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49  structures 173  species 0  interactions 5252  sequences 19  architectures

Family: Flavi_NS5 (PF00972)

Summary: Flavivirus RNA-directed RNA polymerase

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

RNA-dependent RNA polymerase Edit Wikipedia article

RNA-directed RNA polymerase
RNA Replicase structure.png
RNA Replicase structure PDB 3PHU.[1]
Identifiers
EC number 2.7.7.48
CAS number 9026-28-2
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
RNA-directed RNA polymerase, flaviviral
Identifiers
Symbol RNA_pol_flaviviral
Pfam PF00972
InterPro IPR000208

RNA-dependent RNA polymerase (RdRP), (RDR), or RNA replicase, is an enzyme that catalyzes the replication of RNA from an RNA template. This is in contrast to a typical DNA-dependent RNA polymerase, which catalyzes the transcription of RNA from a DNA template.

RNA-dependent RNA polymerase (RdRp) is an essential protein encoded in the genomes of all RNA-containing viruses with no DNA stage that have sense negative RNA.[2][3] It catalyses synthesis of the RNA strand complementary to a given RNA template. The 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), or a primer-dependent mechanism that utilizes a viral protein genome-linked (VPg) primer. 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.[4]

VPg

A VPg primer mechanism is utilized by the picornavirus (entero- aphtho- and others), additional virus groups (poty-, como-, calici- and others) and picornavirus-like (coronavirus, notavirus, etc.) supergroup of RNA viruses. The mechanism has been best studied for the enteroviruses (which include many human pathogens, such as poliovirus and coxsackie viruses) as well as for the aphthovirus, an animal pathogen causing foot and mouth disease (FMDV).

In this group, primer-dependent RNA synthesis utilizes a small 22–25 amino acid long viral protein linked to the genome (VPg)[5] to initiate polymerase activity, where the primer is covalently bound to the 5’ end of the RNA template.[6] The uridylylation occurs at a tyrosine residue at the third position of the VPg. A cis-acting replication element (CRE), which is a RNA stem loop structure, serves as a template for the uridylylation of VPg, resulting in the synthesis of VPgpUpUOH. Mutations within the CRE-RNA structure prevent VPg uridylylation, and mutations within the VPg sequence can severely diminish RdRp catalytic activity.[7] While the tyrosine hydroxyl of VPg can prime negative-strand RNA synthesis in a CRE- and VPgpUpUOH-independent manner, CRE-dependent VPgpUpUOH synthesis is absolutely required for positive-strand RNA synthesis. CRE-dependent VPg uridylylation lowers the Km¬ of UTP required for viral RNA replication and CRE-dependent VPgpUpUOH synthesis, and is required for efficient negative-strand RNA synthesis, especially when UTP concentrations are limiting.[8] The VPgpUpUOH primer is transferred to the 3’ end of the RNA template for elongation, which can continue by addition of nucleotide bases by RdRp. Partial crystal structures for VPgs of foot and mouth disease virus[9] and coxsackie virus B3[10] suggest that there may be two sites on the viral polymerase for the small VPgs of the picornaviruses. NMR solution structures of poliovirus VPg[11] and VPgpU[12] show that uridylylation stabilizes the structure of the VPg, which is otherwise quite flexible in solution. The second site may be used for uridylylation,[13] after which the VPgpU can initiate RNA synthesis. It should be noted that the VPg primers of caliciviruses, whose structures are only beginning to be revealed,[14] are much larger than those of the picornaviruses. Mechanisms for uridylylation and priming may be quite different in all of these groups.

VPg uridylylation may include the use of precursor proteins, allowing for the determination of a possible mechanism for the location of the diuridylylated, VPg-containing precursor at the 3’ end of plus- or minus-strand RNA for production of full-length RNA. Determinants of VPg uridylylation efficiency suggest formation and/or collapse or release of the uridylylated product as the rate-limiting step in vitro depending upon the VPg donor employed.[15] Precursor proteins also have an effect on VPg-CRE specificity and stability.[16] The upper RNA stem loop, to which VPg binds, has a significant impact on both retention, and recruitment, of VPg and Pol. The stem loop of CRE will partially unwind, allowing the precursor components to bind and recruit VPg and Pol4. The CRE loop has a defined consensus sequence to which the initiation components bind, however; there is no consensus sequence for the supporting stem, which suggests that only the structural stability of the CRE is important.[17]

Assembly and organization of the picornavirus VPg ribonucleoprotein complex.

