PMR1
S. cerevisiae
Ca(2+)/Mn(2+)-transporting P-type ATPase PMR1
What the model saw
Gene: PMR1 Organism: Saccharomyces cerevisiae Known functions: Ca(2+)/Mn(2+)-transporting P-type ATPase PMR1. ATP binding. ATP hydrolysis activity. ATPase-coupled monoatomic cation transmembrane transporter activity. P-type calcium transporter activity. P-type ion transporter activity. P-type manganese transporter activity. calcium ion binding. manganese ion transmembrane transporter activity. nucleotide binding.
View unredacted entry
Ca(2+)/Mn(2+)-transporting P-type ATPase PMR1. ATP binding. ATP hydrolysis activity. ATPase-coupled monoatomic cation transmembrane transporter activity. P-type calcium transporter activity. P-type ion transporter activity. P-type manganese transporter activity. calcium ion binding. manganese ion transmembrane transporter activity. nucleotide binding.
Solver output
PMR1 encodes the high-affinity Ca²⁺/Mn²⁺ P-type ATPase of the Golgi apparatus in S. cerevisiae, responsible for pumping Ca²⁺ and Mn²⁺ into the Golgi lumen. Proper Golgi Ca²⁺/Mn²⁺ homeostasis is essential for the activity of glycosyltransferases and other Golgi-resident enzymes that require these ions as cofactors, directly supporting protein glycosylation and secretory pathway proteostasis. Loss of PMR1 leads to Mn²⁺ toxicity, elevated cytosolic Ca²⁺, and impaired protein folding/processing in the secretory pathway, all of which are associated with cellular stress and shortened replicative lifespan. Additionally, Mn²⁺ overload in the cytoplasm causes oxidative stress and mitochondrial dysfunction, further accelerating aging. By maintaining ionic balance in the Golgi and supporting proteostasis in the secretory pathway, PMR1 function is pro-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 predicted PMR1 as pro_longevity, but the ground truth is anti_longevity. This means deletion of PMR1 actually extends lifespan, not shortens it. The model's reasoning was internally consistent but reached the wrong conclusion — it correctly described PMR1's role in Golgi Ca²⁺/Mn²⁺ homeostasis and the consequences of its loss, but incorrectly inferred that this makes PMR1 pro-longevity. In reality, PMR1 deletion extends lifespan in yeast, making it anti-longevity. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning about Mn²⁺ toxicity and proteostasis disruption upon PMR1 loss is partially accurate in describing cellular effects, but the model failed to recognize that these stresses might paradoxically activate longevity pathways (e.g., hormesis, UPR, or other stress responses that extend lifespan). The mechanism class of 'loss_of_proteostasis' is also incorrect given the actual anti-longevity classification.
Raw API responses
solver
{
"reasoning": "PMR1 encodes the high-affinity Ca²⁺/Mn²⁺ P-type ATPase of the Golgi apparatus in S. cerevisiae, responsible for pumping Ca²⁺ and Mn²⁺ into the Golgi lumen. Proper Golgi Ca²⁺/Mn²⁺ homeostasis is essential for the activity of glycosyltransferases and other Golgi-resident enzymes that require these ions as cofactors, directly supporting protein glycosylation and secretory pathway proteostasis. Loss of PMR1 leads to Mn²⁺ toxicity, elevated cytosolic Ca²⁺, and impaired protein folding/processing in the secretory pathway, all of which are associated with cellular stress and shortened replicative lifespan. Additionally, Mn²⁺ overload in the cytoplasm causes oxidative stress and mitochondrial dysfunction, further accelerating aging. By maintaining ionic balance in the Golgi and supporting proteostasis in the secretory pathway, PMR1 function is pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"Golgi Ca2+/Mn2+ homeostasis",
"secretory pathway proteostasis and protein glycosylation",
"manganese detoxification and oxidative stress prevention"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted PMR1 as pro_longevity, but the ground truth is anti_longevity. This means deletion of PMR1 actually extends lifespan, not shortens it. The model's reasoning was internally consistent but reached the wrong conclusion — it correctly described PMR1's role in Golgi Ca²⁺/Mn²⁺ homeostasis and the consequences of its loss, but incorrectly inferred that this makes PMR1 pro-longevity. In reality, PMR1 deletion extends lifespan in yeast, making it anti-longevity. The model was fairly confident (0.72) in its wrong answer. The mechanistic reasoning about Mn²⁺ toxicity and proteostasis disruption upon PMR1 loss is partially accurate in describing cellular effects, but the model failed to recognize that these stresses might paradoxically activate longevity pathways (e.g., hormesis, UPR, or other stress responses that extend lifespan). The mechanism class of 'loss_of_proteostasis' is also incorrect given the actual anti-longevity classification.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}