Summary: Anthrax toxin lethal factor, N- and C-terminal domain
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This is the Wikipedia entry entitled "Anthrax toxin". More...
Anthrax toxin Edit Wikipedia article
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Following the attacks of anthrax-related bioterrorism in 2001, a surge of funding produced a wealth of understanding about anthrax. This disease is caused by Bacillus anthracis, a spore-forming bacterium whose pathogenesis is primarily the result of a tripartite toxin. This toxin is composed of three proteins: the protective antigen (PA), the edema factor (EF) and the lethal factor (LF). These proteins work together to enter a cell and disrupt the signaling pathways, eventually leading to apoptosis. The molecular actions of PA, EF, and LF also provide a model biochemical system that demonstrates a variety of structure-function relationships seen in biochemistry.
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Anthrax toxin lethal factor, N- and C-terminal domain Provide feedback
The C-terminal domain is the catalytically active domain whereas the N-terminal domain is likely to be inactive.
External database links
MEROPS: | M34 |
SCOP: | 1pwq |
This tab holds annotation information from the InterPro database.
InterPro entry IPR014781
Anthrax toxin is a plasmid-encoded toxin complex produced by the Gram-positive, spore-forming bacteria, Bacillus anthracis. The toxin consists of three non-toxic proteins: the protective antigen (PA), the lethal factor (LF) and the edema factor (EF) [ PUBMED:14570563 ]. These component proteins self-assemble at the surface of host cell receptors, yielding a series of toxic complexes that can produce shock-like symptoms and death. Anthrax toxin is one of a large group of Bacillus and Clostridium exotoxins referred to as binary toxins, forming independent enzymatic (A moiety) and binding (B moiety) components. The LF and EF proteins are the enzymes (A moiety) that act on cytosolic substrates, while PA is a multi-functional protein (B moiety) that binds to cell surface receptors, mediates the assembly and internalisation of the complexes, and delivers them to the host cell endosome [ PUBMED:17335404 ]. Once PA is attached to the host receptor [ PUBMED:17381430 ], it must then be cleaved by a host cell surface (furin family) protease before it is able to bind EF and LF. The cleavage of the N terminus of PA enables the C-terminal fragment to self-associate into a ring-shaped heptameric complex (prepore) that can bind LF or EF competitively. The PA-LF/EF complex is then internalised by endocytosis, and delivered to the endosome, where PA forms a pore in the endosomal membrane in order to translocate LF and EF to the cytosol. LF is a Zn-dependent metalloprotease that cleaves and inactivates mitogen-activated protein (MAP) kinases, kills macrophages, and causes death of the host by inhibiting cell proliferation [ PUBMED:14616089 , PUBMED:11700563 ]. EF is a calcium-and calmodulin-dependent adenylyl cyclase that can cause edema (fluid-filled swelling) when associated with PA. EF is not toxic by itself, and is required for the survival of germinated Bacillus spores within macrophages at the early stages of infection. EF dramatically elevates the level of host intracellular cAMP, a ubiquitous messenger that integrates many processes of the cell; increases in cAMP can interfere with host intracellular signalling [ PUBMED:15131111 ].
This entry represents the N- and C-terminal domains found in both lethal factor and edema factor proteins of anthrax toxin.
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan Peptidase_MA (CL0126), which has the following description:
Clan MA is one of two zinc-dependent metallopeptidases that contain the HEXXH motif. The two histidines are zinc ligands. The structures of this clan show the active site is between its two sub-domains.
The clan contains the following 74 members:
Aminopep Aspzincin_M35 Astacin ATLF BSP DA1-like DUF1570 DUF2201_N DUF2268 DUF3152 DUF3267 DUF3810 DUF3920 DUF4157 DUF4344 DUF4953 DUF5700 DUF885 HRXXH Metallopep MPTase-PolyVal Peptidase_M1 Peptidase_M10 Peptidase_M11 Peptidase_M13 Peptidase_M2 Peptidase_M27 Peptidase_M3 Peptidase_M30 Peptidase_M32 Peptidase_M35 Peptidase_M36 Peptidase_M4 Peptidase_M41 Peptidase_M43 Peptidase_M48 Peptidase_M49 Peptidase_M4_C Peptidase_M50 Peptidase_M50B Peptidase_M54 Peptidase_M56 Peptidase_M57 Peptidase_M6 Peptidase_M60 Peptidase_M61 Peptidase_M64 Peptidase_M66 Peptidase_M7 Peptidase_M76 Peptidase_M78 Peptidase_M8 Peptidase_M85 Peptidase_M9 Peptidase_M90 Peptidase_M91 Peptidase_MA_2 Peptidase_Mx Peptidase_Mx1 Peptidase_U49 PhageMetallopep Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like WLM YbeY YgjP-like Zincin_1 Zincin_2 Zn_peptidase Zn_peptidase_2Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (3) |
Full (28) |
Representative proteomes | UniProt (194) |
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RP15 (1) |
RP35 (9) |
RP55 (25) |
RP75 (48) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
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Seed (3) |
Full (28) |
Representative proteomes | UniProt (194) |
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RP15 (1) |
RP35 (9) |
RP55 (25) |
RP75 (48) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Pfam-B_23800 (release 14.0) |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Andreeva A, Bateman A |
Number in seed: | 3 |
Number in full: | 28 |
Average length of the domain: | 129.6 aa |
Average identity of full alignment: | 24 % |
Average coverage of the sequence by the domain: | 44.23 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 218 | ||||||||||||
Family (HMM) version: | 14 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the ATLF domain has been found. There are 178 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.
Protein | Predicted structure | External Information |
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P15917 | View 3D Structure | Click here |
P40136 | View 3D Structure | Click here |
Q183R7 | View 3D Structure | Click here |