smk-1
C. elegans
Serine/threonine-protein phosphatase 4 regulatory subunit 3-like central domain-containing protein
What the model saw
Gene: smk-1 Organism: Caenorhabditis elegans Known functions: Serine/threonine-protein phosphatase 4 regulatory subunit 3-like central domain-containing protein. protein phosphatase activator activity. protein phosphatase regulator activity.
View unredacted entry
Serine/threonine-protein phosphatase 4 regulatory subunit 3-like central domain-containing protein. protein phosphatase activator activity. protein phosphatase regulator activity.
Solver output
SMK-1 is the C. elegans ortholog of the PP4 regulatory subunit 3 (SMEK/PP4R3), which acts as an activator and regulator of the PP4 serine/threonine phosphatase complex. In C. elegans, smk-1 has been shown to function downstream of the DAF-16/FOXO transcription factor in the insulin/IGF-1 signaling (IIS) pathway, where it is required for the full pro-longevity transcriptional program of DAF-16. By activating PP4 phosphatase activity, SMK-1 modulates the phosphorylation state of downstream targets that mediate DAF-16-dependent longevity, innate immunity, and stress resistance. Loss of smk-1 suppresses the lifespan extension conferred by reduced IIS (e.g., daf-2 mutants), placing it as a positive effector of longevity within the IIS/DAF-16 axis. This positions SMK-1's primary mechanism within deregulated nutrient sensing, specifically the insulin/IGF-1 signaling branch that governs FOXO-dependent transcription.
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 smk-1 in C. elegans with high confidence (0.82). The mechanistic reasoning is accurate and detailed: SMK-1 is indeed a PP4 regulatory subunit that functions downstream of DAF-16/FOXO in the insulin/IGF-1 signaling pathway, and loss of smk-1 suppresses lifespan extension in daf-2 mutants. The mechanism class of "deregulated_nutrient_sensing" is appropriate given the IIS/DAF-16 axis involvement. The reasoning demonstrates solid knowledge of the published literature on smk-1 function in C. elegans longevity.
Raw API responses
solver
{
"reasoning": "SMK-1 is the C. elegans ortholog of the PP4 regulatory subunit 3 (SMEK/PP4R3), which acts as an activator and regulator of the PP4 serine/threonine phosphatase complex. In C. elegans, smk-1 has been shown to function downstream of the DAF-16/FOXO transcription factor in the insulin/IGF-1 signaling (IIS) pathway, where it is required for the full pro-longevity transcriptional program of DAF-16. By activating PP4 phosphatase activity, SMK-1 modulates the phosphorylation state of downstream targets that mediate DAF-16-dependent longevity, innate immunity, and stress resistance. Loss of smk-1 suppresses the lifespan extension conferred by reduced IIS (e.g., daf-2 mutants), placing it as a positive effector of longevity within the IIS/DAF-16 axis. This positions SMK-1's primary mechanism within deregulated nutrient sensing, specifically the insulin/IGF-1 signaling branch that governs FOXO-dependent transcription.",
"confidence": 0.82,
"key_pathways": [
"insulin/IGF-1 signaling (IIS) / DAF-16 FOXO pathway",
"PP4 serine/threonine phosphatase complex regulation",
"stress resistance and innate immunity downstream of DAF-16"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for smk-1 in C. elegans with high confidence (0.82). The mechanistic reasoning is accurate and detailed: SMK-1 is indeed a PP4 regulatory subunit that functions downstream of DAF-16/FOXO in the insulin/IGF-1 signaling pathway, and loss of smk-1 suppresses lifespan extension in daf-2 mutants. The mechanism class of \"deregulated_nutrient_sensing\" is appropriate given the IIS/DAF-16 axis involvement. The reasoning demonstrates solid knowledge of the published literature on smk-1 function in C. elegans longevity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}