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 08-NOV-2023, entry version 126. 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; OC Alphainfluenzavirus influenzae; Influenza A virus. 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 OrthoDB; 16129at10239; -. 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 Gene3D; 1.10.287.230; -; 1. DR HAMAP; MF_04067; INFV_NEP; 1. DR InterPro; IPR000968; Flu_NS2. DR Pfam; PF00601; Flu_NS2; 1. DR SUPFAM; SSF101156; Nonstructural protein ns2, Nep, M1-binding domain; 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 //