Summary: Immune inhibitor A peptidase M6

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

No Wikipedia article
Pfam
InterPro

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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

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
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
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

Internal database links

SCOOP:

Peptidase_M7

External database links

MEROPS:

M6

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

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)

Domain organisation

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

Loading domain graphics...

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 DUF45 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 Zincin_1 Zincin_2 Zn_peptidase Zn_peptidase_2

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

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 (4)	Full (2190)	Representative proteomes				UniProt (10644)
	Seed (4)	Full (2190)	RP15 (230)	RP35 (928)	RP55 (2237)	RP75 (3755)	UniProt (10644)
Jalview	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (4)	Full (2190)	Representative proteomes				UniProt (10644)
	Seed (4)	Full (2190)	RP15 (230)	RP35 (928)	RP55 (2237)	RP75 (3755)	UniProt (10644)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

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 (4)	Full (2190)	Representative proteomes				UniProt (10644)
	Seed (4)	Full (2190)	RP15 (230)	RP35 (928)	RP55 (2237)	RP75 (3755)	UniProt (10644)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	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.

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:

Merops

Previous IDs:

none

Type:

Domain

Sequence Ontology:

SO:0000417

Author:

Studholme DJ

Number in seed:

4

Number in full:

2190

Average length of the domain:

369.70 aa

Average identity of full alignment:

22 %

Average coverage of the sequence by the domain:

46.83 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 57096847 -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:

13

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Hide

Weight segments by...

number of sequences
number of species

Change the size of the sunburst

Small

Large

Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

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 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.

Loading structure mapping...

Family: Peptidase_M6 (PF05547)

Jump to...