ulp-1
C. elegans
Sentrin-specific protease
What the model saw
Gene: ulp-1 Organism: Caenorhabditis elegans Known functions: Sentrin-specific protease. cysteine-type peptidase activity. deSUMOylase activity.
View unredacted entry
Sentrin-specific protease. cysteine-type peptidase activity. deSUMOylase activity.
Solver output
ULP-1 is a SUMO-specific protease (sentrin-specific protease) that cleaves SUMO (small ubiquitin-like modifier) from target proteins, reversing SUMOylation. SUMOylation is a post-translational modification that broadly regulates protein localization, stability, transcriptional activity, and DNA damage responses. Because SUMO substrates include transcription factors, chromatin regulators, and DNA repair proteins, deSUMOylation by ULP-1 can either activate or repress longevity-relevant pathways depending on the specific substrate. In C. elegans, SUMO (encoded by smo-1) has been shown to modulate DAF-16/FOXO activity and stress response pathways, but the net effect of removing SUMO modifications via ULP-1 is substrate-context-dependent. The dual role of SUMOylation in both promoting and suppressing longevity pathways (e.g., nuclear localization of DAF-16 vs. repression of stress-response genes) makes it difficult to assign a clear pro- or anti-longevity direction to the deSUMOylase activity of ULP-1 without additional experimental data.
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 "unclear" for ulp-1's longevity influence, but the ground truth is "pro_longevity." The model's reasoning was overly cautious and generic, citing the dual roles of SUMOylation without committing to a direction. While the mechanistic reasoning about SUMO deconjugation and DAF-16/FOXO is plausible in general terms, the model failed to identify the specific experimental evidence in C. elegans showing that ulp-1 promotes longevity. The model's confidence was appropriately low (0.42), but the final classification of "unclear" is incorrect. The mechanism class of "epigenetic_alterations" is a reasonable but imprecise categorization for deSUMOylation activity.
Raw API responses
solver
{
"reasoning": "ULP-1 is a SUMO-specific protease (sentrin-specific protease) that cleaves SUMO (small ubiquitin-like modifier) from target proteins, reversing SUMOylation. SUMOylation is a post-translational modification that broadly regulates protein localization, stability, transcriptional activity, and DNA damage responses. Because SUMO substrates include transcription factors, chromatin regulators, and DNA repair proteins, deSUMOylation by ULP-1 can either activate or repress longevity-relevant pathways depending on the specific substrate. In C. elegans, SUMO (encoded by smo-1) has been shown to modulate DAF-16/FOXO activity and stress response pathways, but the net effect of removing SUMO modifications via ULP-1 is substrate-context-dependent. The dual role of SUMOylation in both promoting and suppressing longevity pathways (e.g., nuclear localization of DAF-16 vs. repression of stress-response genes) makes it difficult to assign a clear pro- or anti-longevity direction to the deSUMOylase activity of ULP-1 without additional experimental data.",
"confidence": 0.42,
"key_pathways": [
"SUMO deconjugation / deSUMOylation",
"DAF-16/FOXO transcriptional regulation",
"DNA damage response and chromatin regulation"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" for ulp-1's longevity influence, but the ground truth is \"pro_longevity.\" The model's reasoning was overly cautious and generic, citing the dual roles of SUMOylation without committing to a direction. While the mechanistic reasoning about SUMO deconjugation and DAF-16/FOXO is plausible in general terms, the model failed to identify the specific experimental evidence in C. elegans showing that ulp-1 promotes longevity. The model's confidence was appropriately low (0.42), but the final classification of \"unclear\" is incorrect. The mechanism class of \"epigenetic_alterations\" is a reasonable but imprecise categorization for deSUMOylation activity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}