Insr
M. musculus
insulin receptor
What the model saw
Gene: Insr Organism: Mus musculus Known functions: insulin receptor. 3-phosphoinositide-dependent protein kinase binding. ATP binding. GTP binding. PTB domain binding. amyloid-beta binding. cargo receptor activity. identical protein binding. insulin binding. insulin receptor activity. insulin receptor substrate binding. insulin-like growth factor I binding. insulin-like growth factor II binding. insulin-like growth factor receptor binding. lipoic acid binding. phosphatidylinositol 3-kinase binding. protein binding. protein domain specific binding. protein kinase activator activity. protein kinase activity. protein kinase binding. protein phosphatase binding. protein tyrosine kinase activity. protein-containing complex binding. structural molecule activity. transmembrane receptor protein tyrosine kinase activity.
View unredacted entry
insulin receptor. 3-phosphoinositide-dependent protein kinase binding. ATP binding. GTP binding. PTB domain binding. amyloid-beta binding. cargo receptor activity. identical protein binding. insulin binding. insulin receptor activity. insulin receptor substrate binding. insulin-like growth factor I binding. insulin-like growth factor II binding. insulin-like growth factor receptor binding. lipoic acid binding. phosphatidylinositol 3-kinase binding. protein binding. protein domain specific binding. protein kinase activator activity. protein kinase activity. protein kinase binding. protein phosphatase binding. protein tyrosine kinase activity. protein-containing complex binding. structural molecule activity. transmembrane receptor protein tyrosine kinase activity.
Solver output
The insulin receptor (Insr) is the master upstream activator of the insulin/IGF-1 signaling (IIS) axis. Upon insulin or IGF-1 binding, its intrinsic protein tyrosine kinase activity autophosphorylates and phosphorylates IRS adaptor proteins, leading to PI3K activation, PIP3 production, and downstream PDK1/AKT/mTORC1 signaling. This pathway is one of the most conserved negative regulators of lifespan across model organisms: reduced IIS signaling (e.g., heterozygous Insr knockout, fat-specific Insr deletion) extends lifespan in mice by promoting FOXO transcription factor nuclear localization and activating stress-resistance and autophagy programs. The normal (full) function of Insr therefore suppresses these pro-longevity transcriptional outputs, promotes anabolic/mTORC1 signaling, and inhibits autophagy, collectively opposing longevity. Its binding to PI3K and protein kinase activator activity directly feeds into the nutrient-sensing network that is a hallmark of aging regulation.
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 anti_longevity for Insr in Mus musculus with high confidence (0.88). The mechanistic reasoning is excellent and accurate: it correctly identifies Insr as the master upstream activator of the IIS axis, explains how reduced IIS signaling (heterozygous knockout, fat-specific deletion) extends lifespan in mice, correctly identifies the downstream PI3K-AKT-mTORC1 and FOXO pathways, and explains why full Insr function opposes longevity by suppressing pro-longevity transcriptional outputs and promoting anabolic signaling. The specific examples cited (heterozygous Insr knockout, fat-specific Insr deletion) are well-established in the literature. The mechanism classification as "deregulated_nutrient_sensing" is appropriate.
Raw API responses
solver
{
"reasoning": "The insulin receptor (Insr) is the master upstream activator of the insulin/IGF-1 signaling (IIS) axis. Upon insulin or IGF-1 binding, its intrinsic protein tyrosine kinase activity autophosphorylates and phosphorylates IRS adaptor proteins, leading to PI3K activation, PIP3 production, and downstream PDK1/AKT/mTORC1 signaling. This pathway is one of the most conserved negative regulators of lifespan across model organisms: reduced IIS signaling (e.g., heterozygous Insr knockout, fat-specific Insr deletion) extends lifespan in mice by promoting FOXO transcription factor nuclear localization and activating stress-resistance and autophagy programs. The normal (full) function of Insr therefore suppresses these pro-longevity transcriptional outputs, promotes anabolic/mTORC1 signaling, and inhibits autophagy, collectively opposing longevity. Its binding to PI3K and protein kinase activator activity directly feeds into the nutrient-sensing network that is a hallmark of aging regulation.",
"confidence": 0.88,
"key_pathways": [
"Insulin/IGF-1 signaling (IIS) pathway",
"PI3K-AKT-mTORC1 nutrient sensing axis",
"FOXO transcription factor regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Insr in Mus musculus with high confidence (0.88). The mechanistic reasoning is excellent and accurate: it correctly identifies Insr as the master upstream activator of the IIS axis, explains how reduced IIS signaling (heterozygous knockout, fat-specific deletion) extends lifespan in mice, correctly identifies the downstream PI3K-AKT-mTORC1 and FOXO pathways, and explains why full Insr function opposes longevity by suppressing pro-longevity transcriptional outputs and promoting anabolic signaling. The specific examples cited (heterozygous Insr knockout, fat-specific Insr deletion) are well-established in the literature. The mechanism classification as \"deregulated_nutrient_sensing\" is appropriate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}