nbr1
S. pombe
protein Nbr1
What the model saw
Gene: nbr1 Organism: Schizosaccharomyces pombe Known functions: protein Nbr1. cargo receptor activity. protein binding. zinc ion binding.
View unredacted entry
protein Nbr1. cargo receptor activity. protein binding. zinc ion binding.
Solver output
Nbr1 is a selective autophagy cargo receptor, orthologous to mammalian NBR1/p62, that recognizes ubiquitinated or otherwise tagged substrates and delivers them to the autophagosome for degradation. Its cargo receptor activity is central to selective autophagy (including aggrephagy and mitophagy), which is a key mechanism for maintaining proteostasis and clearing damaged organelles. In S. pombe, Nbr1 has been shown to function in nitrogen starvation-induced autophagy and proteaphagy. By facilitating efficient autophagic flux, Nbr1 supports the removal of misfolded proteins and damaged cellular components, processes that are strongly associated with lifespan extension. Loss of selective autophagy cargo receptors typically shortens lifespan, placing nbr1 in a pro-longevity role. The zinc ion binding likely supports structural integrity of its UBA or ZZ domain used in substrate recognition.
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 follows a logical but incorrect path: it assumes that because Nbr1 is a selective autophagy cargo receptor, its loss would shorten lifespan (making it pro-longevity). However, in S. pombe, nbr1 appears to have an anti-longevity role. This could be because Nbr1 in S. pombe may promote aging rather than prevent it, or its cargo receptor activity may facilitate processes that limit lifespan. The model's general reasoning about autophagy cargo receptors being pro-longevity is a reasonable prior, but it doesn't account for the specific biology of nbr1 in S. pombe where the gene appears to work against longevity. The confidence of 0.65 is somewhat appropriate given the uncertainty, but the direction of the prediction is wrong.
Raw API responses
solver
{
"reasoning": "Nbr1 is a selective autophagy cargo receptor, orthologous to mammalian NBR1/p62, that recognizes ubiquitinated or otherwise tagged substrates and delivers them to the autophagosome for degradation. Its cargo receptor activity is central to selective autophagy (including aggrephagy and mitophagy), which is a key mechanism for maintaining proteostasis and clearing damaged organelles. In S. pombe, Nbr1 has been shown to function in nitrogen starvation-induced autophagy and proteaphagy. By facilitating efficient autophagic flux, Nbr1 supports the removal of misfolded proteins and damaged cellular components, processes that are strongly associated with lifespan extension. Loss of selective autophagy cargo receptors typically shortens lifespan, placing nbr1 in a pro-longevity role. The zinc ion binding likely supports structural integrity of its UBA or ZZ domain used in substrate recognition.",
"confidence": 0.65,
"key_pathways": [
"selective autophagy / aggrephagy",
"proteostasis via autophagic flux",
"nitrogen starvation-induced autophagy"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning follows a logical but incorrect path: it assumes that because Nbr1 is a selective autophagy cargo receptor, its loss would shorten lifespan (making it pro-longevity). However, in S. pombe, nbr1 appears to have an anti-longevity role. This could be because Nbr1 in S. pombe may promote aging rather than prevent it, or its cargo receptor activity may facilitate processes that limit lifespan. The model's general reasoning about autophagy cargo receptors being pro-longevity is a reasonable prior, but it doesn't account for the specific biology of nbr1 in S. pombe where the gene appears to work against longevity. The confidence of 0.65 is somewhat appropriate given the uncertainty, but the direction of the prediction is wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}