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 .
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
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
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
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.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||peptidase activity (GO:0008233)|
|Biological process||proteolysis (GO:0006508)|
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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 58 members:Aspzincin_M35 Astacin BSP DUF1570 DUF2201_N DUF2268 DUF3152 DUF3267 DUF3633 DUF3810 DUF4157 DUF4344 DUF45 DUF4953 DUF955 HRXXH 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_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_M8 Peptidase_M9 Peptidase_M91 Peptidase_Mx Peptidase_Mx1 Peptidase_U49 Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like WLM Zn_peptidase Zn_peptidase_2
We make a range of alignments for each Pfam-A family:
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Curation and family details
|Number in seed:||5|
|Number in full:||1951|
|Average length of the domain:||464.90 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||57.19 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||7|
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