rpt-1
C. elegans
26S proteasome regulatory subunit 7
What the model saw
Gene: rpt-1 Organism: Caenorhabditis elegans Known functions: 26S proteasome regulatory subunit 7. ATP binding. ATP hydrolysis activity. proteasome-activating activity. protein binding.
View unredacted entry
26S proteasome regulatory subunit 7. ATP binding. ATP hydrolysis activity. proteasome-activating activity. protein binding.
Solver output
RPT-1 is the C. elegans ortholog of the 26S proteasome AAA-ATPase regulatory subunit (Rpt2/PSMC1 family), which forms the base of the 19S regulatory particle. Its ATP hydrolysis and proteasome-activating activities are essential for unfolding and translocating ubiquitinated substrates into the 20S core for degradation. Robust 26S proteasome function is a central pillar of proteostasis maintenance; reduced proteasome activity leads to accumulation of damaged, misfolded, and aggregated proteins—a hallmark of aging. In C. elegans, proteasome activity declines with age, and genetic or pharmacological enhancement of proteasome function extends lifespan, while knockdown of 19S ATPase subunits accelerates proteotoxic stress and shortens lifespan. Therefore, the normal function of rpt-1 supports proteostasis and opposes aging-associated protein aggregation, classifying it as pro-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 rpt-1 in C. elegans. The mechanistic reasoning is thorough and accurate: RPT-1 is indeed a 19S regulatory particle AAA-ATPase subunit essential for 26S proteasome function, proteasome activity declines with age in C. elegans, and maintaining proteostasis through the UPS is well-established as pro-longevity. The model correctly identified that knockdown of 19S ATPase subunits would impair proteostasis and shorten lifespan, while normal function supports longevity. High confidence (0.82) is appropriate given the well-established role of proteasome function in aging.
Raw API responses
solver
{
"reasoning": "RPT-1 is the C. elegans ortholog of the 26S proteasome AAA-ATPase regulatory subunit (Rpt2/PSMC1 family), which forms the base of the 19S regulatory particle. Its ATP hydrolysis and proteasome-activating activities are essential for unfolding and translocating ubiquitinated substrates into the 20S core for degradation. Robust 26S proteasome function is a central pillar of proteostasis maintenance; reduced proteasome activity leads to accumulation of damaged, misfolded, and aggregated proteins—a hallmark of aging. In C. elegans, proteasome activity declines with age, and genetic or pharmacological enhancement of proteasome function extends lifespan, while knockdown of 19S ATPase subunits accelerates proteotoxic stress and shortens lifespan. Therefore, the normal function of rpt-1 supports proteostasis and opposes aging-associated protein aggregation, classifying it as pro-longevity.",
"confidence": 0.82,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"26S proteasome assembly and activation",
"proteostasis maintenance"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for rpt-1 in C. elegans. The mechanistic reasoning is thorough and accurate: RPT-1 is indeed a 19S regulatory particle AAA-ATPase subunit essential for 26S proteasome function, proteasome activity declines with age in C. elegans, and maintaining proteostasis through the UPS is well-established as pro-longevity. The model correctly identified that knockdown of 19S ATPase subunits would impair proteostasis and shorten lifespan, while normal function supports longevity. High confidence (0.82) is appropriate given the well-established role of proteasome function in aging.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}