pcm-1
C. elegans
Protein-L-isoaspartate O-methyltransferase
What the model saw
Gene: pcm-1 Organism: Caenorhabditis elegans Known functions: Protein-L-isoaspartate O-methyltransferase. protein-L-isoaspartate (D-aspartate) O-methyltransferase activity.
View unredacted entry
Protein-L-isoaspartate O-methyltransferase. protein-L-isoaspartate (D-aspartate) O-methyltransferase activity.
Solver output
Protein-L-isoaspartate O-methyltransferase (PIMT) catalyzes the repair of spontaneously damaged aspartyl and asparaginyl residues that have been converted to isoaspartate, a non-standard amino acid linkage that distorts protein structure and impairs function. By methylating L-isoaspartyl residues, pcm-1 initiates a repair cycle that converts them back to normal L-aspartyl residues, thereby restoring protein conformation and preventing accumulation of damaged proteins. This activity directly supports proteostasis by reducing the burden of age-related spontaneous protein damage that accumulates over time. Loss of PIMT function in multiple organisms leads to accelerated accumulation of isoaspartyl-damaged proteins, neurological defects, and shortened lifespan, while overexpression extends lifespan in some models. Thus, pcm-1 acts as a pro-longevity gene by maintaining the integrity of the proteome against a specific form of non-enzymatic, age-associated damage.
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 for pcm-1 in C. elegans. The mechanistic reasoning is excellent and accurate: PIMT (protein-L-isoaspartate O-methyltransferase) repairs spontaneously damaged isoaspartyl residues, maintaining proteostasis and preventing accumulation of age-related protein damage. The model correctly notes that loss of PIMT leads to shortened lifespan while overexpression can extend lifespan. The confidence level of 0.82 is appropriate. The mechanism classification as "loss_of_proteostasis" (i.e., pcm-1 prevents loss of proteostasis) is well-reasoned and accurate.
Raw API responses
solver
{
"reasoning": "Protein-L-isoaspartate O-methyltransferase (PIMT) catalyzes the repair of spontaneously damaged aspartyl and asparaginyl residues that have been converted to isoaspartate, a non-standard amino acid linkage that distorts protein structure and impairs function. By methylating L-isoaspartyl residues, pcm-1 initiates a repair cycle that converts them back to normal L-aspartyl residues, thereby restoring protein conformation and preventing accumulation of damaged proteins. This activity directly supports proteostasis by reducing the burden of age-related spontaneous protein damage that accumulates over time. Loss of PIMT function in multiple organisms leads to accelerated accumulation of isoaspartyl-damaged proteins, neurological defects, and shortened lifespan, while overexpression extends lifespan in some models. Thus, pcm-1 acts as a pro-longevity gene by maintaining the integrity of the proteome against a specific form of non-enzymatic, age-associated damage.",
"confidence": 0.82,
"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 for pcm-1 in C. elegans. The mechanistic reasoning is excellent and accurate: PIMT (protein-L-isoaspartate O-methyltransferase) repairs spontaneously damaged isoaspartyl residues, maintaining proteostasis and preventing accumulation of age-related protein damage. The model correctly notes that loss of PIMT leads to shortened lifespan while overexpression can extend lifespan. The confidence level of 0.82 is appropriate. The mechanism classification as \"loss_of_proteostasis\" (i.e., pcm-1 prevents loss of proteostasis) is well-reasoned and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}