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4  structures 1114  species 0  interactions 2284  sequences 143  architectures

Family: Peptidase_M6 (PF05547)

Summary: Immune inhibitor A peptidase M6

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Immune inhibitor A peptidase M6 Provide feedback

The insect pathogenic Gram-positive Bacillus thuringiensis secretes immune inhibitor A, a metallopeptidase, which specifically cleaves host antibacterial proteins. A homologue of immune inhibitor A, PrtV, has been identified in the Gram-negative human pathogen Vibrio cholerae [4].

Literature references

  1. Grandvalet C, Gominet M, Lereclus D; , Microbiology 2001;147:1805-1813.: Identification of genes involved in the activation of the Bacillus thuringiensis inhA metalloprotease gene at the onset of sporulation. PUBMED:11429458 EPMC:11429458

  2. Charlton S, Moir AJ, Baillie L, Moir A; , J Appl Microbiol 1999;87:241-245.: Characterization of the exosporium of Bacillus cereus. PUBMED:10475957 EPMC:10475957

  3. Lovgren A, Zhang M, Engstrom A, Dalhammar G, Landen R; , Mol Microbiol 1990;4:2137-2146.: Molecular characterization of immune inhibitor A, a secreted virulence protease from Bacillus thuringiensis. PUBMED:2089225 EPMC:2089225

  4. Ogierman MA, Fallarino A, Riess T, Williams SG, Attridge SR, Manning PA; , J Bacteriol 1997;179:7072-7080.: Characterization of the Vibrio cholerae El Tor lipase operon lipAB and a protease gene downstream of the hly region. PUBMED:9371455 EPMC:9371455

  5. Fedhila S, Nel P, Lereclus D; , J Bacteriol 2002;184:3296-3304.: The InhA2 metalloprotease of Bacillus thuringiensis strain 407 is required for pathogenicity in insects infected via the oral route. PUBMED:12029046 EPMC:12029046

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008757

Over 70 metallopeptidase families have been identified to date. In these enzymes a divalent cation which is usually zinc, but may be cobalt, manganese or copper, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. In some families of co-catalytic metallopeptidases, two metal ions are observed in crystal structures ligated by five amino acids, with one amino acid ligating both metal ions. The known metal ligands are His, Glu, Asp or Lys. At least one other residue is required for catalysis, which may play an electrophillic role. Many metalloproteases contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [ PUBMED:7674922 ]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [ PUBMED:7674922 ].

This group of metallopeptidases belong to MEROPS peptidase family M6 (immune inhibitor A family, clan MA(M)). The predicted active site residues for members of this family and thermolysin, the type example for clan MA, occur in the motif HEXXH.

InhA of Bacillus thuringiensis (an entomopathogenic bacterium) specifically cleaves antibacterial peptides produced by insect hosts [ PUBMED:2089225 ]. B. thuringiensis is highly resistant to the insect immune system due to its production of two factors, inhibitor A (InhA or InA) and inhibitor B (InhB or InB), which selectively block the humoral defence system developed by insects against Escherichia coli and Bacillus cereus [ PUBMED:992874 ]. B. thuringiensis is especially resistant to cecropins and attacins, which are the main classes of inducible antibacterial peptides in various lepidopterans and dipterans [ PUBMED:7140755 ], [ PUBMED:3318666 ]. InhA has been shown to specifically hydrolyze cecropins and attacins in the immune hemolymph of Hyalophora cecropia (Cecropia moth) in vitro [ PUBMED:6421577 ]. However, it has been suggested that the role of InhA in resistance to the humoral defence system is not consistent with the time course of InhA production [ PUBMED:12029046 ].

B. thuringiensis has two proteins belonging to this group (InhA and InhA2), and it has been shown that InhA2 has a vital role in virulence when the host is infected via the oral route [ PUBMED:12029046 ]. The B. cereus member has been found as an exosporium component from endospores [ PUBMED:10475957 ]. B. thuringiensis InhA is induced at the onset of sporulation and is regulated by Spo0A and AbrB [ PUBMED:11429458 ]. Vibrio cholerae PrtV is thought to be encoded in the pathogenicity island [ PUBMED:9371455 ]. However, PrtV mutants did not exhibit a reduced virulence phenotype, and thus PrtV is not an indispensable virulence factor [ PUBMED:9371455 ].

Annotation note: due to the presence of PKD repeats in some of the members of this group (e.g., V. cholerae VCA0223), spurious similarity hits may appear (involving unrelated proteins), which may lead to the erroneous transfer of functional annotations and protein names. Also, please note that related Bacillus subtilis Bacillopeptidase F (Bpr or Bpf) contains two different protease domains: N-terminal INTERPRO (peptidase S8, subtilase, a subtilisin-like serine protease) and this C-terminal domain (peptidase M6), which may also complicate annotation.

Gene Ontology

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Domain organisation

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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.

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Curation and family details

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Seed source: Merops
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Studholme DJ
Number in seed: 4
Number in full: 2284
Average length of the domain: 371.3 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 47.08 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.2 29.2
Trusted cut-off 29.2 29.2
Noise cut-off 29.1 29.1
Model length: 656
Family (HMM) version: 14
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 Peptidase_M6 domain has been found. There are 4 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
Q9KMU6 View 3D Structure Click here