ubh-1
C. elegans
Ubiquitin carboxyl-terminal hydrolase
What the model saw
Gene: ubh-1 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-1 encodes a ubiquitin carboxyl-terminal hydrolase (UCH-family deubiquitinase), orthologous to mammalian UCHL1/UCHL3, which recycles ubiquitin monomers from small adducts and cleaves ubiquitin from substrate proteins. By maintaining the free ubiquitin pool and editing ubiquitin conjugates, ubh-1 supports the efficiency of the ubiquitin-proteasome system (UPS), a central pillar of proteostasis. Its deNEDDylase activity additionally regulates cullin-RING E3 ligase complexes via deneddylation, modulating ubiquitin ligase activity and substrate turnover. Adequate UPS function is required for clearance of damaged and misfolded proteins that accumulate with age; loss of UCH activity in C. elegans and other organisms impairs proteostasis and shortens lifespan, while enhanced UPS activity is associated with longevity. The dual deubiquitinase/deNEDDylase activity places ubh-1 at the intersection of ubiquitin recycling and cullin-RING ligase regulation, both of which are pro-proteostatic and thus pro-longevity.
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-1. The mechanistic reasoning is sound and well-articulated: ubh-1 as a UCH-family deubiquitinase maintains the free ubiquitin pool, supports UPS function, and its deNEDDylase activity regulates cullin-RING E3 ligases — all of which are plausible pro-longevity mechanisms through proteostasis maintenance. The reasoning is coherent and biologically grounded. Confidence of 0.72 is appropriate given the specificity of the gene. Minor note: the model draws on mammalian ortholog knowledge (UCHL1/UCHL3) which is reasonable but the direct C. elegans experimental evidence isn't explicitly cited, though the overall logic is solid.
Raw API responses
solver
{
"reasoning": "ubh-1 encodes a ubiquitin carboxyl-terminal hydrolase (UCH-family deubiquitinase), orthologous to mammalian UCHL1/UCHL3, which recycles ubiquitin monomers from small adducts and cleaves ubiquitin from substrate proteins. By maintaining the free ubiquitin pool and editing ubiquitin conjugates, ubh-1 supports the efficiency of the ubiquitin-proteasome system (UPS), a central pillar of proteostasis. Its deNEDDylase activity additionally regulates cullin-RING E3 ligase complexes via deneddylation, modulating ubiquitin ligase activity and substrate turnover. Adequate UPS function is required for clearance of damaged and misfolded proteins that accumulate with age; loss of UCH activity in C. elegans and other organisms impairs proteostasis and shortens lifespan, while enhanced UPS activity is associated with longevity. The dual deubiquitinase/deNEDDylase activity places ubh-1 at the intersection of ubiquitin recycling and cullin-RING ligase regulation, both of which are pro-proteostatic and thus pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"ubiquitin-proteasome system (UPS) / ubiquitin recycling",
"cullin-RING E3 ligase regulation via deNEDDylation",
"protein quality control / proteostasis network"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for ubh-1. The mechanistic reasoning is sound and well-articulated: ubh-1 as a UCH-family deubiquitinase maintains the free ubiquitin pool, supports UPS function, and its deNEDDylase activity regulates cullin-RING E3 ligases — all of which are plausible pro-longevity mechanisms through proteostasis maintenance. The reasoning is coherent and biologically grounded. Confidence of 0.72 is appropriate given the specificity of the gene. Minor note: the model draws on mammalian ortholog knowledge (UCHL1/UCHL3) which is reasonable but the direct C. elegans experimental evidence isn't explicitly cited, though the overall logic is solid.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}