P03508 (NEP_I34A1) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear export protein
Short name=NEP

Alternative name(s):
Non-structural protein 2
Short name=NS2

Gene names

Name:

NS

Organism

Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) [Reference proteome]

Taxonomic identifier

211044 [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	121 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates the nuclear export of encapsidated genomic RNAs (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs complexes and the nuclear export machinery of the cell. Possesses no intrinsic RNA-binding activity, but includes a C-terminal M1-binding domain. This domain is believed to allow recognition of RNPs to which the M1 protein is bound. Because the M1 protein is not available in large quantities until the later stages of infection, such an indirect recognition mechanism probably ensures that genomic RNPs are not exported from the nucleus before sufficient quantities of viral mRNA and progeny genomic RNA have been synthesized. Furthermore, the RNPs enters the cytoplasm only when they have associated with the M1 protein that is necessary to guide them to the plasma membrane. May down-regulate viral RNA synthesis when overproduced.
Subunit structure	Binds M1 protein. May interact with human nucleoporin RAB/HRB and exportin XPO1/CRM1.
Subcellular location	Virion Potential. Host nucleus.
Miscellaneous	Average number present in a viral particle is estimated to be 130-200 molecules.
Sequence similarities	Belongs to the influenza viruses NEP family.

Ontologies

Keywords
Biological process	Host-virus interaction Transport
Cellular component	Host nucleus Virion
Coding sequence diversity	Alternative splicing
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA export from nucleus Inferred from electronic annotation. Source: InterPro uncoating of virus Traceable author statement. Source: Reactome viral entry into host cell via membrane fusion with the plasma membrane Traceable author statement. Source: Reactome viral entry into host cell via receptor-mediated endocytosis Traceable author statement. Source: Reactome viral genome maturation Traceable author statement. Source: Reactome viral genome packaging Traceable author statement. Source: Reactome viral release from host cell Traceable author statement. Source: Reactome viral transcription Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome endocytic vesicle membrane Traceable author statement. Source: Reactome endosome lumen Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Alternative products

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

Isoform NEP (identifier: P03508-1)

Also known as: NS2;

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 NS1 (identifier: P03496-1)

The sequence of this isoform can be found in the external entry P03496.
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 – 121

121

Nuclear export protein

PRO_0000079005

Regions

Motif

12 – 21

10

Nuclear export signal

Motif

85 – 94

10

Nuclear export signal By similarity

Experimental info

Sequence conflict

26

1

G → E in AAA43535. Ref.2

Sequence conflict

26

1

G → E in ABO21704. Ref.3

Sequence conflict

26

1

G → E in ABD77681. Ref.5

Sequence conflict

89

1

I → V in AAA43535. Ref.2

Secondary structure

1

.

.

.

.

.

121

Helix Strand Turn

Details...

Helix

64 – 85

22

Helix

94 – 115

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform NEP (NS2) [UniParc]. Last modified July 21, 1986. Version 1. Checksum: ABFAC522B4F14854	FASTA	121	14,380
	10 20 30 40 50 60 MDPNTVSSFQ DILLRMSKMQ LESSSGDLNG MITQFESLKL YRDSLGEAVM RMGDLHSLQN 70 80 90 100 110 120 RNEKWREQLG QKFEEIRWLI EEVRHKLKIT ENSFEQITFM QALHLLLEVE QEIRTFSFQL I
	Isoform NS1 [UniParc]. See P03496.		–	–

References

[1]	"Complete nucleotide sequence of the influenza A/PR/8/34 virus NS gene and comparison with the NS genes of the A/Udorn/72 and A/FPV/Rostock/34 strains." Baez M., Taussig R., Zazra J.J., Young J.F., Palese P., Reisfeld A., Skalka A.M. Nucleic Acids Res. 8:5845-5858(1980) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Gene 8 of influenza virus: sequences of cDNA transcribed from the 3' ends of viral RNA of influenza A and B strains." Air G.M., Hackett J.A. Virology 103:291-298(1980) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments." de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M. Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[4]	"Plasmid-only rescue of influenza A virus vaccine candidates." Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[5]	"The NIAID influenza genome sequencing project." Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T. Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[6]	"Molecular assembly of influenza virus: association of the NS2 protein with virion matrix." Yasuda J., Nakada S., Kato A., Toyoda T., Ishihama A. Virology 196:249-255(1993) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH M1 PROTEIN.
[7]	"The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins." O'Neill R.E., Talon J., Palese P. EMBO J. 17:288-296(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN RAB/HRB.
[8]	"Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2)." Akarsu H., Burmeister W.P., Petosa C., Petit I., Muller C.W., Ruigrok R.W., Baudin F. EMBO J. 22:4646-4655(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 59-116.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V01104 Genomic RNA. Translation: CAA24293.1.
J02150 Genomic RNA. Translation: AAA43535.1.
EF467817 Genomic RNA. Translation: ABO21704.1.
AF389122 Genomic RNA. Translation: AAM75164.1.
CY009448 Genomic RNA. Translation: ABD77681.1.

RefSeq

NP_040983.1. NC_002020.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PD3	X-ray	2.60	A/B	59-116	[»]

ProteinModelPortal

P03508.

SMR

P03508. Positions 64-116.

ModBase

Search...

Protein-protein interaction databases

IntAct

P03508. 7 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

956532.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Family and domain databases

InterPro

IPR000968. Flu_NS2.
[Graphical view]

Pfam

PF00601. Flu_NS2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P03508.

Entry information

Entry name

NEP_I34A1

Accession

Primary (citable) accession number: P03508
Secondary accession number(s): A4GXG8 , Q20N33, Q67266, Q71QT4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	April 3, 2013
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program