  • Step 1: Two 3CD (VPg complex) molecules bind to CRE with the 3C domains (VPg domain) contacting the upper stem and the 3D domains (VPg domain) contacting the lower stem.
  • Step 2: The 3C dimer opens the RNA stem by forming a more stable interaction with single strands forming the stem.
  • Step 3: 3Dpol is recruited to and retained in this complex by a physical interaction between the back of the thumb subdomain of 3Dpol and a surface of one or both 3C subdomains of 3CD.

VPg may also play an important role in specific recognition of viral genome by movement protein (MP). Movement proteins are non-structural proteins encoded by many, if not all, plant viruses to enable their movement from one infected cell to neighboring cells.[18] MP and VPg interact to provide specificity for the transport of viral RNA from cell to cell. To fulfill energy requirements, MP also interacts with P10, which is a cellular ATPase.

History

Viral RdRPs were discovered in the early 1960s from studies on mengovirus and polio virus when it was observed that these viruses were not sensitive to actinomycin D, a drug that inhibits cellular DNA-directed RNA synthesis. This lack of sensitivity suggested that there is a virus-specific enzyme that could copy RNA from an RNA template and not from a DNA template.

The most famous example of RdRP is that of the polio virus. The viral genome is composed 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 that 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.

Many RdRPs are associated tightly with membranes and are, therefore, difficult to study. The best-known RdRPs are polioviral 3Dpol, vesicular stomatitis virus L, and hepatitis C virus NS5B protein.

Many eukaryotes also have RdRPs involved in an amplification of RNA interference. In them RdRP transcribes secondary- siRNAs, which in turn are bound by class 3 Argonauts (SAGO) to repress target RNA.[19] In fact these same RdRPs that are used in the defense mechanisms can be usurped by RNA viruses for their benefit.[citation needed]

RdRps are highly conserved throughout viruses and is even related to telomerase, though the reason for such high conservation in such diverse organisms is an ongoing question as of 2009.[20] The similarity has led to speculation that viral RdRps are ancestral to human telomerase.

Structure

All the RNA-directed RNA polymerases, and many DNA-directed polymerases, employ a fold whose organization has been likened to the shape of a right hand with three subdomains termed fingers, palm, and thumb.[21] Only the 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 rather than DNA is synthesized.[22] The domain organization[23] and the 3D structure of the catalytic centre of a wide range of RdPps, 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.

Classification

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.[24]

