Pten
D. melanogaster
Phosphatase and tensin homolog
What the model saw
Gene: Pten Organism: Drosophila melanogaster Known functions: Phosphatase and tensin homolog. phosphatase and tensin homolog. PDZ domain binding. inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity. phosphatase activity. phosphatidylinositol phosphate phosphatase activity. phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity. phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity. phosphoprotein phosphatase activity. protein serine/threonine phosphatase activity. protein tyrosine phosphatase activity. protein tyrosine/serine/threonine phosphatase activity.
View unredacted entry
Phosphatase and tensin homolog. phosphatase and tensin homolog. PDZ domain binding. inositol-1,3,4,5-tetrakisphosphate 3-phosphatase activity. phosphatase activity. phosphatidylinositol phosphate phosphatase activity. phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity. phosphatidylinositol-3,4-bisphosphate 3-phosphatase activity. phosphoprotein phosphatase activity. protein serine/threonine phosphatase activity. protein tyrosine phosphatase activity. protein tyrosine/serine/threonine phosphatase activity.
Solver output
PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) back to PIP2, directly antagonizing PI3K activity and thereby suppressing the PI3K/AKT/TOR signaling axis. In Drosophila, this pathway is the primary insulin/IGF-1 signaling (IIS) cascade, and its attenuation is one of the most conserved mechanisms of lifespan extension across model organisms. By reducing PIP3 levels, PTEN limits AKT activation, which in turn reduces TOR complex 1 (TORC1) activity and promotes FOXO (dFOXO in flies) nuclear translocation, upregulating stress-resistance and longevity genes. Loss of Pten in Drosophila leads to hyperactivated IIS/TOR signaling, accelerated growth, and shortened lifespan, while overexpression or partial reduction of IIS through PTEN activity extends lifespan. Thus, PTEN's normal function as a PIP3 phosphatase constitutes a pro-longevity brake on nutrient-sensing pathway overactivation.
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 pro_longevity for Drosophila Pten with high confidence (0.92). The mechanistic reasoning is excellent and accurate: PTEN dephosphorylates PIP3 to PIP2, antagonizing PI3K/AKT/TOR signaling, reducing TORC1 activity, and promoting dFOXO nuclear translocation. The model correctly identifies that loss of Pten leads to hyperactivated IIS/TOR and shortened lifespan, while PTEN activity serves as a pro-longevity brake. The mechanism class "deregulated_nutrient_sensing" is appropriate. All key pathways identified are correct and relevant.
Raw API responses
solver
{
"reasoning": "PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol-3,4,5-trisphosphate (PIP3) back to PIP2, directly antagonizing PI3K activity and thereby suppressing the PI3K/AKT/TOR signaling axis. In Drosophila, this pathway is the primary insulin/IGF-1 signaling (IIS) cascade, and its attenuation is one of the most conserved mechanisms of lifespan extension across model organisms. By reducing PIP3 levels, PTEN limits AKT activation, which in turn reduces TOR complex 1 (TORC1) activity and promotes FOXO (dFOXO in flies) nuclear translocation, upregulating stress-resistance and longevity genes. Loss of Pten in Drosophila leads to hyperactivated IIS/TOR signaling, accelerated growth, and shortened lifespan, while overexpression or partial reduction of IIS through PTEN activity extends lifespan. Thus, PTEN's normal function as a PIP3 phosphatase constitutes a pro-longevity brake on nutrient-sensing pathway overactivation.",
"confidence": 0.92,
"key_pathways": [
"PI3K/AKT/TOR (insulin/IGF-1 signaling)",
"FOXO transcription factor activation",
"PIP3 dephosphorylation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Drosophila Pten with high confidence (0.92). The mechanistic reasoning is excellent and accurate: PTEN dephosphorylates PIP3 to PIP2, antagonizing PI3K/AKT/TOR signaling, reducing TORC1 activity, and promoting dFOXO nuclear translocation. The model correctly identifies that loss of Pten leads to hyperactivated IIS/TOR and shortened lifespan, while PTEN activity serves as a pro-longevity brake. The mechanism class \"deregulated_nutrient_sensing\" is appropriate. All key pathways identified are correct and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}