ubh-3
C. elegans
Ubiquitin carboxyl-terminal hydrolase
What the model saw
Gene: ubh-3 Organism: Caenorhabditis elegans Known functions: Ubiquitin carboxyl-terminal hydrolase. cysteine-type deubiquitinase activity. deNEDDylase activity. deubiquitinase activity.
View unredacted entry
Ubiquitin carboxyl-terminal hydrolase. cysteine-type deubiquitinase activity. deNEDDylase activity. deubiquitinase activity.
Solver output
ubh-3 encodes a cysteine-type deubiquitinase (DUB) with both deubiquitinase and deNEDDylase activities, placing it at the intersection of ubiquitin and NEDD8 signaling. Deubiquitinases recycle ubiquitin and rescue proteins from proteasomal degradation, maintaining the free ubiquitin pool essential for proteostasis. The deNEDDylase activity additionally regulates cullin-RING E3 ligase (CRL) complexes by removing NEDD8 from cullins, modulating substrate ubiquitination rates and thus proteome quality control. In C. elegans, robust ubiquitin-proteasome system (UPS) activity is a hallmark of long-lived animals (e.g., daf-2 mutants), and DUBs that support UPS flux and proteostasis tend to be pro-longevity. The dual DUB/deNEDDylase function of ubh-3 is most analogous to mammalian UCH-L1/UCH-L3 and CSN5, whose activities sustain proteostatic networks that counteract age-related protein aggregation.
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 ubh-3. The mechanistic reasoning is plausible and internally consistent — connecting deubiquitinase/deNEDDylase activity to proteostasis maintenance and UPS function, which are well-established longevity-relevant pathways in C. elegans. However, the reasoning is largely inferential/generic rather than based on specific experimental evidence for ubh-3 itself. The model draws reasonable analogies to mammalian UCH-L1/UCH-L3 and CSN5, but these are somewhat speculative connections. The confidence of 0.62 is appropriately moderate given the lack of direct evidence cited. Overall, the answer is correct with reasonable but not highly specific mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "ubh-3 encodes a cysteine-type deubiquitinase (DUB) with both deubiquitinase and deNEDDylase activities, placing it at the intersection of ubiquitin and NEDD8 signaling. Deubiquitinases recycle ubiquitin and rescue proteins from proteasomal degradation, maintaining the free ubiquitin pool essential for proteostasis. The deNEDDylase activity additionally regulates cullin-RING E3 ligase (CRL) complexes by removing NEDD8 from cullins, modulating substrate ubiquitination rates and thus proteome quality control. In C. elegans, robust ubiquitin-proteasome system (UPS) activity is a hallmark of long-lived animals (e.g., daf-2 mutants), and DUBs that support UPS flux and proteostasis tend to be pro-longevity. The dual DUB/deNEDDylase function of ubh-3 is most analogous to mammalian UCH-L1/UCH-L3 and CSN5, whose activities sustain proteostatic networks that counteract age-related protein aggregation.",
"confidence": 0.62,
"key_pathways": [
"ubiquitin-proteasome system (UPS) / proteostasis",
"cullin-RING ligase (CRL) regulation via deNEDDylation",
"ubiquitin recycling and free ubiquitin pool maintenance"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for ubh-3. The mechanistic reasoning is plausible and internally consistent — connecting deubiquitinase/deNEDDylase activity to proteostasis maintenance and UPS function, which are well-established longevity-relevant pathways in C. elegans. However, the reasoning is largely inferential/generic rather than based on specific experimental evidence for ubh-3 itself. The model draws reasonable analogies to mammalian UCH-L1/UCH-L3 and CSN5, but these are somewhat speculative connections. The confidence of 0.62 is appropriately moderate given the lack of direct evidence cited. Overall, the answer is correct with reasonable but not highly specific mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}