SMART: Pfam domain Flavi

Flavi_NS5

PFAM accession number:	PF00972
Interpro abstract (IPR000208):	RNA-directed RNA polymerase (RdRp) ( EC 2.7.7.48 ) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage [ (PUBMED:2759231) (PUBMED:8709232) ]. It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear. The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product [ (PUBMED:11531403) ]. All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organisation has been likened to the shape of a right hand with three subdomains termed fingers, palm and thumb [ (PUBMED:9309225) ]. Only the catalytic palm subdomain, composed of a four-stranded antiparallel beta-sheet with two alpha-helices, is well conserved among all of these enzymes. In RdRp, the palm subdomain comprises three well conserved motifs (A, B and C). Motif A (D-x(4,5)-D) and motif C (GDD) are spatially juxtaposed; the Asp residues of these motifs are implied in the binding of Mg2+ and/or Mn2+. The Asn residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and thus determines whether RNA is synthesised rather than DNA [ (PUBMED:10827187) ]. The domain organisation [ (PUBMED:9878607) ] and the 3D structure of the catalytic centre of a wide range of RdPp's, even those with a low overall sequence homology, are conserved. The catalytic centre is formed by several motifs containing a number of conserved amino acid residues. There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage: Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families. Mononegavirales (negative-strand RNA viruses with non-segmented genomes). Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses. Birnaviridae family of dsRNA viruses. The RNA-directed RNA polymerases in the first of the above superfamilies can be divided into the following three subgroups: All positive-strand RNA eukaryotic viruses with no DNA stage. All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages). Reoviridae family of dsRNA viruses. Flaviviruses produce a polyprotein from the ssRNA genome. The polyprotein is cleaved to a number of products one of which is NS5. Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. This RNA-directed RNA polymerase possesses a number of short regions and motifs homologous to other RNA-directed RNA polymerases [ (PUBMED:8607261) ].
GO function:	ATP binding (GO:0005524), RNA-directed 5'-3' RNA polymerase activity (GO:0003968)

PFAM accession number:

PF00972

Interpro abstract (IPR000208):

RNA-directed RNA polymerase (RdRp) ( EC 2.7.7.48 ) is an essential protein encoded in the genomes of all RNA containing viruses with no DNA stage [ (PUBMED:2759231) (PUBMED:8709232) ]. It catalyses synthesis of the RNA strand complementary to a given RNA template, but the precise molecular mechanism remains unclear. The postulated RNA replication process is a two-step mechanism. First, the initiation step of RNA synthesis begins at or near the 3' end of the RNA template by means of a primer-independent (de novo) mechanism. The de novo initiation consists in the addition of a nucleotide tri-phosphate (NTP) to the 3'-OH of the first initiating NTP. During the following so-called elongation phase, this nucleotidyl transfer reaction is repeated with subsequent NTPs to generate the complementary RNA product [ (PUBMED:11531403) ].

All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organisation has been likened to the shape of a right hand with three subdomains termed fingers, palm and thumb [ (PUBMED:9309225) ]. Only the catalytic palm subdomain, composed of a four-stranded antiparallel beta-sheet with two alpha-helices, is well conserved among all of these enzymes. In RdRp, the palm subdomain comprises three well conserved motifs (A, B and C). Motif A (D-x(4,5)-D) and motif C (GDD) are spatially juxtaposed; the Asp residues of these motifs are implied in the binding of Mg2+ and/or Mn2+. The Asn residue of motif B is involved in selection of ribonucleoside triphosphates over dNTPs and thus determines whether RNA is synthesised rather than DNA [ (PUBMED:10827187) ]. The domain organisation [ (PUBMED:9878607) ] and the 3D structure of the catalytic centre of a wide range of RdPp's, even those with a low overall sequence homology, are conserved. The catalytic centre is formed by several motifs containing a number of conserved amino acid residues.

There are 4 superfamilies of viruses that cover all RNA containing viruses with no DNA stage:

Viruses containing positive-strand RNA or double-strand RNA, except retroviruses and Birnaviridae: viral RNA-directed RNA polymerases including all positive-strand RNA viruses with no DNA stage, double-strand RNA viruses, and the Cystoviridae, Reoviridae, Hypoviridae, Partitiviridae, Totiviridae families.
Mononegavirales (negative-strand RNA viruses with non-segmented genomes).
Negative-strand RNA viruses with segmented genomes, i.e. Orthomyxoviruses (including influenza A, B, and C viruses, Thogotoviruses, and the infectious salmon anemia virus), Arenaviruses, Bunyaviruses, Hantaviruses, Nairoviruses, Phleboviruses, Tenuiviruses and Tospoviruses.
Birnaviridae family of dsRNA viruses.

The RNA-directed RNA polymerases in the first of the above superfamilies can be divided into the following three subgroups:

All positive-strand RNA eukaryotic viruses with no DNA stage.
All RNA-containing bacteriophages -there are two families of RNA-containing bacteriophages: Leviviridae (positive ssRNA phages) and Cystoviridae (dsRNA phages).
Reoviridae family of dsRNA viruses.

Flaviviruses produce a polyprotein from the ssRNA genome. The polyprotein is cleaved to a number of products one of which is NS5. Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. This RNA-directed RNA polymerase possesses a number of short regions and motifs homologous to other RNA-directed RNA polymerases [ (PUBMED:8607261) ].

GO function:

ATP binding (GO:0005524), RNA-directed 5'-3' RNA polymerase activity (GO:0003968)

This is a PFAM domain. For full annotation and more information, please see the PFAM entry Flavi_NS5