ftt-2
C. elegans
14-3-3 domain-containing protein;14-3-3-like protein 2
What the model saw
Gene: ftt-2 Organism: Caenorhabditis elegans Known functions: 14-3-3 domain-containing protein;14-3-3-like protein 2. DNA-binding transcription factor binding. protein binding. protein sequestering activity.
View unredacted entry
14-3-3 domain-containing protein;14-3-3-like protein 2. DNA-binding transcription factor binding. protein binding. protein sequestering activity.
Solver output
ftt-2 encodes a 14-3-3 family protein in C. elegans, which functions as a scaffold/adaptor through protein sequestering and transcription factor binding. 14-3-3 proteins are well-established regulators of the DAF-16/FOXO transcription factor in the insulin/IGF-1 signaling (IIS) pathway: under high insulin signaling, activated AKT phosphorylates DAF-16, enabling 14-3-3 proteins (ftt-2 and par-5) to sequester DAF-16 in the cytoplasm, thereby suppressing its pro-longevity transcriptional program. However, ftt-2 also directly interacts with and sequesters the DAF-16 kinase complex components and other regulators, and genetic studies in C. elegans show that ftt-2 loss-of-function shortens lifespan, indicating its net role is pro-longevity. Additionally, 14-3-3 proteins modulate the activity of multiple longevity-relevant transcription factors beyond DAF-16, including those in the AMPK and TOR nutrient-sensing axes, and their scaffolding activity is required for proper stress-response signaling that extends 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 predicts ftt-2 as pro_longevity. However, the mechanistic reasoning is internally contradictory and partially incorrect. The model first describes ftt-2/14-3-3 as sequestering DAF-16 in the cytoplasm (which would be anti-longevity), then claims ftt-2 loss-of-function shortens lifespan (making it pro-longevity). The mechanism class assigned is "deregulated_nutrient_sensing," which is a stretch. The actual pro-longevity mechanism of ftt-2 in C. elegans is more nuanced — 14-3-3 proteins like ftt-2 have complex roles beyond just DAF-16 cytoplasmic sequestration, and the model's explanation of why ftt-2 is net pro-longevity is not well-supported or clearly articulated. The model essentially contradicts itself (DAF-16 sequestration would be anti-longevity, yet claims pro-longevity) without adequately resolving the contradiction. The correct answer is reached but the mechanistic explanation is confused.
Raw API responses
solver
{
"reasoning": "ftt-2 encodes a 14-3-3 family protein in C. elegans, which functions as a scaffold/adaptor through protein sequestering and transcription factor binding. 14-3-3 proteins are well-established regulators of the DAF-16/FOXO transcription factor in the insulin/IGF-1 signaling (IIS) pathway: under high insulin signaling, activated AKT phosphorylates DAF-16, enabling 14-3-3 proteins (ftt-2 and par-5) to sequester DAF-16 in the cytoplasm, thereby suppressing its pro-longevity transcriptional program. However, ftt-2 also directly interacts with and sequesters the DAF-16 kinase complex components and other regulators, and genetic studies in C. elegans show that ftt-2 loss-of-function shortens lifespan, indicating its net role is pro-longevity. Additionally, 14-3-3 proteins modulate the activity of multiple longevity-relevant transcription factors beyond DAF-16, including those in the AMPK and TOR nutrient-sensing axes, and their scaffolding activity is required for proper stress-response signaling that extends lifespan.",
"confidence": 0.72,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) / DAF-16 cytoplasmic sequestration",
"14-3-3 scaffold-mediated nutrient sensing (AMPK/TOR)",
"transcription factor regulation via protein sequestering activity"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicts ftt-2 as pro_longevity. However, the mechanistic reasoning is internally contradictory and partially incorrect. The model first describes ftt-2/14-3-3 as sequestering DAF-16 in the cytoplasm (which would be anti-longevity), then claims ftt-2 loss-of-function shortens lifespan (making it pro-longevity). The mechanism class assigned is \"deregulated_nutrient_sensing,\" which is a stretch. The actual pro-longevity mechanism of ftt-2 in C. elegans is more nuanced — 14-3-3 proteins like ftt-2 have complex roles beyond just DAF-16 cytoplasmic sequestration, and the model's explanation of why ftt-2 is net pro-longevity is not well-supported or clearly articulated. The model essentially contradicts itself (DAF-16 sequestration would be anti-longevity, yet claims pro-longevity) without adequately resolving the contradiction. The correct answer is reached but the mechanistic explanation is confused.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}