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P03496 (NS1_I34A1) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Non-structural protein 1

Short name=NS1
Alternative name(s):
NS1A
Gene names
Name:NS
OrganismInfluenza A virus (strain A/Puerto Rico/8/1934 H1N1) [Reference proteome]
Taxonomic identifier211044 [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 existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

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.

Domain

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. Ref.7

Sequence similarities

Belongs to the influenza A viruses NS1 family.

Ontologies

Keywords
   Biological processHost 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
   Cellular componentHost cytoplasm
Host nucleus
   Coding sequence diversityAlternative splicing
   LigandRNA-binding
   Molecular functionSuppressor of RNA silencing
   PTMIsopeptide bond
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

evasion or tolerance by virus of host immune response

Traceable author statement. Source: Reactome

modification by virus of host mRNA processing

Traceable author statement. Source: Reactome

modulation by virus of host morphology or physiology

Traceable author statement. Source: Reactome

modulation by virus of host process

Traceable author statement. Source: Reactome

suppression by virus of host PKR activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host RIG-I activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host mRNA processing

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

viral life cycle

Traceable author statement. Source: Reactome

viral process

Traceable author statement. Source: Reactome

viral transcription

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

host cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

host cell nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PIK3R2O004598EBI-2547442,EBI-346930From a different organism.
STAU1O957933EBI-2547442,EBI-358174From a different organism.
TRIM25Q142583EBI-2547442,EBI-2341129From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform NS1 (identifier: P03496-1)

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: P03508-1)

Also known as: NS2;

The sequence of this isoform can be found in the external entry P03508.
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
PRO_0000078945

Regions

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 Ref.7
Cross-link41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host Ref.7
Cross-link108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host Ref.7
Cross-link110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host Ref.7
Cross-link126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host Ref.7
Cross-link217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host Ref.7
Cross-link219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host Ref.7

Experimental info

Mutagenesis201K → A: No of ISGylation of band I form; when associated with K-41; K-217 and K-219. Ref.7
Mutagenesis381R → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-41. Ref.6
Mutagenesis411K → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-38. Ref.6 Ref.7
Mutagenesis411K → A: No of ISGylation of band I form; when associated with K-20; K-217 and K-219. Ref.6 Ref.7
Mutagenesis961E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-97. Ref.6
Mutagenesis971E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-96. Ref.6
Mutagenesis1081K → A: No of ISGylation of band II form; when associated with K-110 and K-126. Ref.7
Mutagenesis1101K → A: No of ISGylation of band II form; when associated with K-108 and K-126. Ref.7
Mutagenesis1261K → A: No of ISGylation of band II form; when associated with K-108 and K-110. Ref.7
Mutagenesis2171K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-219. Ref.7
Mutagenesis2191K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-217. Ref.7
Sequence conflict551E → K in ABD77680. Ref.4
Sequence conflict1011D → E in AAA43536. Ref.2

Secondary structure

........................... 230
Helix Strand Turn

Details...

Sequences

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

Last modified July 21, 1986. Version 1.
Checksum: 2F7EC18E3EE7A4BE

FASTA23025,868
        10         20         30         40         50         60 
MDPNTVSSFQ VDCFLWHVRK RVADQELGDA PFLDRLRRDQ KSLRGRGSTL GLDIETATRA 

        70         80         90        100        110        120 
GKQIVERILK EESDEALKMT MASVPASRYL TDMTLEEMSR DWSMLIPKQK VAGPLCIRMD 

       130        140        150        160        170        180 
QAIMDKNIIL KANFSVIFDR LETLILLRAF TEEGAIVGEI SPLPSLPGHT AEDVKNAVGV 

       190        200        210        220        230 
LIGGLEWNDN TVRVSETLQR FAWRSSNENG RPPLTPKQKR EMAGTIRSEV 

« Hide

Isoform NEP (NS2) [UniParc].

See P03508.

References

[1]"Complete nucleotide sequence of the influenza A/PR/8/34 virus NS gene and comparison with the NS genes of the A/Udorn/72 and A/FPV/Rostock/34 strains."
Baez M., Taussig R., Zazra J.J., Young J.F., Palese P., Reisfeld A., Skalka A.M.
Nucleic Acids Res. 8:5845-5858(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Plasmid-only rescue of influenza A virus vaccine candidates."
Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P.
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[4]"The NIAID influenza genome sequencing project."
Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. expand/collapse author list , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[5]"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.
[6]"Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I."
Gack M.U., Albrecht R.A., Urano T., Inn K.-S., Huang I.-C., Carnero E., Farzan M., Inoue S., Jung J.U., Garcia-Sastre A.
Cell Host Microbe 5:439-449(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN TRIM25, MUTAGENESIS OF ARG-38; LYS-41; GLU-96 AND GLU-97.
[7]"Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein."
Tang Y., Zhong G., Zhu L., Liu X., Shan Y., Feng H., Bu Z., Chen H., Wang C.
J. Immunol. 184:5777-5790(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ISGYLATION AT LYS-20; LYS-41; LYS-108; LYS-110; LYS-126; LYS-217 AND LYS-219, MUTAGENESIS OF LYS-20; LYS-41; LYS-108; LYS-110; LYS-126; LYS-217 AND LYS-219.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
V01104 Genomic RNA. Translation: CAA24292.1. Sequence problems.
J02150 Genomic RNA. Translation: AAA43536.1.
AF389122 Genomic RNA. Translation: AAM75163.1.
EF467817 Genomic RNA. Translation: ABO21703.1.
CY009448 Genomic RNA. Translation: ABD77680.1.
RefSeqNP_040984.1. NC_002020.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2GX9X-ray2.10A/B79-207[»]
2ZKOX-ray1.70A/B1-70[»]
3L4QX-ray2.30A/B73-230[»]
3O9QX-ray2.50A/B79-230[»]
3O9RX-ray2.00A/B79-230[»]
3O9SX-ray2.48A/B79-230[»]
3O9TX-ray2.20A/B79-230[»]
3O9UX-ray3.20A/B/C/D/E/F/G/H79-230[»]
3RVCX-ray1.80A79-230[»]
ProteinModelPortalP03496.
SMRP03496. Positions 1-72, 79-205.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29081N.
IntActP03496. 172 interactions.
MINTMINT-3381930.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID956533.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.
REACT_6900. Immune System.

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.
ProtoNetSearch...

Other

EvolutionaryTraceP03496.

Entry information

Entry nameNS1_I34A1
AccessionPrimary (citable) accession number: P03496
Secondary accession number(s): Q20N32, Q67267, Q71QT3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 101 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references