Lethal factor

UniProtKB accession:  P15917

Grouped By:  Matching UniProtKB accession

UniProtKB description:  Lethal factor (LF), which constitutes one of the three proteins composing the anthrax toxin, is able to trigger rapid cell death in macrophages (PubMed:3711080, PubMed:8380282, PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991). Acts as a protease that cleaves the N-terminal of most dual specificity mitogen-activated protein kinase kinases (MAPKKs or MAP2Ks) (except for MAP2K5): cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signaling complexes (PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991, PubMed:14718925). Also cleaves mouse Nlrp1b: host Nlrp1b cleavage promotes ubiquitination and degradation of the N-terminal part of Nlrp1b by the proteasome, thereby releasing the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:10338520, PubMed:19651869, PubMed:31268597, PubMed:30872531). Able to cleave mouse Nlrp1b alleles 1 and 5, while it is not able to cleave Nlrp1b alleles 2, 3 and 4 (PubMed:16429160, PubMed:19651869). In contrast, does not cleave NLRP1 human ortholog (PubMed:19651869). LF is not toxic by itself and only acts as a lethal factor when associated with protective antigen (PA) to form the lethal toxin (LeTx): PA is required for LF translocation into the host cytosol (PubMed:9563949, PubMed:10475971, PubMed:11104681, PubMed:9703991).