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O56264

- NS1_I97A1

UniProt

O56264 - NS1_I97A1

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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Status
Reviewed - Annotation score: 3 out of 5- Protein inferred from homologyi

Functioni

Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism (By similarity).By similarity
Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).By similarity

GO - Molecular functioni

  1. RNA binding Source: UniProtKB-KW

GO - Biological processi

  1. suppression by virus of host mRNA processing Source: UniProtKB-KW
  2. suppression by virus of host PKR activity Source: UniProtKB-KW
  3. suppression by virus of host RIG-I activity Source: UniProtKB-KW
  4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Eukaryotic host gene expression shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host PKR by virus, Inhibition of host pre-mRNA processing by virus, Inhibition of host RIG-I by virus, Inhibition of host RLR pathway by virus, Interferon antiviral system evasion, Viral immunoevasion

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural protein 1
Short name:
NS1
Alternative name(s):
NS1A
Gene namesi
Name:NS
OrganismiInfluenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
Taxonomic identifieri130763 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Felis catus (Cat) (Felis silvestris catus) [TaxID: 9685]
Homo sapiens (Human) [TaxID: 9606]
Panthera pardus (Leopard) (Felis pardus) [TaxID: 9691]
Panthera tigris (Tiger) [TaxID: 9694]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000008587: Genome

Subcellular locationi

Host nucleus. Host cytoplasm
Note: In uninfected, transfected cells, NS1 is localized in the nucleus. Only in virus infected cells, the nuclear export signal is unveiled, presumably by a viral protein, and a fraction of NS1 is exported in the cytoplasm.

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-KW
  2. host cell nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 230230Non-structural protein 1PRO_0000078931Add
BLAST

Interactioni

Subunit structurei

Homodimer. Interacts with host TRIM25 (via coiled coil); this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination. Interacts with human EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1 (By similarity).By similarity

Protein-protein interaction databases

IntActiO56264. 108 interactions.

Structurei

3D structure databases

ProteinModelPortaliO56264.
SMRiO56264. Positions 1-72, 79-205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7373RNA-bindingBy similarityAdd
BLAST
Regioni180 – 21536CPSF4-bindingBy similarityAdd
BLAST
Regioni223 – 2308PABPN1-bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi34 – 385Nuclear localization signal 1By similarity
Motifi137 – 14610Nuclear export signalBy similarity
Motifi216 – 2216Nuclear localization signal 2By similarity

Domaini

The dsRNA-binding region is required for suppression of RNA silencing.By similarity

Sequence similaritiesi

Belongs to the influenza A viruses NS1 family.Curated

Family and domain databases

Gene3Di1.10.287.10. 1 hit.
InterProiIPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
[Graphical view]
PfamiPF00600. Flu_NS1. 1 hit.
[Graphical view]
SUPFAMiSSF47060. SSF47060. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform NS1 (identifier: O56264-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDSNTVSSFQ VDCFLWHVRK RFADQELGDA PFLDRLRRDQ KSLRGRGSTL
60 70 80 90 100
GLDIRTATRE GKHIVERILE EESDEALKMT IASVPAPRYL TEMTLEEMSR
110 120 130 140 150
DWLMLIPKQK VTGSLCIRMD QAIMDKDIIL KANFSVIFNR LEALILLRAF
160 170 180 190 200
TDEGAIVGEI SPLPSLPGHT EEDVKNAIGV LIGGLEWNDN TVRVSETLQR
210 220 230
FTWRSSDENG RSPLPPKQKR KMERTIEPEV
Length:230
Mass (Da):26,237
Last modified:June 1, 1998 - v1
Checksum:iE0CA9F181FC60A51
GO
Isoform NEP (identifier: O56263-1) [UniParc]FASTAAdd to Basket

Also known as: NS2

The sequence of this isoform can be found in the external entry O56263.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:121
Mass (Da):14,390
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF036360 Genomic RNA. Translation: AAC34268.1.
AJ404736 Genomic RNA. Translation: CAC04091.1.
AF046091 Genomic RNA. Translation: AAC32092.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF036360 Genomic RNA. Translation: AAC34268.1 .
AJ404736 Genomic RNA. Translation: CAC04091.1 .
AF046091 Genomic RNA. Translation: AAC32092.1 .

3D structure databases

ProteinModelPortali O56264.
SMRi O56264. Positions 1-72, 79-205.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi O56264. 108 interactions.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

Gene3Di 1.10.287.10. 1 hit.
InterProi IPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
[Graphical view ]
Pfami PF00600. Flu_NS1. 1 hit.
[Graphical view ]
SUPFAMi SSF47060. SSF47060. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness."
    Subbarao K., Klimov A., Katz J., Regnery H., Lim W., Hall H., Perdue M., Swayne D., Bender C., Huang J., Hemphill M., Rowe T., Shaw M., Xu X., Fukuda K., Cox N.
    Science 279:393-396(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates."
    Lin Y.P., Shaw M., Gregory V., Cameron K., Lim W., Klimov A., Subbarao K., Guan Y., Krauss S., Shortridge K., Webster R., Cox N., Hay A.
    Proc. Natl. Acad. Sci. U.S.A. 97:9654-9658(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    Strain: A/Hong Kong/1074/99.
  3. "Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong."
    Suarez D.L., Perdue M.L., Cox N., Rowe T., Bender C., Huang J., Swayne D.E.
    J. Virol. 72:6678-6688(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  4. "Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein."
    Krug R.M., Yuan W., Noah D.L., Latham A.G.
    Virology 309:181-189(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiNS1_I97A1
AccessioniPrimary (citable) accession number: O56264
Secondary accession number(s): Q77XR5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: June 1, 1998
Last modified: October 29, 2014
This is version 73 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3