GPA2
S. cerevisiae
guanine nucleotide-binding protein subunit alpha
What the model saw
Gene: GPA2 Organism: Saccharomyces cerevisiae Known functions: guanine nucleotide-binding protein subunit alpha. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. protein binding.
View unredacted entry
guanine nucleotide-binding protein subunit alpha. G protein-coupled receptor binding. G-protein beta/gamma-subunit complex binding. GTP binding. GTPase activity. guanyl nucleotide binding. protein binding.
Solver output
GPA2 encodes the Gα subunit of the glucose-sensing GPCR pathway in S. cerevisiae, where it couples the receptor Gpr1 to adenylyl cyclase (Cyr1) to stimulate cAMP production and activate PKA. Elevated PKA activity suppresses stress resistance, autophagy, and the transcription factors Msn2/Msn4 and Rim15, all of which are required for longevity extension. GPA2 thus acts as a positive regulator of the cAMP-PKA axis, which is a well-established pro-aging pathway in yeast; loss of GPA2 function mimics nutrient limitation and extends chronological and replicative lifespan. Its GTPase activity (GTP binding and hydrolysis) controls the duration of adenylyl cyclase stimulation, and its interaction with Gβγ modulates signal termination, but the net effect of normal GPA2 function is to promote nutrient-sensing signaling that shortens lifespan.
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 identified GPA2 as anti_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: GPA2 encodes the Gα subunit that couples Gpr1 to adenylyl cyclase, stimulating cAMP-PKA signaling, which suppresses stress resistance pathways (Msn2/Msn4, Rim15) and promotes aging. The model correctly notes that loss of GPA2 extends lifespan by mimicking nutrient limitation. All key pathways identified are relevant and correct.
Raw API responses
solver
{
"reasoning": "GPA2 encodes the Gα subunit of the glucose-sensing GPCR pathway in S. cerevisiae, where it couples the receptor Gpr1 to adenylyl cyclase (Cyr1) to stimulate cAMP production and activate PKA. Elevated PKA activity suppresses stress resistance, autophagy, and the transcription factors Msn2/Msn4 and Rim15, all of which are required for longevity extension. GPA2 thus acts as a positive regulator of the cAMP-PKA axis, which is a well-established pro-aging pathway in yeast; loss of GPA2 function mimics nutrient limitation and extends chronological and replicative lifespan. Its GTPase activity (GTP binding and hydrolysis) controls the duration of adenylyl cyclase stimulation, and its interaction with Gβγ modulates signal termination, but the net effect of normal GPA2 function is to promote nutrient-sensing signaling that shortens lifespan.",
"confidence": 0.82,
"key_pathways": [
"cAMP-PKA signaling",
"glucose/GPCR-Gpr1 nutrient sensing",
"Msn2/Msn4 stress response suppression"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly identified GPA2 as anti_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: GPA2 encodes the Gα subunit that couples Gpr1 to adenylyl cyclase, stimulating cAMP-PKA signaling, which suppresses stress resistance pathways (Msn2/Msn4, Rim15) and promotes aging. The model correctly notes that loss of GPA2 extends lifespan by mimicking nutrient limitation. All key pathways identified are relevant and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}