. Loss of TOS3 function would impair Snf1 activation, mimicking a nutrient-replete (pro-aging) state.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about TOS3 being an upstream activating kinase of Snf1/AMPK is factually correct — TOS3 does phosphorylate and activate Snf1. However, the model incorrectly concluded that this makes TOS3 pro-longevity. In reality, TOS3 is anti-longevity, meaning its deletion extends lifespan. This could be because the Snf1 pathway's role in longevity is more nuanced than the model assumed, or because TOS3 has additional functions beyond Snf1 activation that promote aging. The model's logic was internally consistent but led to the wrong conclusion, and it expressed relatively high confidence (0.72) in an incorrect answer.
Raw API responses
solver
{
"reasoning": "TOS3 (Target Of Sbf 3) is a serine/threonine protein kinase in S. cerevisiae that functions as an upstream activating kinase of Snf1 (the yeast ortholog of AMPK). By phosphorylating and activating Snf1/AMPK, TOS3 promotes energy-sensing signaling that is critical for metabolic adaptation under nutrient limitation. Snf1/AMPK activation is well-established as a pro-longevity pathway in yeast, suppressing TORC1 activity and promoting autophagy and stress resistance. Thus, TOS3's normal kinase activity feeds into the Snf1-AMPK axis, which opposes the pro-aging effects of excess nutrient signaling. Loss of TOS3 function would impair Snf1 activation, mimicking a nutrient-replete (pro-aging) state.",
"confidence": 0.72,
"key_pathways": [
"Snf1/AMPK activation",
"nutrient sensing / energy homeostasis",
"TORC1 antagonism"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about TOS3 being an upstream activating kinase of Snf1/AMPK is factually correct — TOS3 does phosphorylate and activate Snf1. However, the model incorrectly concluded that this makes TOS3 pro-longevity. In reality, TOS3 is anti-longevity, meaning its deletion extends lifespan. This could be because the Snf1 pathway's role in longevity is more nuanced than the model assumed, or because TOS3 has additional functions beyond Snf1 activation that promote aging. The model's logic was internally consistent but led to the wrong conclusion, and it expressed relatively high confidence (0.72) in an incorrect answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}