hsp-4
C. elegans
Endoplasmic reticulum chaperone BiP homolog;Heat shock 70 kDa protein D
What the model saw
Gene: hsp-4 Organism: Caenorhabditis elegans Known functions: Endoplasmic reticulum chaperone BiP homolog;Heat shock 70 kDa protein D. ATP binding. ATP hydrolysis activity. RNA polymerase II-specific DNA-binding transcription factor binding. heat shock protein binding. protein folding chaperone.
View unredacted entry
Endoplasmic reticulum chaperone BiP homolog;Heat shock 70 kDa protein D. ATP binding. ATP hydrolysis activity. RNA polymerase II-specific DNA-binding transcription factor binding. heat shock protein binding. protein folding chaperone.
Solver output
hsp-4 encodes the C. elegans homolog of BiP (GRP78/HSPA5), the master ER luminal chaperone that drives the unfolded protein response (UPR-ER). By binding misfolded or unfolded client proteins in the ER lumen via its ATPase-coupled substrate-binding domain, HSP-4/BiP prevents ER stress-induced proteotoxicity and maintains ER proteostasis. Activation of the UPR-ER through hsp-4 upregulation is well-documented to extend lifespan in C. elegans, as it reduces the accumulation of misfolded proteins that would otherwise trigger chronic ER stress and cell death. Its ATP hydrolysis activity drives iterative chaperone cycles essential for proper protein folding, directly countering the age-associated collapse of proteostasis. Additionally, its interaction with transcription factors (e.g., ATF6/XBP-1 pathway components) links it to transcriptional reprogramming that supports cellular stress resistance and longevity.
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 hsp-4 in C. elegans. The mechanistic reasoning is thorough and accurate: hsp-4 encodes the BiP/GRP78 ER chaperone, its role in UPR-ER and proteostasis maintenance is well-described, and the connection to XBP-1/ATF6 pathways and lifespan extension is appropriate. Confidence of 0.75 is reasonable. No significant errors in reasoning or mechanism.
Raw API responses
solver
{
"reasoning": "hsp-4 encodes the C. elegans homolog of BiP (GRP78/HSPA5), the master ER luminal chaperone that drives the unfolded protein response (UPR-ER). By binding misfolded or unfolded client proteins in the ER lumen via its ATPase-coupled substrate-binding domain, HSP-4/BiP prevents ER stress-induced proteotoxicity and maintains ER proteostasis. Activation of the UPR-ER through hsp-4 upregulation is well-documented to extend lifespan in C. elegans, as it reduces the accumulation of misfolded proteins that would otherwise trigger chronic ER stress and cell death. Its ATP hydrolysis activity drives iterative chaperone cycles essential for proper protein folding, directly countering the age-associated collapse of proteostasis. Additionally, its interaction with transcription factors (e.g., ATF6/XBP-1 pathway components) links it to transcriptional reprogramming that supports cellular stress resistance and longevity.",
"confidence": 0.75,
"key_pathways": [
"ER unfolded protein response (UPR-ER)",
"ER proteostasis / chaperone network",
"XBP-1/ATF6 transcriptional stress response"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for hsp-4 in C. elegans. The mechanistic reasoning is thorough and accurate: hsp-4 encodes the BiP/GRP78 ER chaperone, its role in UPR-ER and proteostasis maintenance is well-described, and the connection to XBP-1/ATF6 pathways and lifespan extension is appropriate. Confidence of 0.75 is reasonable. No significant errors in reasoning or mechanism.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}