ufd-1
C. elegans
Ubiquitin fusion degradation protein 1 homolog
What the model saw
Gene: ufd-1 Organism: Caenorhabditis elegans Known functions: Ubiquitin fusion degradation protein 1 homolog. polyubiquitin modification-dependent protein binding. protein binding. protein-containing complex binding.
View unredacted entry
Ubiquitin fusion degradation protein 1 homolog. polyubiquitin modification-dependent protein binding. protein binding. protein-containing complex binding.
Solver output
UFD-1 is a core component of the CDC48/p97-UFD1-NPL4 complex, which recognizes polyubiquitinated substrates and extracts them for proteasomal degradation via the ubiquitin fusion degradation (UFD) pathway. Its polyubiquitin modification-dependent protein binding activity is essential for targeting misfolded or damaged proteins to the 26S proteasome, thereby maintaining proteostasis. In C. elegans, robust proteasomal clearance of damaged proteins is a well-established pro-longevity mechanism, as it prevents toxic protein aggregation associated with aging. Loss of UFD-1 function impairs ubiquitin-dependent protein quality control, leading to accumulation of aberrant proteins—a hallmark of cellular aging. The CDC48/p97 complex also participates in ER-associated degradation (ERAD) and mitochondrial protein quality control, further linking UFD-1 to multiple proteostasis axes relevant to 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 correctly predicted pro_longevity for ufd-1 in C. elegans. The mechanistic reasoning is sound and well-grounded: UFD-1 as part of the CDC48/p97-UFD1-NPL4 complex is indeed involved in ubiquitin-dependent protein quality control, and the connection to proteostasis and longevity in C. elegans is well-established. The model appropriately tied loss of UFD-1 function to impaired protein clearance and aging. Confidence of 0.65 is reasonable given the specificity of the gene. The reasoning is detailed and biologically accurate, though it is somewhat generic in that it doesn't cite specific C. elegans experimental evidence (e.g., RNAi knockdown lifespan studies), which would have strengthened the case further.
Raw API responses
solver
{
"reasoning": "UFD-1 is a core component of the CDC48/p97-UFD1-NPL4 complex, which recognizes polyubiquitinated substrates and extracts them for proteasomal degradation via the ubiquitin fusion degradation (UFD) pathway. Its polyubiquitin modification-dependent protein binding activity is essential for targeting misfolded or damaged proteins to the 26S proteasome, thereby maintaining proteostasis. In C. elegans, robust proteasomal clearance of damaged proteins is a well-established pro-longevity mechanism, as it prevents toxic protein aggregation associated with aging. Loss of UFD-1 function impairs ubiquitin-dependent protein quality control, leading to accumulation of aberrant proteins—a hallmark of cellular aging. The CDC48/p97 complex also participates in ER-associated degradation (ERAD) and mitochondrial protein quality control, further linking UFD-1 to multiple proteostasis axes relevant to longevity.",
"confidence": 0.65,
"key_pathways": [
"ubiquitin-proteasome system (UPS)",
"CDC48/p97-UFD1-NPL4 complex / UFD pathway",
"ER-associated degradation (ERAD)"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for ufd-1 in C. elegans. The mechanistic reasoning is sound and well-grounded: UFD-1 as part of the CDC48/p97-UFD1-NPL4 complex is indeed involved in ubiquitin-dependent protein quality control, and the connection to proteostasis and longevity in C. elegans is well-established. The model appropriately tied loss of UFD-1 function to impaired protein clearance and aging. Confidence of 0.65 is reasonable given the specificity of the gene. The reasoning is detailed and biologically accurate, though it is somewhat generic in that it doesn't cite specific C. elegans experimental evidence (e.g., RNAi knockdown lifespan studies), which would have strengthened the case further.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}