See also

References

  1. ^ Akutsu, M; Ye, Y; Virdee, S; Chin, JW; Komander, D (February 2011). "Molecular basis for ubiquitin and ISG15 cross-reactivity in viral ovarian tumor domains". Proc. Natl. Acad. Sci. U.S.A. 108 (6): 2228–33. doi:10.1073/pnas.1015287108. PMC 3038727. PMID 21266548. 
  2. ^ Koonin EV, Gorbalenya AE, Chumakov KM (July 1989). "Tentative identification of RNA-dependent RNA polymerases of dsRNA viruses and their relationship to positive strand RNA viral polymerases". FEBS Lett. 252 (1–2): 42–6. doi:10.1016/0014-5793(89)80886-5. PMID 2759231. 
  3. ^ Zanotto PM, Gibbs MJ, Gould EA, Holmes EC (September 1996). "A reevaluation of the higher taxonomy of viruses based on RNA polymerases". J. Virol. 70 (9): 6083–96. PMC 190630. PMID 8709232. 
  4. ^ Kao CC, Singh P, Ecker DJ (September 2001). "De novo initiation of viral RNA-dependent RNA synthesis". Virology 287 (2): 251–60. doi:10.1006/viro.2001.1039. PMID 11531403. 
  5. ^ Flanegan, JB; Baltimore, D (September 1977). "Poliovirus-specific primer-dependent RNA polymerase able to copy poly(A)". Proc. Natl. Acad. Sci. U.S.A. 74 (9): 3677–80. Bibcode:1977PNAS...74.3677F. doi:10.1073/pnas.74.9.3677. PMC 431685. PMID 198796. 
  6. ^ Ambros V, Baltimore D (August 1978). "Protein is linked to the 5' end of poliovirus RNA by a phosphodiester linkage to tyrosine". J. Biol. Chem. 253 (15): 5263–6. PMID 209034. 
  7. ^ Gu C, Zeng T, Li Y, Xu Z, Mo Z, Zheng C (October 2009). "Structure-function analysis of mutant RNA-dependent RNA polymerase complexes with VPg". Biochemistry Mosc. 74 (10): 1132–41. doi:10.1134/S0006297909100095. PMID 19916926. 
  8. ^ Steil BP, Barton DJ (October 2008). "Poliovirus cis-Acting Replication Element-Dependent VPg Uridylylation Lowers the Km of the Initiating Nucleoside Triphosphate for Viral RNA Replication". J. Virol. 82 (19): 9400–8. doi:10.1128/JVI.00427-08. PMC 2546976. PMID 18653453. 
  9. ^ Ferrer-Orta C, Arias A, Agudo R, Pérez-Luque R, Escarmís C, Domingo E, Verdaguer N (February 2006). "The structure of a protein primer-polymerase complex in the initiation of genome replication". EMBO J. 25 (4): 880–8. doi:10.1038/sj.emboj.7600971. PMC 1383552. PMID 16456546. 
  10. ^ Gruez A, Selisko B, Roberts M, Bricogne G, Bussetta C, Jabafi I, Coutard B, De Palma AM, Neyts J, Canard B (October 2008). "The crystal structure of coxsackievirus B3 RNA-dependent RNA polymerase in complex with its protein primer VPg confirms the existence of a second VPg binding site on Picornaviridae polymerases". J. Virol. 82 (19): 9577–90. doi:10.1128/JVI.00631-08. PMC 2546979. PMID 18632861. 
  11. ^ Schein CH, Oezguen N, Volk DE, Garimella R, Paul A, Braun W (July 2006). "NMR structure of the viral peptide linked to the genome (VPg) of poliovirus". Peptides 27 (7): 1676–84. doi:10.1016/j.peptides.2006.01.018. PMC 1629084. PMID 16540201. 
  12. ^ Schein CH, Oezguen N, van der Heden van Noort GJ, Filippov DV, Paul A, Kumar E, Braun W (August 2010). "NMR solution structure of poliovirus uridylyated peptide linked to the genome (VPgpU)". Peptides 31 (8): 1441–8. doi:10.1016/j.peptides.2010.04.021. PMC 2905501. PMID 20441784. 
  13. ^ Schein CH, Volk DE, Oezguen N, Paul A (June 2006). "Novel, structure-based mechanism for uridylylation of the genome-linked peptide (VPg) of picornaviruses". Proteins 63 (4): 719–26. doi:10.1002/prot.20891. PMID 16498624. 
  14. ^ Leen EN, Kwok KY, Birtley JR, Simpson PJ, Subba-Reddy CV, Chaudhry Y, Sosnovtsev SV, Green KY, Prater SN, Tong M, Young JC, Chung LM, Marchant J, Roberts LO, Kao CC, Matthews S, Goodfellow IG, Curry S (May 2013). "Structures of the Compact Helical Core Domains of Feline Calicivirus and Murine Norovirus VPg Proteins". J. Virol. 87 (10): 5318–30. doi:10.1128/JVI.03151-12. PMC 3648151. PMID 23487472. 
  15. ^ Pathak HB, Oh HS, Goodfellow IG, Arnold JJ, Cameron CE (November 2008). "Picornavirus Genome Replication: ROLES OF PRECURSOR PROTEINS AND RATE-LIMITING STEPS IN oriI-DEPENDENT VPg URIDYLYLATION". J. Biol. Chem. 283 (45): 30677–88. doi:10.1074/jbc.M806101200. PMC 2576561. PMID 18779320. 
  16. ^ Shen M, Wang Q, Yang Y, Pathak HB, Arnold JJ, Castro C, Lemon SM, Cameron CE (November 2007). "Human Rhinovirus Type 14 Gain-of-Function Mutants for oriI Utilization Define Residues of 3C(D) and 3Dpol That Contribute to Assembly and Stability of the Picornavirus VPg Uridylylation Complex". J. Virol. 81 (22): 12485–95. doi:10.1128/JVI.00972-07. PMC 2169002. PMID 17855535. 
  17. ^ Yang Y, Rijnbrand R, McKnight KL, Wimmer E, Paul A, Martin A, Lemon SM (August 2002). "Sequence Requirements for Viral RNA Replication and VPg Uridylylation Directed by the Internal cis-Acting Replication Element (cre) of Human Rhinovirus Type 14". J. Virol. 76 (15): 7485–94. doi:10.1128/JVI.76.15.7485-7494.2002. PMC 136355. PMID 12097561. 
  18. ^ Roy Chowdhury S, Savithri HS (2011). "Interaction of Sesbania Mosaic Virus Movement Protein with VPg and P10: Implication to Specificity of Genome Recognition". In Pfeffer, Sebastien. PLoS ONE 6 (1): e15609. doi:10.1371/journal.pone.0015609. PMC 3016346. PMID 21246040. 
  19. ^ Iyer LM, Koonin EV, Aravind L (January 2003). "Evolutionary connection between the catalytic subunits of DNA-dependent RNA polymerases and eukaryotic RNA-dependent RNA polymerases and the origin of RNA polymerases". BMC Struct. Biol. 3: 1. doi:10.1186/1472-6807-3-1. PMC 151600. PMID 12553882. 
  20. ^ Suttle CA (September 2005). "Viruses in the sea". Nature 437 (7057): 356–61. doi:10.1038/nature04160. PMID 16163346. 
  21. ^ Hansen JL, Long AM, Schultz SC (August 1997). "Structure of the RNA-dependent RNA polymerase of poliovirus". Structure 5 (8): 1109–22. doi:10.1016/S0969-2126(97)00261-X. PMID 9309225. 
  22. ^ Gohara DW, Crotty S, Arnold JJ, Yoder JD, Andino R, Cameron CE (August 2000). "Poliovirus RNA-dependent RNA polymerase (3Dpol): structural, biochemical, and biological analysis of conserved structural motifs A and B". J. Biol. Chem. 275 (33): 25523–32. doi:10.1074/jbc.M002671200. PMID 10827187. 
  23. ^ O'Reilly EK, Kao CC (December 1998). "Analysis of RNA-dependent RNA polymerase structure and function as guided by known polymerase structures and computer predictions of secondary structure". Virology 252 (2): 287–303. doi:10.1006/viro.1998.9463. PMID 9878607. 
  24. ^ Tan BH, Fu J, Sugrue RJ, Yap EH, Chan YC, Tan YH (February 1996). "Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity". Virology 216 (2): 317–25. doi:10.1006/viro.1996.0067. PMID 8607261. 

