Summary: Peptidase C39 family
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Lantibiotic and non-lantibiotic bacteriocins are synthesised as precursor peptides containing N-terminal extensions (leader peptides) which are cleaved off during maturation. Most non-lantibiotics and also some lantibiotics have leader peptides of the so-called double-glycine type. These leader peptides share consensus sequences and also a common processing site with two conserved glycine residues in positions -1 and -2. The double- glycine-type leader peptides are unrelated to the N-terminal signal sequences which direct proteins across the cytoplasmic membrane via the sec pathway. Their processing sites are also different from typical signal peptidase cleavage sites, suggesting that a different processing enzyme is involved. Peptide bacteriocins are exported across the cytoplasmic membrane by a dedicated ATP-binding cassette (ABC) transporter. The ABC transporter is the maturation protease and its proteolytic domain resides in the N-terminal part of the protein . This peptidase domain is found in a wide range of ABC transporters, however the presumed catalytic cysteine and histidine are not conserved in all members of this family.
Havarstein LS, Diep DB, Nes IF; , Mol Microbiol 1995;16:229-240.: A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. PUBMED:7565085 EPMC:7565085
Internal database links
|SCOOP:||DUF3335 Guanylate_cyc_2 Peptidase_C39_2 Peptidase_C70 SMC_N|
|Similarity to PfamA using HHSearch:||Phytochelatin Guanylate_cyc_2 DUF3335 Peptidase_C70 Peptidase_C39_2|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR005074
This group of sequences defined by this cysteine peptidase domain belong to the MEROPS peptidase family C39 (clan CA). It is found in a wide range of ABC transporters, which are maturation proteases for peptide bacteriocins, the proteolytic domain residing in the N-terminal region of the protein [PUBMED:7674922]. A number of the proteins are classified as non-peptidase homologues as they either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity.
Lantibiotic and non-lantibiotic bacteriocins are synthesised as precursor peptides containing N-terminal extensions (leader peptides) which are cleaved off during maturation. Most non-lantibiotics and also some lantibiotics have leader peptides of the so-called double-glycine type. These leader peptides share consensus sequences and also a common processing site with two conserved glycine residues in positions -1 and -2. The double- glycine-type leader peptides are unrelated to the N-terminal signal sequences which direct proteins across the cytoplasmic membrane via the sec pathway. Their processing sites are also different from typical signal peptidase cleavage sites, suggesting that a different processing enzyme is involved.
A cysteine peptidase is a proteolytic enzyme that hydrolyses a peptide bond using the thiol group of a cysteine residue as a nucleophile. Hydrolysis involves usually a catalytic triad consisting of the thiol group of the cysteine, the imidazolium ring of a histidine, and a third residue, usually asparagine or aspartic acid, to orientate and activate the imidazolium ring. In only one family of cysteine peptidases, is the role of the general base assigned to a residue other than a histidine: in peptidases from family C89 (acid ceramidase) an arginine is the general base. Cysteine peptidases can be grouped into fourteen different clans, with members of each clan possessing a tertiary fold unique to the clan. Four clans of cysteine peptidases share structural similarities with serine and threonine peptidases and asparagine lyases. From sequence similarities, cysteine peptidases can be clustered into over 80 different families [PUBMED:11517925]. Clans CF, CM, CN, CO, CP and PD contain only one family.
Cysteine peptidases are often active at acidic pH and are therefore confined to acidic environments, such as the animal lysosome or plant vacuole. Cysteine peptidases can be endopeptidases, aminopeptidases, carboxypeptidases, dipeptidyl-peptidases or omega-peptidases. They are inhibited by thiol chelators such as iodoacetate, iodoacetic acid, N-ethylmaleimide or p-chloromercuribenzoate.
