Protein: LEF_BACAN
Sequence: MNIKKEFIKVISMSCLVTAITLSGPVFIPLVQGAGGHGDVGMHVKEKEKNKDENKRKDEERNKTQEEHLKEIMKHIVKIEVKGEEAVKKEAAEKLLEKVPSDVLEMYKAIGGKIYIVDGDITKHISLEALSEDKKKIKDIYGKDALLHEHYVYAKEGYEPVLVIQSSEDYVENTEKALNVYYEIGKILSRDILSKINQPYQKFLDVLNTIKNASDSDGQDLLFTNQLKEHPTDFSVEFLEQNSNEVQEVFAKAFAYYIEPQHRDVLQLYAPEAFNYMDKFNEQEINLSLEELKDQRMLARYEKWEKIKQHYQHWSDSLSEEGRGLLKKLQIPIEPKKDDIIHSLSQEEKELLKRIQIDSSDFLSTEEKEFLKKLQIDIRDSLSEEEKELLNRIQVDSSNPLSEKEKEFLKKLKLDIQPYDINQRLQDTGGLIDSPSINLDVRKQYKRDIQNIDALLHQSIGSTLYNKIYLYENMNINNLTATLGADLVDSTDNTKINRGIFNEFKKNFKYSISSNYMIVDINERPALDNERLKWRIQLSPDTRAGYLENGKLILQRNIGLEIKDVQIIKQSEKEYIRIDAKVVPKSKIDTKIQEAQLNINQEWNKALGLPKYTKLITFNVHNRYASNIVESAYLILNEWKNNIQSDLIKKVTNYLVDGNGRFVFTDITLPNIAEQYTHQDEIYEQVHSKGLYVPESRSILLHGPSKGVELRNDSEGFIHEFGHAVDDYAGYLLDKNQSDLVTNSKKFIDIFKEEGSNLTSYGRTNEAEFFAEAFRLMHSTDHAERLKVQKNAPKTFQFINDQIKFIINS
What is the function of this protein?
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).
What are the official names of this protein?
Lethal factor, LF, Anthrax lethal toxin endopeptidase component.
What is the protein family that this protein belongs to?
Belongs to the peptidase M34 family.
What are the subcellular locations of this protein?
Secreted. Host cytoplasm, host cytosol. Note=Translocation into host cytosol is mediated via interaction with the cleaved form of protective antigen (PA-63): following secretion, LF binds via its N-terminal region to the upper rim of the ring-shaped homooligomer formed by PA-63 on the host cell membrane (PubMed:21037566, PubMed:32810181). In this PA-63 pre-pore state, the N-terminal segment of LF refolds into an alpha helix engaged in the alpha-clamp of the PA-63 pre-pore (PubMed:32047164, PubMed:32521227). Loaded complexes are then endocytosed, followed by a conformational change of oligomerized PA-63 from the pre-pore to pore state, which is triggered by the low pH in the endosome (PubMed:3711080, PubMed:8380282, PubMed:10085027, PubMed:12551953). LF is then unfolded to pass through the PA-63 pore and translocate into the host cytosol (PubMed:21037566, PubMed:32047164, PubMed:32521227).