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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Udorn/307/1972 H3N2)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.3 Publications
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

  • double-stranded RNA binding Source: BHF-UCL

GO - Biological processi

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/Udorn/307/1972 H3N2)
Taxonomic identifieri381517 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008862 Componenti: 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

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi7 – 82SS → AA: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi7 – 82SS → DL: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi19 – 202RK → AA or DL: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi31 – 322PF → AA: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi35 – 384RLRR → ALAA: 75% loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi39 – 402DQ → AA: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi48 – 492ST → DL: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi62 – 632KQ → AA: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi62 – 632KQ → DL: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi73 – 742SD → DL: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi87 – 882SR → DL: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi99 – 1002SR → DL: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi116 – 1172CI → DL: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi134 – 1363FSV → AAA or LDL: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi141 – 1411L → A: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi144 – 1441L → A: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi146 – 1461L → A: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi150 – 1512FT → AA or DL: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi160 – 1612IS → AA or DL: Complete loss of nuclear mRNA export inhibition. 1 Publication
Mutagenesisi175 – 1762KN → AA: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi186 – 1872EW → AS: Complete loss of CPSF4 binding. 1 Publication
Mutagenesisi199 – 2002QR → AA: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi201 – 2033FAW → AAA: No effect on CPSF4 binding. 1 Publication
Mutagenesisi205 – 2062SS → AA: No effect on nuclear mRNA export inhibition. 1 Publication
Mutagenesisi212 – 2132PP → AA: No effect on CPSF4 binding. 1 Publication
Mutagenesisi219 – 2213KRK → ARA: No effect on nuclear mRNA export inhibition. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 237237Non-structural protein 1PRO_0000078952Add
BLAST

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BADQ929342EBI-2548993,EBI-700771From a different organism.
BCL2L11O435212EBI-2548993,EBI-526406From a different organism.
EDF1O608692EBI-2548993,EBI-781301From a different organism.
IL10RAQ136512EBI-2548993,EBI-1031656From a different organism.
IRS1P355682EBI-2548993,EBI-517592From a different organism.
PI4KBQ9UBF82EBI-2548993,EBI-1053214From a different organism.
RAF1P040492EBI-2548993,EBI-365996From a different organism.
SHC1P293532EBI-2548993,EBI-78835From a different organism.
TANKQ928442EBI-2548993,EBI-356349From a different organism.
UCP3P559162EBI-2548993,EBI-9116865From a different organism.

Protein-protein interaction databases

DIPiDIP-46282N.
IntActiP03495. 58 interactions.

Structurei

Secondary structure

1
237
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 2422Combined sources
Helixi30 – 5021Combined sources
Helixi54 – 6916Combined sources
Beta strandi88 – 914Combined sources
Helixi95 – 995Combined sources
Beta strandi105 – 1128Combined sources
Beta strandi115 – 1206Combined sources
Beta strandi127 – 13711Combined sources
Beta strandi140 – 15112Combined sources
Beta strandi156 – 1627Combined sources
Beta strandi164 – 1663Combined sources
Helixi171 – 18717Combined sources
Beta strandi191 – 1944Combined sources
Helixi196 – 2016Combined sources
Turni202 – 2054Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AILX-ray1.90A1-72[»]
1NS1NMR-A/B1-73[»]
2KKZNMR-A85-215[»]
2RHKX-ray1.95A/B85-215[»]
3EE8X-ray2.60A/B84-205[»]
3EE9X-ray2.14A/B84-205[»]
3KWGX-ray2.21A/B78-205[»]
3KWIX-ray2.21A/B78-205[»]
4NW2X-ray1.90B/D216-230[»]
4O45X-ray1.87B216-230[»]
ProteinModelPortaliP03495.
SMRiP03495. Positions 1-73, 85-203.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03495.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7373RNA-binding and homodimerizationAdd
BLAST
Regioni180 – 21536CPSF4-bindingAdd
BLAST
Regioni223 – 23715PABPN1-bindingAdd
BLAST

Motif

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

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. AlignAdd to basket

Isoform NS1 (identifier: P03495-1) [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 QVVDQELGDA PFLDRLRRDQ KSLRGRGSTL
60 70 80 90 100
GLNIEAATHV GKQIVEKILK EESDEALKMT MASTPASRYI TDMTIEELSR
110 120 130 140 150
DWFMLMPKQK VEGPLCIRID QAIMDKNIML KANFSVIFDR LETLILLRAF
160 170 180 190 200
TEEGAIVGEI SPLPSFPGHT IEDVKNAIGV LIGGLEWNDN TVRVSKTLQR
210 220 230
FAWGSSNENG RPPLTPKQKR KMARTARSKV RRDKMAD
Length:237
Mass (Da):26,846
Last modified:July 21, 1986 - v1
Checksum:i14D0308795627E5E
GO
Isoform NEP (identifier: P69258-1) [UniParc]FASTAAdd to basket

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.
Length:121
Mass (Da):14,365
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01102 Genomic RNA. Translation: CAA24288.1.
DQ508933 Genomic RNA. Translation: ABF21224.1.
PIRiA04088. MNIV1A.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01102 Genomic RNA. Translation: CAA24288.1.
DQ508933 Genomic RNA. Translation: ABF21224.1.
PIRiA04088. MNIV1A.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AILX-ray1.90A1-72[»]
1NS1NMR-A/B1-73[»]
2KKZNMR-A85-215[»]
2RHKX-ray1.95A/B85-215[»]
3EE8X-ray2.60A/B84-205[»]
3EE9X-ray2.14A/B84-205[»]
3KWGX-ray2.21A/B78-205[»]
3KWIX-ray2.21A/B78-205[»]
4NW2X-ray1.90B/D216-230[»]
4O45X-ray1.87B216-230[»]
ProteinModelPortaliP03495.
SMRiP03495. Positions 1-73, 85-203.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-46282N.
IntActiP03495. 58 interactions.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP03495.

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.
ProtoNetiSearch...

Publicationsi

  1. "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].
  2. "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].
  3. "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.
  4. "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.
  5. "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.
  6. "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.
  7. "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.
  8. "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.
  9. "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.
  10. "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.
  11. "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.
  12. "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.
  13. "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.
  14. "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.

Entry informationi

Entry nameiNS1_I72A2
AccessioniPrimary (citable) accession number: P03495
Secondary accession number(s): Q1K9D5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 14, 2015
This is version 112 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

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.