daf-2
C. elegans
Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase
What the model saw
Gene: daf-2 Organism: Caenorhabditis elegans Known functions: Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase. ATP binding. PTB domain binding. SH2 domain binding. insulin receptor activity. peptide hormone binding. protein kinase activity. protein kinase binding. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
View unredacted entry
Insulin-like receptor subunit beta;Protein kinase domain-containing protein;receptor protein-tyrosine kinase. ATP binding. PTB domain binding. SH2 domain binding. insulin receptor activity. peptide hormone binding. protein kinase activity. protein kinase binding. protein tyrosine kinase activity. transmembrane receptor protein tyrosine kinase activity.
Solver output
DAF-2 is the C. elegans ortholog of the insulin/IGF-1 receptor, a transmembrane receptor tyrosine kinase that binds insulin-like peptides and autophosphorylates to activate downstream signaling via the PI3K-AKT pathway. Active DAF-2 signaling phosphorylates and inactivates the FOXO transcription factor DAF-16, suppressing expression of stress-resistance, detoxification, and longevity-promoting genes. Loss-of-function mutations in daf-2 are among the most potent single-gene interventions known to extend lifespan in C. elegans (up to ~2-fold), demonstrating that the normal activity of this receptor opposes longevity. This places DAF-2 squarely within the insulin/IGF-1 signaling (IIS) axis, a canonical nutrient-sensing pathway whose attenuation is pro-longevity across multiple model organisms. The receptor's kinase activity (ATP binding, protein tyrosine kinase activity) is the critical molecular step that initiates the anti-longevity cascade by phosphorylating adaptor proteins containing PTB and SH2 domains.
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 daf-2 as anti_longevity with very high confidence (0.99). The mechanistic reasoning is exemplary: it accurately describes DAF-2 as the C. elegans insulin/IGF-1 receptor ortholog, explains the PI3K-AKT downstream signaling, the phosphorylation and inactivation of DAF-16/FOXO, and correctly notes that loss-of-function mutations extend lifespan ~2-fold. The mechanism class "deregulated_nutrient_sensing" is appropriate. All key pathways listed are correct and relevant. This is a well-known landmark gene in aging research and the model's response reflects deep, accurate knowledge.
Raw API responses
solver
{
"reasoning": "DAF-2 is the C. elegans ortholog of the insulin/IGF-1 receptor, a transmembrane receptor tyrosine kinase that binds insulin-like peptides and autophosphorylates to activate downstream signaling via the PI3K-AKT pathway. Active DAF-2 signaling phosphorylates and inactivates the FOXO transcription factor DAF-16, suppressing expression of stress-resistance, detoxification, and longevity-promoting genes. Loss-of-function mutations in daf-2 are among the most potent single-gene interventions known to extend lifespan in C. elegans (up to ~2-fold), demonstrating that the normal activity of this receptor opposes longevity. This places DAF-2 squarely within the insulin/IGF-1 signaling (IIS) axis, a canonical nutrient-sensing pathway whose attenuation is pro-longevity across multiple model organisms. The receptor's kinase activity (ATP binding, protein tyrosine kinase activity) is the critical molecular step that initiates the anti-longevity cascade by phosphorylating adaptor proteins containing PTB and SH2 domains.",
"confidence": 0.99,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) pathway",
"DAF-2/DAF-16 (FOXO) axis",
"PI3K-AKT nutrient-sensing cascade"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified daf-2 as anti_longevity with very high confidence (0.99). The mechanistic reasoning is exemplary: it accurately describes DAF-2 as the C. elegans insulin/IGF-1 receptor ortholog, explains the PI3K-AKT downstream signaling, the phosphorylation and inactivation of DAF-16/FOXO, and correctly notes that loss-of-function mutations extend lifespan ~2-fold. The mechanism class \"deregulated_nutrient_sensing\" is appropriate. All key pathways listed are correct and relevant. This is a well-known landmark gene in aging research and the model's response reflects deep, accurate knowledge.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}