dve-1
C. elegans
Homeobox protein dve-1
What the model saw
Gene: dve-1 Organism: Caenorhabditis elegans Known functions: Homeobox protein dve-1. DNA binding. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. enzyme binding. protein binding. protein-containing complex binding. protein-folding chaperone binding.
View unredacted entry
Homeobox protein dve-1. DNA binding. DNA-binding transcription activator activity, RNA polymerase II-specific. DNA-binding transcription factor activity. DNA-binding transcription factor activity, RNA polymerase II-specific. RNA polymerase II cis-regulatory region sequence-specific DNA binding. enzyme binding. protein binding. protein-containing complex binding. protein-folding chaperone binding.
Solver output
DVE-1 is a homeobox transcription factor in C. elegans that functions as a DNA-binding transcriptional activator, and its annotation for protein-folding chaperone binding is a key mechanistic clue. DVE-1 is a core component of the mitochondrial unfolded protein response (UPRmt) pathway: upon mitochondrial stress, DVE-1 is imported into the nucleus and, together with UBL-5, activates transcription of mitochondrial chaperones (e.g., hsp-60, hsp-6) via RNA Pol II-dependent transcription. This UPRmt activation maintains proteostasis under stress conditions and is required for the lifespan extension observed in animals with reduced mitochondrial function (e.g., clk-1, isp-1 mutants). Loss of dve-1 abrogates UPRmt-mediated longevity, while its activation promotes survival and extended lifespan. Thus, DVE-1's normal function in driving chaperone gene expression to restore mitochondrial and cellular proteostasis is fundamentally 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 correctly predicted pro_longevity for dve-1 in C. elegans. The mechanistic reasoning is excellent and accurate: DVE-1 is indeed a key transcription factor in the mitochondrial unfolded protein response (UPRmt), working with UBL-5 to activate mitochondrial chaperone genes (hsp-60, hsp-6). The model correctly identified that loss of dve-1 abrogates UPRmt-mediated longevity in mitochondrial mutants. The protein-folding chaperone binding annotation was correctly identified as a key mechanistic clue. The confidence level of 0.82 is appropriate given the well-established role of this gene.
Raw API responses
solver
{
"reasoning": "DVE-1 is a homeobox transcription factor in C. elegans that functions as a DNA-binding transcriptional activator, and its annotation for protein-folding chaperone binding is a key mechanistic clue. DVE-1 is a core component of the mitochondrial unfolded protein response (UPRmt) pathway: upon mitochondrial stress, DVE-1 is imported into the nucleus and, together with UBL-5, activates transcription of mitochondrial chaperones (e.g., hsp-60, hsp-6) via RNA Pol II-dependent transcription. This UPRmt activation maintains proteostasis under stress conditions and is required for the lifespan extension observed in animals with reduced mitochondrial function (e.g., clk-1, isp-1 mutants). Loss of dve-1 abrogates UPRmt-mediated longevity, while its activation promotes survival and extended lifespan. Thus, DVE-1's normal function in driving chaperone gene expression to restore mitochondrial and cellular proteostasis is fundamentally pro-longevity.",
"confidence": 0.82,
"key_pathways": [
"mitochondrial unfolded protein response (UPRmt)",
"chaperone gene transcription (hsp-60/hsp-6)",
"RNA polymerase II-dependent stress response transcription"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for dve-1 in C. elegans. The mechanistic reasoning is excellent and accurate: DVE-1 is indeed a key transcription factor in the mitochondrial unfolded protein response (UPRmt), working with UBL-5 to activate mitochondrial chaperone genes (hsp-60, hsp-6). The model correctly identified that loss of dve-1 abrogates UPRmt-mediated longevity in mitochondrial mutants. The protein-folding chaperone binding annotation was correctly identified as a key mechanistic clue. The confidence level of 0.82 is appropriate given the well-established role of this gene.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}