UBC12
S. cerevisiae
NEDD8-conjugating protein UBC12
What the model saw
Gene: UBC12 Organism: Saccharomyces cerevisiae Known functions: NEDD8-conjugating protein UBC12. NEDD8 conjugating enzyme activity. NEDD8 transferase activity. protein binding. ubiquitin-like protein transferase activity.
View unredacted entry
NEDD8-conjugating protein UBC12. NEDD8 conjugating enzyme activity. NEDD8 transferase activity. protein binding. ubiquitin-like protein transferase activity.
Solver output
UBC12 is the dedicated E2 conjugating enzyme for the NEDD8 pathway (neddylation), responsible for transferring NEDD8 to cullin subunits of Cullin-RING E3 ubiquitin ligase (CRL) complexes. Neddylation of cullins activates CRL complexes, which are the largest family of E3 ubiquitin ligases and are essential for ubiquitin-mediated proteasomal degradation of a wide range of substrates including cell cycle regulators, damaged proteins, and stress-response factors. By enabling CRL-dependent proteolysis, UBC12 supports proteostasis and the timely clearance of misfolded or damaged proteins. Impaired neddylation leads to accumulation of CRL substrates, disrupted cell cycle progression, and proteotoxic stress — all of which are associated with accelerated aging. Thus, the normal function of UBC12 in activating CRL complexes via neddylation is expected to promote longevity by maintaining proteostasis.
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 about UBC12's role in neddylation and CRL activation is mechanistically plausible in general terms, but it drew the wrong conclusion about the longevity effect. In yeast, UBC12 (neddylation) appears to have an anti-longevity role, meaning its loss or reduction extends lifespan. The model assumed that supporting proteostasis via CRL activation would be pro-longevity, but failed to consider that neddylation/CRL activity may promote aging in yeast (e.g., by degrading pro-longevity factors or activating pathways that limit lifespan). The reasoning is coherent but leads to the wrong answer, and the confidence of 0.65 is somewhat high for an incorrect prediction.
Raw API responses
solver
{
"reasoning": "UBC12 is the dedicated E2 conjugating enzyme for the NEDD8 pathway (neddylation), responsible for transferring NEDD8 to cullin subunits of Cullin-RING E3 ubiquitin ligase (CRL) complexes. Neddylation of cullins activates CRL complexes, which are the largest family of E3 ubiquitin ligases and are essential for ubiquitin-mediated proteasomal degradation of a wide range of substrates including cell cycle regulators, damaged proteins, and stress-response factors. By enabling CRL-dependent proteolysis, UBC12 supports proteostasis and the timely clearance of misfolded or damaged proteins. Impaired neddylation leads to accumulation of CRL substrates, disrupted cell cycle progression, and proteotoxic stress — all of which are associated with accelerated aging. Thus, the normal function of UBC12 in activating CRL complexes via neddylation is expected to promote longevity by maintaining proteostasis.",
"confidence": 0.65,
"key_pathways": [
"NEDD8 conjugation / neddylation pathway",
"Cullin-RING E3 ubiquitin ligase (CRL) activation",
"ubiquitin-proteasome system (UPS) / proteostasis"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about UBC12's role in neddylation and CRL activation is mechanistically plausible in general terms, but it drew the wrong conclusion about the longevity effect. In yeast, UBC12 (neddylation) appears to have an anti-longevity role, meaning its loss or reduction extends lifespan. The model assumed that supporting proteostasis via CRL activation would be pro-longevity, but failed to consider that neddylation/CRL activity may promote aging in yeast (e.g., by degrading pro-longevity factors or activating pathways that limit lifespan). The reasoning is coherent but leads to the wrong answer, and the confidence of 0.65 is somewhat high for an incorrect prediction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}