Summary

Peptidase C13 family

Members of this family are asparaginyl peptidases [1]. The blood fluke parasite Schistosoma mansoni has at least five Clan CA cysteine peptidases in its digestive tract including cathepsins B (2 isoforms), C, F and L. All have been recombinantly expressed as active enzymes, albeit in various stages of activation [2]. In addition, a Clan CD peptidase, termed asparaginyl endopeptidase or 'legumain' has been identified. This has formerly been characterised as a 'haemoglobinase', but this term is probably incorrect [2]. Two cDNAs have been described for Schistosoma mansoni legumain; one encodes an active enzyme whereas the active site cysteine residue encoded by the second cDNA is substituted by an asparagine residue. Both forms have been recombinantly expressed [3].

Literature references

Chen JM, Dando PM, Rawlings ND, Brown MA, Young NE, Stevens RA, Hewitt E, Watts C, Barrett AJ; , J Biol Chem 1997;272:8090-8098.: Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase. PUBMED:9065484
Caffrey CR, McKerrow JH, Salter JP, Sajid M; , Trends Parasitol 2004;20:241-248.: Blood 'n' guts: an update on schistosome digestive peptidases. PUBMED:15105025
Caffrey CR, Mathieu MA, Gaffney AM, Salter JP, Sajid M, Lucas KD, Franklin C, Bogyo M, McKerrow JH; , FEBS Lett 2000;466:244-248.: Identification of a cDNA encoding an active asparaginyl endopeptidase of Schistosoma mansoni and its expression in Pichia pastoris. PUBMED:10682836

InterPro entry IPR001096

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-, 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; 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 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.

Cysteine peptidases have characteristic molecular topologies, which can be seen not only in their three-dimensional structures, but commonly also in the two-dimensional structures. These are peptidases in which the nucleophile is the sulphydryl group of a cysteine residue. Cysteine proteases are divided into clans (proteins which are evolutionary related), and further sub-divided into families, on the basis of the architecture of their catalytic dyad or triad PUBMED:11517925.

This group of cysteine peptidases belong to the MEROPS peptidase family C13 (legumain family, clan CD). A type example is legumain from Canavalia ensiformis (Jack bean, Horse bean). The blood fluke parasite Schistosoma mansoni has two cysteine proteases in its digestive tract, one a cathepsin B-like protease, the other termed hemoglobinase PUBMED:7845226, PUBMED:3305515. The latter has been hard to purify, free of cathepsin B, and expressed forms in Escherichia coli prove to be inactive, suggesting that hemoglobinase may act in association with cathepsin B PUBMED:7845226, PUBMED:8457210. Plant vacuolar processing enzyme and legumain from legumes PUBMED:7845226 have been shown to have sequence and functional similarity to hemoglobinase. The catalytic residues of the family are currently unknown, but sequence alignments reveal one totally conserved cysteine and two totally conserved histidines.

Clan

This family is a member of clan Peptidase_CD (CL0093), which contains the following 6 members:

Peptidase_C11 Peptidase_C13 Peptidase_C14 Peptidase_C25 Peptidase_C50 Peptidase_C80

Gene Ontology

Molecular function	cysteine-type endopeptidase activity (GO:0004197)
Biological process	proteolysis (GO:0006508)

External database links

MEROPS:	C13
PANDIT:	PF01650
SYSTERS:	Peptidase_C13

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 (35) Full (445) NCBI (593) Metagenomics (51)
Viewer:

Formatting options

Alignment:	Seed (35) Full (445)
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 (35) Full (445) NCBI (593) Metagenomics (51)
Full length sequences	Full-sequences (445)

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:

Pfam-B_1302 (release 4.1)

Previous IDs:

none

Type:

Family

Author:

Bateman A, Caffrey C

Number in seed:

35

Number in full:

445

Average length of the domain:

229.20 aa

Average identity of full alignment:

30 %

Average coverage of the sequence by the domain:

53.11 %

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	20.4	20.4
Trusted cut-off	20.4	20.6
Noise cut-off	20.3	20.0

Model length:

256

Family (HMM) version:

11

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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Family: Peptidase_C13 (PF01650)

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