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48  structures 1520  species 0  interactions 6366  sequences 106  architectures

Family: Peptidase_C12 (PF01088)

Summary: Ubiquitin carboxyl-terminal hydrolase, family 1

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Ubiquitin carboxyl-terminal hydrolase, family 1 Provide feedback

No Pfam abstract.

Literature references

  1. Johnston SC, Larsen CN, Cook WJ, Wilkinson KD, Hill CP; , EMBO J 1997;16:3787-3796.: Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. PUBMED:9233788 EPMC:9233788

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001578

This group of cysteine peptidases belong to the MEROPS peptidase family C12 (ubiquitin C-terminal hydrolase family, clan CA). Families within the CA clan are loosely termed papain-like as protein fold of the peptidase unit resembles that of papain, the type example for clan CA. The type example is the human ubiquitin C-terminal hydrolase UCH-L1.

Ubiquitin is highly conserved, commonly found conjugated to proteins in eukaryotic cells, where it may act as a marker for rapid degradation, or it may have a chaperone function in protein assembly [ PUBMED:7845226 ]. The ubiquitin is released by cleavage from the bound protein by a protease [ PUBMED:7845226 ]. A number of deubiquitinising proteases are known: all are activated by thiol compounds [ PUBMED:7845226 , PUBMED:3015923 ], and inhibited by thiol-blocking agents and ubiquitin aldehyde [ PUBMED:7845226 , PUBMED:3031653 ], and as such have the properties of cysteine proteases [ PUBMED:7845226 ].

The deubiquitinsing proteases can be split into 2 size ranges: 20-30kDa (this entry) and 100-200kDa ( INTERPRO ) [ PUBMED:7845226 ]. The 20-30kDa group includes the yeast yuh1, which is known to be active only against small ubiquitin conjugates, being inactive against conjugated beta-galactosidase [ PUBMED:7845226 ]. A mammalian homologue, UCH (ubiquitin conjugate hydrolase), is one of the most abundant proteins in the brain [ PUBMED:7845226 ]. Only one conserved cysteine can be identified, along with two conserved histidines. The spacing between the cysteine and the second histidine is thought to be more representative of the cysteine/histidine spacing of a cysteine protease catalytic dyad [ PUBMED:7845226 ].

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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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: Prosite
Previous IDs: UCH;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Bateman A
Number in seed: 349
Number in full: 6366
Average length of the domain: 196.00 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 59.88 %

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 27.0 27.0
Trusted cut-off 27.2 27.0
Noise cut-off 26.9 26.9
Model length: 211
Family (HMM) version: 24
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_C12 domain has been found. There are 48 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
A0A0G2K2A5 View 3D Structure Click here
A0A0P0WD30 View 3D Structure Click here
A0A0R0K2F0 View 3D Structure Click here
A0A1D6HEZ2 View 3D Structure Click here
A0A1D6HPV4 View 3D Structure Click here
A0A1D6JHG9 View 3D Structure Click here
A0A1D6JHH2 View 3D Structure Click here
A0A1D6KM35 View 3D Structure Click here
A0A1D6MD20 View 3D Structure Click here
A0A1D6N6H3 View 3D Structure Click here
A0A1D6P5A3 View 3D Structure Click here
A0A1D6PYP0 View 3D Structure Click here
A0A1D8PDR9 View 3D Structure Click here
A0A1D8PNY8 View 3D Structure Click here
A0A2R8QDN8 View 3D Structure Click here
A1L2G3 View 3D Structure Click here
A4I161 View 3D Structure Click here
B6SI96 View 3D Structure Click here
B6TLS0 View 3D Structure Click here
D3ZHS6 View 3D Structure Click here
E9AH53 View 3D Structure Click here
I1LBV4 View 3D Structure Click here
I1MV53 View 3D Structure Click here
I1NIJ5 View 3D Structure Click here
K7K4Y1 View 3D Structure Click here
K7LJ38 View 3D Structure Click here
O04482 View 3D Structure Click here
P09936 View 3D Structure Click here
P15374 View 3D Structure Click here
P35122 View 3D Structure Click here
P35127 View 3D Structure Click here
P58321 View 3D Structure Click here
Q00981 View 3D Structure Click here
Q09444 View 3D Structure Click here
Q0J985 View 3D Structure Click here
Q10171 View 3D Structure Click here
Q4CL92 View 3D Structure Click here
Q4D1R0 View 3D Structure Click here
Q4DR39 View 3D Structure Click here
Q504C0 View 3D Structure Click here