elc-1
C. elegans
Elongin-C
What the model saw
Gene: elc-1 Organism: Caenorhabditis elegans Known functions: Elongin-C. protein binding. protein domain specific binding. protein-macromolecule adaptor activity.
View unredacted entry
Elongin-C. protein binding. protein domain specific binding. protein-macromolecule adaptor activity.
Solver output
Elongin-C (ELC-1) is a core component of the Cullin-RING E3 ubiquitin ligase (CRL) complex, where it acts as an adaptor bridging substrate-recognition subunits (via protein domain-specific binding) to Cullin scaffolds. In C. elegans, ELC-1 participates in the ECS (Elongin B/C–Cullin–SOCS-box) complex that targets specific substrates for ubiquitin-mediated proteasomal degradation. One well-characterized role is in the degradation of HIF-1 (hypoxia-inducible factor), the C. elegans homolog of mammalian HIF-1α, under normoxic conditions. Since HIF-1 activity is generally anti-longevity in C. elegans (its reduction extends lifespan in some contexts), ELC-1-mediated degradation of HIF-1 would promote longevity. Additionally, CRL-mediated proteostasis supports removal of damaged or misfolded proteins, aligning with maintenance of protein quality control. The adaptor/scaffolding role of ELC-1 in ubiquitin ligase complexes thus broadly supports proteostasis and regulated protein turnover, which are pro-longevity functions.
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 about ELC-1/Elongin-C degrading HIF-1 to promote longevity is plausible in isolation, but it gets the direction wrong. In C. elegans, HIF-1 has complex roles - it can be pro-longevity in certain contexts (e.g., under hypoxia or in daf-2 mutants). More importantly, ELC-1 as an anti-longevity gene suggests that its loss (reducing ubiquitin-mediated degradation of certain substrates) extends lifespan, meaning ELC-1 activity normally shortens lifespan. The model's reasoning selectively focuses on HIF-1 degradation as pro-longevity without considering that ELC-1 may target pro-longevity factors for degradation. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanistic interpretation. The reasoning quality is poor because it cherry-picks one substrate (HIF-1) while ignoring that ELC-1 could degrade pro-longevity proteins, and mischaracterizes HIF-1's role in C. elegans longevity.
Raw API responses
solver
{
"reasoning": "Elongin-C (ELC-1) is a core component of the Cullin-RING E3 ubiquitin ligase (CRL) complex, where it acts as an adaptor bridging substrate-recognition subunits (via protein domain-specific binding) to Cullin scaffolds. In C. elegans, ELC-1 participates in the ECS (Elongin B/C–Cullin–SOCS-box) complex that targets specific substrates for ubiquitin-mediated proteasomal degradation. One well-characterized role is in the degradation of HIF-1 (hypoxia-inducible factor), the C. elegans homolog of mammalian HIF-1α, under normoxic conditions. Since HIF-1 activity is generally anti-longevity in C. elegans (its reduction extends lifespan in some contexts), ELC-1-mediated degradation of HIF-1 would promote longevity. Additionally, CRL-mediated proteostasis supports removal of damaged or misfolded proteins, aligning with maintenance of protein quality control. The adaptor/scaffolding role of ELC-1 in ubiquitin ligase complexes thus broadly supports proteostasis and regulated protein turnover, which are pro-longevity functions.",
"confidence": 0.62,
"key_pathways": [
"ECS/CRL E3 ubiquitin ligase complex",
"HIF-1 degradation pathway",
"ubiquitin-proteasome proteostasis"
],
"mechanism_class": "cellular_senescence",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ELC-1/Elongin-C degrading HIF-1 to promote longevity is plausible in isolation, but it gets the direction wrong. In C. elegans, HIF-1 has complex roles - it can be pro-longevity in certain contexts (e.g., under hypoxia or in daf-2 mutants). More importantly, ELC-1 as an anti-longevity gene suggests that its loss (reducing ubiquitin-mediated degradation of certain substrates) extends lifespan, meaning ELC-1 activity normally shortens lifespan. The model's reasoning selectively focuses on HIF-1 degradation as pro-longevity without considering that ELC-1 may target pro-longevity factors for degradation. The model had moderate confidence (0.62) but was still wrong on both the answer and the mechanistic interpretation. The reasoning quality is poor because it cherry-picks one substrate (HIF-1) while ignoring that ELC-1 could degrade pro-longevity proteins, and mischaracterizes HIF-1's role in C. elegans longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}