Non-structural protein 1 - NS - Influenza A virus (strain A/Hickox/1940 H1N1)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Amino acid modifications

Preferred order of sections

Molecule processing

Regions

Amino acid modifications

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Family and domain databases

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Q0HD54 (NS1_I40A0) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 42. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Protein names

Recommended name:
Non-structural protein 1
Short name=NS1

Alternative name(s):
NS1A

Gene names

Name:

Organism

Influenza A virus (strain A/Hickox/1940 H1N1) [Complete proteome]

Taxonomic identifier

383543 [NCBI]

Taxonomic lineage

Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›

Virus host

Aves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Sequence length	237 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

Function	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. 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.
Subunit structure	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.
Subcellular location	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.
Domain	The dsRNA-binding region is required for suppression of RNA silencing By similarity.
Post-translational modification	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 By similarity.
Sequence similarities	Belongs to the influenza A viruses NS1 family.

Keywords
Biological process	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
Cellular component	Host cytoplasm Host nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
Molecular function	Suppressor of RNA silencing
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome
Gene Ontology (GO)
Biological_process	suppression by virus of host PKR activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host RIG-I activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 237

237

Non-structural protein 1

PRO_0000372982

Region

1 – 73

RNA-binding and homodimerization By similarity

Region

180 – 215

CPSF4-binding By similarity

Region

223 – 237

PABPN1-binding By similarity

Motif

34 – 38

Nuclear localization signal 1 By similarity

Motif

137 – 146

Nuclear export signal By similarity

Motif

216 – 221

Nuclear localization signal 2 By similarity

Cross-link

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity

Cross-link

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity

Cross-link

108

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity

Cross-link

110

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity

Cross-link

126

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host By similarity

Cross-link

217

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity

Cross-link

219

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity

Sequence

Length

Mass (Da)

Tools

Isoform NS1 [UniParc].

Last modified October 3, 2006. Version 1.
Checksum: E419A374F7DF4E34
Show »

FASTA

237

26,831

        10         20         30         40         50         60 
MDPNTVSSFQ VDCFLWHVRK RVADQELGDA PFLDRLRRDQ KSLKGRGSTL GLNIETATRV 

        70         80         90        100        110        120 
GKQIVERILK EESDEALKMT MASAPASRYL TDMTIEEMSR DWFMLMPKQK VAGPLCIRMD 

       130        140        150        160        170        180 
QAVMDKSIIL KANFSVIFDR LETLILLRAF TEEGAIVGEI SPLPSLPGHT NEDVKNAIGV 

       190        200        210        220        230 
LIGGLEWNDN TVRVSKTLQR FAWRSSNENG GPPLTPKQKR KMARTIRSEV RRNKMVD

« Hide

Isoform NEP (NS2) [UniParc].

See Q0HD55.

–

[1]	"The NIAID influenza genome sequencing project." Spiro D., Ghedin E., Sengamalay N., Halpin R., Boyne A., Zaborsky J., Feldblyum T., Subbu V., Sparenborg J., Shumway M., Sitz J., Katzel D., Koo H., Salzberg S.L., Griesemer S., St George K., Bennett R., Taylor J. Tatusova T. Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	The NIAID Influenza Genome Sequencing Consortium Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Sequence databases
EMBL GenBank DDBJ	CY013275 Other RNA. Translation: ABI20831.1.
3D structure databases
ProteinModelPortal	Q0HD54.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
IntAct	Q0HD54. 70 interactions.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	1.10.287.10. 1 hit.
InterPro	IPR000256. Flu_NS1. IPR009068. S15_NS1_RNA-bd. [Graphical view]
Pfam	PF00600. Flu_NS1. 1 hit. [Graphical view]
SUPFAM	SSF47060. SSF47060. 1 hit.
ProtoNet	Search...

Entry name

NS1_I40A0

Accession

Primary (citable) accession number: Q0HD54

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 5, 2009
Last sequence update:	October 3, 2006
Last modified:	February 19, 2014
This is version 42 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform NS1 (identifier: Q0HD54-1)

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.

Isoform NEP (identifier: Q0HD55-1)

Also known as: NS2;

The sequence of this isoform can be found in the external entry Q0HD55.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.