UBR2
S. cerevisiae
putative ubiquitin-protein ligase UBR2
What the model saw
Gene: UBR2 Organism: Saccharomyces cerevisiae Known functions: putative ubiquitin-protein ligase UBR2. protein binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
View unredacted entry
putative ubiquitin-protein ligase UBR2. protein binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
Solver output
UBR2 encodes an E3 ubiquitin-protein ligase belonging to the N-end rule pathway (N-recognin family), which targets substrates bearing destabilizing N-terminal residues for proteasomal degradation. While ubiquitin-mediated proteolysis is generally essential for proteostasis, UBR-family E3 ligases in the N-end rule pathway have been shown to degrade short-lived regulatory proteins and can promote degradation of pro-longevity factors. In yeast, hyperactive protein ubiquitylation via N-end rule E3s can reduce the stability of stress-response or autophagy-related regulators, thereby impairing the cell's ability to maintain proteostatic balance under stress. Loss of UBR2 function in yeast has been associated with extended chronological or replicative lifespan in some contexts, consistent with its normal role being anti-longevity. The zinc ion binding activity supports the RING/RING-like domain architecture required for E3 ligase catalysis, reinforcing its role as an active ubiquitylation enzyme rather than a scaffold.
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 UBR2 in S. cerevisiae. The mechanistic reasoning about UBR2 as an N-end rule E3 ubiquitin ligase is plausible and generally correct in terms of its biochemical function. However, the reasoning is somewhat speculative - the model says "has been associated with extended lifespan in some contexts" without citing specific evidence, and the mechanism by which UBR2 acts as anti-longevity (degrading pro-longevity factors) is reasonable but not definitively established. The confidence of 0.62 is appropriately moderate. Overall the answer is correct with reasonable mechanistic reasoning, though the specific details about how UBR2 deletion extends lifespan are somewhat vague.
Raw API responses
solver
{
"reasoning": "UBR2 encodes an E3 ubiquitin-protein ligase belonging to the N-end rule pathway (N-recognin family), which targets substrates bearing destabilizing N-terminal residues for proteasomal degradation. While ubiquitin-mediated proteolysis is generally essential for proteostasis, UBR-family E3 ligases in the N-end rule pathway have been shown to degrade short-lived regulatory proteins and can promote degradation of pro-longevity factors. In yeast, hyperactive protein ubiquitylation via N-end rule E3s can reduce the stability of stress-response or autophagy-related regulators, thereby impairing the cell's ability to maintain proteostatic balance under stress. Loss of UBR2 function in yeast has been associated with extended chronological or replicative lifespan in some contexts, consistent with its normal role being anti-longevity. The zinc ion binding activity supports the RING/RING-like domain architecture required for E3 ligase catalysis, reinforcing its role as an active ubiquitylation enzyme rather than a scaffold.",
"confidence": 0.62,
"key_pathways": [
"N-end rule ubiquitin-proteasome pathway",
"protein ubiquitylation and degradation",
"proteostasis regulation"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for UBR2 in S. cerevisiae. The mechanistic reasoning about UBR2 as an N-end rule E3 ubiquitin ligase is plausible and generally correct in terms of its biochemical function. However, the reasoning is somewhat speculative - the model says \"has been associated with extended lifespan in some contexts\" without citing specific evidence, and the mechanism by which UBR2 acts as anti-longevity (degrading pro-longevity factors) is reasonable but not definitively established. The confidence of 0.62 is appropriately moderate. Overall the answer is correct with reasonable mechanistic reasoning, though the specific details about how UBR2 deletion extends lifespan are somewhat vague.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}