MEP2
S. cerevisiae
ammonium permease MEP2
What the model saw
Gene: MEP2 Organism: Saccharomyces cerevisiae Known functions: ammonium permease MEP2. ammonium channel activity.
View unredacted entry
ammonium permease MEP2. ammonium channel activity.
Solver output
MEP2 encodes a high-affinity ammonium permease that transports ammonium (a nitrogen source) into yeast cells. Nitrogen availability is a key upstream signal for TORC1 activation in S. cerevisiae; ammonium permeases like MEP2 facilitate nitrogen sensing and uptake, thereby promoting TORC1 signaling. Elevated TORC1 activity is well-established as anti-longevity, as it suppresses autophagy and stress responses. MEP2 also acts as a transceptor (transporter-receptor), directly activating the PKA pathway in response to ammonium, further reinforcing pro-growth, anti-longevity signaling. Loss of MEP2 function would reduce nitrogen-driven TORC1/PKA activation, mimicking dietary restriction conditions that extend lifespan in yeast.
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 MEP2 as anti_longevity. The mechanistic reasoning is solid and well-grounded: MEP2 as a high-affinity ammonium permease/transceptor that activates TORC1 and PKA signaling, promoting growth at the expense of longevity. The transceptor role of MEP2 in activating PKA is a known function. The reasoning that loss of MEP2 mimics dietary restriction is logical. Confidence of 0.65 is appropriately calibrated given the limited direct evidence typically available for less-studied genes. Overall a high-quality prediction with correct answer and sound mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "MEP2 encodes a high-affinity ammonium permease that transports ammonium (a nitrogen source) into yeast cells. Nitrogen availability is a key upstream signal for TORC1 activation in S. cerevisiae; ammonium permeases like MEP2 facilitate nitrogen sensing and uptake, thereby promoting TORC1 signaling. Elevated TORC1 activity is well-established as anti-longevity, as it suppresses autophagy and stress responses. MEP2 also acts as a transceptor (transporter-receptor), directly activating the PKA pathway in response to ammonium, further reinforcing pro-growth, anti-longevity signaling. Loss of MEP2 function would reduce nitrogen-driven TORC1/PKA activation, mimicking dietary restriction conditions that extend lifespan in yeast.",
"confidence": 0.65,
"key_pathways": [
"TORC1 nitrogen sensing",
"PKA/cAMP signaling",
"nitrogen transceptor signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted MEP2 as anti_longevity. The mechanistic reasoning is solid and well-grounded: MEP2 as a high-affinity ammonium permease/transceptor that activates TORC1 and PKA signaling, promoting growth at the expense of longevity. The transceptor role of MEP2 in activating PKA is a known function. The reasoning that loss of MEP2 mimics dietary restriction is logical. Confidence of 0.65 is appropriately calibrated given the limited direct evidence typically available for less-studied genes. Overall a high-quality prediction with correct answer and sound mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}