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110  structures 119  species 2  interactions 8309  sequences 46  architectures

Family: Peptidase_S29 (PF02907)

Summary: Hepatitis C virus NS3 protease

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The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Hepatitis C virus NS3 protease Provide feedback

Hepatitis C virus NS3 protein is a serine protease which has a trypsin-like fold. The non-structural (NS) protein NS3 is one of the NS proteins involved in replication of the HCV genome. NS2-3 proteinase, a zinc-dependent enzyme, performs a single proteolytic cut to release the N-terminus of NS3. The action of NS3 proteinase (NS3P), which resides in the N-terminal one-third of the NS3 protein, then yields all remaining non-structural proteins. The C-terminal two-thirds of the NS3 protein contain a helicase. The functional relationship between the proteinase and helicase domains is unknown. NS3 has a structural zinc-binding site and requires cofactor NS4A.

Literature references

  1. Yan Y, Li Y, Munshi S, Sardana V, Cole JL, Sardana M, Steinkuehler C, Tomei L, De Francesco R, Kuo LC, Chen Z; , Protein Sci 1998;7:837-847.: Complex of NS3 protease and NS4A peptide of BK strain hepatitis C virus: a 2.2 A resolution structure in a hexagonal crystal form. PUBMED:9568891 EPMC:9568891

  2. Love RA, Parge HE, Wickersham JA, Hostomsky Z, Habuka N, Moomaw EW, Adachi T, Hostomska Z; , Cell 1996;87:331-342.: The crystal structure of hepatitis C virus NS3 proteinase reveals a trypsin-like fold and a structural zinc binding site. PUBMED:8861916 EPMC:8861916

  3. Urbani A, Bianchi E, Narjes F, Tramontano A, De Francesco R, Steinkuhler C, Pessi A; , J Biol Chem 1997;272:9204-9209.: Substrate specificity of the hepatitis C virus serine protease NS3. PUBMED:9083052 EPMC:9083052


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004109

In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:

  • Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, N-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
  • Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; N, asparagine; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule. In the case of the asparagine endopeptidases, the nucleophile is asparagine and all are self-processing endopeptidases.

In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.

Proteolytic enzymes that exploit serine in their catalytic activity are ubiquitous, being found in viruses, bacteria and eukaryotes [PUBMED:7845208]. They include a wide range of peptidase activity, including exopeptidase, endopeptidase, oligopeptidase and omega-peptidase activity. Many families of serine protease have been identified, these being grouped into clans on the basis of structural similarity and other functional evidence [PUBMED:7845208]. Structures are known for members of the clans and the structures indicate that some appear to be totally unrelated, suggesting different evolutionary origins for the serine peptidases [PUBMED:7845208].

Not withstanding their different evolutionary origins, there are similarities in the reaction mechanisms of several peptidases. Chymotrypsin, subtilisin and carboxypeptidase C have a catalytic triad of serine, aspartate and histidine in common: serine acts as a nucleophile, aspartate as an electrophile, and histidine as a base [PUBMED:7845208]. The geometric orientations of the catalytic residues are similar between families, despite different protein folds [PUBMED:7845208]. The linear arrangements of the catalytic residues commonly reflect clan relationships. For example the catalytic triad in the chymotrypsin clan (PA) is ordered HDS, but is ordered DHS in the subtilisin clan (SB) and SDH in the carboxypeptidase clan (SC) [PUBMED:7845208, PUBMED:8439290].

This signature identifies the Hepatitis C virus NS3 protein as a serine protease which belongs to MEROPS peptidase family S29 (hepacivirin family, clan PA(S)), which has a trypsin-like fold. The non-structural (NS) protein NS3 is one of the NS proteins involved in replication of the HCV genome. The NS2 proteinase (INTERPRO), a zinc-dependent enzyme, performs a single proteolytic cut to release the N terminus of NS3. The action of NS3 proteinase (NS3P), which resides in the N-terminal one-third of the NS3 protein, then yields all remaining non-structural proteins. The C-terminal two-thirds of the NS3 protein contain a helicase. The functional relationship between the proteinase and helicase domains is unknown. NS3 has a structural zinc-binding site and requires cofactor NS4. It has been suggested that the NS3 serine protease of hepatitus C is involved in cell transformation and that the ability to transform requires an active enzyme [PUBMED:11264729].

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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Pfam Clan

This family is a member of clan Peptidase_PA (CL0124), which has the following description:

This clan contains a diverse set of peptidases with the trypsin fold.

The clan contains the following 24 members:

DUF1986 DUF31 DUF316 Peptidase_C24 Peptidase_C3 Peptidase_C30 Peptidase_C37 Peptidase_C3G Peptidase_C4 Peptidase_C62 Peptidase_S29 Peptidase_S3 Peptidase_S30 Peptidase_S31 Peptidase_S32 Peptidase_S39 Peptidase_S46 Peptidase_S55 Peptidase_S6 Peptidase_S7 Peptidase_S76 Pico_P2A Trypsin Trypsin_2

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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
(9)
Full
(8309)
Representative proteomes NCBI
(6342)
Meta
(8)
RP15
(0)
RP35
(1)
RP55
(1)
RP75
(1)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(9)
Full
(8309)
Representative proteomes NCBI
(6342)
Meta
(8)
RP15
(0)
RP35
(1)
RP55
(1)
RP75
(1)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(9)
Full
(8309)
Representative proteomes NCBI
(6342)
Meta
(8)
RP15
(0)
RP35
(1)
RP55
(1)
RP75
(1)
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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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: Structural domain
Previous IDs: HCV_NS3;
Type: Domain
Author: Griffiths-Jones SR, Knutson S
Number in seed: 9
Number in full: 8309
Average length of the domain: 144.80 aa
Average identity of full alignment: 87 %
Average coverage of the sequence by the domain: 19.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 20.5
Trusted cut-off 20.5 20.5
Noise cut-off 20.4 20.4
Model length: 149
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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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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Interactions

There are 2 interactions for this family. More...

Flavi_DEAD Peptidase_S29

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_S29 domain has been found. There are 110 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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