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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: -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. 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 annotation3 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 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

GO - Molecular functioni

  • double-stranded RNA binding Source: BHF-UCL
  • identical protein binding Source: IntAct

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/Udorn/307/1972 H3N2)
Taxonomic identifieri381517 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeAlphainfluenzavirus
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000153055 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7 – 8SS → AA: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi7 – 8SS → DL: Complete loss of nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi19 – 20RK → AA or DL: Complete loss of nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi31 – 32PF → AA: Complete loss of nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi35 – 38RLRR → ALAA: 75% loss of nuclear mRNA export inhibition. 1 Publication4
Mutagenesisi39 – 40DQ → AA: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi48 – 49ST → DL: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi62 – 63KQ → AA: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi62 – 63KQ → DL: Complete loss of nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi73 – 74SD → DL: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi87 – 88SR → DL: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi99 – 100SR → DL: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi116 – 117CI → DL: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi134 – 136FSV → AAA or LDL: Complete loss of nuclear mRNA export inhibition. 1 Publication3
Mutagenesisi141L → A: No effect on nuclear mRNA export inhibition. 1 Publication1
Mutagenesisi144L → A: Complete loss of nuclear mRNA export inhibition. 1 Publication1
Mutagenesisi146L → A: Complete loss of nuclear mRNA export inhibition. 1 Publication1
Mutagenesisi150 – 151FT → AA or DL: Complete loss of nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi160 – 161IS → AA or DL: Complete loss of nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi175 – 176KN → AA: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi186 – 187EW → AS: Complete loss of CPSF4 binding. 1 Publication2
Mutagenesisi199 – 200QR → AA: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi201 – 203FAW → AAA: No effect on CPSF4 binding. 1 Publication3
Mutagenesisi205 – 206SS → AA: No effect on nuclear mRNA export inhibition. 1 Publication2
Mutagenesisi212 – 213PP → AA: No effect on CPSF4 binding. 1 Publication2
Mutagenesisi219 – 221KRK → ARA: No effect on nuclear mRNA export inhibition. 1 Publication3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000789521 – 237Non-structural protein 1Add BLAST237

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 annotation4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-46282N
ELMiP03495
IntActiP03495, 61 interactors
MINTiP03495

Structurei

Secondary structure

1237
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP03495
SMRiP03495
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03495

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 73RNA-binding and homodimerizationUniRule annotationAdd BLAST73
Regioni180 – 215CPSF4-bindingUniRule annotationAdd BLAST36
Regioni223 – 237PABPN1-bindingAdd BLAST15
Regioni223 – 230PABPN1-bindingUniRule annotation8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi34 – 38Nuclear localization signalUniRule annotation5
Motifi34 – 38Nuclear localization signal 15
Motifi137 – 146Nuclear export signalUniRule annotation10
Motifi216 – 221Nuclear localization signal 26

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

OrthoDBiVOG090000NT

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: 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

Similar proteinsi

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
PDB 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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-46282N
ELMiP03495
IntActiP03495, 61 interactors
MINTiP03495

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

OrthoDBiVOG090000NT

Miscellaneous databases

EvolutionaryTraceiP03495

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
ProtoNetiSearch...

Entry informationi

Entry nameiNS1_I72A2
AccessioniPrimary (citable) accession number: P03495
Secondary accession number(s): Q1K9D5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 25, 2018
This is version 124 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. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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