aakg-2
C. elegans
CBS domain-containing protein
What the model saw
Gene: aakg-2 Organism: Caenorhabditis elegans Known functions: CBS domain-containing protein. AMP binding. protein kinase binding. protein kinase regulator activity.
View unredacted entry
CBS domain-containing protein. AMP binding. protein kinase binding. protein kinase regulator activity.
Solver output
aakg-2 encodes a gamma regulatory subunit of AMP-activated protein kinase (AMPK), as indicated by its CBS domain (which binds AMP/ADP), AMP-binding activity, and protein kinase regulator activity. The gamma subunit senses the AMP:ATP ratio and allosterically activates the AMPK heterotrimer when energy is low. In C. elegans, AMPK (aak-1/aak-2 catalytic subunits regulated by aakg subunits) is a well-established pro-longevity kinase that phosphorylates and inhibits TORC1, activates autophagy, and promotes mitochondrial homeostasis. Loss of AMPK signaling shortens lifespan, while enhanced AMPK activity extends it, placing aakg-2 firmly in the pro-longevity category through its role as a positive regulator of this energy-sensing axis.
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 aakg-2. The mechanistic reasoning is excellent: it correctly identifies aakg-2 as encoding the gamma regulatory subunit of AMPK, explains the CBS domain's role in AMP/ADP sensing, describes how the gamma subunit allosterically activates the AMPK heterotrimer, and accurately connects AMPK signaling to longevity in C. elegans through TORC1 inhibition, autophagy activation, and mitochondrial homeostasis. The confidence level of 0.78 is appropriate given the indirect nature of the evidence (regulatory subunit rather than catalytic subunit). All key pathways identified are relevant and correct.
Raw API responses
solver
{
"reasoning": "aakg-2 encodes a gamma regulatory subunit of AMP-activated protein kinase (AMPK), as indicated by its CBS domain (which binds AMP/ADP), AMP-binding activity, and protein kinase regulator activity. The gamma subunit senses the AMP:ATP ratio and allosterically activates the AMPK heterotrimer when energy is low. In C. elegans, AMPK (aak-1/aak-2 catalytic subunits regulated by aakg subunits) is a well-established pro-longevity kinase that phosphorylates and inhibits TORC1, activates autophagy, and promotes mitochondrial homeostasis. Loss of AMPK signaling shortens lifespan, while enhanced AMPK activity extends it, placing aakg-2 firmly in the pro-longevity category through its role as a positive regulator of this energy-sensing axis.",
"confidence": 0.78,
"key_pathways": [
"AMPK energy sensing pathway",
"TOR/nutrient signaling",
"autophagy regulation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for aakg-2. The mechanistic reasoning is excellent: it correctly identifies aakg-2 as encoding the gamma regulatory subunit of AMPK, explains the CBS domain's role in AMP/ADP sensing, describes how the gamma subunit allosterically activates the AMPK heterotrimer, and accurately connects AMPK signaling to longevity in C. elegans through TORC1 inhibition, autophagy activation, and mitochondrial homeostasis. The confidence level of 0.78 is appropriate given the indirect nature of the evidence (regulatory subunit rather than catalytic subunit). All key pathways identified are relevant and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}