f49c12.9
C. elegans
UBA domain-containing protein
What the model saw
Gene: F49C12.9 Organism: Caenorhabditis elegans Known functions: UBA domain-containing protein. polyubiquitin modification-dependent protein binding. protein binding.
View unredacted entry
UBA domain-containing protein. polyubiquitin modification-dependent protein binding. protein binding.
Solver output
F49C12.9 contains a UBA (ubiquitin-associated) domain, which is a well-characterized module that binds polyubiquitin chains, particularly K48-linked chains that serve as degradation signals. UBA domain-containing proteins typically act as ubiquitin receptors or shuttle factors that recognize polyubiquitinated substrates and deliver them to the 26S proteasome for degradation, thereby maintaining proteostasis. Efficient clearance of misfolded and damaged proteins via the ubiquitin-proteasome system (UPS) is a key determinant of longevity in C. elegans, as impaired proteostasis accelerates aging. By facilitating recognition and routing of polyubiquitinated cargo, this protein supports the UPS, which opposes the accumulation of proteotoxic aggregates — a hallmark of aging. Loss of such UBA shuttle factors in worms is associated with reduced proteasome activity and shortened lifespan, while enhanced UPS function is 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 about UBA domain proteins supporting proteostasis and being pro-longevity is plausible in general, but it got the direction wrong for this specific gene. The model assumed that a UBA domain protein would support the UPS and thus be pro-longevity, but F49C12.9 is actually anti-longevity, meaning its loss likely extends lifespan. This could be because the protein competes with or inhibits proteasomal degradation, or acts in a pathway that promotes aging rather than opposing it. The model's confidence of 0.62 is moderate but still committed to the wrong answer. The mechanistic reasoning, while internally consistent, led to the wrong conclusion about the direction of effect.
Raw API responses
solver
{
"reasoning": "F49C12.9 contains a UBA (ubiquitin-associated) domain, which is a well-characterized module that binds polyubiquitin chains, particularly K48-linked chains that serve as degradation signals. UBA domain-containing proteins typically act as ubiquitin receptors or shuttle factors that recognize polyubiquitinated substrates and deliver them to the 26S proteasome for degradation, thereby maintaining proteostasis. Efficient clearance of misfolded and damaged proteins via the ubiquitin-proteasome system (UPS) is a key determinant of longevity in C. elegans, as impaired proteostasis accelerates aging. By facilitating recognition and routing of polyubiquitinated cargo, this protein supports the UPS, which opposes the accumulation of proteotoxic aggregates — a hallmark of aging. Loss of such UBA shuttle factors in worms is associated with reduced proteasome activity and shortened lifespan, while enhanced UPS function is pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"polyubiquitin chain recognition and substrate shuttling",
"proteostasis maintenance"
],
"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 about UBA domain proteins supporting proteostasis and being pro-longevity is plausible in general, but it got the direction wrong for this specific gene. The model assumed that a UBA domain protein would support the UPS and thus be pro-longevity, but F49C12.9 is actually anti-longevity, meaning its loss likely extends lifespan. This could be because the protein competes with or inhibits proteasomal degradation, or acts in a pathway that promotes aging rather than opposing it. The model's confidence of 0.62 is moderate but still committed to the wrong answer. The mechanistic reasoning, while internally consistent, led to the wrong conclusion about the direction of effect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}