Q0HD54 (NS1_I40A0) 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/Hickox/1940 H1N1) [Complete proteome]

Taxonomic identifier

383543 [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	237 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

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 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.

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: 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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 237	237	Non-structural protein 1		PRO_0000372982
Regions
	Region	1 – 73	73	RNA-binding and homodimerization By similarity
	Region	180 – 215	36	CPSF4-binding By similarity
	Region	223 – 237	15	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 October 3, 2006. Version 1. Checksum: E419A374F7DF4E34	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
	Isoform NEP (NS2) [UniParc]. See Q0HD55.		–	–

References

[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. , Bennink J.R., Yewdell J.W., Bao Y., Bolotov P., Dernovoy D., Kiryutin B., Lipman D.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].

Cross-references

Sequence databases
EMBL GenBank DDBJ	CY013275 Other RNA. Translation: ABI20831.1.
3D structure databases
ProteinModelPortal	Q0HD54.
ModBase	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. S15/NS1_bind. 1 hit.
ProtoNet	Search...

Entry information

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:	March 6, 2013
This is version 39 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program