Q82506 (NS1_I33A0) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 65. History...
Names and origin
|Protein names||Recommended name:|
Non-structural protein 1
|Organism||Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1)) [Complete proteome]|
|Taxonomic identifier||381518 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›|
|Virus host||Aves [TaxID: 8782]|
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
|Sequence length||230 AA.|
|Protein existence||Evidence at protein level|
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. Ref.3
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. Ref.3
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. Ref.2
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.
The dsRNA-binding region is required for suppression of RNA silencing By similarity.
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.
Belongs to the influenza A viruses NS1 family.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform NS1 (identifier: Q82506-1) |
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: Q89733-1) |
Also known as: NS2;
The sequence of this isoform can be found in the external entry Q89733.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 230||230||Non-structural protein 1||PRO_0000078955|
|Region||1 – 73||73||RNA-binding By similarity|
|Region||180 – 215||36||CPSF4-binding By similarity|
|Region||223 – 230||8||PABPN1-binding By similarity|
|Motif||34 – 38||5||Nuclear localization signal 1 By similarity|
|Motif||137 – 146||10||Nuclear export signal By similarity|
|Motif||216 – 221||6||Nuclear localization signal 2 By similarity|
Amino acid modifications
|Cross-link||20||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity|
|Cross-link||41||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity|
|Cross-link||108||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity|
|Cross-link||110||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity|
|Cross-link||126||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity|
|Cross-link||217||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity|
|Mutagenesis||38||1||R → A: Complete loss of suppression of RNA silencing in Drosophila cells; when associated with A-41. Ref.3|
|Mutagenesis||41||1||K → A: Complete loss of suppression of RNA silencing in Drosophila cells; when associated with A-38. Ref.3|
|Mutagenesis||92||1||D → E: Enhanced suppression of RNA silencing in Drosophila cells. Ref.3|
Thesis (1994), Robert Wood Johnson Medical School, United States
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"NS1-Binding protein (NS1-BP): a novel human protein that interacts with the influenza A virus nonstructural NS1 protein is relocalized in the nuclei of infected cells."|
Wolff T., O'Neill R.E., Palese P.
J. Virol. 72:7170-7180(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IVNS1ABP.
|||"Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing."|
Li W.-X., Li H., Lu R., Li F., Dus M., Atkinson P., Brydon E.W.A., Johnson K.L., Garcia-Sastre A., Ball L.A., Palese P., Ding S.-W.
Proc. Natl. Acad. Sci. U.S.A. 101:1350-1355(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A SUPPRESSOR OF RNA SILENCING, MUTAGENESIS OF ARG-38; LYS-41 AND ASP-92.
|||"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.
|U13683 Genomic RNA. Translation: AAA21582.1.|
3D structure databases
|SMR||Q82506. Positions 1-72, 79-205. |
Protein-protein interaction databases
|IntAct||Q82506. 3 interactions.|
Protocols and materials databases
Family and domain databases
|Gene3D||1.10.287.10. 1 hit. |
|InterPro||IPR000256. Flu_NS1. |
|Pfam||PF00600. Flu_NS1. 1 hit. |
|SUPFAM||SSF47060. SSF47060. 1 hit. |
|Accession||Primary (citable) accession number: Q82506|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|
Index of protein domains and families