tpa-1
C. elegans
Protein kinase C-like 1
What the model saw
Gene: tpa-1 Organism: Caenorhabditis elegans Known functions: Protein kinase C-like 1. ATP binding. diacylglycerol-dependent serine/threonine kinase activity. mitogen-activated protein kinase kinase kinase binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
View unredacted entry
Protein kinase C-like 1. ATP binding. diacylglycerol-dependent serine/threonine kinase activity. mitogen-activated protein kinase kinase kinase binding. protein kinase activity. protein serine kinase activity. protein serine/threonine kinase activity.
Solver output
TPA-1 is a diacylglycerol (DAG)-dependent Protein Kinase C (PKC) homolog in C. elegans. DAG-activated PKC signaling is a downstream effector of the insulin/IGF-1 signaling (IIS) pathway and also interfaces with MAPK kinase kinase cascades, both of which are well-established regulators of longevity. In C. elegans, elevated DAG levels and PKC activity (via tpa-1) have been shown to antagonize DAF-16/FOXO nuclear localization and activity, thereby suppressing the pro-longevity transcriptional program. Additionally, PKC-mediated activation of MAPKKK cascades can promote stress-response pathways in a context-dependent manner, but the dominant role of DAG/PKC signaling in worms is to promote growth and reproduction at the expense of longevity. Loss-of-function of tpa-1 has been associated with lifespan extension, consistent with its role as an anti-longevity factor through deregulated nutrient/growth sensing.
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 tpa-1 as anti_longevity. The mechanistic reasoning is sound - TPA-1 is indeed a DAG-dependent PKC homolog, and the model correctly identifies that loss-of-function extends lifespan. The connection to DAF-16/FOXO suppression and IIS pathway is biologically plausible. The mechanism class "deregulated_nutrient_sensing" is a reasonable categorization, though PKC/DAG signaling is perhaps more directly categorized as a growth/stress signaling pathway rather than nutrient sensing per se. The reasoning is well-constructed and consistent with known C. elegans biology. Confidence of 0.72 is appropriate given the complexity of the pathway.
Raw API responses
solver
{
"reasoning": "TPA-1 is a diacylglycerol (DAG)-dependent Protein Kinase C (PKC) homolog in C. elegans. DAG-activated PKC signaling is a downstream effector of the insulin/IGF-1 signaling (IIS) pathway and also interfaces with MAPK kinase kinase cascades, both of which are well-established regulators of longevity. In C. elegans, elevated DAG levels and PKC activity (via tpa-1) have been shown to antagonize DAF-16/FOXO nuclear localization and activity, thereby suppressing the pro-longevity transcriptional program. Additionally, PKC-mediated activation of MAPKKK cascades can promote stress-response pathways in a context-dependent manner, but the dominant role of DAG/PKC signaling in worms is to promote growth and reproduction at the expense of longevity. Loss-of-function of tpa-1 has been associated with lifespan extension, consistent with its role as an anti-longevity factor through deregulated nutrient/growth sensing.",
"confidence": 0.72,
"key_pathways": [
"DAG/PKC signaling",
"Insulin/IGF-1 signaling (IIS) / DAF-16 FOXO regulation",
"MAPK kinase kinase cascade"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted tpa-1 as anti_longevity. The mechanistic reasoning is sound - TPA-1 is indeed a DAG-dependent PKC homolog, and the model correctly identifies that loss-of-function extends lifespan. The connection to DAF-16/FOXO suppression and IIS pathway is biologically plausible. The mechanism class \"deregulated_nutrient_sensing\" is a reasonable categorization, though PKC/DAG signaling is perhaps more directly categorized as a growth/stress signaling pathway rather than nutrient sensing per se. The reasoning is well-constructed and consistent with known C. elegans biology. Confidence of 0.72 is appropriate given the complexity of the pathway.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}