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111  structures 9  species 0  interactions 9  sequences 4  architectures

Family: Flavi_NS5_thumb (PF20483)

Summary: Flavivirus RNA-directed RNA polymerase, thumb domain

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This is the Wikipedia entry entitled "RNA-dependent RNA polymerase". More...

RNA-dependent RNA polymerase Edit Wikipedia article

RNA dependent RNA polymerase, or RDRP, is an enzyme that catalyzes the replication of RNA from an RNA template. In contrast to a typical RNA polymerase, which uses DNA as a template, RDRP is, as its name suggests, dependent on RNA.

The most famous example of RDRP is the polio virus. The virus is made up of RNA which enters the cell through receptor-mediated endocytosis. From there, the RNA is able to act as a template for complementary RNA synthesis, immediately. The complementary strand is then, itself, able to act as a template for the production of new viral genomes which are further packaged and released from the cell ready to infect more host cells. The advantage of this method of replication is that there is no DNA stage, replication is quick and easy. The disadvantage is that there is no 'back-up' DNA copy.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Flavivirus RNA-directed RNA polymerase, thumb domain Provide feedback

Flaviviruses produce a large polyprotein from the ssRNA genome, encoding structural proteins required for virus assembly and non-structural (NS1-5) proteins involved in replication of the viral genome [1,2,3]. This polyprotein is cleaved by viral and cellular proteases to produce mature viral proteins. NS5 is the largest mature viral protein and contains a N-terminal methyltransferase (MTase) domain separated by a short linker from the C-terminal RNA-directed RNA polymerase domain (RdRp) that adopts a characteristic right-handed fingers-palm-thumb fold and possesses a number of short regions and motifs homologous to other RNA-directed RNA polymerases [2,3]. This entry represents the thumb domain of NS5 RdRp. NS5 binds to a the stem loop A (SLA) at the 5' extremity of Flavivirus genome and regulates translation of the viral genome [3].

Literature references

  1. 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

  2. Zhao B, Yi G, Du F, Chuang YC, Vaughan RC, Sankaran B, Kao CC, Li P;, Nat Commun. 2017;8:14762.: Structure and function of the Zika virus full-length NS5 protein. PUBMED:28345656 EPMC:28345656

  3. Fajardo T, Sanford TJ, Mears HV, Jasper A, Storrie S, Mansur DS, Sweeney TR;, Nucleic Acids Res. 2020;48:5081-5093.: The flavivirus polymerase NS5 regulates translation of viral genomic RNA. PUBMED:32313955 EPMC:32313955

External database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

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 RdRP (CL0027), which has the following description:

This clan represents the replicative RNA dependent RNA polymerase. from a variety of RNA viruses [1].

The clan contains the following 12 members:

Birna_RdRp_palm Birna_VP1_thumb DUF6451 Flavi_NS5 Flavi_NS5_thumb Mitovir_RNA_pol RdRP_1 RdRP_2 RdRP_3 RdRP_4 RVT_1 RVT_2


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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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

This family is new in this Pfam release.

Seed source: Pfam-B_200 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Chuguransky S
Number in seed: 7
Number in full: 9
Average length of the domain: 162.4 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 9.73 %

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 25.0 25.0
Trusted cut-off 28.6 42.4
Noise cut-off 24.0 22.5
Model length: 164
Family (HMM) version: 1
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 Flavi_NS5_thumb domain has been found. There are 111 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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