PMT5
S. cerevisiae
putative dolichyl-phosphate-mannose-protein mannosyltransferase PMT5
What the model saw
Gene: PMT5 Organism: Saccharomyces cerevisiae Known functions: putative dolichyl-phosphate-mannose-protein mannosyltransferase PMT5. dolichyl-phosphate-mannose-protein mannosyltransferase activity. mannosyltransferase activity. protein binding.
View unredacted entry
putative dolichyl-phosphate-mannose-protein mannosyltransferase PMT5. dolichyl-phosphate-mannose-protein mannosyltransferase activity. mannosyltransferase activity. protein binding.
Solver output
PMT5 encodes a dolichyl-phosphate-mannose-protein mannosyltransferase involved in O-mannosylation of proteins in the ER. O-mannosylation is a critical post-translational modification that affects protein folding, stability, and secretion. In yeast, the PMT family (PMT1-7) initiates O-glycosylation, and their activity influences ER protein quality control and proteostasis. Hyperactive or dysregulated O-mannosylation can burden the secretory pathway and contribute to ER stress, impairing proteostasis. Studies in yeast have shown that deletion of certain PMT genes (particularly PMT1 and PMT2) can extend chronological or replicative lifespan, suggesting that reducing O-mannosyltransferase activity is pro-longevity; conversely, the normal function of PMT5 in promoting O-mannosylation would be anti-longevity by maintaining a pathway whose attenuation extends lifespan. PMT5 specifically forms heteromeric complexes with PMT1 or PMT2 to modulate substrate specificity, and its normal enzymatic activity contributes to the overall O-mannosylation flux that, when reduced, has been linked to lifespan extension.
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 anti_longevity for PMT5. The mechanistic reasoning is sound and well-articulated: PMT5 is part of the O-mannosyltransferase family, and the model correctly notes that deletion of PMT family members (particularly PMT1/PMT2) can extend lifespan, making the normal function of PMT5 anti-longevity. The reasoning about ER proteostasis, O-mannosylation flux, and heteromeric complex formation with PMT1/PMT2 is biologically plausible and consistent with the literature. The confidence of 0.62 is appropriately moderate given the indirect nature of the evidence. Minor caveat: the model's framing of "loss_of_proteostasis" as the mechanism class is somewhat indirect — the anti-longevity effect is more directly tied to O-mannosylation activity itself rather than proteostasis loss per se — but this is a minor issue and the overall reasoning is coherent.
Raw API responses
solver
{
"reasoning": "PMT5 encodes a dolichyl-phosphate-mannose-protein mannosyltransferase involved in O-mannosylation of proteins in the ER. O-mannosylation is a critical post-translational modification that affects protein folding, stability, and secretion. In yeast, the PMT family (PMT1-7) initiates O-glycosylation, and their activity influences ER protein quality control and proteostasis. Hyperactive or dysregulated O-mannosylation can burden the secretory pathway and contribute to ER stress, impairing proteostasis. Studies in yeast have shown that deletion of certain PMT genes (particularly PMT1 and PMT2) can extend chronological or replicative lifespan, suggesting that reducing O-mannosyltransferase activity is pro-longevity; conversely, the normal function of PMT5 in promoting O-mannosylation would be anti-longevity by maintaining a pathway whose attenuation extends lifespan. PMT5 specifically forms heteromeric complexes with PMT1 or PMT2 to modulate substrate specificity, and its normal enzymatic activity contributes to the overall O-mannosylation flux that, when reduced, has been linked to lifespan extension.",
"confidence": 0.62,
"key_pathways": [
"O-mannosylation / ER protein glycosylation",
"dolichyl-phosphate-mannose (DPM) transfer pathway",
"ER proteostasis and unfolded protein response"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for PMT5. The mechanistic reasoning is sound and well-articulated: PMT5 is part of the O-mannosyltransferase family, and the model correctly notes that deletion of PMT family members (particularly PMT1/PMT2) can extend lifespan, making the normal function of PMT5 anti-longevity. The reasoning about ER proteostasis, O-mannosylation flux, and heteromeric complex formation with PMT1/PMT2 is biologically plausible and consistent with the literature. The confidence of 0.62 is appropriately moderate given the indirect nature of the evidence. Minor caveat: the model's framing of \"loss_of_proteostasis\" as the mechanism class is somewhat indirect — the anti-longevity effect is more directly tied to O-mannosylation activity itself rather than proteostasis loss per se — but this is a minor issue and the overall reasoning is coherent.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}