ACS2
S. cerevisiae
acetate--CoA ligase ACS2
What the model saw
Gene: ACS2 Organism: Saccharomyces cerevisiae Known functions: acetate--CoA ligase ACS2. AMP binding. acetyl-CoA synthetase activity. acid-ammonia (or amide) ligase activity.
View unredacted entry
acetate--CoA ligase ACS2. AMP binding. acetyl-CoA synthetase activity. acid-ammonia (or amide) ligase activity.
Solver output
ACS2 encodes the primary acetyl-CoA synthetase in S. cerevisiae that converts acetate to acetyl-CoA in the nucleus and cytoplasm. Nuclear acetyl-CoA is the obligate acetyl-donor for histone acetyltransferases (HATs), and ACS2-derived acetyl-CoA directly fuels histone H3 and H4 acetylation, maintaining transcriptionally active chromatin states. Loss of ACS2 reduces global histone acetylation, leading to epigenetic silencing of stress-response and metabolic genes. Because histone acetylation levels decline with age in yeast and maintenance of proper acetylation marks is associated with extended replicative lifespan, ACS2 activity supports pro-longevity epigenetic states. Additionally, acetyl-CoA availability links nutrient sensing (glucose metabolism) to chromatin regulation, placing ACS2 at a key node connecting metabolic status to aging-relevant gene expression programs.
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 ACS2 in S. cerevisiae with high confidence (0.72). The mechanistic reasoning is excellent and well-supported by the literature: ACS2 is the primary nuclear/cytoplasmic acetyl-CoA synthetase, and its role in supplying acetyl-CoA for histone acetyltransferases (HATs) is well-established. The connection between ACS2-derived nuclear acetyl-CoA, histone acetylation maintenance, and replicative lifespan extension is accurate. The model correctly identifies the epigenetic mechanism as the primary pathway and appropriately links it to nutrient sensing. This is a high-quality, mechanistically sound prediction.
Raw API responses
solver
{
"reasoning": "ACS2 encodes the primary acetyl-CoA synthetase in S. cerevisiae that converts acetate to acetyl-CoA in the nucleus and cytoplasm. Nuclear acetyl-CoA is the obligate acetyl-donor for histone acetyltransferases (HATs), and ACS2-derived acetyl-CoA directly fuels histone H3 and H4 acetylation, maintaining transcriptionally active chromatin states. Loss of ACS2 reduces global histone acetylation, leading to epigenetic silencing of stress-response and metabolic genes. Because histone acetylation levels decline with age in yeast and maintenance of proper acetylation marks is associated with extended replicative lifespan, ACS2 activity supports pro-longevity epigenetic states. Additionally, acetyl-CoA availability links nutrient sensing (glucose metabolism) to chromatin regulation, placing ACS2 at a key node connecting metabolic status to aging-relevant gene expression programs.",
"confidence": 0.72,
"key_pathways": [
"Histone acetylation / chromatin remodeling (nuclear acetyl-CoA supply)",
"Acetate-CoA metabolism (acetyl-CoA biosynthesis)",
"Nutrient sensing-epigenome axis (glucose-acetyl-CoA-HAT signaling)"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for ACS2 in S. cerevisiae with high confidence (0.72). The mechanistic reasoning is excellent and well-supported by the literature: ACS2 is the primary nuclear/cytoplasmic acetyl-CoA synthetase, and its role in supplying acetyl-CoA for histone acetyltransferases (HATs) is well-established. The connection between ACS2-derived nuclear acetyl-CoA, histone acetylation maintenance, and replicative lifespan extension is accurate. The model correctly identifies the epigenetic mechanism as the primary pathway and appropriately links it to nutrient sensing. This is a high-quality, mechanistically sound prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}