Summary: Peptidase C13 family
Peptidase C13 family Provide feedback
Members of this family are asparaginyl peptidases . 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 . 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 . 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 .
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 EPMC:9065484
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 EPMC:10682836
External database links
This tab holds annotation information from the InterPro database.
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-, 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.
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.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||cysteine-type endopeptidase activity (GO:0004197)|
|Biological process||proteolysis (GO:0006508)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
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The members of this clan are all endopeptidase that have the catalytic dyad histidine followed by cysteine. The catalytic histidine is preceded by a block of hydrophobic residues and a glycine, where as the cysteine is preceded by a block of hydrophobic residues and a glutamine and an alanine. The members with a know structure adopt an alpha/beta fold .
The clan contains the following 9 members:CHAT GVQW Peptidase_C11 Peptidase_C13 Peptidase_C14 Peptidase_C25 Peptidase_C50 Peptidase_C80 Raptor_N
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
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- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Curation and family details
|Seed source:||Pfam-B_1302 (release 4.1)|
|Author:||Bateman A, Caffrey C|
|Number in seed:||34|
|Number in full:||2746|
|Average length of the domain:||218.50 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||49.60 %|
|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:||14|
|Download:||download the raw HMM for this family|
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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_C13 domain has been found. There are 11 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 seqence.
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