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54  structures 583  species 3  interactions 3362  sequences 97  architectures

Family: OTU (PF02338)

Summary: OTU-like cysteine protease

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OTU-like cysteine protease Provide feedback

This family is comprised of a group of predicted cysteine proteases, homologous to the Ovarian Tumour (OTU) gene in Drosophila. Members include proteins from eukaryotes, viruses and pathogenic bacterium. The conserved cysteine and histidine, and possibly the aspartate, represent the catalytic residues in this putative group of proteases.

Literature references

  1. Makarova KS, Aravind L, Koonin EV; , Trends Biochem Sci 2000;25:50-52.: A novel superfamily of predicted cysteine proteases from eukaryotes, viruses and Chlamydia pneumoniae. PUBMED:10664582 EPMC:10664582


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003323

An homology region containing four conserved motifs has been identified in proteins from eukaryotes, several groups of viruses and the pathogenic bacteria Chlamydia pneumoniae [PUBMED:10664582]. None of these proteins has a known biochemical function but low sequence similarity with the polyprotein regions of arteriviruses has lead to suggest that it could possess cysteine protease activity [PUBMED:10664582]. In this case, the conserved cysteine and aspartate in motif I and the histidine in motif IV could be the catalytic residues. Motifs II and III have a more limited sequence conservation and could be involved in substrate recognition [PUBMED:10664582].

It has been proposed that the eukaryotic proteins containing an OTU domain could mediate proteolytic events involved in signalling associated with the modification of chromatin structure and control of cell proliferation [PUBMED:10664582].

In viruses proteins containing this domain are annotated as replicase or RNA-dependent RNA polymerase. The eukaryotic sequences are related to the Ovarian Tumour (OTU) gene in Drosophila, cezanne deubiquitinating peptidase and tumor necrosis factor, alpha-induced protein 3 (MEROPS peptidase family C64) and otubain 1 and otubain 2 (MEROPS peptidase family C65).

A cysteine peptidase is a proteolytic enzymes 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 cysteine 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.

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

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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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
(14)
Full
(3362)
Representative proteomes UniProt
(5995)
NCBI
(8500)
Meta
(69)
RP15
(853)
RP35
(1685)
RP55
(2543)
RP75
(3157)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

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  Seed
(14)
Full
(3362)
Representative proteomes UniProt
(5995)
NCBI
(8500)
Meta
(69)
RP15
(853)
RP35
(1685)
RP55
(2543)
RP75
(3157)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(14)
Full
(3362)
Representative proteomes UniProt
(5995)
NCBI
(8500)
Meta
(69)
RP15
(853)
RP35
(1685)
RP55
(2543)
RP75
(3157)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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 View help on the curation process

Seed source: medline:20130692
Previous IDs: none
Type: Family
Author: Mian N, Bateman A, Finn RD
Number in seed: 14
Number in full: 3362
Average length of the domain: 125.00 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 27.41 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.3 23.3
Trusted cut-off 23.3 23.3
Noise cut-off 23.2 23.2
Model length: 127
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There are 3 interactions for this family. More...

OTU ubiquitin ubiquitin

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 OTU domain has been found. There are 54 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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