Prkar2b
M. musculus
protein kinase, cAMP dependent regulatory, type II beta
What the model saw
Gene: Prkar2b Organism: Mus musculus Known functions: protein kinase, cAMP dependent regulatory, type II beta. cAMP-dependent protein kinase type II-beta regulatory subunit. cAMP binding. cAMP-dependent protein kinase inhibitor activity. cAMP-dependent protein kinase regulator activity. protein binding. protein domain specific binding. protein kinase A catalytic subunit binding. protein kinase binding. ubiquitin protein ligase binding.
View unredacted entry
protein kinase, cAMP dependent regulatory, type II beta. cAMP-dependent protein kinase type II-beta regulatory subunit. cAMP binding. cAMP-dependent protein kinase inhibitor activity. cAMP-dependent protein kinase regulator activity. protein binding. protein domain specific binding. protein kinase A catalytic subunit binding. protein kinase binding. ubiquitin protein ligase binding.
Solver output
Prkar2b encodes the regulatory subunit IIβ of cAMP-dependent protein kinase A (PKA). In its normal function, this subunit binds cAMP and holds the PKA catalytic subunit inactive; upon cAMP elevation, it releases the catalytic subunit, activating downstream signaling. PKA is a central effector of cAMP signaling downstream of G-protein-coupled receptors and is tightly integrated with nutrient-sensing pathways including AMPK and mTOR crosstalk. Elevated PKA/cAMP signaling has been associated with increased adiposity, reduced insulin sensitivity, and metabolic dysregulation in mice, all of which are pro-aging phenotypes. Notably, Prkar2b knockout mice show leanness and improved metabolic profiles, suggesting that normal Prkar2b activity (maintaining PKA regulatory tone in adipose and brain tissue) promotes metabolic states that shorten lifespan. The regulatory subunit's role in modulating PKA activity places it within the deregulated nutrient-sensing hallmark, as PKA is a key node linking cAMP to energy homeostasis and metabolic aging.
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 anti_longevity for Prkar2b. The mechanistic reasoning is sound: Prkar2b encodes the PKA regulatory subunit IIβ, and the model correctly identifies that knockout mice show leanness and improved metabolic profiles, suggesting the normal gene activity promotes pro-aging metabolic states. The classification as "deregulated_nutrient_sensing" is reasonable given PKA's role in energy homeostasis. The reasoning about Prkar2b knockout mice showing improved metabolic phenotypes is consistent with published literature. Confidence of 0.62 is appropriately calibrated for this somewhat specialized gene. Minor deduction: the AMPK/mTOR crosstalk framing is somewhat speculative and not directly established for Prkar2b specifically.
Raw API responses
solver
{
"reasoning": "Prkar2b encodes the regulatory subunit IIβ of cAMP-dependent protein kinase A (PKA). In its normal function, this subunit binds cAMP and holds the PKA catalytic subunit inactive; upon cAMP elevation, it releases the catalytic subunit, activating downstream signaling. PKA is a central effector of cAMP signaling downstream of G-protein-coupled receptors and is tightly integrated with nutrient-sensing pathways including AMPK and mTOR crosstalk. Elevated PKA/cAMP signaling has been associated with increased adiposity, reduced insulin sensitivity, and metabolic dysregulation in mice, all of which are pro-aging phenotypes. Notably, Prkar2b knockout mice show leanness and improved metabolic profiles, suggesting that normal Prkar2b activity (maintaining PKA regulatory tone in adipose and brain tissue) promotes metabolic states that shorten lifespan. The regulatory subunit's role in modulating PKA activity places it within the deregulated nutrient-sensing hallmark, as PKA is a key node linking cAMP to energy homeostasis and metabolic aging.",
"confidence": 0.62,
"key_pathways": [
"cAMP-PKA signaling",
"nutrient and energy sensing (AMPK/mTOR crosstalk)",
"adipose tissue metabolism and insulin sensitivity"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Prkar2b. The mechanistic reasoning is sound: Prkar2b encodes the PKA regulatory subunit IIβ, and the model correctly identifies that knockout mice show leanness and improved metabolic profiles, suggesting the normal gene activity promotes pro-aging metabolic states. The classification as \"deregulated_nutrient_sensing\" is reasonable given PKA's role in energy homeostasis. The reasoning about Prkar2b knockout mice showing improved metabolic phenotypes is consistent with published literature. Confidence of 0.62 is appropriately calibrated for this somewhat specialized gene. Minor deduction: the AMPK/mTOR crosstalk framing is somewhat speculative and not directly established for Prkar2b specifically.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}