Irs2
M. musculus
insulin receptor substrate 2
What the model saw
Gene: Irs2 Organism: Mus musculus Known functions: insulin receptor substrate 2. 14-3-3 protein binding. insulin receptor binding. phosphatidylinositol 3-kinase activator activity. phosphatidylinositol 3-kinase binding. protein binding. protein domain specific binding. protein kinase binding. protein phosphatase binding. protein-macromolecule adaptor activity. signaling adaptor activity. transmembrane receptor protein tyrosine kinase adaptor activity.
View unredacted entry
insulin receptor substrate 2. 14-3-3 protein binding. insulin receptor binding. phosphatidylinositol 3-kinase activator activity. phosphatidylinositol 3-kinase binding. protein binding. protein domain specific binding. protein kinase binding. protein phosphatase binding. protein-macromolecule adaptor activity. signaling adaptor activity. transmembrane receptor protein tyrosine kinase adaptor activity.
Solver output
IRS2 is a key adaptor protein in the insulin/IGF-1 signaling (IIS) pathway, directly binding the insulin receptor and activating PI3K, which leads to downstream AKT/mTOR activation. In the context of aging, heightened IIS/PI3K/AKT signaling is well-established as pro-aging; reduced IIS signaling consistently extends lifespan across model organisms. Notably, Irs2 knockout mice show extended lifespan compared to wild-type controls, demonstrating that IRS2-mediated signaling is net anti-longevity. IRS2 acts as a signaling adaptor that amplifies insulin and IGF-1 receptor signals through PI3K activation, promoting anabolic and growth-promoting programs that antagonize longevity-associated pathways such as FOXO transcription factor activation. The 14-3-3 binding activity further supports its role in sustaining pro-growth signaling cascades. Thus, the normal function of IRS2 promotes nutrient-sensing pathway activity in a manner that opposes longevity.
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 Irs2 in Mus musculus. The mechanistic reasoning is accurate and well-supported: IRS2 is an adaptor in the insulin/IGF-1 signaling pathway, activating PI3K/AKT/mTOR, and Irs2 knockout mice are indeed known to show extended lifespan. The model correctly identifies that heightened IIS signaling is pro-aging and that IRS2's normal function opposes longevity. The mention of FOXO suppression as a downstream consequence is also mechanistically sound. Confidence of 0.82 is appropriate given the well-established literature on this topic.
Raw API responses
solver
{
"reasoning": "IRS2 is a key adaptor protein in the insulin/IGF-1 signaling (IIS) pathway, directly binding the insulin receptor and activating PI3K, which leads to downstream AKT/mTOR activation. In the context of aging, heightened IIS/PI3K/AKT signaling is well-established as pro-aging; reduced IIS signaling consistently extends lifespan across model organisms. Notably, Irs2 knockout mice show extended lifespan compared to wild-type controls, demonstrating that IRS2-mediated signaling is net anti-longevity. IRS2 acts as a signaling adaptor that amplifies insulin and IGF-1 receptor signals through PI3K activation, promoting anabolic and growth-promoting programs that antagonize longevity-associated pathways such as FOXO transcription factor activation. The 14-3-3 binding activity further supports its role in sustaining pro-growth signaling cascades. Thus, the normal function of IRS2 promotes nutrient-sensing pathway activity in a manner that opposes longevity.",
"confidence": 0.82,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"PI3K/AKT/mTOR signaling",
"FOXO transcription factor regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Irs2 in Mus musculus. The mechanistic reasoning is accurate and well-supported: IRS2 is an adaptor in the insulin/IGF-1 signaling pathway, activating PI3K/AKT/mTOR, and Irs2 knockout mice are indeed known to show extended lifespan. The model correctly identifies that heightened IIS signaling is pro-aging and that IRS2's normal function opposes longevity. The mention of FOXO suppression as a downstream consequence is also mechanistically sound. Confidence of 0.82 is appropriate given the well-established literature on this topic.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}