PIB1
S. cerevisiae
phosphatidylinositol-3-phosphate-binding ubiquitin-protein ligase
What the model saw
Gene: PIB1 Organism: Saccharomyces cerevisiae Known functions: phosphatidylinositol-3-phosphate-binding ubiquitin-protein ligase. metal ion binding. phosphatidylinositol-3-phosphate binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
View unredacted entry
phosphatidylinositol-3-phosphate-binding ubiquitin-protein ligase. metal ion binding. phosphatidylinositol-3-phosphate binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
Solver output
PIB1 encodes a RING-domain E3 ubiquitin ligase that binds phosphatidylinositol-3-phosphate (PI3P), a lipid enriched on early endosomes and autophagosome membranes generated by the Vps34 PI3-kinase complex. By localizing to PI3P-rich membranes, PIB1 can ubiquitinate cargo or regulatory proteins at these compartments, coupling the endosomal/vacuolar sorting pathway with ubiquitin-mediated proteolysis. Proper ubiquitination of misfolded or damaged proteins and their delivery to the vacuole (yeast lysosome) is essential for proteostasis and autophagic flux. Loss of such E3 ligase activity at PI3P membranes could impair cargo ubiquitination and vacuolar degradation, reducing proteostatic capacity and shortening lifespan. The zinc ion binding reflects the RING domain required for E3 ligase catalytic activity, which is the direct effector of ubiquitin transfer. Thus, PIB1's normal function supports proteostasis and autophagic/vacuolar degradation, processes that are broadly pro-longevity 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 predicted pro_longevity but the ground truth is anti_longevity. PIB1 is an anti-longevity gene in yeast, meaning its deletion extends lifespan. The model reasoned that PIB1's role in PI3P-dependent ubiquitination supports proteostasis and vacuolar degradation, concluding it would be pro-longevity. This reasoning is plausible on the surface but leads to the wrong conclusion. The model failed to consider that PIB1 deletion (loss of function) extends lifespan, making it anti-longevity. The mechanistic reasoning about PI3P binding and ubiquitin ligase activity supporting proteostasis is speculative and not well-grounded in the actual biology of PIB1's role in aging. The confidence of 0.55 is relatively low, but the model still committed to the wrong answer.
Raw API responses
solver
{
"reasoning": "PIB1 encodes a RING-domain E3 ubiquitin ligase that binds phosphatidylinositol-3-phosphate (PI3P), a lipid enriched on early endosomes and autophagosome membranes generated by the Vps34 PI3-kinase complex. By localizing to PI3P-rich membranes, PIB1 can ubiquitinate cargo or regulatory proteins at these compartments, coupling the endosomal/vacuolar sorting pathway with ubiquitin-mediated proteolysis. Proper ubiquitination of misfolded or damaged proteins and their delivery to the vacuole (yeast lysosome) is essential for proteostasis and autophagic flux. Loss of such E3 ligase activity at PI3P membranes could impair cargo ubiquitination and vacuolar degradation, reducing proteostatic capacity and shortening lifespan. The zinc ion binding reflects the RING domain required for E3 ligase catalytic activity, which is the direct effector of ubiquitin transfer. Thus, PIB1's normal function supports proteostasis and autophagic/vacuolar degradation, processes that are broadly pro-longevity in yeast.",
"confidence": 0.55,
"key_pathways": [
"PI3P-dependent endosomal/vacuolar sorting",
"ubiquitin-proteasome/vacuolar proteostasis",
"macroautophagy regulation via Vps34-PI3P signaling"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. PIB1 is an anti-longevity gene in yeast, meaning its deletion extends lifespan. The model reasoned that PIB1's role in PI3P-dependent ubiquitination supports proteostasis and vacuolar degradation, concluding it would be pro-longevity. This reasoning is plausible on the surface but leads to the wrong conclusion. The model failed to consider that PIB1 deletion (loss of function) extends lifespan, making it anti-longevity. The mechanistic reasoning about PI3P binding and ubiquitin ligase activity supporting proteostasis is speculative and not well-grounded in the actual biology of PIB1's role in aging. The confidence of 0.55 is relatively low, but the model still committed to the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}