Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed-Annotation score: 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

GO - Biological processi

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

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
R-HSA-168315. Inhibition of Host mRNA Processing and RNA Silencing.
R-HSA-168888. Inhibition of IFN-beta.
R-HSA-169131. Inhibition of PKR.
R-HSA-192823. 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 virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000009255 Componenti: 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

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20K → A: No of ISGylation of band I form; when associated with K-41; K-217 and K-219. 1 Publication1
Mutagenesisi38R → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-41. 1 Publication1
Mutagenesisi41K → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-38. 2 Publications1
Mutagenesisi41K → A: No of ISGylation of band I form; when associated with K-20; K-217 and K-219. 2 Publications1
Mutagenesisi96E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-97. 1 Publication1
Mutagenesisi97E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-96. 1 Publication1
Mutagenesisi108K → A: No of ISGylation of band II form; when associated with K-110 and K-126. 1 Publication1
Mutagenesisi110K → A: No of ISGylation of band II form; when associated with K-108 and K-126. 1 Publication1
Mutagenesisi126K → A: No of ISGylation of band II form; when associated with K-108 and K-110. 1 Publication1
Mutagenesisi217K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-219. 1 Publication1
Mutagenesisi219K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-217. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000789451 – 230Non-structural protein 1Add BLAST230

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host1 Publication
Cross-linki41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host1 Publication
Cross-linki108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host1 Publication
Cross-linki110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host1 Publication
Cross-linki126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host1 Publication
Cross-linki217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host1 Publication
Cross-linki219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host1 Publication

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
ADARP552658EBI-2547442,EBI-2462104From a different organism.
ILF3Q129063EBI-2547442,EBI-78756From a different organism.
PIK3R1P279865EBI-2547442,EBI-79464From a different organism.
PIK3R2O004599EBI-2547442,EBI-346930From a different organism.
PRKRAO755693EBI-2547442,EBI-713955From a different organism.
STAU1O957935EBI-2547442,EBI-358174From a different organism.
TRIM25Q142583EBI-2547442,EBI-2341129From a different organism.

Protein-protein interaction databases

DIPiDIP-29081N.
IntActiP03496. 208 interactors.
MINTiMINT-3381930.

Structurei

Secondary structure

1230
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 24Combined sources22
Helixi30 – 50Combined sources21
Helixi54 – 69Combined sources16
Beta strandi88 – 93Combined sources6
Helixi95 – 99Combined sources5
Beta strandi105 – 112Combined sources8
Beta strandi115 – 120Combined sources6
Beta strandi127 – 137Combined sources11
Beta strandi140 – 151Combined sources12
Beta strandi156 – 162Combined sources7
Helixi171 – 187Combined sources17
Beta strandi191 – 194Combined sources4
Helixi196 – 201Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03496.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 73RNA-binding and homodimerizationBy similarityAdd BLAST73
Regioni180 – 215CPSF4-bindingBy similarityAdd BLAST36
Regioni223 – 230PABPN1-bindingBy similarity8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi34 – 38Nuclear localization signal 1By similarity5
Motifi137 – 146Nuclear export signalBy similarity10
Motifi216 – 221Nuclear localization signal 2By similarity6

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

Phylogenomic databases

KOiK19396.

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. AlignAdd to basket

Isoform NS1 (identifier: P03496-1) [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
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)DescriptionActionsGraphical viewLength
Sequence conflicti55E → K in ABD77680 (Ref. 4) Curated1
Sequence conflicti101D → E in AAA43536 (PubMed:11779399).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
KEGGivg:956533.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-29081N.
IntActiP03496. 208 interactors.
MINTiMINT-3381930.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi956533.
KEGGivg:956533.

Phylogenomic databases

KOiK19396.

Enzyme and pathway databases

ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
R-HSA-168276. NS1 Mediated Effects on Host Pathways.
R-HSA-168315. Inhibition of Host mRNA Processing and RNA Silencing.
R-HSA-168888. Inhibition of IFN-beta.
R-HSA-169131. Inhibition of PKR.
R-HSA-192823. Viral mRNA Translation.

Miscellaneous databases

EvolutionaryTraceiP03496.

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.
ProtoNetiSearch...

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: November 2, 2016
This is version 117 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

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.