skr-2
C. elegans
Skp1-related protein
What the model saw
Gene: skr-2 Organism: Caenorhabditis elegans Known functions: Skp1-related protein. cullin family protein binding. protein binding.
View unredacted entry
Skp1-related protein. cullin family protein binding. protein binding.
Solver output
skr-2 encodes a Skp1-related protein in C. elegans, which functions as an adaptor subunit of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex, as evidenced by its cullin family protein binding activity. SCF complexes are central regulators of ubiquitin-mediated proteolysis, targeting key cell cycle regulators, stress response proteins, and signaling components for degradation. Proper SCF-mediated proteostasis is essential for clearing damaged or misfolded proteins and regulating pathways such as DAF-16/FOXO and cell cycle progression that influence lifespan. In C. elegans, SKR proteins (Skp1-related) are required for normal development and stress responses; loss of SCF adaptor function can impair proteostasis and stress resistance, which are hallmarks of aging. The pro-longevity prediction is tentative, as the specific F-box partner of skr-2 determines which substrates are degraded, and some SCF complexes can target pro-longevity factors for degradation.
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 pro_longevity for skr-2, but the mechanistic reasoning is speculative and not well-grounded. The model assigns "loss_of_proteostasis" as the mechanism class, which is somewhat contradictory — if skr-2 is pro-longevity, its loss would impair proteostasis, but the model frames it as if skr-2 itself promotes longevity through proteostasis maintenance. The reasoning is generic SCF complex biology without specific evidence for skr-2's role in longevity. The model acknowledges uncertainty ("tentative") and notes that some SCF complexes can target pro-longevity factors for degradation, which actually undermines its own prediction. The confidence of 0.52 is appropriately low. The mechanism class "loss_of_proteostasis" is an odd choice for a pro-longevity gene — it would make more sense for an anti-longevity gene. Overall, the answer is correct but the reasoning is weak and partially contradictory.
Raw API responses
solver
{
"reasoning": "skr-2 encodes a Skp1-related protein in C. elegans, which functions as an adaptor subunit of the SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase complex, as evidenced by its cullin family protein binding activity. SCF complexes are central regulators of ubiquitin-mediated proteolysis, targeting key cell cycle regulators, stress response proteins, and signaling components for degradation. Proper SCF-mediated proteostasis is essential for clearing damaged or misfolded proteins and regulating pathways such as DAF-16/FOXO and cell cycle progression that influence lifespan. In C. elegans, SKR proteins (Skp1-related) are required for normal development and stress responses; loss of SCF adaptor function can impair proteostasis and stress resistance, which are hallmarks of aging. The pro-longevity prediction is tentative, as the specific F-box partner of skr-2 determines which substrates are degraded, and some SCF complexes can target pro-longevity factors for degradation.",
"confidence": 0.52,
"key_pathways": [
"SCF E3 ubiquitin ligase complex",
"ubiquitin-proteasome proteostasis",
"DAF-16/FOXO signaling regulation"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for skr-2, but the mechanistic reasoning is speculative and not well-grounded. The model assigns \"loss_of_proteostasis\" as the mechanism class, which is somewhat contradictory — if skr-2 is pro-longevity, its loss would impair proteostasis, but the model frames it as if skr-2 itself promotes longevity through proteostasis maintenance. The reasoning is generic SCF complex biology without specific evidence for skr-2's role in longevity. The model acknowledges uncertainty (\"tentative\") and notes that some SCF complexes can target pro-longevity factors for degradation, which actually undermines its own prediction. The confidence of 0.52 is appropriately low. The mechanism class \"loss_of_proteostasis\" is an odd choice for a pro-longevity gene — it would make more sense for an anti-longevity gene. Overall, the answer is correct but the reasoning is weak and partially contradictory.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}