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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Leningrad/1/1954 H1N1)
Status
Reviewed-Annotation score: -Protein inferred from homologyi

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

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/Leningrad/1/1954 H1N1)
Taxonomic identifieri393557 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeAlphainfluenzavirus
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

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_00000789351 – 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

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

Structurei

3D structure databases

ProteinModelPortaliP17042
SMRiP17042
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

Family and domain databases

Gene3Di3.30.420.330, 1 hit
HAMAPiMF_04066 INFV_NS1, 1 hit
InterProiView protein in InterPro
IPR004208 NS1
IPR000256 NS1A
IPR038064 NS1A_effect_dom_like_sp
IPR009068 S15_NS1_RNA-bd
PfamiView protein in Pfam
PF00600 Flu_NS1, 1 hit
SUPFAMiSSF143021 SSF143021, 1 hit
SSF47060 SSF47060, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform NS1 (identifier: P17042-1) [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
MDPNTVSSFQ VDCFLWHVRK RVADQELGDA PFLDRLRRDQ KSLRGRGSTL
60 70 80 90 100
GLDIKTATRA GKQIVERILK EESDEALKMT MASVPASRYL TDMTLEEMSR
110 120 130 140 150
DWSMLIPKQK VAGPLCIRMD QAIMDKNIIL KANFSVIFDR LETLILLRAF
160 170 180 190 200
TEEGAIVGEI SPLPSLPGHT AEDVKNAVGV LIGGLEWNDN TVRVSETLQR
210 220 230
FAWRSSNENG RPPLTPKQKR EMAGTIRSEV
Length:230
Mass (Da):25,867
Last modified:August 1, 1990 - v1
Checksum:i9F7A6520344D04B9
GO
Isoform NEP (identifier: P17043-1) [UniParc]FASTAAdd to basket
Also known as: NS2
The sequence of this isoform can be found in the external entry P17043.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:121
Mass (Da):14,453
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X52146 Genomic RNA Translation: CAA36392.1

Keywords - Coding sequence diversityi

Alternative splicing

Entry informationi

Entry nameiNS1_I54A0
AccessioniPrimary (citable) accession number: P17042
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: April 25, 2018
This is version 91 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

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