External links

This article incorporates text from the public domain Pfam and InterPro IPR000208

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 Provide feedback

Flaviviruses produce a polyprotein from the ssRNA genome. This protein is also known as NS5. This RNA-directed RNA polymerase possesses a number of short regions and motifs homologous to other RNA-directed RNA polymerases [2].

Literature references

  1. Marin MS, Zanotto PM, Gritsun TS, Gould EA; , Virology 1995;206:1133-1139.: Phylogeny of TYU, SRE, and CFA virus: different evolutionary rates in the genus Flavivirus. PUBMED:7856087 EPMC:7856087

  2. Tan BH, Fu J, Sugrue RJ, Yap EH, Chan YC, Tan YH; , Virology 1996;216:317-325.: Recombinant dengue type 1 virus NS5 protein expressed in Escherichia coli exhibits RNA-dependent RNA polymerase activity. PUBMED:8607261 EPMC:8607261

  3. Koonin EV; , J Gen Virol 1993;74:733-740.: Computer-assisted identification of a putative methyltransferase domain in NS5 protein of flaviviruses and lambda 2 protein of reovirus. PUBMED:8385698 EPMC:8385698

  4. 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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000208

RNA-directed RNA polymerase (RdRp) (EC) 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].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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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 8 members:

Flavi_NS5 Mitovir_RNA_pol RdRP_1 RdRP_2 RdRP_3 RdRP_4 RVT_1 RVT_2

Alignments

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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.

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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_200 (release 3.0)
Previous IDs: none
Type: Family
Author: Finn RD, Bateman A
Number in seed: 7
Number in full: 5252
Average length of the domain: 449.30 aa
Average identity of full alignment: 66 %
Average coverage of the sequence by the domain: 21.01 %

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 19.0 19.0
Trusted cut-off 19.0 19.1
Noise cut-off 18.9 18.9
Model length: 649
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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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 Flavi_NS5 domain has been found. There are 49 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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