Crystal toxin triggered necrosis pathway (WP3648)

Caenorhabditis elegans

This pathway is modeled on a description provided in Zhang et al. under the title "A deficiency in the necrosis pathway confers tolerance to Cry6Aa". Cry6Aa binds to the calcium channel ITR-1 and increases intracellular Ca2+ levels. Ca2+ binds to and activates Calpain TRA-3 which promotes cysteine protease activity. Cysteine Protease activates VHA-12 that uses ATP to increase pH of the cytosol. The increase in H+ concentration signals to the ASP-1/ASP-3/ASP-4 complex which leads to activation of killer cathepsin protease and leads to cell necrosis.


AAR&Co , Elisa Cirillo , Kristina Hanspers , and Eric Weitz


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Caenorhabditis elegans



Disease Ontology

gas gangrene

Pathway Ontology

signaling pathway necrosis pathway


Label Type Compact URI Comment
Ca2+ Metabolite pubchem.compound:271
H+ Metabolite pubchem.compound:1038
ATP Metabolite hmdb:HMDB0001532
ITR-1 Channel GeneProduct ensembl:WBGene00002173
VHA-12 GeneProduct ensembl:WBGene00006921
Killer Cathepsin Protease GeneProduct ensembl:WBGene00000783
ASP-1 GeneProduct ensembl:WBGene00000214
Cysteine Protease GeneProduct ensembl:WBGene00000543
Cry6Aa GeneProduct uniprot:Q45757
ASP-3 GeneProduct ensembl:WBGene00000216
ASP-4 GeneProduct ensembl:WBGene00000217
Calpain TRA-3 GeneProduct ensembl:WBGene00006606


  1. Bacillus thuringiensis Crystal Protein Cry6Aa Triggers Caenorhabditis elegans Necrosis Pathway Mediated by Aspartic Protease (ASP-1). Zhang F, Peng D, Cheng C, Zhou W, Ju S, Wan D, et al. PLoS Pathog. 2016 Jan 21;12(1):e1005389. PubMed Europe PMC Scholia