TPK2
S. cerevisiae
cAMP-dependent protein kinase catalytic subunit TPK2
What the model saw
Gene: TPK2 Organism: Saccharomyces cerevisiae Known functions: cAMP-dependent protein kinase catalytic subunit TPK2. ATP binding. cAMP-dependent protein kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
cAMP-dependent protein kinase catalytic subunit TPK2. ATP binding. cAMP-dependent protein kinase activity. protein binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
TPK2 is one of the three catalytic subunits (TPK1, TPK2, TPK3) of the cAMP-dependent protein kinase A (PKA) complex in S. cerevisiae. PKA is a central effector of the Ras/cAMP/PKA nutrient-sensing pathway, which is activated by glucose and promotes growth while suppressing stress resistance, autophagy, and entry into quiescence. Elevated PKA activity phosphorylates and inhibits transcription factors such as Msn2/Msn4 (stress response) and Rim15 (pro-longevity kinase), thereby suppressing the expression of stress-response and longevity-promoting genes. Reduced PKA signaling — through deletion or attenuation of TPK subunits — is well established to extend both chronological and replicative lifespan in yeast by mimicking a calorie-restriction-like state. Thus, the normal catalytic function of TPK2 (serine/threonine kinase activity driven by cAMP) actively opposes longevity by sustaining pro-growth, anti-stress signaling.
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 TPK2 as anti_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: TPK2 is indeed a catalytic subunit of PKA in the Ras/cAMP/PKA pathway, which promotes growth and suppresses stress resistance and longevity. The model correctly identifies the downstream targets (Msn2/Msn4, Rim15) and explains how PKA activity opposes longevity by sustaining pro-growth signaling. The reasoning about deletion of TPK subunits extending lifespan is well-established in the yeast aging literature.
Raw API responses
solver
{
"reasoning": "TPK2 is one of the three catalytic subunits (TPK1, TPK2, TPK3) of the cAMP-dependent protein kinase A (PKA) complex in S. cerevisiae. PKA is a central effector of the Ras/cAMP/PKA nutrient-sensing pathway, which is activated by glucose and promotes growth while suppressing stress resistance, autophagy, and entry into quiescence. Elevated PKA activity phosphorylates and inhibits transcription factors such as Msn2/Msn4 (stress response) and Rim15 (pro-longevity kinase), thereby suppressing the expression of stress-response and longevity-promoting genes. Reduced PKA signaling — through deletion or attenuation of TPK subunits — is well established to extend both chronological and replicative lifespan in yeast by mimicking a calorie-restriction-like state. Thus, the normal catalytic function of TPK2 (serine/threonine kinase activity driven by cAMP) actively opposes longevity by sustaining pro-growth, anti-stress signaling.",
"confidence": 0.82,
"key_pathways": [
"Ras/cAMP/PKA nutrient-sensing pathway",
"Msn2/Msn4 stress-response transcription factor regulation",
"Rim15-Gis1/Msn2 pro-longevity signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted TPK2 as anti_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: TPK2 is indeed a catalytic subunit of PKA in the Ras/cAMP/PKA pathway, which promotes growth and suppresses stress resistance and longevity. The model correctly identifies the downstream targets (Msn2/Msn4, Rim15) and explains how PKA activity opposes longevity by sustaining pro-growth signaling. The reasoning about deletion of TPK subunits extending lifespan is well-established in the yeast aging literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}