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Q99AU3

- NS1_I18A0

UniProt

Q99AU3 - NS1_I18A0

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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
Status
Reviewed - Annotation score: 3 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. suppression by virus of host mRNA processing Source: UniProtKB-KW
  2. suppression by virus of host PKR activity Source: UniProtKB-KW
  3. suppression by virus of host RIG-I activity Source: UniProtKB-KW
  4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
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

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/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
Taxonomic identifieri88776 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
ProteomesiUP000008430: 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. host cell cytoplasm Source: UniProtKB-KW
  2. host cell nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 230230Non-structural protein 1PRO_0000310570Add
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 hostBy similarity
Cross-linki41 – 41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
Cross-linki108 – 108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
Cross-linki110 – 110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
Cross-linki126 – 126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
Cross-linki217 – 217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
Cross-linki219 – 219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity

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 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PRIDEiQ99AU3.

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 host EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1 (By similarity).By similarity

Protein-protein interaction databases

IntActiQ99AU3. 23 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ99AU3.
SMRiQ99AU3. Positions 1-72, 79-205.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7373RNA-bindingBy 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: Q99AU3-1) [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 RFADQELGDA PFLDRLRRDQ KSLRGRGSTL
60 70 80 90 100
GLDIETATRA GKQIVERILK EESDEALKMT IASVPASRYL TDMTLEEMSR
110 120 130 140 150
DWFMLMPKQK VAGSLCIRMD QAIMDKNIIL KANFSVIFDR LETLILLRAF
160 170 180 190 200
TEEGAIVGEI SPLPSLPGHT DEDVKNAVGV LIGGLEWNDN TVRVSETLQR
210 220 230
FAWRSSNENG RPPLPPKQKR KMARTIKSEV
Length:230
Mass (Da):26,066
Last modified:June 1, 2001 - v1
Checksum:iB3257EA296ADA840
GO
Isoform NEP (identifier: Q77IX1-1) [UniParc]FASTAAdd to Basket

Also known as: NS2

The sequence of this isoform can be found in the external entry Q77IX1.
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
AF333238 Genomic RNA. Translation: AAK14368.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF333238 Genomic RNA. Translation: AAK14368.1 .

3D structure databases

ProteinModelPortali Q99AU3.
SMRi Q99AU3. Positions 1-72, 79-205.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q99AU3. 23 interactions.

Proteomic databases

PRIDEi Q99AU3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

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. "Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes."
    Basler C.F., Reid A.H., Dybing J.K., Janczewski T.A., Fanning T.G., Zheng H., Salvatore M., Perdue M.L., Swayne D.E., Garcia-Sastre A., Palese P., Taubenberger J.K.
    Proc. Natl. Acad. Sci. U.S.A. 98:2746-2751(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "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.

Entry informationi

Entry nameiNS1_I18A0
AccessioniPrimary (citable) accession number: Q99AU3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: June 1, 2001
Last modified: October 29, 2014
This is version 60 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

South Carolina isolate has been sequenced from formalid fixed-lung tissues of a 21-year-old male which died in 1918 at Ft. Jackson, SC. Brevig Mission isolate has been sequenced from lung tissues of an Inuit woman buried in the permafrost in a gravesite near Brevig Mission, Alaska. This sample was recovered by John Hultin, retired pathologist.

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3