Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

lef (P15917) - Overview - Molecular Target Synopsis


lef, Lethal factor
Enzyme Classification
UniProt P15917

Also Known as LEF_BACAN, lef

One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. LF is the lethal factor that, when associated with PA, causes death. LF is not toxic by itself. It is 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. There may be other cytosolic targets of LF involved in cytotoxicity. The proteasome may mediate a toxic process initiated by LF in the cell cytosol involving degradation of unidentified molecules that are essential for macrophage homeostasis. This is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates. Also cleaves mouse Nlrp1b allele 1, leading to NLRP1 inflammasome activation, IL1B release and eventually host inflammatory response (PubMed:19651869). Anthrax toxins are composed of three distinct proteins, a protective antigen (PA), a lethal factor (LF) and an edema factor (EF). None of these is toxic by itself. PA+LF forms the lethal toxin (LeTx); PA+EF forms the edema toxin (EdTx).

Inspect Structure
See all 3D Structures for lef

Isoforms / Transcripts (Protein Coding)

Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform

Sub-cellular localization

UniProt: lef is active in the following subcellular-locations: secreted.
GO terms: lef is active in the following subcellular-locations: extracellular region.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project lef has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 0 cell-lines. (see details)

3D Structures

For lef there are:
25 structures (32 chains) solved
19 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

lef has been screened with 905 compounds (1260 bioactivities), 123 compounds have bioactivities that show binding affinity of <= 500nM (177 bioactivities). (see details)