Htra2
M. musculus
HtrA serine peptidase 2
What the model saw
Gene: Htra2 Organism: Mus musculus Known functions: HtrA serine peptidase 2. serine protease HTRA2, mitochondrial. identical protein binding. peptidase activity. protein binding. protein serine/threonine kinase inhibitor activity. serine-type endopeptidase activity. serine-type peptidase activity. ubiquitin ligase inhibitor activity.
View unredacted entry
HtrA serine peptidase 2. serine protease HTRA2, mitochondrial. identical protein binding. peptidase activity. protein binding. protein serine/threonine kinase inhibitor activity. serine-type endopeptidase activity. serine-type peptidase activity. ubiquitin ligase inhibitor activity.
Solver output
HTRA2 (Omi) is a mitochondrial serine protease that, upon apoptotic stress, is released from the mitochondrial intermembrane space into the cytosol where it cleaves and inactivates IAP (inhibitor of apoptosis) family proteins via its serine endopeptidase activity, thereby promoting proper elimination of damaged cells. Its ubiquitin ligase inhibitor and protein serine/threonine kinase inhibitor activities further modulate apoptotic and proteostatic signaling. Loss-of-function mutations in Htra2 in mice cause a neurodegenerative parkinsonian phenotype with mitochondrial dysfunction and accumulation of misfolded proteins, indicating that normal HTRA2 activity is required to maintain mitochondrial quality control and proteostasis. By clearing damaged mitochondrial proteins and enabling apoptosis of dysfunctional cells, HTRA2 opposes the accumulation of mitochondrial damage and cellular senescence that drive aging. Thus, its normal function is pro-longevity, primarily through mitochondrial protein quality control and regulated apoptosis.
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 Htra2 in Mus musculus. The mechanistic reasoning is accurate and well-detailed: HTRA2/Omi is indeed a mitochondrial serine protease whose loss causes a parkinsonian neurodegenerative phenotype with mitochondrial dysfunction in mice, supporting its pro-longevity classification. The model correctly identifies the key mechanisms including mitochondrial protein quality control, IAP inhibition, and proteostasis. The confidence level of 0.72 is appropriate given the complexity of the biology.
Raw API responses
solver
{
"reasoning": "HTRA2 (Omi) is a mitochondrial serine protease that, upon apoptotic stress, is released from the mitochondrial intermembrane space into the cytosol where it cleaves and inactivates IAP (inhibitor of apoptosis) family proteins via its serine endopeptidase activity, thereby promoting proper elimination of damaged cells. Its ubiquitin ligase inhibitor and protein serine/threonine kinase inhibitor activities further modulate apoptotic and proteostatic signaling. Loss-of-function mutations in Htra2 in mice cause a neurodegenerative parkinsonian phenotype with mitochondrial dysfunction and accumulation of misfolded proteins, indicating that normal HTRA2 activity is required to maintain mitochondrial quality control and proteostasis. By clearing damaged mitochondrial proteins and enabling apoptosis of dysfunctional cells, HTRA2 opposes the accumulation of mitochondrial damage and cellular senescence that drive aging. Thus, its normal function is pro-longevity, primarily through mitochondrial protein quality control and regulated apoptosis.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial protein quality control",
"IAP inhibition / apoptosis signaling",
"proteostasis via serine protease activity"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Htra2 in Mus musculus. The mechanistic reasoning is accurate and well-detailed: HTRA2/Omi is indeed a mitochondrial serine protease whose loss causes a parkinsonian neurodegenerative phenotype with mitochondrial dysfunction in mice, supporting its pro-longevity classification. The model correctly identifies the key mechanisms including mitochondrial protein quality control, IAP inhibition, and proteostasis. The confidence level of 0.72 is appropriate given the complexity of the biology.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}