park
D. melanogaster
parkin
What the model saw
Gene: park Organism: Drosophila melanogaster Known functions: parkin. protein binding. ubiquitin conjugating enzyme binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
View unredacted entry
parkin. protein binding. ubiquitin conjugating enzyme binding. ubiquitin protein ligase activity. ubiquitin-protein transferase activity. zinc ion binding.
Solver output
Park (Drosophila parkin) is an E3 ubiquitin-protein ligase that is the central effector of PINK1/Parkin-mediated mitophagy, the selective autophagic clearance of damaged mitochondria. By ubiquitinating outer mitochondrial membrane proteins (e.g., Mfn/Marf, VDAC), Parkin targets dysfunctional mitochondria for degradation, thereby maintaining a healthy mitochondrial pool and preventing accumulation of ROS-generating, depolarized organelles. Loss of park in Drosophila leads to mitochondrial dysfunction, muscle degeneration, and reduced lifespan, while its normal function suppresses age-associated mitochondrial deterioration. This places park squarely within the mitochondrial quality-control axis of the mitochondrial dysfunction hallmark of aging. Its ubiquitin ligase and zinc-binding (RING domain) activities are the molecular basis for substrate recognition and ubiquitin transfer in this pathway.
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 Drosophila park (parkin). The mechanistic reasoning is excellent and accurate: park encodes an E3 ubiquitin-protein ligase that functions in PINK1/Parkin-mediated mitophagy, maintaining mitochondrial quality. Loss of park leads to mitochondrial dysfunction and reduced lifespan, while normal function is pro-longevity. The model correctly identifies the RING domain zinc-binding activity as the molecular basis for ubiquitin transfer, and correctly names key substrates (Mfn/Marf, VDAC). The confidence level of 0.82 is appropriate given the well-established literature on this gene.
Raw API responses
solver
{
"reasoning": "Park (Drosophila parkin) is an E3 ubiquitin-protein ligase that is the central effector of PINK1/Parkin-mediated mitophagy, the selective autophagic clearance of damaged mitochondria. By ubiquitinating outer mitochondrial membrane proteins (e.g., Mfn/Marf, VDAC), Parkin targets dysfunctional mitochondria for degradation, thereby maintaining a healthy mitochondrial pool and preventing accumulation of ROS-generating, depolarized organelles. Loss of park in Drosophila leads to mitochondrial dysfunction, muscle degeneration, and reduced lifespan, while its normal function suppresses age-associated mitochondrial deterioration. This places park squarely within the mitochondrial quality-control axis of the mitochondrial dysfunction hallmark of aging. Its ubiquitin ligase and zinc-binding (RING domain) activities are the molecular basis for substrate recognition and ubiquitin transfer in this pathway.",
"confidence": 0.82,
"key_pathways": [
"PINK1/Parkin mitophagy",
"ubiquitin-proteasome system",
"mitochondrial quality control"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Drosophila park (parkin). The mechanistic reasoning is excellent and accurate: park encodes an E3 ubiquitin-protein ligase that functions in PINK1/Parkin-mediated mitophagy, maintaining mitochondrial quality. Loss of park leads to mitochondrial dysfunction and reduced lifespan, while normal function is pro-longevity. The model correctly identifies the RING domain zinc-binding activity as the molecular basis for ubiquitin transfer, and correctly names key substrates (Mfn/Marf, VDAC). The confidence level of 0.82 is appropriate given the well-established literature on this gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}