Shc1
M. musculus
src homology 2 domain-containing transforming protein C1
What the model saw
Gene: Shc1 Organism: Mus musculus Known functions: src homology 2 domain-containing transforming protein C1. SHC-transforming protein 1. ephrin receptor binding. epidermal growth factor binding. epidermal growth factor receptor binding. identical protein binding. insulin receptor binding. insulin-like growth factor receptor binding. neurotrophin TRKA receptor binding. phosphoprotein binding. phosphotyrosine residue binding. protein binding. protein phosphatase 2A binding. protein-containing complex binding. protein-macromolecule adaptor activity. receptor tyrosine kinase binding. transmembrane receptor protein tyrosine kinase adaptor activity.
View unredacted entry
src homology 2 domain-containing transforming protein C1. SHC-transforming protein 1. ephrin receptor binding. epidermal growth factor binding. epidermal growth factor receptor binding. identical protein binding. insulin receptor binding. insulin-like growth factor receptor binding. neurotrophin TRKA receptor binding. phosphoprotein binding. phosphotyrosine residue binding. protein binding. protein phosphatase 2A binding. protein-containing complex binding. protein-macromolecule adaptor activity. receptor tyrosine kinase binding. transmembrane receptor protein tyrosine kinase adaptor activity.
Solver output
Shc1 (p66Shc isoform in particular) acts as a critical adaptor protein downstream of insulin and IGF-1 receptors, coupling receptor tyrosine kinase activation to RAS/MAPK and PI3K/AKT signaling. By binding phosphotyrosine residues on activated insulin and IGF-1 receptors and recruiting downstream effectors, Shc1 amplifies anabolic/growth signaling that opposes longevity in the context of the conserved IIS (insulin/IGF-1 signaling) pathway. Notably, p66Shc knockout mice are long-lived and show reduced oxidative stress, demonstrating that the normal pro-growth, pro-oxidative function of Shc1 is anti-longevity. Additionally, Shc1 promotes mitochondrial ROS production by translocating to mitochondria and oxidizing cytochrome c, directly linking it to oxidative damage and cellular senescence. Its role as a transmembrane receptor protein tyrosine kinase adaptor further reinforces its function as a positive transducer of growth factor signals that shorten lifespan when chronically activated.
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 Shc1/p66Shc in mice. The mechanistic reasoning is excellent and accurate: p66Shc knockout mice are indeed long-lived, p66Shc promotes mitochondrial ROS production via cytochrome c oxidation, and it acts as an adaptor in the IIS pathway. The model correctly identified the p66Shc isoform as the key longevity-relevant isoform and provided accurate pathway information. Confidence of 0.82 is appropriate given the well-established literature on this gene.
Raw API responses
solver
{
"reasoning": "Shc1 (p66Shc isoform in particular) acts as a critical adaptor protein downstream of insulin and IGF-1 receptors, coupling receptor tyrosine kinase activation to RAS/MAPK and PI3K/AKT signaling. By binding phosphotyrosine residues on activated insulin and IGF-1 receptors and recruiting downstream effectors, Shc1 amplifies anabolic/growth signaling that opposes longevity in the context of the conserved IIS (insulin/IGF-1 signaling) pathway. Notably, p66Shc knockout mice are long-lived and show reduced oxidative stress, demonstrating that the normal pro-growth, pro-oxidative function of Shc1 is anti-longevity. Additionally, Shc1 promotes mitochondrial ROS production by translocating to mitochondria and oxidizing cytochrome c, directly linking it to oxidative damage and cellular senescence. Its role as a transmembrane receptor protein tyrosine kinase adaptor further reinforces its function as a positive transducer of growth factor signals that shorten lifespan when chronically activated.",
"confidence": 0.82,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) pathway",
"RAS/MAPK pro-growth signaling",
"mitochondrial ROS generation via cytochrome c oxidation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Shc1/p66Shc in mice. The mechanistic reasoning is excellent and accurate: p66Shc knockout mice are indeed long-lived, p66Shc promotes mitochondrial ROS production via cytochrome c oxidation, and it acts as an adaptor in the IIS pathway. The model correctly identified the p66Shc isoform as the key longevity-relevant isoform and provided accurate pathway information. Confidence of 0.82 is appropriate given the well-established literature on this gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}