EUG1
S. cerevisiae
protein disulfide isomerase EUG1
What the model saw
Gene: EUG1 Organism: Saccharomyces cerevisiae Known functions: protein disulfide isomerase EUG1. protein binding. protein disulfide isomerase activity. protein-disulfide reductase (glutathione) activity. protein-disulfide reductase activity. unfolded protein binding.
View unredacted entry
protein disulfide isomerase EUG1. protein binding. protein disulfide isomerase activity. protein-disulfide reductase (glutathione) activity. protein-disulfide reductase activity. unfolded protein binding.
Solver output
EUG1 encodes a protein disulfide isomerase (PDI) in the yeast ER that catalyzes the formation, reduction, and isomerization of disulfide bonds in nascent secretory and membrane proteins. By correctly folding disulfide-bonded proteins and binding unfolded proteins as a chaperone, EUG1 directly supports proteostasis in the ER. Its protein-disulfide reductase activity (both glutathione-dependent and direct) allows it to resolve aberrant disulfide bonds, preventing the accumulation of misfolded proteins that would otherwise trigger ER stress and the unfolded protein response (UPR). Maintenance of ER proteostasis through PDI activity is well-established as a pro-longevity mechanism in yeast and other model organisms, as chronic ER stress and proteotoxicity are hallmarks of aging. EUG1's unfolded protein binding further reinforces its role as an ER chaperone that buffers proteotoxic insults associated with aging.
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 is plausible in general terms (PDI activity supports proteostasis), but it fails to account for the specific role of EUG1 in yeast aging. EUG1 is actually anti-longevity, meaning its activity shortens lifespan rather than extending it. The model made a confident (0.72) but incorrect prediction by applying generic reasoning about proteostasis without considering that EUG1 specifically has been found to negatively impact longevity in yeast. The mechanistic reasoning is also incorrect since it assumes proteostasis support = pro-longevity, but EUG1's actual effect is the opposite. This is a case of confident wrong prediction with incorrect mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "EUG1 encodes a protein disulfide isomerase (PDI) in the yeast ER that catalyzes the formation, reduction, and isomerization of disulfide bonds in nascent secretory and membrane proteins. By correctly folding disulfide-bonded proteins and binding unfolded proteins as a chaperone, EUG1 directly supports proteostasis in the ER. Its protein-disulfide reductase activity (both glutathione-dependent and direct) allows it to resolve aberrant disulfide bonds, preventing the accumulation of misfolded proteins that would otherwise trigger ER stress and the unfolded protein response (UPR). Maintenance of ER proteostasis through PDI activity is well-established as a pro-longevity mechanism in yeast and other model organisms, as chronic ER stress and proteotoxicity are hallmarks of aging. EUG1's unfolded protein binding further reinforces its role as an ER chaperone that buffers proteotoxic insults associated with aging.",
"confidence": 0.72,
"key_pathways": [
"ER proteostasis / protein folding",
"Unfolded Protein Response (UPR)",
"Disulfide bond formation and isomerization"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is plausible in general terms (PDI activity supports proteostasis), but it fails to account for the specific role of EUG1 in yeast aging. EUG1 is actually anti-longevity, meaning its activity shortens lifespan rather than extending it. The model made a confident (0.72) but incorrect prediction by applying generic reasoning about proteostasis without considering that EUG1 specifically has been found to negatively impact longevity in yeast. The mechanistic reasoning is also incorrect since it assumes proteostasis support = pro-longevity, but EUG1's actual effect is the opposite. This is a case of confident wrong prediction with incorrect mechanistic reasoning.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}