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80  structures 1618  species 0  interactions 20417  sequences 502  architectures

Family: Peptidase_C48 (PF02902)

Summary: Ulp1 protease family, C-terminal catalytic domain

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Ulp1 protease family, C-terminal catalytic domain Provide feedback

This domain contains the catalytic triad Cys-His-Asn.

Literature references

  1. Mossessova E, Lima CD; , Mol Cell 2000;5:865-876.: Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast. PUBMED:10882122 EPMC:10882122

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003653

This entry represents the C-terminal part of ubiquitin-like proteases that displays full proteolytic activity [ PUBMED:10882122 ].

Deubiquitinating enzymes (DUB) form a large family of cysteine protease that can deconjugate ubiquitin or ubiquitin-like proteins from ubiquitin-conjugated proteins. They can be classified in 3 families according to sequence homology [ PUBMED:10603300 , PUBMED:8982460 ]: ubiquitin carboxyl-terminal hydrolases (UCH), ubiquitin-specific processing proteases (UBP), and ubiquitin-like proteases (ULP) ( EC ) specific for deconjugating ubiquitin-like proteins. In contrast to the UBP pathway, which is very redundant (16 UBP enzymes in yeast), there is few ubiquitin-like protease (only one in yeast, ULP1).

ULP1 catalyses two critical functions in the SUMO/Smt3 pathway via its cysteine protease activity. ULP1 processes the Smt3 C-terminal sequence (-GGATY) to its mature form (-GG), and it deconjugates Smt3 from the lysine epsilon-amino group of the target protein [ PUBMED:10094048 ].

Crystal structure of yeast ULP1 bound to Smt3 [ PUBMED:10882122 ] revealed that the catalytic and interaction interface is situated in a shallow and narrow cleft where conserved residues recognise the Gly-Gly motif at the C-terminal extremity of Smt3 protein. Ulp1 adopts a novel architecture despite some structural similarity with other cysteine protease. The secondary structure is composed of seven alpha helices and seven beta strands. The catalytic domain includes the central alpha helix, beta-strands 4 to 6, and the catalytic triad (Cys-His-Asp).

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.

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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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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 and the UniProtKB 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.

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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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Representative proteomes UniProt

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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.

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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...


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: Structural domain
Previous IDs: Ulp1_C;
Type: Domain
Sequence Ontology: SO:0000417
Author: Griffiths-Jones SR
Number in seed: 27
Number in full: 20417
Average length of the domain: 164.1 aa
Average identity of full alignment: 15 %
Average coverage of the sequence by the domain: 29.81 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 216
Family (HMM) version: 22
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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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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_C48 domain has been found. There are 80 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A044QPC8 View 3D Structure Click here
A0A044R2E9 View 3D Structure Click here
A0A044V7C9 View 3D Structure Click here
A0A077Z231 View 3D Structure Click here
A0A077Z9D3 View 3D Structure Click here
A0A077ZHP5 View 3D Structure Click here
A0A0A2V589 View 3D Structure Click here
A0A0D2G535 View 3D Structure Click here
A0A0D2GGT5 View 3D Structure Click here
A0A0D2H136 View 3D Structure Click here
A0A0G2JVE7 View 3D Structure Click here
A0A0G2JZW2 View 3D Structure Click here
A0A0G2K935 View 3D Structure Click here
A0A0J9XMY4 View 3D Structure Click here
A0A0J9Y250 View 3D Structure Click here
A0A0K0DXS6 View 3D Structure Click here
A0A0K0E4W1 View 3D Structure Click here
A0A0K0E702 View 3D Structure Click here
A0A0K0E8F8 View 3D Structure Click here
A0A0K0EAA2 View 3D Structure Click here
A0A0K0EQ21 View 3D Structure Click here
A0A0K0J716 View 3D Structure Click here
A0A0N4UDY8 View 3D Structure Click here
A0A0N4UKG6 View 3D Structure Click here
A0A0N7KH75 View 3D Structure Click here
A0A0N7KIU0 View 3D Structure Click here
A0A0N7KKG4 View 3D Structure Click here
A0A0N7KLF8 View 3D Structure Click here
A0A0P0UXP1 View 3D Structure Click here
A0A0P0V1F8 View 3D Structure Click here
A0A0P0V4Q3 View 3D Structure Click here
A0A0P0V7Z8 View 3D Structure Click here
A0A0P0VF79 View 3D Structure Click here
A0A0P0VHJ2 View 3D Structure Click here
A0A0P0VIX7 View 3D Structure Click here
A0A0P0VM85 View 3D Structure Click here
A0A0P0VPS2 View 3D Structure Click here
A0A0P0VXV0 View 3D Structure Click here
A0A0P0W0V2 View 3D Structure Click here
A0A0P0W7P1 View 3D Structure Click here