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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

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 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.UniRule annotation
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. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. 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.UniRule annotation

Miscellaneous

South Carolina isolate has been sequenced from formalid fixed-lung tissues of a 21-year-old male which died in 1918 at Ft. Jackson, SC. Brevig Mission isolate has been sequenced from lung tissues of an Inuit woman buried in the permafrost in a gravesite near Brevig Mission, Alaska. This sample was recovered by John Hultin, retired pathologist.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processEukaryotic 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

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural protein 1UniRule annotation
Short name:
NS1UniRule annotation
Alternative name(s):
NS1AUniRule annotation
Gene namesi
Name:NSUniRule annotation
OrganismiInfluenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
Taxonomic identifieri88776 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008430 Componenti: Genome

Subcellular locationi

  • Host nucleus UniRule annotation
  • Host cytoplasm UniRule annotation

  • 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.UniRule annotation

GO - Cellular componenti

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003105701 – 230Non-structural protein 1Add BLAST230

Post-translational modificationi

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.UniRule annotation

Keywords - PTMi

Ubl conjugation

Proteomic databases

PRIDEiQ99AU3.

Interactioni

Subunit structurei

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.UniRule annotation

Protein-protein interaction databases

DIPiDIP-61813N.
IntActiQ99AU3. 23 interactors.

Structurei

Secondary structure

1230
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 23Combined sources20
Turni24 – 26Combined sources3
Helixi31 – 50Combined sources20
Helixi54 – 71Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N74NMR-A/B1-73[»]
ProteinModelPortaliQ99AU3.
SMRiQ99AU3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 73RNA-binding and homodimerizationUniRule annotationAdd BLAST73
Regioni180 – 215CPSF4-bindingUniRule annotationAdd BLAST36
Regioni223 – 230PABPN1-bindingUniRule annotation8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi34 – 38Nuclear localization signalUniRule annotation5
Motifi137 – 146Nuclear export signalUniRule annotation10

Domaini

The dsRNA-binding region is required for suppression of RNA silencing.UniRule annotation

Sequence similaritiesi

Belongs to the influenza A viruses NS1 family.UniRule annotation

Phylogenomic databases

OrthoDBiVOG090001BO.

Family and domain databases

HAMAPiMF_04066. INFV_NS1. 1 hit.
InterProiView protein in InterPro
IPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
PfamiView protein in Pfam
PF00600. Flu_NS1. 1 hit.
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: Q99AU3-1) [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 RFADQELGDA PFLDRLRRDQ KSLRGRGSTL
60 70 80 90 100
GLDIETATRA GKQIVERILK EESDEALKMT IASVPASRYL TDMTLEEMSR
110 120 130 140 150
DWFMLMPKQK VAGSLCIRMD QAIMDKNIIL KANFSVIFDR LETLILLRAF
160 170 180 190 200
TEEGAIVGEI SPLPSLPGHT DEDVKNAVGV LIGGLEWNDN TVRVSETLQR
210 220 230
FAWRSSNENG RPPLPPKQKR KMARTIKSEV
Length:230
Mass (Da):26,066
Last modified:June 1, 2001 - v1
Checksum:iB3257EA296ADA840
GO
Isoform NEP (identifier: Q77IX1-1) [UniParc]FASTAAdd to basket
Also known as: NS2
The sequence of this isoform can be found in the external entry Q77IX1.
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
AF333238 Genomic RNA. Translation: AAK14368.1.

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiNS1_I18A0
AccessioniPrimary (citable) accession number: Q99AU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: June 1, 2001
Last modified: June 7, 2017
This is version 73 of the entry and version 1 of the sequence. See 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