skr-1
C. elegans
Skp1-related protein
What the model saw
Gene: skr-1 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-1 is a Skp1-related protein in C. elegans that 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. The SCF complex is a central regulator of ubiquitin-mediated proteolysis, targeting key substrates for degradation to maintain proteostasis. In C. elegans, SKR-1/2 have been shown to interact with the CUL-1 cullin scaffold and are required for proper cell cycle regulation and protein quality control. Importantly, skr-1 has been linked to the DAF-16/FOXO transcription factor pathway; loss of skr-1 function impairs DAF-16 nuclear localization and reduces lifespan extension in daf-2 mutants, suggesting that SCF-mediated ubiquitination promotes longevity by enabling proper IIS/DAF-16 signaling. Thus, the normal function of SKR-1 in assembling a functional SCF complex supports proteostasis and pro-longevity signaling.
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-1 in C. elegans. The mechanistic reasoning is well-grounded: SKR-1 as an SCF complex adaptor subunit, its role in ubiquitin-mediated proteolysis, and its connection to the DAF-16/FOXO pathway are all plausible and consistent with published literature. The model correctly identifies that loss of skr-1 impairs DAF-16 nuclear localization and reduces lifespan extension in daf-2 mutants. The confidence level (0.62) is appropriately moderate. The mechanism class "loss_of_proteostasis" is a reasonable categorization, though the IIS/DAF-16 pathway connection might be considered the primary mechanism. Overall, solid reasoning with correct answer.
Raw API responses
solver
{
"reasoning": "SKR-1 is a Skp1-related protein in C. elegans that 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. The SCF complex is a central regulator of ubiquitin-mediated proteolysis, targeting key substrates for degradation to maintain proteostasis. In C. elegans, SKR-1/2 have been shown to interact with the CUL-1 cullin scaffold and are required for proper cell cycle regulation and protein quality control. Importantly, skr-1 has been linked to the DAF-16/FOXO transcription factor pathway; loss of skr-1 function impairs DAF-16 nuclear localization and reduces lifespan extension in daf-2 mutants, suggesting that SCF-mediated ubiquitination promotes longevity by enabling proper IIS/DAF-16 signaling. Thus, the normal function of SKR-1 in assembling a functional SCF complex supports proteostasis and pro-longevity signaling.",
"confidence": 0.62,
"key_pathways": [
"SCF E3 ubiquitin ligase complex / ubiquitin-proteasome system",
"DAF-2/IIS - DAF-16/FOXO longevity pathway",
"CUL-1 cullin-RING ligase assembly"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for skr-1 in C. elegans. The mechanistic reasoning is well-grounded: SKR-1 as an SCF complex adaptor subunit, its role in ubiquitin-mediated proteolysis, and its connection to the DAF-16/FOXO pathway are all plausible and consistent with published literature. The model correctly identifies that loss of skr-1 impairs DAF-16 nuclear localization and reduces lifespan extension in daf-2 mutants. The confidence level (0.62) is appropriately moderate. The mechanism class \"loss_of_proteostasis\" is a reasonable categorization, though the IIS/DAF-16 pathway connection might be considered the primary mechanism. Overall, solid reasoning with correct answer.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}