UBX2
S. cerevisiae
Ubx2p
What the model saw
Gene: UBX2 Organism: Saccharomyces cerevisiae Known functions: Ubx2p. protein binding. protein-macromolecule adaptor activity. ubiquitin binding.
View unredacted entry
Ubx2p. protein binding. protein-macromolecule adaptor activity. ubiquitin binding.
Solver output
UBX2 (Ubx2p) is a UBX-domain containing adaptor protein in S. cerevisiae that bridges ubiquitinated substrates to the Cdc48/p97 AAA-ATPase complex, a central hub for ER-associated degradation (ERAD) and protein quality control. Its ubiquitin-binding and protein-macromolecule adaptor activities position it as a key facilitator of the extraction and degradation of misfolded or damaged proteins from the ER membrane. By promoting efficient clearance of proteotoxic species through the ubiquitin-proteasome system, UBX2 supports proteostasis, which is a well-established pro-longevity mechanism. Loss of ERAD components in yeast is associated with accumulation of misfolded proteins and reduced replicative lifespan. Therefore, the normal function of UBX2 is expected to promote longevity by maintaining protein quality control.
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 UBX2's role in ERAD and protein quality control is plausible on the surface, but it reaches the wrong conclusion. In yeast, deletion of UBX2 has been shown to extend lifespan, meaning UBX2 normally acts against longevity (anti_longevity). The model incorrectly assumed that because UBX2 supports proteostasis via ERAD, it must be pro-longevity. However, the actual experimental data shows the opposite — loss of UBX2 extends lifespan, making it anti_longevity. The mechanistic reasoning, while coherent, is also incorrect in its conclusion about the direction of effect. The model was moderately confident (0.65) in the wrong direction.
Raw API responses
solver
{
"reasoning": "UBX2 (Ubx2p) is a UBX-domain containing adaptor protein in S. cerevisiae that bridges ubiquitinated substrates to the Cdc48/p97 AAA-ATPase complex, a central hub for ER-associated degradation (ERAD) and protein quality control. Its ubiquitin-binding and protein-macromolecule adaptor activities position it as a key facilitator of the extraction and degradation of misfolded or damaged proteins from the ER membrane. By promoting efficient clearance of proteotoxic species through the ubiquitin-proteasome system, UBX2 supports proteostasis, which is a well-established pro-longevity mechanism. Loss of ERAD components in yeast is associated with accumulation of misfolded proteins and reduced replicative lifespan. Therefore, the normal function of UBX2 is expected to promote longevity by maintaining protein quality control.",
"confidence": 0.65,
"key_pathways": [
"ERAD (ER-associated degradation)",
"Cdc48/p97-mediated protein quality control",
"ubiquitin-proteasome system"
],
"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 UBX2's role in ERAD and protein quality control is plausible on the surface, but it reaches the wrong conclusion. In yeast, deletion of UBX2 has been shown to extend lifespan, meaning UBX2 normally acts against longevity (anti_longevity). The model incorrectly assumed that because UBX2 supports proteostasis via ERAD, it must be pro-longevity. However, the actual experimental data shows the opposite — loss of UBX2 extends lifespan, making it anti_longevity. The mechanistic reasoning, while coherent, is also incorrect in its conclusion about the direction of effect. The model was moderately confident (0.65) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}