Clan CA includes proteins with a papain-like fold. There is a catalytic triad which occurs in the order: Cys/His/Asn (or Asp). A fourth residue, usually Gln, is important for stabilising the acyl intermediate that forms during catalysis, and this precedes the active site Cys. The fold consists of two subdomains with the active site between them. One subdomain consists of a bundle of helices, with the catalytic Cys at the end of one of them, and the other subdomain is a beta-barrel with the active site His and Asn (or Asp). There are over thirty families in the clan, and tertiary structures have been solved for members of most of these. Peptidases in clan CA are usually sensitive to the small molecule inhibitor E64, which is ineffective against peptidases from other clans of cysteine peptidases [PUBMED:7044372].
Clan CD includes proteins with a caspase-like fold. Proteins in the clan have an alpha/beta/alpha sandwich structure. There is a catalytic dyad which occurs in the order His/Cys. The active site His occurs in a His-Gly motif and the active site Cys occurs in an Ala-Cys motif; both motifs are preceded by a block of hydrophobic residues [PUBMED:9891971]. Specificity is predominantly directed towards residues that occupy the S1 binding pocket, so that caspases cleave aspartyl bonds, legumains cleave asparaginyl bonds, and gingipains cleave lysyl or arginyl bonds.
Clan CE includes proteins with an adenain-like fold. The fold consists of two subdomains with the active site between them. One domain is a bundle of helices, and the other a beta barrell. The subdomains are in the opposite order to those found in peptidases from clan CA, and this is reflected in the order of active site residues: His/Asn/Gln/Cys. This has prompted speculation that proteins in clans CA and CE are related, and that members of one clan are derived from a circular permutation of the structure of the other.
Clan CL includes proteins with a sortase B-like fold. Peptidases in the clan hydrolyse and transfer bacterial cell wall peptides. The fold shows a closed beta barrel decorated with helices with the active site at one end of the barrel [PUBMED:14725770]. The active site consists of a His/Cys catalytic dyad.
Cysteine peptidases with a chymotrypsin-like fold are included in clan PA, which also includes serine peptidases. Cysteine peptidases that are N-terminal nucleophile hydrolases are included in clan PB. Cysteine peptidases with a tertiary structure similar to that of the serine-type aspartyl dipeptidase are included in clan PC. Cysteine peptidases with an intein-like fold are included in clan PD, which also includes asparagine lyases.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||integral component of membrane (GO:0016021)|
|Molecular function||peptidase activity (GO:0008233)|
|ATP binding (GO:0005524)|
|Biological process||proteolysis (GO:0006508)|
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This clan includes peptidases with the papain-like fold.
The clan contains the following 71 members:Acetyltransf_2 Amidase_5 Amidase_6 BtrH_N CHAP CIF DUF1175 DUF1287 DUF1460 DUF2026 DUF2272 DUF3335 DUF553 EDR1 Guanylate_cyc_2 Herpes_teg_N Josephin LRAT Mac-1 Menin NLPC_P60 Nt_Gln_amidase OTU Peptidase_C1 Peptidase_C10 Peptidase_C101 Peptidase_C12 Peptidase_C16 Peptidase_C1_2 Peptidase_C2 Peptidase_C21 Peptidase_C23 Peptidase_C27 Peptidase_C28 Peptidase_C31 Peptidase_C32 Peptidase_C33 Peptidase_C34 Peptidase_C36 Peptidase_C39 Peptidase_C39_2 Peptidase_C42 Peptidase_C47 Peptidase_C48 Peptidase_C5 Peptidase_C54 Peptidase_C58 Peptidase_C6 Peptidase_C65 Peptidase_C7 Peptidase_C70 Peptidase_C71 Peptidase_C78 Peptidase_C8 Peptidase_C9 Peptidase_C92 Peptidase_C93 Peptidase_C97 Peptidase_C98 Phytochelatin Rad4 Tae4 TGase_elicitor Tox-PLDMTX Transglut_core Transglut_core2 Transglut_core3 Transglut_prok UCH UCH_1 Viral_protease
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Curation and family details
|Seed source:||Bateman A|
|Number in seed:||36|
|Number in full:||2608|
|Average length of the domain:||128.70 aa|
|Average identity of full alignment:||23 %|
|Average coverage of the sequence by the domain:||20.28 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -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_C39 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 seqence.
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