NEP_I34A1
ID NEP_I34A1 Reviewed; 121 AA.
AC P03508; A4GXG8; Q20N33; Q67266; Q71QT4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Nuclear export protein {ECO:0000255|HAMAP-Rule:MF_04067};
DE Short=NEP {ECO:0000255|HAMAP-Rule:MF_04067};
DE AltName: Full=Non-structural protein 2 {ECO:0000255|HAMAP-Rule:MF_04067};
DE Short=NS2 {ECO:0000255|HAMAP-Rule:MF_04067};
GN Name=NS {ECO:0000255|HAMAP-Rule:MF_04067};
OS Influenza A virus (strain A/Puerto Rico/8/1934 H1N1).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=211044;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7465426; DOI=10.1093/nar/8.23.5845;
RA Baez M., Taussig R., Zazra J.J., Young J.F., Palese P., Reisfeld A.,
RA Skalka A.M.;
RT "Complete nucleotide sequence of the influenza A/PR/8/34 virus NS gene and
RT comparison with the NS genes of the A/Udorn/72 and A/FPV/Rostock/34
RT strains.";
RL Nucleic Acids Res. 8:5845-5858(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7385583; DOI=10.1016/0042-6822(80)90188-9;
RA Air G.M., Hackett J.A.;
RT "Gene 8 of influenza virus: sequences of cDNA transcribed from the 3' ends
RT of viral RNA of influenza A and B strains.";
RL Virology 103:291-298(1980).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND REVERSE GENETICS.
RX PubMed=15163504; DOI=10.1016/j.virusres.2004.02.028;
RA de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F.,
RA Osterhaus A.D.M.E., Fouchier R.A.M.;
RT "Efficient generation and growth of influenza virus A/PR/8/34 from eight
RT cDNA fragments.";
RL Virus Res. 103:155-161(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=11779399; DOI=10.1098/rstb.2001.0979;
RA Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L.,
RA Garcia-Sastre A., Palese P.;
RT "Plasmid-only rescue of influenza A virus vaccine candidates.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V.,
RA Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H.,
RA Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y.,
RA Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.;
RT "The NIAID influenza genome sequencing project.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP INTERACTION WITH M1 PROTEIN.
RX PubMed=8356796; DOI=10.1006/viro.1993.1473;
RA Yasuda J., Nakada S., Kato A., Toyoda T., Ishihama A.;
RT "Molecular assembly of influenza virus: association of the NS2 protein with
RT virion matrix.";
RL Virology 196:249-255(1993).
RN [7]
RP INTERACTION WITH HUMAN RAB/HRB.
RX PubMed=9427762; DOI=10.1093/emboj/17.1.288;
RA O'Neill R.E., Talon J., Palese P.;
RT "The influenza virus NEP (NS2 protein) mediates the nuclear export of viral
RT ribonucleoproteins.";
RL EMBO J. 17:288-296(1998).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 59-116.
RX PubMed=12970177; DOI=10.1093/emboj/cdg449;
RA Akarsu H., Burmeister W.P., Petosa C., Petit I., Muller C.W., Ruigrok R.W.,
RA Baudin F.;
RT "Crystal structure of the M1 protein-binding domain of the influenza A
RT virus nuclear export protein (NEP/NS2).";
RL EMBO J. 22:4646-4655(2003).
CC -!- FUNCTION: Mediates the nuclear export of encapsidated genomic RNAs
CC (ribonucleoproteins, RNPs). Acts as an adapter between viral RNPs
CC complexes and the nuclear export machinery of the cell. Possesses no
CC intrinsic RNA-binding activity, but includes a C-terminal M1-binding
CC domain. This domain is believed to allow recognition of RNPs bound to
CC the protein M1. Since protein M1 is not available in large quantities
CC before late stages of infection, such an indirect recognition mechanism
CC probably ensures that genomic RNPs are not exported from the host
CC nucleus until sufficient quantities of viral mRNA and progeny genomic
CC RNA have been synthesized. Furthermore, the RNPs enter the host
CC cytoplasm only when associated with the M1 protein that is necessary to
CC guide them to the plasma membrane. May down-regulate viral RNA
CC synthesis when overproduced. {ECO:0000255|HAMAP-Rule:MF_04067}.
