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0  structures 467  species 0  interactions 820  sequences 51  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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR008757

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

  • Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
  • Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role. Of the known metalloproteases, around half 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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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
(5)
Full
(820)
Representative proteomes NCBI
(739)
Meta
(218)
RP15
(83)
RP35
(136)
RP55
(171)
RP75
(195)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(5)
Full
(820)
Representative proteomes NCBI
(739)
Meta
(218)
RP15
(83)
RP35
(136)
RP55
(171)
RP75
(195)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(5)
Full
(820)
Representative proteomes NCBI
(739)
Meta
(218)
RP15
(83)
RP35
(136)
RP55
(171)
RP75
(195)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

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

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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 View help on the curation process

Seed source: Merops
Previous IDs: none
Type: Domain
Author: Studholme DJ
Number in seed: 5
Number in full: 820
Average length of the domain: 459.10 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 56.97 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.7 23.7
Trusted cut-off 23.7 23.7
Noise cut-off 23.5 23.6
Model length: 646
Family (HMM) version: 6
Download: download the raw HMM for this family

Species distribution

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