URE2
S. cerevisiae
glutathione peroxidase
What the model saw
Gene: URE2 Organism: Saccharomyces cerevisiae Known functions: glutathione peroxidase. glutathione peroxidase activity. glutathione transferase activity. phosphoprotein binding. protein binding. transcription corepressor activity.
View unredacted entry
glutathione peroxidase. glutathione peroxidase activity. glutathione transferase activity. phosphoprotein binding. protein binding. transcription corepressor activity.
Solver output
URE2 in S. cerevisiae is a well-characterized negative regulator of the TORC1/nitrogen catabolite repression (NCR) pathway. It acts as a transcription corepressor by sequestering the GATA transcription factors Gln3 and Gat1 in the cytoplasm under nitrogen-rich conditions, thereby repressing NCR-sensitive genes. Crucially, URE2 also functions as a glutathione peroxidase/transferase, contributing to oxidative stress defense. Loss of URE2 leads to derepression of NCR targets and mimics aspects of nitrogen starvation signaling, which is analogous to reduced TOR signaling — a well-established pro-longevity intervention. The corepressor activity of URE2 keeps nutrient-sensing transcription factors in check, and its glutathione peroxidase activity provides additional protection against reactive oxygen species, both of which support cellular health and longevity. Together, these functions place URE2 as a pro-longevity factor operating at the intersection of nutrient sensing and redox homeostasis.
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 URE2 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning is flawed in a key way: it argues that URE2's role as a corepressor of NCR targets (keeping Gln3/Gat1 in the cytoplasm under nutrient-rich conditions) is analogous to reduced TOR signaling and thus pro-longevity. However, this logic is inverted — URE2 actually suppresses the transcriptional response to nitrogen limitation, meaning it acts to maintain a nutrient-sensing "fed" state rather than mimicking starvation. Loss of URE2 derepresses NCR targets, which could be seen as mimicking reduced TOR/nutrient sensing, making URE2 deletion potentially pro-longevity — but the ground truth says URE2 itself is anti_longevity, consistent with the idea that URE2 deletion extends lifespan. The model correctly identifies URE2's molecular functions (NCR corepressor, glutathione peroxidase) but then draws the wrong conclusion about its longevity influence. The model also incorrectly frames URE2's glutathione peroxidase activity as a pro-longevity mechanism without evidence that this is the dominant effect. The confidence of 0.72 is too high for an incorrect answer.
Raw API responses
solver
{
"reasoning": "URE2 in S. cerevisiae is a well-characterized negative regulator of the TORC1/nitrogen catabolite repression (NCR) pathway. It acts as a transcription corepressor by sequestering the GATA transcription factors Gln3 and Gat1 in the cytoplasm under nitrogen-rich conditions, thereby repressing NCR-sensitive genes. Crucially, URE2 also functions as a glutathione peroxidase/transferase, contributing to oxidative stress defense. Loss of URE2 leads to derepression of NCR targets and mimics aspects of nitrogen starvation signaling, which is analogous to reduced TOR signaling — a well-established pro-longevity intervention. The corepressor activity of URE2 keeps nutrient-sensing transcription factors in check, and its glutathione peroxidase activity provides additional protection against reactive oxygen species, both of which support cellular health and longevity. Together, these functions place URE2 as a pro-longevity factor operating at the intersection of nutrient sensing and redox homeostasis.",
"confidence": 0.72,
"key_pathways": [
"TORC1/nitrogen catabolite repression (NCR) pathway",
"glutathione-mediated oxidative stress defense",
"Gln3/Gat1 transcription factor regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted URE2 as pro_longevity, but the ground truth is anti_longevity. The model's reasoning is flawed in a key way: it argues that URE2's role as a corepressor of NCR targets (keeping Gln3/Gat1 in the cytoplasm under nutrient-rich conditions) is analogous to reduced TOR signaling and thus pro-longevity. However, this logic is inverted — URE2 actually suppresses the transcriptional response to nitrogen limitation, meaning it acts to maintain a nutrient-sensing \"fed\" state rather than mimicking starvation. Loss of URE2 derepresses NCR targets, which could be seen as mimicking reduced TOR/nutrient sensing, making URE2 deletion potentially pro-longevity — but the ground truth says URE2 itself is anti_longevity, consistent with the idea that URE2 deletion extends lifespan. The model correctly identifies URE2's molecular functions (NCR corepressor, glutathione peroxidase) but then draws the wrong conclusion about its longevity influence. The model also incorrectly frames URE2's glutathione peroxidase activity as a pro-longevity mechanism without evidence that this is the dominant effect. The confidence of 0.72 is too high for an incorrect answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}