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P17042 (NS1_I54A0) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Non-structural protein 1

Short name=NS1
Alternative name(s):
Gene names
OrganismInfluenza A virus (strain A/Leningrad/1/1954 H1N1)
Taxonomic identifier393557 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length230 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)


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.

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.

Subunit structure

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.

Subcellular location

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 By similarity.


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

Post-translational modification

Upon interferon induction, ISGylated via host HERC5; this results in the impairment of NS1 interaction with RNA targets due to its inability to form homodimers and to interact with host EIF2AK2/PKR. There are two ISGylated forms: one form is ISGylated at Lys-20, Lys-41, Lys-217, and Lys-219, and another one at Lys-108, Lys-110, and Lys-126, they represent band I and II respectively. Lys-126 and Lys-217 are critical for host antiviral response in vivo By similarity.

Sequence similarities

Belongs to the influenza A viruses NS1 family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform NS1 (identifier: P17042-1)

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.
Isoform NEP (identifier: P17043-1)

Also known as: NS2;

The sequence of this isoform can be found in the external entry P17043.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 230230Non-structural protein 1


Region1 – 7373RNA-binding and homodimerization By similarity
Region180 – 21536CPSF4-binding By similarity
Region223 – 2308PABPN1-binding By similarity
Motif34 – 385Nuclear localization signal 1 By similarity
Motif137 – 14610Nuclear export signal By similarity
Motif216 – 2216Nuclear localization signal 2 By similarity

Amino acid modifications

Cross-link20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity
Cross-link41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity
Cross-link108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity
Cross-link110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity
Cross-link126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity
Cross-link217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity
Cross-link219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity


Sequence LengthMass (Da)Tools
Isoform NS1 [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: 9F7A6520344D04B9

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Isoform NEP (NS2) [UniParc].

See P17043.


[1]"Synthesis, cloning and determination of the primary structure of a full-size DNA copy of fragment 8 from the influenza virus type A genome."
Beklemishev A.B., Blinov V.M., Vasilenko S.K., Golovin S.Y., Karginov V.A., Mamaev L.V., Mikriukov N.N., Netesov S.V., Petrenko V.A., Petrov V.A., Frolov I.V.
Bioorg. Khim. 11:641-645(1985) [PubMed] [Europe PMC] [Abstract]
[2]"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.


Sequence databases

X52146 Genomic RNA. Translation: CAA36392.1.

3D structure databases

SMRP17042. Positions 1-72, 79-205.

Protocols and materials databases


Family and domain databases

Gene3D1.10.287.10. 1 hit.
InterProIPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
[Graphical view]
PfamPF00600. Flu_NS1. 1 hit.
[Graphical view]
SUPFAMSSF47060. SSF47060. 1 hit.

Entry information

Entry nameNS1_I54A0
AccessionPrimary (citable) accession number: P17042
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: July 9, 2014
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents


Index of protein domains and families