prx-5
C. elegans
TPR_REGION domain-containing protein
What the model saw
Gene: prx-5 Organism: Caenorhabditis elegans Known functions: TPR_REGION domain-containing protein. peroxisome matrix targeting signal-1 binding. peroxisome targeting sequence binding. phosphotransferase activity, alcohol group as acceptor. protein binding. protein-macromolecule adaptor activity.
View unredacted entry
TPR_REGION domain-containing protein. peroxisome matrix targeting signal-1 binding. peroxisome targeting sequence binding. phosphotransferase activity, alcohol group as acceptor. protein binding. protein-macromolecule adaptor activity.
Solver output
prx-5 encodes a peroxin with a TPR (tetratricopeptide repeat) domain that binds peroxisome targeting signal-1 (PTS1), a hallmark of the PEX5 import receptor family responsible for shuttling PTS1-bearing proteins into the peroxisome matrix. Proper peroxisomal import is essential for maintaining peroxisomal function, including fatty acid β-oxidation, ether lipid synthesis, and reactive oxygen species (H2O2) detoxification via catalase. In C. elegans, peroxisomal integrity supports lipid metabolism and redox homeostasis, both of which are linked to lifespan regulation. Loss of peroxisomal import machinery disrupts these metabolic and antioxidant functions, which would be expected to shorten lifespan, indicating the normal function of prx-5 is pro-longevity. The phosphotransferase activity may reflect a regulatory phosphorylation step in the PEX5 recycling cycle (monoubiquitination/phosphorylation-dependent receptor export), further supporting peroxisomal homeostasis.
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 pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that loss of peroxisomal import function would shorten lifespan (making prx-5 pro-longevity), but the actual GenAge classification is anti_longevity, meaning prx-5 activity shortens lifespan (or its loss extends it). The model's mechanistic reasoning about PEX5-like peroxisomal import is plausible in general terms but leads to the wrong conclusion. In C. elegans, prx-5 (a peroxin) appears to have an anti-longevity role, possibly because peroxisomal activity promotes aging rather than protecting against it in this context. The model's confidence of 0.62 is moderate but still committed to the wrong answer. The reasoning quality is poor because it failed to consider that peroxisomal function could be anti-longevity in C. elegans.
Raw API responses
solver
{
"reasoning": "prx-5 encodes a peroxin with a TPR (tetratricopeptide repeat) domain that binds peroxisome targeting signal-1 (PTS1), a hallmark of the PEX5 import receptor family responsible for shuttling PTS1-bearing proteins into the peroxisome matrix. Proper peroxisomal import is essential for maintaining peroxisomal function, including fatty acid β-oxidation, ether lipid synthesis, and reactive oxygen species (H2O2) detoxification via catalase. In C. elegans, peroxisomal integrity supports lipid metabolism and redox homeostasis, both of which are linked to lifespan regulation. Loss of peroxisomal import machinery disrupts these metabolic and antioxidant functions, which would be expected to shorten lifespan, indicating the normal function of prx-5 is pro-longevity. The phosphotransferase activity may reflect a regulatory phosphorylation step in the PEX5 recycling cycle (monoubiquitination/phosphorylation-dependent receptor export), further supporting peroxisomal homeostasis.",
"confidence": 0.62,
"key_pathways": [
"peroxisomal matrix protein import (PTS1 pathway)",
"peroxisomal fatty acid beta-oxidation and redox homeostasis",
"PEX5 receptor recycling cycle"
],
"mechanism_class": "other",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that loss of peroxisomal import function would shorten lifespan (making prx-5 pro-longevity), but the actual GenAge classification is anti_longevity, meaning prx-5 activity shortens lifespan (or its loss extends it). The model's mechanistic reasoning about PEX5-like peroxisomal import is plausible in general terms but leads to the wrong conclusion. In C. elegans, prx-5 (a peroxin) appears to have an anti-longevity role, possibly because peroxisomal activity promotes aging rather than protecting against it in this context. The model's confidence of 0.62 is moderate but still committed to the wrong answer. The reasoning quality is poor because it failed to consider that peroxisomal function could be anti-longevity in C. elegans.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}