NS - Non-structural protein 1 - Influenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1)

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

RNA binding Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

suppression by virus of host mRNA processing Source: UniProtKB-KW
suppression by virus of host PKR activity Source: UniProtKB-KW
suppression by virus of host RIG-I activity Source: UniProtKB-KW
suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	RNA-binding
Biological process	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

Molecular function

RNA-binding

Biological process

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

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
Organismⁱ	Influenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1)
Taxonomic identifierⁱ	455880 [NCBI]
Taxonomic lineageⁱ	Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Alphainfluenzavirus › Influenza A virus › H1N1 subtype
Virus hostⁱ	Aves [TaxID: 8782] Homo sapiens (Human) [TaxID: 9606] Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationⁱ

Host nucleus
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04066
Host cytoplasm
UniRule annotation
Manual assertion according to rulesⁱ
- HAMAP-Rule:MF_04066

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

host cell cytoplasm Source: UniProtKB-SubCell
host cell nucleus Source: UniProtKB-SubCell

View the complete GO annotation on QuickGO ...

Keywords - Cellular componentⁱ

Host cytoplasm, Host nucleus

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000372979	1 – 230	Non-structural protein 1Add BLAST		230

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

ProteinModelPortalⁱ	A8C8K0
SMRⁱ	A8C8K0
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	1 – 73	RNA-binding and homodimerizationUniRule annotationAdd BLAST	73
Regionⁱ	180 – 215	CPSF4-bindingUniRule annotationAdd BLAST	36
Regionⁱ	223 – 230	PABPN1-bindingUniRule annotation	8

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	34 – 38	Nuclear localization signalUniRule annotation		5
Motifⁱ	137 – 146	Nuclear export signalUniRule annotation		10

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

Gene3Dⁱ	3.30.420.330, 1 hit
HAMAPⁱ	MF_04066 INFV_NS1, 1 hit
InterProⁱ	View protein in InterPro IPR004208 NS1 IPR000256 NS1A IPR038064 NS1A_effect_dom_like_sp IPR009068 S15_NS1_RNA-bd
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00600 Flu_NS1, 1 hit
SUPFAMⁱ	SSF143021 SSF143021, 1 hit SSF47060 SSF47060, 1 hit

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket Added to basket

Isoform NS1 (identifier: A8C8K0-1) [UniParc]FASTA Add 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
MDSHTVSSFQ VDCFLWHVRK QVADQDLGDA PFLDRLRRDQ KSLKGRGSTL 
        60         70         80         90        100
GLNIETATCV GKQIVERILK EESDEALKMT MASALASRYL TDMTVEEMSR 
       110        120        130        140        150
DWFMLMPKQK VAGPLCVRMD QAIMDKNIIL KANFSVIFDR LENLTLLRAF 
       160        170        180        190        200
TEEGAIVGEI SPLPSFPGHT NEDVKNAIGV LIGGLEWNDN TVRVSETLQR 
       210        220        230
FAWRSSNETG GPPFTTTQKR KMAGTTRSEI

Length:230

Mass (Da):25,815

Last modified:November 13, 2007 - v1

Checksum:ⁱEB0B53149B12F196

GO

Isoform NEP (identifier: A8C8J9-1) [UniParc]FASTA Add to basket

Also known as: NS2

The sequence of this isoform can be found in the external entry A8C8J9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

Length:121

Mass (Da):14,285

GO

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	CY026215 Viral cRNA Translation: ABV45931.1

Select the link destinations:
EMBLⁱ
GenBankⁱ
DDBJⁱ

Links Updated

CY026215 Viral cRNA Translation: ABV45931.1

Keywords - Coding sequence diversityⁱ

Alternative splicing

Protein	Similar proteins	Organisms	Length	Cluster ID	Cluster name	Size
A8C8K0	A8C7K6 X2DZY9 E1TX27 A9C7R9 A9C5A0 A9C5S6 B0KVL0 A9C8U2 A9C7J2 A8C8G5 +44	Influenza A virus (A/Texas/UR06-0174/2007(H1N1)) Influenza A virus (A/New York/1054/2007(H1N1)) Influenza A virus (A/California/VRDL298/2009(H1N1)) Influenza A virus (A/North Carolina/UR06-0011/2006(H1N1)) Influenza A virus (A/Kentucky/UR06-0057/2007(H1N1)) Influenza A virus (A/New York/UR06-0253/2007(H1N1)) Influenza A virus (A/Virginia/UR06-0361/2007(H1N1)) Influenza A virus (A/Tennessee/UR06-0262/2007(H1N1)) Influenza A virus (A/Illinois/UR06-0137/2007(H1N1)) Influenza A virus (A/Texas/UR06-0303/2007(H1N1)) And more	230	UniRef100_A8C8K0	Cluster: Non-structural protein 1	55

