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P03496

- NS1_I34A1

UniProt

P03496 - NS1_I34A1

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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed - 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 (By similarity).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).By similarity

GO - Molecular functioni

  1. RNA binding Source: UniProtKB-KW

GO - Biological processi

  1. cytokine-mediated signaling pathway Source: Reactome
  2. evasion or tolerance by virus of host immune response Source: Reactome
  3. modification by virus of host mRNA processing Source: Reactome
  4. modulation by virus of host morphology or physiology Source: Reactome
  5. modulation by virus of host process Source: Reactome
  6. suppression by virus of host mRNA processing Source: UniProtKB-KW
  7. suppression by virus of host PKR activity Source: UniProtKB-KW
  8. suppression by virus of host RIG-I activity Source: UniProtKB-KW
  9. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  10. viral life cycle Source: Reactome
  11. viral process Source: Reactome
  12. viral transcription Source: Reactome
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

Enzyme and pathway databases

ReactomeiREACT_115831. ISG15 antiviral mechanism.
REACT_6173. Inhibition of Host mRNA Processing and RNA Silencing.
REACT_6320. Inhibition of IFN-beta.
REACT_6350. Inhibition of PKR.
REACT_9491. Viral mRNA Translation.

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/Puerto Rico/8/1934 H1N1)
Taxonomic identifieri211044 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000009255: 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 (By similarity).By similarity

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. host cell cytoplasm Source: UniProtKB-KW
  3. host cell nucleus Source: UniProtKB-KW
  4. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi20 – 201K → A: No of ISGylation of band I form; when associated with K-41; K-217 and K-219. 1 Publication
Mutagenesisi38 – 381R → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-41. 1 Publication
Mutagenesisi41 – 411K → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-38. 2 Publications
Mutagenesisi41 – 411K → A: No of ISGylation of band I form; when associated with K-20; K-217 and K-219. 2 Publications
Mutagenesisi96 – 961E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-97. 1 Publication
Mutagenesisi97 – 971E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-96. 1 Publication
Mutagenesisi108 – 1081K → A: No of ISGylation of band II form; when associated with K-110 and K-126. 1 Publication
Mutagenesisi110 – 1101K → A: No of ISGylation of band II form; when associated with K-108 and K-126. 1 Publication
Mutagenesisi126 – 1261K → A: No of ISGylation of band II form; when associated with K-108 and K-110. 1 Publication
Mutagenesisi217 – 2171K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-219. 1 Publication
Mutagenesisi219 – 2191K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-217. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 230230Non-structural protein 1PRO_0000078945Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki20 – 20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host
Cross-linki41 – 41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host
Cross-linki108 – 108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host
Cross-linki110 – 110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host
Cross-linki126 – 126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host
Cross-linki217 – 217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host
Cross-linki219 – 219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host

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. 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.1 Publication

Keywords - PTMi

Isopeptide bond, 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 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
PIK3R2O004598EBI-2547442,EBI-346930From a different organism.
STAU1O957933EBI-2547442,EBI-358174From a different organism.
TRIM25Q142583EBI-2547442,EBI-2341129From a different organism.

Protein-protein interaction databases

DIPiDIP-29081N.
IntActiP03496. 172 interactions.
MINTiMINT-3381930.

Structurei

Secondary structure

1
230
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 2422
Helixi30 – 5021
Helixi54 – 6916
Beta strandi88 – 936
Helixi95 – 995
Beta strandi105 – 1128
Beta strandi115 – 1206
Beta strandi127 – 13711
Beta strandi140 – 15112
Beta strandi156 – 1627
Helixi171 – 18717
Beta strandi191 – 1944
Helixi196 – 2016

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP03496.
SMRiP03496. Positions 1-72, 79-205.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03496.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7373RNA-binding and homodimerizationBy similarityAdd
BLAST
Regioni180 – 21536CPSF4-bindingBy similarityAdd
BLAST
Regioni223 – 2308PABPN1-bindingBy similarity

Motif

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

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. Align

Isoform NS1 (identifier: P03496) [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
GLDIETATRA 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):25,868
Last modified:July 21, 1986 - v1
Checksum:i2F7EC18E3EE7A4BE
GO
Isoform NEP (identifier: P03508-1) [UniParc]FASTAAdd to Basket

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.
Length:121
Mass (Da):14,380
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti55 – 551E → K in ABD77680. 1 PublicationCurated
Sequence conflicti101 – 1011D → E in AAA43536. (PubMed:11779399)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
RefSeqiNP_040984.1. NC_002020.1.

Genome annotation databases

GeneIDi956533.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
RefSeqi NP_040984.1. NC_002020.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2GX9 X-ray 2.10 A/B 79-207 [» ]
2ZKO X-ray 1.70 A/B 1-70 [» ]
3L4Q X-ray 2.30 A/B 73-230 [» ]
3O9Q X-ray 2.50 A/B 79-230 [» ]
3O9R X-ray 2.00 A/B 79-230 [» ]
3O9S X-ray 2.48 A/B 79-230 [» ]
3O9T X-ray 2.20 A/B 79-230 [» ]
3O9U X-ray 3.20 A/B/C/D/E/F/G/H 79-230 [» ]
3RVC X-ray 1.80 A 79-230 [» ]
ProteinModelPortali P03496.
SMRi P03496. Positions 1-72, 79-205.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-29081N.
IntActi P03496. 172 interactions.
MINTi MINT-3381930.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 956533.

Enzyme and pathway databases

Reactomei REACT_115831. ISG15 antiviral mechanism.
REACT_6173. Inhibition of Host mRNA Processing and RNA Silencing.
REACT_6320. Inhibition of IFN-beta.
REACT_6350. Inhibition of PKR.
REACT_9491. Viral mRNA Translation.

Miscellaneous databases

EvolutionaryTracei P03496.

Family and domain databases

Gene3Di 1.10.287.10. 1 hit.
InterProi IPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
[Graphical view ]
Pfami PF00600. Flu_NS1. 1 hit.
[Graphical view ]
SUPFAMi SSF47060. SSF47060. 1 hit.
ProtoNeti Search...

Publicationsi

  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. 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. 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.

Entry informationi

Entry nameiNS1_I34A1
AccessioniPrimary (citable) accession number: P03496
Secondary accession number(s): Q20N32, Q67267, Q71QT3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 29, 2014
This is version 106 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, Reference proteome

Documents

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

External Data

Dasty 3