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Nuclear export protein (NEP) (Non-structural protein 2) (NS2)

 NEP_I34A1               Reviewed;         121 AA.
P03508; A4GXG8; Q20N33; Q67266; Q71QT4;
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
21-JUL-1986, sequence version 1.
07-JUN-2017, entry version 104.
RecName: Full=Nuclear export protein {ECO:0000255|HAMAP-Rule:MF_04067};
Short=NEP {ECO:0000255|HAMAP-Rule:MF_04067};
AltName: Full=Non-structural protein 2 {ECO:0000255|HAMAP-Rule:MF_04067};
Short=NS2 {ECO:0000255|HAMAP-Rule:MF_04067};
Name=NS {ECO:0000255|HAMAP-Rule:MF_04067};
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1).
Viruses; ssRNA viruses; ssRNA negative-strand viruses;
Orthomyxoviridae; Influenzavirus A.
NCBI_TaxID=211044;
NCBI_TaxID=8782; Aves.
NCBI_TaxID=9606; Homo sapiens (Human).
NCBI_TaxID=9823; Sus scrofa (Pig).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
PubMed=7465426; DOI=10.1093/nar/8.23.5845;
Baez M., Taussig R., Zazra J.J., Young J.F., Palese P., Reisfeld A.,
Skalka A.M.;
"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.";
Nucleic Acids Res. 8:5845-5858(1980).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
PubMed=7385583; DOI=10.1016/0042-6822(80)90188-9;
Air G.M., Hackett J.A.;
"Gene 8 of influenza virus: sequences of cDNA transcribed from the 3'
ends of viral RNA of influenza A and B strains.";
Virology 103:291-298(1980).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND REVERSE GENETICS.
PubMed=15163504; DOI=10.1016/j.virusres.2004.02.028;
de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F.,
Osterhaus A.D.M.E., Fouchier R.A.M.;
"Efficient generation and growth of influenza virus A/PR/8/34 from
eight cDNA fragments.";
Virus Res. 103:155-161(2004).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
PubMed=11779399; DOI=10.1098/rstb.2001.0979;
Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L.,
Garcia-Sastre A., Palese P.;
"Plasmid-only rescue of influenza A virus vaccine candidates.";
Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
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.;
"The NIAID influenza genome sequencing project.";
Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
[6]
INTERACTION WITH M1 PROTEIN.
PubMed=8356796; DOI=10.1006/viro.1993.1473;
Yasuda J., Nakada S., Kato A., Toyoda T., Ishihama A.;
"Molecular assembly of influenza virus: association of the NS2 protein
with virion matrix.";
Virology 196:249-255(1993).
[7]
INTERACTION WITH HUMAN RAB/HRB.
PubMed=9427762; DOI=10.1093/emboj/17.1.288;
O'Neill R.E., Talon J., Palese P.;
"The influenza virus NEP (NS2 protein) mediates the nuclear export of
viral ribonucleoproteins.";
EMBO J. 17:288-296(1998).
[8]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 59-116.
PubMed=12970177; DOI=10.1093/emboj/cdg449;
Akarsu H., Burmeister W.P., Petosa C., Petit I., Muller C.W.,
Ruigrok R.W., Baudin F.;
"Crystal structure of the M1 protein-binding domain of the influenza A
virus nuclear export protein (NEP/NS2).";
EMBO J. 22:4646-4655(2003).
-!- 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 bound to the protein M1. Since protein M1 is not available in
large quantities before late stages of infection, such an indirect
recognition mechanism probably ensures that genomic RNPs are not
exported from the host nucleus until sufficient quantities of
viral mRNA and progeny genomic RNA have been synthesized.
Furthermore, the RNPs enter the host cytoplasm only when
associated with the M1 protein that is necessary to guide them to
the plasma membrane. May down-regulate viral RNA synthesis when
overproduced. {ECO:0000255|HAMAP-Rule:MF_04067}.
-!- SUBUNIT: Interacts with protein M1. May interact with host
nucleoporin RAB/HRB and exportin XPO1/CRM1. {ECO:0000255|HAMAP-
Rule:MF_04067}.
-!- INTERACTION:
Q96RP9:GFM1 (xeno); NbExp=2; IntAct=EBI-2547979, EBI-2255048;
P03485:M; NbExp=3; IntAct=EBI-2547979, EBI-2547543;
-!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04067}.
