ire-1
C. elegans
Serine/threonine-protein kinase;non-specific serine/threonine protein kinase
What the model saw
Gene: ire-1 Organism: Caenorhabditis elegans Known functions: Serine/threonine-protein kinase;non-specific serine/threonine protein kinase. ATP binding. RNA endonuclease activity. RNA nuclease activity. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. unfolded protein binding.
View unredacted entry
Serine/threonine-protein kinase;non-specific serine/threonine protein kinase. ATP binding. RNA endonuclease activity. RNA nuclease activity. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity. unfolded protein binding.
Solver output
IRE-1 is the C. elegans ortholog of the conserved IRE1 kinase/endonuclease, which serves as the primary sensor and transducer of the Unfolded Protein Response (UPR) in the endoplasmic reticulum. Its dual enzymatic activities — serine/threonine kinase (autophosphorylation for activation) and RNA endonuclease (unconventional splicing of xbp-1 mRNA) — are central to restoring ER proteostasis under stress. By splicing xbp-1 mRNA to produce the active XBP-1 transcription factor, IRE-1 upregulates ER chaperones and ERAD components, reducing the burden of misfolded proteins. In C. elegans, the IRE-1/XBP-1 branch of the UPR is well-established to promote longevity, particularly in the context of dietary restriction and proteotoxic stress; loss of ire-1 shortens lifespan and impairs stress resistance. Additionally, IRE-1's unfolded protein binding activity directly couples ER stress sensing to adaptive transcriptional responses, maintaining proteome integrity across aging.
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 pro_longevity for ire-1 in C. elegans. The mechanistic reasoning is excellent and accurate: IRE-1 is indeed the conserved IRE1 kinase/endonuclease that serves as the primary UPR sensor, splices xbp-1 mRNA to produce active XBP-1 transcription factor, and promotes longevity through ER proteostasis maintenance. The model correctly notes that loss of ire-1 shortens lifespan. The confidence level of 0.78 is appropriate given the well-established literature on this pathway. All key pathways identified are relevant and correct.
Raw API responses
solver
{
"reasoning": "IRE-1 is the C. elegans ortholog of the conserved IRE1 kinase/endonuclease, which serves as the primary sensor and transducer of the Unfolded Protein Response (UPR) in the endoplasmic reticulum. Its dual enzymatic activities — serine/threonine kinase (autophosphorylation for activation) and RNA endonuclease (unconventional splicing of xbp-1 mRNA) — are central to restoring ER proteostasis under stress. By splicing xbp-1 mRNA to produce the active XBP-1 transcription factor, IRE-1 upregulates ER chaperones and ERAD components, reducing the burden of misfolded proteins. In C. elegans, the IRE-1/XBP-1 branch of the UPR is well-established to promote longevity, particularly in the context of dietary restriction and proteotoxic stress; loss of ire-1 shortens lifespan and impairs stress resistance. Additionally, IRE-1's unfolded protein binding activity directly couples ER stress sensing to adaptive transcriptional responses, maintaining proteome integrity across aging.",
"confidence": 0.78,
"key_pathways": [
"Unfolded Protein Response (UPR) / IRE-1–XBP-1 axis",
"ER proteostasis and ERAD",
"Stress-responsive transcriptional regulation"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for ire-1 in C. elegans. The mechanistic reasoning is excellent and accurate: IRE-1 is indeed the conserved IRE1 kinase/endonuclease that serves as the primary UPR sensor, splices xbp-1 mRNA to produce active XBP-1 transcription factor, and promotes longevity through ER proteostasis maintenance. The model correctly notes that loss of ire-1 shortens lifespan. The confidence level of 0.78 is appropriate given the well-established literature on this pathway. All key pathways identified are relevant and correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}