akt-1
C. elegans
Serine/threonine-protein kinase akt-1
What the model saw
Gene: akt-1 Organism: Caenorhabditis elegans Known functions: Serine/threonine-protein kinase akt-1. ATP binding. calmodulin binding. phosphatidylinositol-3,4,5-trisphosphate binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Serine/threonine-protein kinase akt-1. ATP binding. calmodulin binding. phosphatidylinositol-3,4,5-trisphosphate binding. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
AKT-1 is the C. elegans ortholog of the serine/threonine kinase Akt, a central effector of the insulin/IGF-1 signaling (IIS) pathway. Upon activation by PIP3 (phosphatidylinositol-3,4,5-trisphosphate binding), AKT-1 phosphorylates and inactivates the FOXO transcription factor DAF-16, preventing its nuclear translocation and suppression of stress-resistance and longevity genes. Loss-of-function mutations in akt-1 (and its paralog akt-2) extend lifespan in C. elegans by allowing DAF-16 nuclear accumulation, mirroring the longevity phenotype of daf-2 (insulin/IGF-1 receptor) mutants. Thus, the normal (active) function of AKT-1 promotes aging by dampening DAF-16-mediated pro-longevity transcription, placing it squarely in the deregulated nutrient/insulin sensing hallmark of 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 correctly identified akt-1 as anti_longevity with very high confidence (0.95). The mechanistic reasoning is excellent and accurate: AKT-1 is indeed a central effector of the insulin/IGF-1 signaling pathway in C. elegans, it phosphorylates and inactivates DAF-16/FOXO, and loss-of-function mutations extend lifespan. The model correctly identified the PIP3 binding as a clue to its role in the IIS pathway. The mechanism class "deregulated_nutrient_sensing" is appropriate. All key pathways listed are correct and relevant.
Raw API responses
solver
{
"reasoning": "AKT-1 is the C. elegans ortholog of the serine/threonine kinase Akt, a central effector of the insulin/IGF-1 signaling (IIS) pathway. Upon activation by PIP3 (phosphatidylinositol-3,4,5-trisphosphate binding), AKT-1 phosphorylates and inactivates the FOXO transcription factor DAF-16, preventing its nuclear translocation and suppression of stress-resistance and longevity genes. Loss-of-function mutations in akt-1 (and its paralog akt-2) extend lifespan in C. elegans by allowing DAF-16 nuclear accumulation, mirroring the longevity phenotype of daf-2 (insulin/IGF-1 receptor) mutants. Thus, the normal (active) function of AKT-1 promotes aging by dampening DAF-16-mediated pro-longevity transcription, placing it squarely in the deregulated nutrient/insulin sensing hallmark of aging.",
"confidence": 0.95,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"DAF-16/FOXO transcription factor regulation",
"PI3K-AKT signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified akt-1 as anti_longevity with very high confidence (0.95). The mechanistic reasoning is excellent and accurate: AKT-1 is indeed a central effector of the insulin/IGF-1 signaling pathway in C. elegans, it phosphorylates and inactivates DAF-16/FOXO, and loss-of-function mutations extend lifespan. The model correctly identified the PIP3 binding as a clue to its role in the IIS pathway. The mechanism class \"deregulated_nutrient_sensing\" is appropriate. All key pathways listed are correct and relevant.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}