BRE5
S. cerevisiae
Bre5p
What the model saw
Gene: BRE5 Organism: Saccharomyces cerevisiae Known functions: Bre5p. RNA binding. identical protein binding. mRNA binding. protein binding.
View unredacted entry
Bre5p. RNA binding. identical protein binding. mRNA binding. protein binding.
Solver output
BRE5 encodes a ubiquitin protease cofactor in S. cerevisiae that forms a complex with Ubp3p to deubiquitinate substrates involved in mRNA decapping and transport. Its RNA-binding and mRNA-binding activities reflect its role in regulating mRNA stability and translation, which are critical for proteostasis. The Ubp3-Bre5 deubiquitinase complex is known to regulate autophagy (specifically ribophagy) and stress granule dynamics; loss of BRE5 impairs selective autophagy pathways that clear damaged ribosomes and proteins, thereby compromising proteostasis maintenance. Proper proteostasis and selective autophagy are established pro-longevity mechanisms in yeast, suggesting BRE5's normal function supports longevity. The identical protein binding annotation is consistent with its known homodimerization required for cofactor activity.
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 BRE5's role in the Ubp3-Bre5 deubiquitinase complex and ribophagy is partially correct in terms of known biology, but the model incorrectly concluded that BRE5 supports longevity. In reality, BRE5 is anti-longevity, meaning its deletion extends lifespan. The model's logic that "proper proteostasis and selective autophagy are pro-longevity" led it astray - the Ubp3-Bre5 complex actually negatively regulates ribophagy, so deletion of BRE5 would enhance ribophagy and extend lifespan. The model had the mechanistic relationship backwards: it assumed BRE5 promotes autophagy when in fact it inhibits it (as a deubiquitinase that removes ubiquitin marks needed for selective autophagy). The confidence of 0.55 is relatively low but still committed to the wrong answer.
Raw API responses
solver
{
"reasoning": "BRE5 encodes a ubiquitin protease cofactor in S. cerevisiae that forms a complex with Ubp3p to deubiquitinate substrates involved in mRNA decapping and transport. Its RNA-binding and mRNA-binding activities reflect its role in regulating mRNA stability and translation, which are critical for proteostasis. The Ubp3-Bre5 deubiquitinase complex is known to regulate autophagy (specifically ribophagy) and stress granule dynamics; loss of BRE5 impairs selective autophagy pathways that clear damaged ribosomes and proteins, thereby compromising proteostasis maintenance. Proper proteostasis and selective autophagy are established pro-longevity mechanisms in yeast, suggesting BRE5's normal function supports longevity. The identical protein binding annotation is consistent with its known homodimerization required for cofactor activity.",
"confidence": 0.55,
"key_pathways": [
"Ubp3-Bre5 deubiquitinase complex / ribophagy",
"mRNA decapping and stability regulation",
"proteostasis via selective autophagy"
],
"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 BRE5's role in the Ubp3-Bre5 deubiquitinase complex and ribophagy is partially correct in terms of known biology, but the model incorrectly concluded that BRE5 supports longevity. In reality, BRE5 is anti-longevity, meaning its deletion extends lifespan. The model's logic that \"proper proteostasis and selective autophagy are pro-longevity\" led it astray - the Ubp3-Bre5 complex actually negatively regulates ribophagy, so deletion of BRE5 would enhance ribophagy and extend lifespan. The model had the mechanistic relationship backwards: it assumed BRE5 promotes autophagy when in fact it inhibits it (as a deubiquitinase that removes ubiquitin marks needed for selective autophagy). The confidence of 0.55 is relatively low but still committed to the wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}