ID NRAM_I02A7 Reviewed; 454 AA. AC Q6DPI6; DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 2. DT 10-JUN-2026, entry version 90. DE RecName: Full=Neuraminidase {ECO:0000255|HAMAP-Rule:MF_04071}; DE EC=3.2.1.18 {ECO:0000255|HAMAP-Rule:MF_04071}; DE Flags: Fragment; GN Name=NA {ECO:0000255|HAMAP-Rule:MF_04071}; OS Influenza A virus (strain A/Teal/China/2978.1/2002 H5N1 genotype W). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus; OC Alphainfluenzavirus influenzae; Influenza A virus. OX NCBI_TaxID=284215; OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=9685; Felis catus (Cat) (Felis silvestris catus). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9691; Panthera pardus (Leopard) (Felis pardus). OH NCBI_TaxID=9694; Panthera tigris (Tiger). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=15241415; DOI=10.1038/nature02746; RA Li K.S., Guan Y., Wang J., Smith G.J.D., Xu K.M., Duan L., Rahardjo A.P., RA Puthavathana P., Buranathai C., Nguyen T.D., Estoepangestie A.T.S., RA Chaisingh A., Auewarakul P., Long H.T., Hanh N.T.H., Webby R.J., RA Poon L.L.M., Chen H., Shortridge K.F., Yuen K.Y., Webster R.G., RA Peiris J.S.M.; RT "Genesis of a highly pathogenic and potentially pandemic H5N1 influenza RT virus in eastern Asia."; RL Nature 430:209-213(2004). RN [2] RP SEQUENCE REVISION. RA Li K.S., Guan Y., Wang J., Smith G.J.D., Xu K.M., Duan L., Rahardjo A.P., RA Puthavathana P., Buranathai C., Nguyen T.D., Estoepangestie A.T.S., RA Chaisingh A., Auewarakul P., Long H.T., Hanh N.T.H., Lim W., Webby R.J., RA Poon L.L.M., Chen H., Shortridge K.F., Yuen K.Y., Webster R.G., RA Peiris J.S.M.; RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues from CC viral and cellular glycoconjugates. Cleaves off the terminal sialic CC acids on the glycosylated HA during virus budding to facilitate virus CC release. Additionally helps virus spread through the circulation by CC further removing sialic acids from the cell surface. These cleavages CC prevent self-aggregation and ensure the efficient spread of the progeny CC virus from cell to cell. Otherwise, infection would be limited to one CC round of replication. Described as a receptor-destroying enzyme because CC it cleaves a terminal sialic acid from the cellular receptors. May CC facilitate viral invasion of the upper airways by cleaving the sialic CC acid moieties on the mucin of the airway epithelial cells. Likely to CC plays a role in the budding process through its association with lipid CC rafts during intracellular transport. May additionally display a raft- CC association independent effect on budding. Plays a role in the CC determination of host range restriction on replication and virulence. CC Sialidase activity in late endosome/lysosome traffic seems to enhance CC virus replication. {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha- CC (2->8)- glycosidic linkages of terminal sialic acid residues in CC oligosaccharides, glycoproteins, glycolipids, colominic acid and CC synthetic substrates.; EC=3.2.1.18; Evidence={ECO:0000255|HAMAP- CC Rule:MF_04071}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|HAMAP- CC Rule:MF_04071}; CC -!- ACTIVITY REGULATION: Inhibited by the neuraminidase inhibitors CC zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs interfere CC with the release of progeny virus from infected cells and are effective CC against all influenza strains. Resistance to neuraminidase inhibitors CC is quite rare. {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP- CC Rule:MF_04071}. Host apical cell membrane {ECO:0000255|HAMAP- CC Rule:MF_04071}; Single-pass type II membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04071}. Note=Preferentially accumulates at CC the apical plasma membrane in infected polarized epithelial cells, CC which is the virus assembly site. Uses lipid rafts for cell surface CC transport and apical sorting. In the virion, forms a mushroom-shaped CC spike on the surface of the membrane. {ECO:0000255|HAMAP- CC Rule:MF_04071}. CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis. CC Possesses two apical sorting signals, one in the ectodomain, which is CC likely to be a glycan, and the other in the transmembrane domain. The CC transmembrane domain also plays a role in lipid raft association. CC {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- PTM: N-glycosylated. {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- MISCELLANEOUS: The influenza A genome consists of 8 RNA segments. CC Genetic variation of hemagglutinin and/or neuraminidase genes results CC in the emergence of new influenza strains. The mechanism of variation CC can be the result of point mutations or the result of genetic CC reassortment between segments of two different strains. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family. CC {ECO:0000255|HAMAP-Rule:MF_04071}. 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; AY651473; AAT73355.2; -; Genomic_RNA. DR SMR; Q6DPI6; -. DR GlyCosmos; Q6DPI6; 7 sites, No reported glycans. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:InterPro. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004308; F:exo-alpha-sialidase activity; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:InterPro. DR CDD; cd15483; Influenza_NA; 1. DR FunFam; 2.120.10.10:FF:000001; Neuraminidase; 1. DR Gene3D; 2.120.10.10; -; 1. DR HAMAP; MF_04071; INFV_NRAM; 1. DR InterPro; IPR001860; Glyco_hydro_34. DR InterPro; IPR033654; Sialidase_Influenza_A/B. DR InterPro; IPR036278; Sialidase_sf. DR Pfam; PF00064; Neur; 1. DR SUPFAM; SSF50939; Sialidases; 1. PE 3: Inferred from homology; KW Calcium; Disulfide bond; Glycoprotein; Glycosidase; Host cell membrane; KW Host membrane; Hydrolase; Membrane; Metal-binding; Signal-anchor; KW Transmembrane; Transmembrane helix; Virion. FT CHAIN <1..454 FT /note="Neuraminidase" FT /id="PRO_0000310940" FT TRANSMEM <1..13 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 14..454 FT /note="Virion surface" FT /evidence="ECO:0000255" FT REGION 21..75 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 76..454 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 136 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 387 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 103 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 137 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 262..263 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 278 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 279 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 283 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 309 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 353 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 43 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 53 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 73 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 131 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 220 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 371 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 77..402 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 109..114 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 169..216 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 218..223 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 264..277 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 266..275 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 303..320 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 406..431 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT NON_TER 1 SQ SEQUENCE 454 AA; 49799 MW; 09163590DFA4E0F0 CRC64; VIGIVSLMLQ IGNIISIWVS HSIQTGNQHQ AEPCIQSIIT YENNTWVNQT YVNISNTNFL TEKTVASVTL AGNSSLCPIS GWAVYSKDNG IRIGSKGDVF VIREPFISCS HLECRTFFLT QGALLNDKHS NGTVKDRSPH RTLMSCPVGE APSPYNSRFE SVAWSASACH DGTNWLTIGI SGPDNGAVAV LKYNGIITDT IKSWRNNILR TQESECACVN GSCFTVMTDG PSNGQASYKI FRIEKGKVVK SVELNAPNYH YEECSCYPDA GEITCVCRDN WHGSNRPWVS FNQNLEYQIG YICSGIFGDN PRPNDGTGSC GPVSSNGAYG IKGFSYKYGN GVWIGRTKST NSRSGFEMIW DPNGWTGTDS NFSVKQDIVA ITDWSGYSGS FVQHPELTGL DCIRPCFWVE LIRGRPKEST IWTSGSSISF CGVNSDTVGW SWPDGAELPF TIDK //