daf-3
C. elegans
Smad protein daf-3
What the model saw
Gene: daf-3 Organism: Caenorhabditis elegans Known functions: Smad protein daf-3. DNA-binding transcription factor activity, RNA polymerase II-specific. I-SMAD binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. cis-regulatory region sequence-specific DNA binding. protein binding.
View unredacted entry
Smad protein daf-3. DNA-binding transcription factor activity, RNA polymerase II-specific. I-SMAD binding. RNA polymerase II cis-regulatory region sequence-specific DNA binding. cis-regulatory region sequence-specific DNA binding. protein binding.
Solver output
DAF-3 is a Co-SMAD/R-SMAD transcription factor that acts as the primary transcriptional effector of the TGF-β/DAF-7 signaling pathway in C. elegans. In the absence of DAF-7 signaling, DAF-3 is active and drives expression of genes that promote dauer formation and suppress longevity-associated programs. DAF-3 functions antagonistically to the pro-longevity DAF-16/FOXO transcription factor network; loss-of-function mutations in daf-3 extend lifespan and suppress dauer formation, while its activity opposes the longevity benefits conferred by reduced insulin/IGF-1 signaling. Its I-SMAD binding activity further positions it as a repressor of pro-longevity TGF-β signaling outputs. Thus, the normal (active) function of DAF-3 suppresses longevity by antagonizing nutrient-sensing and stress-response pathways that extend lifespan.
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 identified daf-3 as anti_longevity with high confidence (0.82). The mechanistic reasoning is accurate: DAF-3 is indeed a SMAD transcription factor in the TGF-β/DAF-7 pathway, and loss-of-function mutations in daf-3 extend lifespan in C. elegans. The model correctly notes that DAF-3 activity suppresses longevity by antagonizing pro-longevity pathways. The mechanism class of "deregulated_nutrient_sensing" is reasonable, though TGF-β signaling is perhaps more precisely categorized separately from insulin/IGF-1 nutrient sensing — however, the overall mechanistic description in the reasoning text is accurate. Minor note: DAF-3 is technically an R-SMAD/Co-SMAD (it's actually classified as a Co-SMAD in C. elegans literature), but this doesn't affect the correctness of the longevity prediction or the overall mechanistic understanding.
Raw API responses
solver
{
"reasoning": "DAF-3 is a Co-SMAD/R-SMAD transcription factor that acts as the primary transcriptional effector of the TGF-β/DAF-7 signaling pathway in C. elegans. In the absence of DAF-7 signaling, DAF-3 is active and drives expression of genes that promote dauer formation and suppress longevity-associated programs. DAF-3 functions antagonistically to the pro-longevity DAF-16/FOXO transcription factor network; loss-of-function mutations in daf-3 extend lifespan and suppress dauer formation, while its activity opposes the longevity benefits conferred by reduced insulin/IGF-1 signaling. Its I-SMAD binding activity further positions it as a repressor of pro-longevity TGF-β signaling outputs. Thus, the normal (active) function of DAF-3 suppresses longevity by antagonizing nutrient-sensing and stress-response pathways that extend lifespan.",
"confidence": 0.82,
"key_pathways": [
"TGF-beta/DAF-7 signaling pathway",
"DAF-16/FOXO transcriptional regulation",
"Dauer formation and lifespan regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified daf-3 as anti_longevity with high confidence (0.82). The mechanistic reasoning is accurate: DAF-3 is indeed a SMAD transcription factor in the TGF-β/DAF-7 pathway, and loss-of-function mutations in daf-3 extend lifespan in C. elegans. The model correctly notes that DAF-3 activity suppresses longevity by antagonizing pro-longevity pathways. The mechanism class of \"deregulated_nutrient_sensing\" is reasonable, though TGF-β signaling is perhaps more precisely categorized separately from insulin/IGF-1 nutrient sensing — however, the overall mechanistic description in the reasoning text is accurate. Minor note: DAF-3 is technically an R-SMAD/Co-SMAD (it's actually classified as a Co-SMAD in C. elegans literature), but this doesn't affect the correctness of the longevity prediction or the overall mechanistic understanding.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}