MEP3
S. cerevisiae
ammonium permease MEP3
What the model saw
Gene: MEP3 Organism: Saccharomyces cerevisiae Known functions: ammonium permease MEP3. ammonium channel activity. protein binding.
View unredacted entry
ammonium permease MEP3. ammonium channel activity. protein binding.
Solver output
MEP3 encodes a high-affinity ammonium permease responsible for transporting ammonium (NH4+) into yeast cells, serving as a primary nitrogen source sensor and transporter. Ammonium availability is a key activator of the TORC1 (Target of Rapamycin Complex 1) signaling pathway in S. cerevisiae; MEP proteins, including MEP3, are known to act as transceptors that directly stimulate TORC1 activity upon ammonium uptake. Hyperactivation of TORC1 suppresses autophagy, promotes anabolic metabolism, and is a well-established driver of accelerated aging in yeast. Loss of MEP3 function (or reduced ammonium import) would dampen TORC1 signaling, mimicking nitrogen limitation and extending chronological/replicative lifespan. Therefore, the normal pro-transport function of MEP3 promotes TORC1 activation and opposes 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 MEP3 as anti_longevity. The mechanistic reasoning is well-grounded: MEP3 as an ammonium permease/transceptor activates TORC1 signaling, which promotes aging. Loss of MEP3 would reduce TORC1 activity, mimicking nitrogen limitation and extending lifespan. This is a coherent and plausible mechanism. The confidence of 0.65 is appropriately calibrated given that MEP3 is not a commonly discussed longevity gene. The reasoning about ammonium transceptors and TORC1 is consistent with published literature on MEP2 (the better-studied paralog), and the extrapolation to MEP3 is reasonable.
Raw API responses
solver
{
"reasoning": "MEP3 encodes a high-affinity ammonium permease responsible for transporting ammonium (NH4+) into yeast cells, serving as a primary nitrogen source sensor and transporter. Ammonium availability is a key activator of the TORC1 (Target of Rapamycin Complex 1) signaling pathway in S. cerevisiae; MEP proteins, including MEP3, are known to act as transceptors that directly stimulate TORC1 activity upon ammonium uptake. Hyperactivation of TORC1 suppresses autophagy, promotes anabolic metabolism, and is a well-established driver of accelerated aging in yeast. Loss of MEP3 function (or reduced ammonium import) would dampen TORC1 signaling, mimicking nitrogen limitation and extending chronological/replicative lifespan. Therefore, the normal pro-transport function of MEP3 promotes TORC1 activation and opposes longevity.",
"confidence": 0.65,
"key_pathways": [
"TORC1 nitrogen sensing",
"ammonium transceptor signaling",
"nitrogen catabolite repression (NCR)"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted MEP3 as anti_longevity. The mechanistic reasoning is well-grounded: MEP3 as an ammonium permease/transceptor activates TORC1 signaling, which promotes aging. Loss of MEP3 would reduce TORC1 activity, mimicking nitrogen limitation and extending lifespan. This is a coherent and plausible mechanism. The confidence of 0.65 is appropriately calibrated given that MEP3 is not a commonly discussed longevity gene. The reasoning about ammonium transceptors and TORC1 is consistent with published literature on MEP2 (the better-studied paralog), and the extrapolation to MEP3 is reasonable.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}