CC -!- SUBUNIT: Interacts with protein M1. May interact with host nucleoporin
CC RAB/HRB and exportin XPO1/CRM1. {ECO:0000255|HAMAP-Rule:MF_04067}.
CC -!- INTERACTION:
CC P03508; P03485: M; NbExp=3; IntAct=EBI-2547979, EBI-2547543;
CC P03508; Q96RP9: GFM1; Xeno; NbExp=2; IntAct=EBI-2547979, EBI-2255048;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04067}. Host
CC nucleus {ECO:0000255|HAMAP-Rule:MF_04067}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=NEP; Synonyms=NS2;
CC IsoId=P03508-1; Sequence=Displayed;
CC Name=NS1;
CC IsoId=P03496-1; Sequence=External;
CC -!- MISCELLANEOUS: Average number present in a viral particle is estimated
CC to be 130-200 molecules.
CC -!- SIMILARITY: Belongs to the influenza viruses NEP family.
CC {ECO:0000255|HAMAP-Rule:MF_04067}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; V01104; CAA24293.1; -; Genomic_RNA.
DR EMBL; J02150; AAA43535.1; -; Genomic_RNA.
DR EMBL; EF467817; ABO21704.1; -; Genomic_RNA.
DR EMBL; AF389122; AAM75164.1; -; Genomic_RNA.
DR EMBL; CY009448; ABD77681.1; -; Genomic_RNA.
DR RefSeq; NP_040983.1; NC_002020.1.
DR PDB; 1PD3; X-ray; 2.60 A; A/B=59-116.
DR PDBsum; 1PD3; -.
DR SMR; P03508; -.
DR IntAct; P03508; 60.
DR MINT; P03508; -.
DR GeneID; 956532; -.
DR KEGG; vg:956532; -.
DR Reactome; R-HSA-168255; Influenza Infection.
DR Reactome; R-HSA-168275; Entry of Influenza Virion into Host Cell via Endocytosis.
DR Reactome; R-HSA-168288; Fusion of the Influenza Virion to the Host Cell Endosome.
DR Reactome; R-HSA-168298; Release.
DR Reactome; R-HSA-168302; Budding.
DR Reactome; R-HSA-168303; Packaging of Eight RNA Segments.
DR Reactome; R-HSA-168330; Viral RNP Complexes in the Host Cell Nucleus.
DR Reactome; R-HSA-168333; NEP/NS2 Interacts with the Cellular Export Machinery.
DR Reactome; R-HSA-168336; Uncoating of the Influenza Virion.
DR Reactome; R-HSA-192823; Viral mRNA Translation.
DR EvolutionaryTrace; P03508; -.
DR Proteomes; UP000009255; Genome.
DR Proteomes; UP000116373; Genome.
DR Proteomes; UP000170967; Genome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0039675; P:exit of virus from host cell nucleus through nuclear pore; IDA:UniProtKB.
DR HAMAP; MF_04067; INFV_NEP; 1.
DR InterPro; IPR000968; Flu_NS2.
DR Pfam; PF00601; Flu_NS2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Host nucleus; Host-virus interaction;
KW Reference proteome; Transport; Virion.
FT CHAIN 1..121
FT /note="Nuclear export protein"
FT /id="PRO_0000079005"
FT MOTIF 12..21
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04067"
FT MOTIF 85..94
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04067"
FT CONFLICT 26
FT /note="G -> E (in Ref. 2; AAA43535, 3; ABO21704 and 5;
FT ABD77681)"
FT CONFLICT 89
FT /note="I -> V (in Ref. 2; AAA43535)"
FT HELIX 64..85
FT /evidence="ECO:0007829|PDB:1PD3"
FT HELIX 94..115
FT /evidence="ECO:0007829|PDB:1PD3"
SQ SEQUENCE 121 AA; 14380 MW; ABFAC522B4F14854 CRC64;
MDPNTVSSFQ DILLRMSKMQ LESSSGDLNG MITQFESLKL YRDSLGEAVM RMGDLHSLQN
RNEKWREQLG QKFEEIRWLI EEVRHKLKIT ENSFEQITFM QALHLLLEVE QEIRTFSFQL
I
