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15  structures 150  species 3  interactions 3378  sequences 23  architectures

Family: Peptidase_S7 (PF00949)

Summary: Peptidase S7, Flavivirus NS3 serine protease

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Peptidase S7, Flavivirus NS3 serine protease Provide feedback

The viral genome is a positive strand RNA that encodes a single polyprotein precursor. Processing of the polyprotein precursor into mature proteins is carried out by the host signal peptidase and by NS3 serine protease, which requires NS2B (PF01002) as a cofactor [4].

Literature references

  1. Kapoor M, Zhang L, Ramachandra M, Kusukawa J, Ebner KE, Padmanabhan R; , J Biol Chem 1995;270:19100-19106.: Association between NS3 and NS5 proteins of dengue virus type 2 in the putative RNA replicase is linked to differential phosphorylation of NS5. PUBMED:7642575 EPMC:7642575

  2. Chambers TJ, Hahn CS, Galler R, Rice CM; , Annu Rev Microbiol 1990;44:649-688.: Flavivirus genome organization, expression, and replication. PUBMED:2174669 EPMC:2174669

  3. Koonin EV, Dolja VV; , Crit Rev Biochem Mol Biol 1993;28:375-430.: Evolution and taxonomy of positive-strand RNA viruses: implications of comparative analysis of amino acid sequences. PUBMED:8269709 EPMC:8269709

  4. Murthy HM, Clum S, Padmanabhan R; , J Biol Chem 1999;274:5573-5580.: Dengue virus NS3 serine protease. Crystal structure and insights into interaction of the active site with substrates by molecular modeling and structural analysis of mutational effects. PUBMED:10026173 EPMC:10026173


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001850

The viral genome of Flavivirus is a positive strand RNA that encodes a single polyprotein precursor. Processing of the polyprotein precursor into mature proteins is carried out by the host signal peptidase and by NS3 serine protease, which requires NS2B (INTERPRO) as a cofactor [PUBMED:10026173].

Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The genome encodes three structural proteins found in the mature virion (C, prM, and E) and seven "nonstructural" (i.e., not part of the virion architecture) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). Full-length NS3 is a bifunctional protein. The N-terminal 175 residues comprise a chymotrypsin-like protease, while the C-terminal portion is a helicase. The NS2B protein, which is located in the polypeptide precursor immediately upstream of the NS3 protease domain, functions as the cofactor for NS3 protease. A 35-48 residue central portion is required for protease activity in vitro, while N- and C-terminal flanking hydrophobic regions are predicted to anchor the NS2B-NS3 complex into the host endoplasmic reticulum membrane. The two component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication [PUBMED:17400917, PUBMED:19693793, PUBMED:20042502]. The NS3 protease forms the MEROPS peptidase family S7 (flavivirin family), clan PA.

The NS3 protease has a classical serine protease catalytic triad (His, Asp, and Ser). The enzymatic activity is enhanced by interacting with the central 40 amino acid of NS2B which acts as an essential cofactor. The NS3 protease domain has an overall structure of two barrels made of six beta sheets each, with the active site located in the cleft between the barrels. The NS2B hydrophilic core cofactor contributes one of the N-terminal beta sheets [PUBMED:17400917, PUBMED:19693793, PUBMED:20042502].

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...

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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
(50)
Full
(3378)
Representative proteomes NCBI
(3915)
Meta
(116)
RP15
(13)
RP35
(14)
RP55
(14)
RP75
(17)
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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
(50)
Full
(3378)
Representative proteomes NCBI
(3915)
Meta
(116)
RP15
(13)
RP35
(14)
RP55
(14)
RP75
(17)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(50)
Full
(3378)
Representative proteomes NCBI
(3915)
Meta
(116)
RP15
(13)
RP35
(14)
RP55
(14)
RP75
(17)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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: Pfam-B_199 (release 3.0)
Previous IDs: Flavi_helicase;
Type: Family
Author: Finn RD
Number in seed: 50
Number in full: 3378
Average length of the domain: 149.10 aa
Average identity of full alignment: 68 %
Average coverage of the sequence by the domain: 4.59 %

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 20.0 20.0
Trusted cut-off 20.0 20.0
Noise cut-off 19.9 19.9
Model length: 132
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

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

Kunitz_BPTI Flavi_DEAD Bowman-Birk_leg

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_S7 domain has been found. There are 15 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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