DNF1
S. cerevisiae
aminophospholipid-translocating P4-type ATPase DNF1
What the model saw
Gene: DNF1 Organism: Saccharomyces cerevisiae Known functions: aminophospholipid-translocating P4-type ATPase DNF1. ATP binding. ATP hydrolysis activity. ATPase-coupled intramembrane lipid carrier activity. glycosylceramide flippase activity. identical protein binding. magnesium ion binding. nucleotide binding. phosphatidylcholine flippase activity. phosphatidylcholine floppase activity. phosphatidylethanolamine flippase activity. phosphatidylserine flippase activity. phosphatidylserine floppase activity. protein binding.
View unredacted entry
aminophospholipid-translocating P4-type ATPase DNF1. ATP binding. ATP hydrolysis activity. ATPase-coupled intramembrane lipid carrier activity. glycosylceramide flippase activity. identical protein binding. magnesium ion binding. nucleotide binding. phosphatidylcholine flippase activity. phosphatidylcholine floppase activity. phosphatidylethanolamine flippase activity. phosphatidylserine flippase activity. phosphatidylserine floppase activity. protein binding.
Solver output
DNF1 encodes a P4-type ATPase (flippase) that actively translocates aminophospholipids—particularly phosphatidylserine (PS) and phosphatidylethanolamine (PE)—from the outer to the inner leaflet of the plasma membrane, maintaining membrane phospholipid asymmetry. This asymmetry is critical for proper cellular signaling, vesicle trafficking, and suppression of apoptotic "eat-me" signals (PS externalization). Loss of flippase activity leads to PS exposure on the outer leaflet, which triggers premature apoptotic signaling and disrupts membrane-dependent processes including TORC2 signaling and sphingolipid homeostasis. Proper phospholipid asymmetry also supports autophagosome biogenesis and mitophagy, processes that are pro-longevity. Additionally, glycosylceramide flippase activity links DNF1 to sphingolipid metabolism, which is connected to chronological and replicative lifespan regulation in yeast. Therefore, the normal function of DNF1 in maintaining membrane asymmetry and lipid homeostasis is expected to be 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that DNF1's flippase activity is beneficial for longevity by maintaining membrane asymmetry and suppressing apoptotic signals. However, DNF1 is actually anti-longevity in yeast, meaning its deletion or loss extends lifespan. The mechanistic reasoning is plausible in isolation but leads to the wrong conclusion. The model was moderately confident (0.65) in an incorrect answer. The mechanism class of "altered_intercellular_communication" is also questionable for a lipid flippase whose primary role is intracellular membrane asymmetry maintenance.
Raw API responses
solver
{
"reasoning": "DNF1 encodes a P4-type ATPase (flippase) that actively translocates aminophospholipids—particularly phosphatidylserine (PS) and phosphatidylethanolamine (PE)—from the outer to the inner leaflet of the plasma membrane, maintaining membrane phospholipid asymmetry. This asymmetry is critical for proper cellular signaling, vesicle trafficking, and suppression of apoptotic \"eat-me\" signals (PS externalization). Loss of flippase activity leads to PS exposure on the outer leaflet, which triggers premature apoptotic signaling and disrupts membrane-dependent processes including TORC2 signaling and sphingolipid homeostasis. Proper phospholipid asymmetry also supports autophagosome biogenesis and mitophagy, processes that are pro-longevity. Additionally, glycosylceramide flippase activity links DNF1 to sphingolipid metabolism, which is connected to chronological and replicative lifespan regulation in yeast. Therefore, the normal function of DNF1 in maintaining membrane asymmetry and lipid homeostasis is expected to be pro-longevity.",
"confidence": 0.65,
"key_pathways": [
"phospholipid asymmetry maintenance / aminophospholipid translocation",
"sphingolipid/glycosylceramide homeostasis",
"apoptotic signal suppression via PS asymmetry"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that DNF1's flippase activity is beneficial for longevity by maintaining membrane asymmetry and suppressing apoptotic signals. However, DNF1 is actually anti-longevity in yeast, meaning its deletion or loss extends lifespan. The mechanistic reasoning is plausible in isolation but leads to the wrong conclusion. The model was moderately confident (0.65) in an incorrect answer. The mechanism class of \"altered_intercellular_communication\" is also questionable for a lipid flippase whose primary role is intracellular membrane asymmetry maintenance.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}