Pcmt
D. melanogaster
Protein-L-isoaspartate (D-aspartate) O-methyltransferase
What the model saw
Gene: Pcmt Organism: Drosophila melanogaster Known functions: Protein-L-isoaspartate (D-aspartate) O-methyltransferase. protein-L-isoaspartate (D-aspartate) O-methyltransferase activity.
View unredacted entry
Protein-L-isoaspartate (D-aspartate) O-methyltransferase. protein-L-isoaspartate (D-aspartate) O-methyltransferase activity.
Solver output
Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) catalyzes the repair of damaged, age-accumulated isoaspartyl residues in proteins. These abnormal isoaspartyl linkages arise spontaneously from asparagine deamidation and aspartate isomerization, causing protein misfolding and loss of function. PIMT initiates a repair cycle by methylating isoaspartyl residues, converting them back toward normal L-aspartyl forms, thereby restoring protein structure and function. This activity directly counteracts age-related protein damage accumulation, a key driver of proteostasis decline. Loss of PCMT in model organisms (including Drosophila and mice) leads to accelerated accumulation of damaged proteins and shortened lifespan, while overexpression extends lifespan, firmly establishing its pro-longevity role through proteostasis maintenance.
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 pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: PIMT repairs isoaspartyl residues in damaged proteins, counteracting age-related protein damage accumulation. The model correctly notes that loss of PCMT leads to shortened lifespan while overexpression extends lifespan in Drosophila, which aligns with the known biology. The mechanism class (loss_of_proteostasis) and key pathways are all appropriate and well-reasoned.
Raw API responses
solver
{
"reasoning": "Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) catalyzes the repair of damaged, age-accumulated isoaspartyl residues in proteins. These abnormal isoaspartyl linkages arise spontaneously from asparagine deamidation and aspartate isomerization, causing protein misfolding and loss of function. PIMT initiates a repair cycle by methylating isoaspartyl residues, converting them back toward normal L-aspartyl forms, thereby restoring protein structure and function. This activity directly counteracts age-related protein damage accumulation, a key driver of proteostasis decline. Loss of PCMT in model organisms (including Drosophila and mice) leads to accelerated accumulation of damaged proteins and shortened lifespan, while overexpression extends lifespan, firmly establishing its pro-longevity role through proteostasis maintenance.",
"confidence": 0.85,
"key_pathways": [
"isoaspartyl protein repair",
"proteostasis maintenance",
"protein damage reversal"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity with high confidence (0.85). The mechanistic reasoning is excellent and accurate: PIMT repairs isoaspartyl residues in damaged proteins, counteracting age-related protein damage accumulation. The model correctly notes that loss of PCMT leads to shortened lifespan while overexpression extends lifespan in Drosophila, which aligns with the known biology. The mechanism class (loss_of_proteostasis) and key pathways are all appropriate and well-reasoned.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}