P03495 (NS1_I72A2) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 97. History...
Names and origin
|Protein names||Recommended name:|
Non-structural protein 1
|Organism||Influenza A virus (strain A/Udorn/307/1972 H3N2) [Complete proteome]|
|Taxonomic identifier||381517 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›|
|Virus host||Aves [TaxID: 8782]|
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]
|Sequence length||237 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. Ref.6 Ref.8 Ref.12
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.6 Ref.8 Ref.12
Homodimer. Interacts with host TRIM25 (via coiled coil); this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination By similarity. Interacts with human EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1. Ref.4 Ref.6 Ref.7 Ref.9 Ref.12
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.
Belongs to the influenza A viruses NS1 family.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform NS1 (identifier: P03495-1) |
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: P69258-1) |
Also known as: NS2;
The sequence of this isoform can be found in the external entry P69258.
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 – 237||237||Non-structural protein 1||PRO_0000078952|
|Region||1 – 73||73||RNA-binding and homodimerization|
|Region||180 – 215||36||CPSF4-binding|
|Region||223 – 237||15||PABPN1-binding|
|Motif||34 – 38||5||Nuclear localization signal 1|
|Motif||137 – 146||10||Nuclear export signal|
|Motif||216 – 221||6||Nuclear localization signal 2|
|Mutagenesis||7 – 8||2||SS → AA: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||7 – 8||2||SS → DL: Complete loss of nuclear mRNA export inhibition.|
|Mutagenesis||19 – 20||2||RK → AA or DL: Complete loss of nuclear mRNA export inhibition.|
|Mutagenesis||31 – 32||2||PF → AA: Complete loss of nuclear mRNA export inhibition.|
|Mutagenesis||35 – 38||4||RLRR → ALAA: 75% loss of nuclear mRNA export inhibition. Ref.3|
|Mutagenesis||39 – 40||2||DQ → AA: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||48 – 49||2||ST → DL: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||62 – 63||2||KQ → AA: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||62 – 63||2||KQ → DL: Complete loss of nuclear mRNA export inhibition.|
|Mutagenesis||73 – 74||2||SD → DL: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||87 – 88||2||SR → DL: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||99 – 100||2||SR → DL: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||116 – 117||2||CI → DL: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||134 – 136||3||FSV → AAA or LDL: Complete loss of nuclear mRNA export inhibition. Ref.3|
|Mutagenesis||141||1||L → A: No effect on nuclear mRNA export inhibition. Ref.3|
|Mutagenesis||144||1||L → A: Complete loss of nuclear mRNA export inhibition. Ref.3|
|Mutagenesis||146||1||L → A: Complete loss of nuclear mRNA export inhibition. Ref.3|
|Mutagenesis||150 – 151||2||FT → AA or DL: Complete loss of nuclear mRNA export inhibition.|
|Mutagenesis||160 – 161||2||IS → AA or DL: Complete loss of nuclear mRNA export inhibition.|
|Mutagenesis||175 – 176||2||KN → AA: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||186 – 187||2||EW → AS: Complete loss of CPSF4 binding.|
|Mutagenesis||199 – 200||2||QR → AA: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||201 – 203||3||FAW → AAA: No effect on CPSF4 binding. Ref.10|
|Mutagenesis||205 – 206||2||SS → AA: No effect on nuclear mRNA export inhibition.|
|Mutagenesis||212 – 213||2||PP → AA: No effect on CPSF4 binding.|
|Mutagenesis||219 – 221||3||KRK → ARA: No effect on nuclear mRNA export inhibition.|
Helix Strand Turn
|Helix||3 – 24||22|
|Helix||30 – 50||21|
|Helix||54 – 69||16|
|Beta strand||88 – 91||4|
|Helix||95 – 99||5|
|Beta strand||105 – 112||8|
|Beta strand||115 – 120||6|
|Beta strand||127 – 137||11|
|Beta strand||140 – 151||12|
|Beta strand||156 – 162||7|
|Beta strand||164 – 166||3|
|Helix||171 – 187||17|
|Beta strand||191 – 194||4|
|Helix||196 – 201||6|
|Turn||202 – 205||4|
|||"Sequence of interrupted and uninterrupted mRNAs and cloned DNA coding for the two overlapping nonstructural proteins of influenza virus."|
Lamb R.A., Lai C.-J.
