ari-2
C. elegans
putative E3 ubiquitin-protein ligase ariadne-2
What the model saw
Gene: ari-2 Organism: Caenorhabditis elegans Known functions: putative E3 ubiquitin-protein ligase ariadne-2. ubiquitin conjugating enzyme binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
View unredacted entry
putative E3 ubiquitin-protein ligase ariadne-2. ubiquitin conjugating enzyme binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
Solver output
ari-2 encodes a putative E3 ubiquitin-protein ligase of the Ariadne/RBR (RING-between-RING) family, which functions in ubiquitin-mediated protein degradation by catalyzing ubiquitin transfer to substrate proteins via ubiquitin conjugating enzyme (E2) binding. Proper E3 ligase activity is essential for maintaining proteostasis by targeting misfolded, damaged, or regulatory proteins for proteasomal degradation. The Ariadne family of RBR E3 ligases in particular has been linked to mitochondrial quality control and regulation of protein homeostasis networks. Loss of such E3 ligase activity typically leads to accumulation of aberrant proteins and proteotoxic stress, a hallmark of aging. Therefore, the normal function of ari-2 in facilitating ubiquitin-mediated proteolysis is expected to support proteostasis and promote 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that E3 ubiquitin ligases generally promote longevity by maintaining proteostasis, but ari-2 is actually anti-longevity, meaning its loss (or reduction) extends lifespan. The model's generic reasoning about E3 ligases and proteostasis is plausible in principle but leads to the wrong conclusion here. The model had moderate confidence (0.62) but was still wrong. The mechanistic reasoning is also incorrect in the context of this specific gene's role in longevity.
Raw API responses
solver
{
"reasoning": "ari-2 encodes a putative E3 ubiquitin-protein ligase of the Ariadne/RBR (RING-between-RING) family, which functions in ubiquitin-mediated protein degradation by catalyzing ubiquitin transfer to substrate proteins via ubiquitin conjugating enzyme (E2) binding. Proper E3 ligase activity is essential for maintaining proteostasis by targeting misfolded, damaged, or regulatory proteins for proteasomal degradation. The Ariadne family of RBR E3 ligases in particular has been linked to mitochondrial quality control and regulation of protein homeostasis networks. Loss of such E3 ligase activity typically leads to accumulation of aberrant proteins and proteotoxic stress, a hallmark of aging. Therefore, the normal function of ari-2 in facilitating ubiquitin-mediated proteolysis is expected to support proteostasis and promote longevity.",
"confidence": 0.62,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"RBR E3 ligase-mediated protein quality control",
"mitochondrial protein homeostasis"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that E3 ubiquitin ligases generally promote longevity by maintaining proteostasis, but ari-2 is actually anti-longevity, meaning its loss (or reduction) extends lifespan. The model's generic reasoning about E3 ligases and proteostasis is plausible in principle but leads to the wrong conclusion here. The model had moderate confidence (0.62) but was still wrong. The mechanistic reasoning is also incorrect in the context of this specific gene's role in longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}