MCA1
S. cerevisiae
Ca(2+)-dependent cysteine protease MCA1
What the model saw
Gene: MCA1 Organism: Saccharomyces cerevisiae Known functions: Ca(2+)-dependent cysteine protease MCA1. calcium-dependent cysteine-type endopeptidase activity. cysteine-type endopeptidase activity.
View unredacted entry
Ca(2+)-dependent cysteine protease MCA1. calcium-dependent cysteine-type endopeptidase activity. cysteine-type endopeptidase activity.
Solver output
MCA1 encodes the sole yeast metacaspase, a Ca²⁺-dependent cysteine protease that is a functional ortholog of metazoan caspases. In S. cerevisiae, MCA1 is a key executioner of yeast apoptosis/programmed cell death (PCD), cleaving substrates in a calcium-dependent manner to drive cell death. Activation of MCA1-mediated PCD shortens replicative and chronological lifespan by eliminating cells that could otherwise survive. Deletion of MCA1 has been shown to extend chronological lifespan by reducing apoptotic cell death under stress conditions, confirming that its normal pro-apoptotic function is detrimental to longevity. This places MCA1 in a cellular senescence/cell death axis rather than a survival-promoting pathway, making its normal activity anti-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 MCA1 as anti_longevity, but the ground truth is pro_longevity. The model's reasoning is based on the classic view that MCA1 (yeast metacaspase) drives apoptosis/PCD and thus shortens lifespan. However, the actual GenAge classification is pro_longevity, suggesting that MCA1 plays a beneficial role in longevity — likely through its role in protein quality control, clearance of damaged/aggregated proteins, or regulation of cellular proteostasis rather than simply executing cell death. Research has shown MCA1 can promote longevity by clearing protein aggregates and damaged proteins, which is a pro-survival function. The model was confident (0.72) in the wrong direction and provided mechanistic reasoning that contradicts the ground truth. The model's claim that "deletion of MCA1 has been shown to extend chronological lifespan" appears to be incorrect or at least not the dominant finding captured in GenAge.
Raw API responses
solver
{
"reasoning": "MCA1 encodes the sole yeast metacaspase, a Ca²⁺-dependent cysteine protease that is a functional ortholog of metazoan caspases. In S. cerevisiae, MCA1 is a key executioner of yeast apoptosis/programmed cell death (PCD), cleaving substrates in a calcium-dependent manner to drive cell death. Activation of MCA1-mediated PCD shortens replicative and chronological lifespan by eliminating cells that could otherwise survive. Deletion of MCA1 has been shown to extend chronological lifespan by reducing apoptotic cell death under stress conditions, confirming that its normal pro-apoptotic function is detrimental to longevity. This places MCA1 in a cellular senescence/cell death axis rather than a survival-promoting pathway, making its normal activity anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"yeast metacaspase-mediated apoptosis",
"calcium-dependent programmed cell death",
"cysteine protease-driven cell elimination"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model predicted MCA1 as anti_longevity, but the ground truth is pro_longevity. The model's reasoning is based on the classic view that MCA1 (yeast metacaspase) drives apoptosis/PCD and thus shortens lifespan. However, the actual GenAge classification is pro_longevity, suggesting that MCA1 plays a beneficial role in longevity — likely through its role in protein quality control, clearance of damaged/aggregated proteins, or regulation of cellular proteostasis rather than simply executing cell death. Research has shown MCA1 can promote longevity by clearing protein aggregates and damaged proteins, which is a pro-survival function. The model was confident (0.72) in the wrong direction and provided mechanistic reasoning that contradicts the ground truth. The model's claim that \"deletion of MCA1 has been shown to extend chronological lifespan\" appears to be incorrect or at least not the dominant finding captured in GenAge.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}