HAP4
S. cerevisiae
transcription factor HAP4
What the model saw
Gene: HAP4 Organism: Saccharomyces cerevisiae Known functions: transcription factor HAP4. RNA polymerase II-specific DNA-binding transcription factor binding. transcription coactivator activity.
View unredacted entry
transcription factor HAP4. RNA polymerase II-specific DNA-binding transcription factor binding. transcription coactivator activity.
Solver output
HAP4 is the transcriptional activator subunit of the HAP2/3/4/5 complex in S. cerevisiae, which functions as a master regulator of respiratory gene expression. By binding to CCAAT motifs and activating genes encoding mitochondrial respiratory chain components and TCA cycle enzymes, HAP4 promotes oxidative phosphorylation over fermentation, effectively mimicking a caloric restriction-like metabolic state. Overexpression of HAP4 has been experimentally shown to extend replicative lifespan in yeast by shifting metabolism toward respiration and away from fermentation (the Crabtree effect), which reduces reactive oxygen species accumulation and improves mitochondrial function. This metabolic reprogramming intersects with the TOR/nutrient-sensing axis, as respiratory metabolism is associated with reduced TORC1 signaling. HAP4's coactivator activity at RNA Pol II promoters directly drives the transcriptional program that supports mitochondrial biogenesis and longevity.
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 HAP4 as pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: HAP4 is indeed the activating subunit of the HAP2/3/4/5 complex, it does regulate respiratory gene expression, and its overexpression has been experimentally shown to extend replicative lifespan in yeast by shifting metabolism toward respiration (mimicking caloric restriction). The connection to TOR/nutrient-sensing and mitochondrial biogenesis is also well-reasoned. The model demonstrates deep knowledge of yeast aging biology.
Raw API responses
solver
{
"reasoning": "HAP4 is the transcriptional activator subunit of the HAP2/3/4/5 complex in S. cerevisiae, which functions as a master regulator of respiratory gene expression. By binding to CCAAT motifs and activating genes encoding mitochondrial respiratory chain components and TCA cycle enzymes, HAP4 promotes oxidative phosphorylation over fermentation, effectively mimicking a caloric restriction-like metabolic state. Overexpression of HAP4 has been experimentally shown to extend replicative lifespan in yeast by shifting metabolism toward respiration and away from fermentation (the Crabtree effect), which reduces reactive oxygen species accumulation and improves mitochondrial function. This metabolic reprogramming intersects with the TOR/nutrient-sensing axis, as respiratory metabolism is associated with reduced TORC1 signaling. HAP4's coactivator activity at RNA Pol II promoters directly drives the transcriptional program that supports mitochondrial biogenesis and longevity.",
"confidence": 0.85,
"key_pathways": [
"HAP2/3/4/5 transcriptional complex / respiratory gene activation",
"Caloric restriction / TOR nutrient-sensing pathway",
"Mitochondrial biogenesis and oxidative phosphorylation"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted HAP4 as pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: HAP4 is indeed the activating subunit of the HAP2/3/4/5 complex, it does regulate respiratory gene expression, and its overexpression has been experimentally shown to extend replicative lifespan in yeast by shifting metabolism toward respiration (mimicking caloric restriction). The connection to TOR/nutrient-sensing and mitochondrial biogenesis is also well-reasoned. The model demonstrates deep knowledge of yeast aging biology.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}