Host nucleus {ECO:0000255|HAMAP-Rule:MF_04067}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=NEP; Synonyms=NS2;
IsoId=P03508-1; Sequence=Displayed;
Name=NS1;
IsoId=P03496-1; Sequence=External;
-!- MISCELLANEOUS: Average number present in a viral particle is
estimated to be 130-200 molecules.
-!- SIMILARITY: Belongs to the influenza viruses NEP family.
{ECO:0000255|HAMAP-Rule:MF_04067}.
-----------------------------------------------------------------------
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EMBL; V01104; CAA24293.1; -; Genomic_RNA.
EMBL; J02150; AAA43535.1; -; Genomic_RNA.
EMBL; EF467817; ABO21704.1; -; Genomic_RNA.
EMBL; AF389122; AAM75164.1; -; Genomic_RNA.
EMBL; CY009448; ABD77681.1; -; Genomic_RNA.
RefSeq; NP_040983.1; NC_002020.1.
PDB; 1PD3; X-ray; 2.60 A; A/B=59-116.
PDBsum; 1PD3; -.
ProteinModelPortal; P03508; -.
SMR; P03508; -.
IntAct; P03508; 60.
MINT; MINT-6376762; -.
GeneID; 956532; -.
KEGG; vg:956532; -.
KO; K19395; -.
OrthoDB; VOG090000NT; -.
Reactome; R-HSA-168255; Influenza Life Cycle.
Reactome; R-HSA-168275; Entry of Influenza Virion into Host Cell via Endocytosis.
Reactome; R-HSA-168288; Fusion of the Influenza Virion to the Host Cell Endosome.
Reactome; R-HSA-168298; Release.
Reactome; R-HSA-168302; Budding.
Reactome; R-HSA-168303; Packaging of Eight RNA Segments.
Reactome; R-HSA-168330; Viral RNP Complexes in the Host Cell Nucleus.
Reactome; R-HSA-168333; NEP/NS2 Interacts with the Cellular Export Machinery.
Reactome; R-HSA-168336; Uncoating of the Influenza Virion.
Reactome; R-HSA-192823; Viral mRNA Translation.
EvolutionaryTrace; P03508; -.
Proteomes; UP000009255; Genome.
Proteomes; UP000109386; Genome.
Proteomes; UP000116373; Genome.
Proteomes; UP000170967; Genome.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
GO; GO:0031904; C:endosome lumen; TAS:Reactome.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0019012; C:virion; IEA:UniProtKB-SubCell.
GO; GO:0039675; P:exit of virus from host cell nucleus through nuclear pore; IDA:UniProtKB.
GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; TAS:Reactome.
GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; TAS:Reactome.
GO; GO:0006405; P:RNA export from nucleus; IEA:InterPro.
GO; GO:0019061; P:uncoating of virus; TAS:Reactome.
GO; GO:0046761; P:viral budding from plasma membrane; TAS:Reactome.
GO; GO:0019072; P:viral genome packaging; TAS:Reactome.
GO; GO:0019076; P:viral release from host cell; TAS:Reactome.
GO; GO:0019083; P:viral transcription; TAS:Reactome.
GO; GO:0019062; P:virion attachment to host cell; TAS:Reactome.
HAMAP; MF_04067; INFV_NEP; 1.
InterPro; IPR000968; Flu_NS2.
Pfam; PF00601; Flu_NS2; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome; Host nucleus;
Host-virus interaction; Reference proteome; Transport; Virion.
CHAIN 1 121 Nuclear export protein.
/FTId=PRO_0000079005.
MOTIF 12 21 Nuclear export signal.
{ECO:0000255|HAMAP-Rule:MF_04067}.
MOTIF 85 94 Nuclear export signal.
{ECO:0000255|HAMAP-Rule:MF_04067}.
CONFLICT 26 26 G -> E (in Ref. 2; AAA43535, 3; ABO21704
and 5; ABD77681).
CONFLICT 89 89 I -> V (in Ref. 2; AAA43535).
HELIX 64 85 {ECO:0000244|PDB:1PD3}.
HELIX 94 115 {ECO:0000244|PDB:1PD3}.
SEQUENCE 121 AA; 14380 MW; ABFAC522B4F14854 CRC64;
MDPNTVSSFQ DILLRMSKMQ LESSSGDLNG MITQFESLKL YRDSLGEAVM RMGDLHSLQN
RNEKWREQLG QKFEEIRWLI EEVRHKLKIT ENSFEQITFM QALHLLLEVE QEIRTFSFQL
I


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