Protein	Similar proteins	Organisms	Length	Cluster ID	Cluster name	Size
A8C8K0	Q07FH9 Q0HCZ9 Q0HCV5 Q0HCX7 I7CB49 Q07FG8 Q00PU4 I7C0Z2 Q09YY2 Q07FF7 +1441	Influenza A virus (strain A/China:Nanchang/11/1996 H1N1) Influenza A virus (A/Nanchang/15/1996(H1N1)) Influenza A virus (A/Nanchang/26/1996(H1N1)) Influenza A virus (A/Nanchang/17/1996(H1N1)) Influenza A virus (A/Ostrava/801/1998(H1N1)) Influenza A virus (A/Nanchang/23/1996(H1N1)) Influenza A virus (A/Nanchang/14/1996(H1N1)) Influenza A virus (A/Nanchang/16A/1999(H1N1)) Influenza A virus (A/Nanchang/21/1996(H1N1)) Influenza A virus (A/Nanchang/25/1996(H1N1)) And more	230	UniRef90_Q07FH9	Cluster: Non-structural protein 1	1,452

Protein	Similar proteins	Organisms	Length	Cluster ID	Cluster name	Size
A8C8K0	P03495 Q6XST2 H9XCJ7 Q6XST4 Q20MD0 H9XI80 Q2LNT3 UPI000011285E UPI00018BF9E7 Q463W9 +50487	Influenza A virus (strain A/Udorn/307/1972 H3N2) Influenza A virus (A/Victoria/4/72(H3N2)) Influenza A virus (A/Bilthoven/748/1973(H3N2)) Influenza A virus (A/Tokyo/31/72(H3N2)) Influenza A virus (strain A/Udorn/1972 H3N2) Influenza A virus (A/Bilthoven/3517/1973(H3N2)) Influenza A virus (A/Guandong/243/1972(H3N2)) Influenza A virus Influenza A virus (strain A/Memphis/102/1972 H3N2) Influenza A virus (strain A/Memphis/101/1972 H3N2) And more	237	UniRef50_P03495	Cluster: Non-structural protein 1	50,498

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	CY026215 Viral cRNA Translation: ABV45931.1

Select the link destinations:
EMBLⁱ
GenBankⁱ
DDBJⁱ

Links Updated

CY026215 Viral cRNA Translation: ABV45931.1

3D structure databases

ProteinModelPortalⁱ	A8C8K0
SMRⁱ	A8C8K0
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Family and domain databases

Gene3Dⁱ	3.30.420.330, 1 hit
HAMAPⁱ	MF_04066 INFV_NS1, 1 hit
InterProⁱ	View protein in InterPro IPR004208 NS1 IPR000256 NS1A IPR038064 NS1A_effect_dom_like_sp IPR009068 S15_NS1_RNA-bd
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00600 Flu_NS1, 1 hit
SUPFAMⁱ	SSF143021 SSF143021, 1 hit SSF47060 SSF47060, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	NS1_I07A0
Accessionⁱ	A8C8K0Primary (citable) accession number: A8C8K0
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	May 5, 2009
	Last sequence update:	November 13, 2007
	Last modified:	April 25, 2018
	This is version 47 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Viral Protein Annotation Program

UniProtKB - A8C8K0 (NS1_I07A0)

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Non-structural protein 1

NS

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Keywordsⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Keywords - Cellular componentⁱ

PTM / Processingⁱ

Molecule processing

Post-translational modificationⁱ

Keywords - PTMⁱ

Interactionⁱ

Subunit structureⁱ

Structureⁱ

3D structure databases

Family & Domainsⁱ

Region

Motif

Domainⁱ

Sequence similaritiesⁱ

Family and domain databases

Sequences (2)ⁱ

Sequence databases

Keywords - Coding sequence diversityⁱ

Similar proteinsⁱ

Cross-referencesⁱ

Sequence databases

3D structure databases

Protocols and materials databases

Family and domain databases

Entry informationⁱ

UniProt is an ELIXIR core data resource

UniProtKB

UniParc

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UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - A8C8K0 (NS1_I07A0)

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Non-structural protein 1

NS

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Motif

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Family and domain databases

Sequence databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protocols and materials databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

PTM / Processingⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Cross-referencesⁱ

Entry informationⁱ