aakb-2
C. elegans
Association with the SNF1 complex (ASC) domain-containing protein
What the model saw
Gene: aakb-2 Organism: Caenorhabditis elegans Known functions: Association with the SNF1 complex (ASC) domain-containing protein. protein binding. protein kinase binding.
View unredacted entry
Association with the SNF1 complex (ASC) domain-containing protein. protein binding. protein kinase binding.
Solver output
aakb-2 encodes a beta subunit of the AMP-activated protein kinase (AMPK) complex in C. elegans, as indicated by its ASC (Association with SNF1 Complex) domain and protein kinase binding activity. AMPK is a central energy sensor that, when activated under low-energy conditions, promotes catabolic processes and suppresses anabolic pathways. In C. elegans, AMPK (aak-1/aak-2 catalytic subunits) activation is well-established to extend lifespan by inhibiting mTORC1 signaling and activating autophagy and mitochondrial biogenesis. The beta regulatory subunit (aakb-2) scaffolds the AMPK heterotrimer and is required for proper complex assembly and substrate targeting, thus supporting the pro-longevity function of the AMPK complex. Loss of beta subunit function would impair AMPK activity, reducing the organism's ability to respond to nutrient stress and shortening 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 predicted pro_longevity for aakb-2. The mechanistic reasoning is excellent: it correctly identifies aakb-2 as encoding the beta regulatory subunit of the AMPK complex in C. elegans, explains the role of the ASC domain in scaffolding the AMPK heterotrimer, and correctly links AMPK activation to lifespan extension via mTORC1 inhibition and autophagy. The model also correctly notes that loss of the beta subunit would impair AMPK activity and shorten lifespan. The confidence level of 0.65 is appropriately calibrated given the indirect nature of the evidence (the gene's function is inferred from domain annotations rather than direct experimental data shown in the entry).
Raw API responses
solver
{
"reasoning": "aakb-2 encodes a beta subunit of the AMP-activated protein kinase (AMPK) complex in C. elegans, as indicated by its ASC (Association with SNF1 Complex) domain and protein kinase binding activity. AMPK is a central energy sensor that, when activated under low-energy conditions, promotes catabolic processes and suppresses anabolic pathways. In C. elegans, AMPK (aak-1/aak-2 catalytic subunits) activation is well-established to extend lifespan by inhibiting mTORC1 signaling and activating autophagy and mitochondrial biogenesis. The beta regulatory subunit (aakb-2) scaffolds the AMPK heterotrimer and is required for proper complex assembly and substrate targeting, thus supporting the pro-longevity function of the AMPK complex. Loss of beta subunit function would impair AMPK activity, reducing the organism's ability to respond to nutrient stress and shortening lifespan.",
"confidence": 0.65,
"key_pathways": [
"AMPK/SNF1 energy sensing pathway",
"mTORC1 inhibition",
"autophagy regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for aakb-2. The mechanistic reasoning is excellent: it correctly identifies aakb-2 as encoding the beta regulatory subunit of the AMPK complex in C. elegans, explains the role of the ASC domain in scaffolding the AMPK heterotrimer, and correctly links AMPK activation to lifespan extension via mTORC1 inhibition and autophagy. The model also correctly notes that loss of the beta subunit would impair AMPK activity and shorten lifespan. The confidence level of 0.65 is appropriately calibrated given the indirect nature of the evidence (the gene's function is inferred from domain annotations rather than direct experimental data shown in the entry).",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}