Summary

Peptidase propeptide and YPEB domain

This region is likely to have an protease inhibitory function (personal obs:C Yeats). This model is likely to miss some members of this family as the separation from signal to noise is not clear. The name is derived from Peptidase & Bacillus subtilis YPEB.

Literature references

Rawlings ND, Barrett AJ; , Meth Enzymol 1995;248:183-228.: Evolutionary families of metallopeptidases. PUBMED:7674922
Yeats C, Rawlings ND, Bateman A; , Trends Biochem Sci 2004;29:169-172.: The PepSY domain: a regulator of peptidase activity in the microbial environment?. PUBMED:15124630
McIver KS, Kessler E, Ohman DE; , Microbiology 2004;150:3969-3977.: Identification of residues in the Pseudomonas aeruginosa elastase propeptide required for chaperone and secretion activities. PUBMED:15583150

InterPro entry IPR005075

This signature, PepSY, is found in the propeptide of members of the MEROPS peptidase family M4 (clan MA(E)), which contains the thermostable thermolysins (), and related thermolabile neutral proteases (bacillolysins) () from various species of Bacillus. It is also in many non-peptidase proteins, including Bacillus subtilis YpeB protein - a regulator of SleB spore cortex lytic enzyme - and a large number of eubacterial and archaeal cell wall-associated and secreted proteins which are mostly annotated as 'hypothetical protein'.

Many extracellular bacterial proteases are produced as proenzymes. The propeptides usually have a dual function, i.e. they function as an intramolecular chaperone required for the folding of the polypeptide and as an inhibitor preventing premature activation of the enzyme. Analysis of the propeptide region of the M4 family of peptidases reveals two regions of conservation, the PepSY domain and a second domain, proximate to the N terminus, the FTP domain (), which is also found in isolation in the propeptide of eukaryotic peptidases belong to MEROPS peptidase family M36.

Propeptide domain swapping experiments, for example swapping the propeptide domain of PA protease with that of vibrolysin, both propeptides contain the FTP and PepSY domains, allows the PA protease domain to fold correctly and inhibits the C-terminal autoprocessing activity. However, swapping the propeptide of PA protease for the thermolysin propeptide, does not facilitate the correct folding nor the processing of the chimaeric protein into an active peptidase PUBMED:12589825. Mutational analysis of the Pseudomonas aeruginosa elastase gene revealed two mutations in the propeptide which resulted in the loss of inhibitory activity but not chaperone activity: A-15V and T-153I (where +1 is defined as the first residue of the mature peptidase). Both mutations resulted in peptidase activity, the T-153V mutation being much less effective than the A-15I mutation PUBMED:11021931 in activating peptidase activity. The T-153V mutation lies N-terminal to the FTP domain while the A-15I mutation is C-terminal to the PepSY domain.

Given the diverse range of other proteins, both domains occur in in isolation, the exact function of each is still unclear; though it has been proposed that the PepSY domain primarily has inhibitory activity and in conjunction with the FTP domain in chaperone activity.

Clan

This family is a member of clan PepSY (CL0320), which contains the following 5 members:

BLIP DUF2874 DUF3192 PepSY SmpA_OmlA

Gene Ontology

Cellular component	extracellular region (GO:0005576)
Molecular function	metallopeptidase activity (GO:0008237)
Molecular function	zinc ion binding (GO:0008270)
Biological process	proteolysis (GO:0006508)

External database links

MEROPS:	M4
PANDIT:	PF03413
PROSITE:	PDOC00129
SCOP:	1qf2
SYSTERS:	PepSY

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

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (354) Full (1891) NCBI (1493) Metagenomics (161)
Viewer:

Formatting options

Alignment:	Seed (354) Full (1891)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (354) Full (1891) NCBI (1493) Metagenomics (161)
Full length sequences	Full-sequences (1891)

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 HMMER2.

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. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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:

Yeats C

Previous IDs:

Pep_M4_propep;

Type:

Domain

Author:

Bateman A, Yeats C, Rawlings N

Number in seed:

354

Number in full:

1891

Average length of the domain:

66.80 aa

Average identity of full alignment:

19 %

Average coverage of the sequence by the domain:

18.55 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.9	15.0
Trusted cut-off	20.9	15.0
Noise cut-off	20.8	14.9

Model length:

64

Family (HMM) version:

12

Download:

download the raw HMM for this family

Species distribution

Tree controls

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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

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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 MSD 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 PepSY domain has been found.

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Family: PepSY (PF03413)

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