Cell 21:475-485(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Complete genome sequencing and analysis of selected influenza virus vaccine strains spanning six decades (1933-1999)."|
Mbawuike I.N., Zhang Y., Yamada R.E., Nino D., Bui H.-H., Sette A., Couch R.B.
Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Two functional domains of the influenza virus NS1 protein are required for regulation of nuclear export of mRNA."|
Qian X.Y., Alonso-Caplen F., Krug R.M.
J. Virol. 68:2433-2441(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 7-SER-SER-8; 19-ARG-PHE-20; 31-PRO-PHE-32; 35-ARG--ARG-38; 39-ASP-GLN-40; 48-SER-THR-49; 62-LYS-GLN-63; 73-SER-ASP-74; 87-SER-ARG-88; 99-SER-ARG-100; 116-CYS-ILE-117; 134-PHE--VAL-136; LEU-141; LEU-144; LEU-146; 150-PHE-THR-151; 160-ILE-SER-161; 175-LYS-ASN-176; 199-GLN-ARG-200; 205-SER-SER-206 AND 219-LYS-LYS-221.
|||"The influenza virus NS1 protein forms multimers in vitro and in vivo."|
Nemeroff M.E., Qian X.Y., Krug R.M.
Virology 212:422-428(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DIMERIZATION.
|||"The RNA-binding and effector domains of the viral NS1 protein are conserved to different extents among influenza A and B viruses."|
Wang W., Krug R.M.
Virology 223:41-50(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: RNA-BINDING.
|||"Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs."|
Nemeroff M.E., Barabino S.M.L., Li Y., Keller W., Krug R.M.
Mol. Cell 1:991-1000(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HUMAN CPSF4.
|||"Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase."|
Tan S.L., Katze M.G.
J. Interferon Cytokine Res. 18:757-766(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN EIF2AK2/PKR.
|||"Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein."|
Li Y., Yamakita Y., Krug R.M.
Proc. Natl. Acad. Sci. U.S.A. 95:4864-4869(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery."|
Chen Z., Li Y., Krug R.M.
EMBO J. 18:2273-2283(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN PABPN1.
|||"The 3'-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo."|
Li Y., Chen Z.Y., Wang W., Baker C.C., Krug R.M.
RNA 7:920-931(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 186-GLU-TRP-187; 201-PHE--TRP-203 AND 212-PRO-PRO-213.
|||"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.
|||"The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target."|
Twu K.Y., Noah D.L., Rao P., Kuo R.L., Krug R.M.
J. Virol. 80:3957-3965(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST CPSF4.
|||"A novel RNA-binding motif in influenza A virus non-structural protein 1."|
Chien C.Y., Tejero R., Huang Y., Zimmerman D.E., Rios C.B., Krug R.M., Montelione G.T.
Nat. Struct. Biol. 4:891-895(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-73.
|||"Crystal structure of the unique RNA-binding domain of the influenza virus NS1 protein."|
Liu J., Lynch P.A., Chien C.Y., Montelione G.T., Krug R.M., Berman H.M.
Nat. Struct. Biol. 4:896-899(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 1-72.
|+||Additional computationally mapped references.|
|V01102 Genomic RNA. Translation: CAA24288.1.|
DQ508933 Genomic RNA. Translation: ABF21224.1.
|PIR||MNIV1A. A04088. |
3D structure databases
|SMR||P03495. Positions 1-73, 85-203. |
Protein-protein interaction databases
|IntAct||P03495. 44 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. S15/NS1_bind. 1 hit. |
|Accession||Primary (citable) accession number: P03495|
Secondary accession number(s): Q1K9D5
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|