rpn-11
C. elegans
26S proteasome non-ATPase regulatory subunit 14
What the model saw
Gene: rpn-11 Organism: Caenorhabditis elegans Known functions: 26S proteasome non-ATPase regulatory subunit 14. metal-dependent deubiquitinase activity. metallopeptidase activity. peptidase activity. proteasome binding. protein binding.
View unredacted entry
26S proteasome non-ATPase regulatory subunit 14. metal-dependent deubiquitinase activity. metallopeptidase activity. peptidase activity. proteasome binding. protein binding.
Solver output
rpn-11 encodes the 26S proteasome non-ATPase regulatory subunit 14 (PSMD14/POH1 ortholog), a metalloprotease-type deubiquitinase (DUB) that is an integral component of the 19S regulatory particle lid. Its metal-dependent deubiquitinase activity removes ubiquitin chains from substrates at the proteasome entry gate, a critical step that enables substrate unfolding and translocation into the 20S catalytic core for degradation. Proper rpn-11 function is therefore essential for efficient ubiquitin-proteasome system (UPS) activity and the clearance of misfolded, damaged, or aggregated proteins. Maintenance of proteostasis via robust proteasomal degradation is well-established as pro-longevity in C. elegans; loss of proteasome function accelerates aging and aggregation pathology, while enhanced proteasome activity extends lifespan. As a non-redundant, stoichiometric component of the 26S proteasome lid, rpn-11 activity directly sustains UPS flux and proteome 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 correctly predicted pro_longevity for rpn-11. The mechanistic reasoning is thorough and accurate: rpn-11 encodes the PSMD14/POH1 ortholog, a deubiquitinase in the 19S proteasome lid that is essential for UPS function and proteostasis. The model correctly identifies that proteasome function supports longevity in C. elegans and that rpn-11 is a non-redundant component of this system. The reasoning about loss of proteostasis as the mechanism class is appropriate. Confidence of 0.82 is well-calibrated.
Raw API responses
solver
{
"reasoning": "rpn-11 encodes the 26S proteasome non-ATPase regulatory subunit 14 (PSMD14/POH1 ortholog), a metalloprotease-type deubiquitinase (DUB) that is an integral component of the 19S regulatory particle lid. Its metal-dependent deubiquitinase activity removes ubiquitin chains from substrates at the proteasome entry gate, a critical step that enables substrate unfolding and translocation into the 20S catalytic core for degradation. Proper rpn-11 function is therefore essential for efficient ubiquitin-proteasome system (UPS) activity and the clearance of misfolded, damaged, or aggregated proteins. Maintenance of proteostasis via robust proteasomal degradation is well-established as pro-longevity in C. elegans; loss of proteasome function accelerates aging and aggregation pathology, while enhanced proteasome activity extends lifespan. As a non-redundant, stoichiometric component of the 26S proteasome lid, rpn-11 activity directly sustains UPS flux and proteome quality control.",
"confidence": 0.82,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"26S proteasome lid deubiquitination",
"proteostasis/protein quality control"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for rpn-11. The mechanistic reasoning is thorough and accurate: rpn-11 encodes the PSMD14/POH1 ortholog, a deubiquitinase in the 19S proteasome lid that is essential for UPS function and proteostasis. The model correctly identifies that proteasome function supports longevity in C. elegans and that rpn-11 is a non-redundant component of this system. The reasoning about loss of proteostasis as the mechanism class is appropriate. Confidence of 0.82 is well-calibrated.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}