NMT1
S. cerevisiae
glycylpeptide N-tetradecanoyltransferase NMT1
What the model saw
Gene: NMT1 Organism: Saccharomyces cerevisiae Known functions: glycylpeptide N-tetradecanoyltransferase NMT1. glycylpeptide N-tetradecanoyltransferase activity.
View unredacted entry
glycylpeptide N-tetradecanoyltransferase NMT1. glycylpeptide N-tetradecanoyltransferase activity.
Solver output
NMT1 encodes N-myristoyltransferase, which catalyzes the co-translational attachment of myristate (C14:0 fatty acid) to the N-terminal glycine of target proteins. This lipid modification is essential for membrane anchoring and proper subcellular localization of numerous signaling proteins, including those in the cAMP/PKA pathway (e.g., Gpa1), AMPK-related kinases, and small GTPases. Correct myristoylation is required for the functional integrity of these nutrient-sensing and signal transduction cascades. Disruption of NMT1 is lethal in yeast, underscoring its essential role; proper myristoylation supports regulated nutrient sensing (TOR/PKA pathways) and membrane-associated signaling fidelity. Loss of myristoylation leads to mislocalization of key regulatory proteins, potentially deregulating nutrient-sensing pathways that are central to lifespan control in yeast.
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 focuses on NMT1 being essential and supporting proper signaling, which would suggest a pro-longevity role. However, as an anti-longevity gene, NMT1 (N-myristoyltransferase) likely promotes aging - perhaps through myristoylation of proteins that activate pro-aging pathways like cAMP/PKA. The model's mechanistic reasoning is also incorrect in direction - it argues that NMT1 supports regulated nutrient sensing that is beneficial for lifespan, when in fact the gene has an anti-longevity influence. The model's confidence of 0.62 is moderate but still wrong. The mechanism class of 'altered_intercellular_communication' is also questionable for a protein lipid modification enzyme.
Raw API responses
solver
{
"reasoning": "NMT1 encodes N-myristoyltransferase, which catalyzes the co-translational attachment of myristate (C14:0 fatty acid) to the N-terminal glycine of target proteins. This lipid modification is essential for membrane anchoring and proper subcellular localization of numerous signaling proteins, including those in the cAMP/PKA pathway (e.g., Gpa1), AMPK-related kinases, and small GTPases. Correct myristoylation is required for the functional integrity of these nutrient-sensing and signal transduction cascades. Disruption of NMT1 is lethal in yeast, underscoring its essential role; proper myristoylation supports regulated nutrient sensing (TOR/PKA pathways) and membrane-associated signaling fidelity. Loss of myristoylation leads to mislocalization of key regulatory proteins, potentially deregulating nutrient-sensing pathways that are central to lifespan control in yeast.",
"confidence": 0.62,
"key_pathways": [
"N-myristoylation / lipid modification of signaling proteins",
"cAMP/PKA nutrient-sensing pathway",
"TOR signaling and membrane-associated kinase regulation"
],
"mechanism_class": "altered_intercellular_communication",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning focuses on NMT1 being essential and supporting proper signaling, which would suggest a pro-longevity role. However, as an anti-longevity gene, NMT1 (N-myristoyltransferase) likely promotes aging - perhaps through myristoylation of proteins that activate pro-aging pathways like cAMP/PKA. The model's mechanistic reasoning is also incorrect in direction - it argues that NMT1 supports regulated nutrient sensing that is beneficial for lifespan, when in fact the gene has an anti-longevity influence. The model's confidence of 0.62 is moderate but still wrong. The mechanism class of 'altered_intercellular_communication' is also questionable for a protein lipid modification enzyme.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}