Q99AU3 (NS1_I18A0) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
NS1A

Gene names

Name:

NS

Organism

Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1)) [Complete proteome]

Taxonomic identifier

88776 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A › Influenza A virus › H1N1 subtype

Virus host

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

Protein attributes

Sequence length	230 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 host EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1 By similarity. Ref.2
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.
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.
Sequence similarities	Belongs to the influenza A viruses NS1 family.

Ontologies

Keywords
Biological process	Host gene expression shutoff by virus Host mRNA suppression by virus Host-virus interaction Inhibition of host IFN-mediated response initiation by virus Inhibition of host PKR by virus Inhibition of host RIG-I by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Inhibition of host pre-mRNA processing 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 production 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...

Alternative products

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

Isoform NS1 (identifier: Q99AU3-1)

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: Q77IX1-1)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 230	230	Non-structural protein 1		PRO_0000310570
Regions
	Region	1 – 73	73	RNA-binding By similarity
	Region	180 – 215	36	CPSF4-binding By similarity
	Region	223 – 230	8	PABPN1-binding By similarity
	Motif	34 – 38	5	Nuclear localization signal 1 By similarity
	Motif	137 – 146	10	Nuclear export signal By similarity
	Motif	216 – 221	6	Nuclear localization signal 2 By similarity
Amino acid modifications
	Cross-link	20		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host By similarity
	Cross-link	41		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

Sequences

	Sequence		Length	Mass (Da)
	Isoform NS1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: B3257EA296ADA840	FASTA	230	26,066
	10 20 30 40 50 60 MDSNTVSSFQ VDCFLWHVRK RFADQELGDA PFLDRLRRDQ KSLRGRGSTL GLDIETATRA 70 80 90 100 110 120 GKQIVERILK EESDEALKMT IASVPASRYL TDMTLEEMSR DWFMLMPKQK VAGSLCIRMD 130 140 150 160 170 180 QAIMDKNIIL KANFSVIFDR LETLILLRAF TEEGAIVGEI SPLPSLPGHT DEDVKNAVGV 190 200 210 220 230 LIGGLEWNDN TVRVSETLQR FAWRSSNENG RPPLPPKQKR KMARTIKSEV
	Isoform NEP (NS2) [UniParc]. See Q77IX1.		–	–

References

[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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF333238 Genomic RNA. Translation: AAK14368.1.
3D structure databases
HSSP	HSSP built from PDB template 2GX9 based on UniProtKB Q6LD08.
ProteinModelPortal	Q99AU3.
SMR	Q99AU3. Positions 1-72, 79-205.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q99AU3. 23 interactions.
Proteomic databases
PRIDE	Q99AU3.
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. S15/NS1_bind. 1 hit.
ProtoNet	Search...

Entry information

Entry name

NS1_I18A0

Accession

Primary (citable) accession number: Q99AU3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 13, 2007
Last sequence update:	June 1, 2001
Last modified:	April 3, 2013
This is version 53 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program