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153  structures 99  species 0  interactions 111  sequences 30  architectures

Family: Peptidase_C3 (PF00548)

Summary: 3C cysteine protease (picornain 3C)

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3C cysteine protease (picornain 3C) Provide feedback

Picornaviral proteins are expressed as a single polyprotein which is cleaved by the viral 3C cysteine protease.

Literature references

  1. Matthews DA, Smith WW, Ferre RA, Condon B, Budahazi G, Sisson W, Villafranca JE, Janson CA, McElroy HE, Gribskov CL, et al; , Cell 1994;77:761-771.: Structure of human rhinovirus 3C protease reveals a trypsin- like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein. PUBMED:7515772 EPMC:7515772

  2. Allaire M, Chernaia MM, Malcolm BA, James MN; , Nature 1994;369:72-76.: Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases. PUBMED:8164744 EPMC:8164744


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000199

This entry includes cysteine peptidases that belong to MEROPS peptidase family C3 (picornain, clan PA(C)), subfamilies C3A and C3B.

Viruses in the order Picornavirales infect different vertebrate, invertebrate, and plant hosts and are responsible for a variety of human, animal, and plant diseases. These viruses have a single-stranded, positive sense RNA genome that generally translates a large precursor polyprotein which is proteolytically cleaved after translation to generate mature functional viral proteins. This process is usually mediated by (more than one) proteases, and a 3C (for the family Picornaviridae) or 3C-like (3CL) protease (for other families) plays a central role in the cleavage of the viral precursor polyprotein. In addition to this key role, 3C/3C-like protease is able to cleave a number of host proteins to remodel the cellular environment for virus reproduction [ PUBMED:15654079 , PUBMED:18293057 , PUBMED:19144641 , PUBMED:21835784 , PUBMED:21795339 , PUBMED:22534091 ]. The Picornavirales 3C/3C-like protease domain forms the MEROPS peptidase family C3 (picornain family) of clan PA.

The 3C/3CL protease domain adopts a chymotrypsin-like fold with a cysteine nucleophile in place of a commonly found serine which suggests that the cysteine and serine perform an analogous catalytic function. The catalytic triad is made of a histidine, an aspartate/glutamate and the conserved cysteine in this sequential order. The 3C/3CL protease domain folds into two antiparallel beta barrels that are linked by a loop with a short alpha-helix in its middle, and flanked by two other alpha-helices at the N- and C-terminal. The two barrels are topologically equivalent and are formed by six antiparallel beta strands with the first four organised into a Greek key motif. The active-site residues are located in the cleft between the two barrels with the nucleophilic Cys from the C-terminal barrel and the general acid base His-Glu/Asp from the N-terminal barrel [ PUBMED:15654079 , PUBMED:18293057 , PUBMED:21835784 ].

Gene Ontology

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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 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.

  Seed
(6)
Full
(111)
Representative proteomes UniProt
(12771)
RP15
(108)
RP35
(108)
RP55
(112)
RP75
(112)
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PP/heatmap 1 View           

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

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

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  Seed
(6)
Full
(111)
Representative proteomes UniProt
(12771)
RP15
(108)
RP35
(108)
RP55
(112)
RP75
(112)
Alignment:
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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
(6)
Full
(111)
Representative proteomes UniProt
(12771)
RP15
(108)
RP35
(108)
RP55
(112)
RP75
(112)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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: SCOP
Previous IDs: Cys-protease-3C;
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A
Number in seed: 6
Number in full: 111
Average length of the domain: 154.50 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 7.04 %

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 22.0 22.0
Trusted cut-off 22.1 22.0
Noise cut-off 21.9 21.9
Model length: 174
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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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 Peptidase_C3 domain has been found. There are 153 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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